Cyclic photobase generators for polyimide formation

Abstract

The present disclosure relates to photobase generators which include a cyclic or heterocyclic moiety, a visible light absorbing moiety, and a linker complex. Application of visible light to the photobase generator may provide a basic entity for manufacturing polyimide.

Description

[0001] CYCLIC PHOTOBASE GENERATORS FOR POLYIMIDE FORMATION

[0002] Inventors: Raghunath R. Dasari, Xinliang Ding, Shijun Zheng, Ussa Sajoto, Cheng- Kang Mai, Kota Nishino, Kumpei Otsuka, and Peng Wang

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004] This application claims priority to U.S. Provisional Application No. 63 / 570,228, filed March 26, 2024, which is incorporated by reference in its entirety.

[0005] FIELD

[0006] The present disclosure relates to photobase generators which may be used for polyimide formation.

[0007] BACKGROUND

[0008] Photobase Generators (PBGs) typically include three parts: a chromophore, responsible for light absorption and thus transforming the energy of photons into chemical energy, a latent base, which is the moiety that releases the actual base upon application of light, and a linker that connects the base with the chromophore. PBGs release amine bases upon light irradiation and are being explored in the areas of photoinitiated polymerization, photoinduced crosslinking of polymers, photo-patterning, adhesives, and lithography. However, photobase generators are less developed than photoacid generators. PBGs are based on both non-ionic and ionic types. A wide range of materials has been used as chromophores for the absorption of light, including those limited to absorption in the ultra-violet region. Typical PBG linkers include carbamates, O- acyloximes, ammonium salts, sulfonamides, formamides, nifedipines, and o- aminoketones. By way of example, O-acyloximes require water to release the base so they may not be ideal in polymeric substrates that are sensitive to water. Overall, carbamate linker based PBGs are efficient and synthetically versatile.

[0009] Polyimides have been widely used as protection and insulation layers in microelectronics due to their excellent chemical, mechanical stability, and electrical properties. Photosensitive polyimides (PSPIs) may be attractive for microelectronics because they can be patterned by direct exposure and developed without a photoresist. PSPIs may find applications in various electronic, electro-optic, waveguide, and nonlinear optical materials. A photosensitive polyimide system typically includes a polyimide precursor and a photobase generator as an accelerator to form a polyimide by a photoreaction. However, a polyimide precursor with an aromatic ring as a basic skeleton typically has a broad absorption band in the ultraviolet (UV) region of wavelengths below 400 nm. Therefore, when ultraviolet light is applied, the photochemical reaction may not proceed effectively in the exposed area because the absorption of light is predominantly by the polyimide precursor, which results in low sensitivity and deterioration of the pattern shape.

[0010] Most PBGs have minimal absorption above 400 nm, so the base generation can only be triggered by UV light. Compared to visible-light initiators, UV responsive catalysts require high photon energy, often achieve reduced curing depths, and may also cause irreversible damage to UV-sensitive materials. Moreover, existing photobase generators also show high thermal residue, and low photolytic base release efficiency, which are undesirable for improving efficiency of a photosensitive polyimide-based electronic device. Thus, there is a need for additional contributions in this area of technology.

[0011] SUMMARY

[0012] Photobase generator compounds described herein may be used to provide good absorption in the visible spectral region, efficient photolytic base release efficiency under photo-irradiation, and low thermal residue. In some embodiments, a photobase generator absorbs light of a first wavelength and emits light of a second, higher wavelength than the first wavelength. The photobase generators disclosed herein may be utilized in methods of making a polyimide film which may be used in microelectronics, printed circuit boards, and / or optical devices, just to provide a few examples. In some aspects, a polyimide film disclosed herein may exhibit high thermal and mechanical stability properties.

[0013] In one embodiment, a compound according to formula (1) is provided:

[0014] In formula (1), n may be 0, 1, or 2; X is C, O or N; Y is O or N; X and Y are optionally connected together to form a ring when n is 1 or 2; R1 is a hydrogen, nitro, phenyl, substituted phenyl, alkynyl, substituted alkynyl or methoxy; R2 is hydrogen, or cyano (

[0015] ), phenyl, substituted phenyl or methoxy, Ra is hydrogen, a Ci-Ce alkyl (cyclopropyl or a trihalomethyl group;and R4is a C3-C8alkyl and Rs is a C3-C8alkyl or R4and Rs are connected together to form a nitrogen containing ring provided that when R4and Rs are connected together to form the nitrogen containing ring Ra is hydrogen, a C3-C8alkyl, or a trihalomethyl group. In some embodiments, n is 1 or 2 and X and Y are connected together to form one of the following rings : , In some embodiments, R1 is In some embodiments,R2is In some embodiments, In some embodiments,

[0016] R4and Rs are connected together and the nitrogen containing ring is one of

[0017] , and . In some embodiments, the compound according to formula (1) may be one of the following:

[0018]

[0019] In one embodiment, a method for making a polyimide includes providing a photobase generator compound as described herein and a polyimide precursor dispersion in a dispersant; covering a substrate with the PBG compound and polyimide precursor; applying visible light to the PBG compound and polyimide precursor on the substrate; and heating the substrate to accomplish at least one of removing the dispersant from the covering and curing the covered substrate. In some forms, the method may further include masking portions of the covered substrate to selectively apply visible light to unmasked portions of the substrate.

[0020] In another embodiment, a method for measuring the base release efficiency of a photobase generator compound includes dissolving a photobase generator as described herein in acetonitrile; measuring the pH of a solution including the compound dissolved in the acetonitrile; exposing the solution to visible light; and measuring the pH of the solution following exposure to visible light.

[0021] In one aspect, a photobase generator compound described herein may exhibit excellent absorption in the visible spectral region, low thermal residue upon heating up to 450 °C and / or base moiety separation. In another aspect, a method for manufacturing polyimide films using a photobase generator compound described herein is provided. These and other embodiments are described in greater detail below.

[0022] BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 is a graphical illustration of polyimidization efficiency.

[0024] FIG. 2 is graphical illustration of absorption spectra of different photobase generator compounds. DETAILED DESCRIPTION

[0025] The present disclosure relates to photobase generator compounds and their use(s) in generating reactive precursors for polyimide generation. The photobase generator compounds disclosed herein may be used for formation of a polyimide under light irradiation conditions, which in turn may be useful for fabrication of efficient microelectronic devices. In some embodiments, the photobase generator may absorb light in the visible region, for example from about 380 nm to about 440 nm, exhibit high photobase release activity, and / or may have a very low thermal residue upon heating above 400 °C.

[0026] The photobase generator compounds described herein may absorb light energy of first wavelength and on heterolytic cleavage, form an aci-nitro intermediate and carbamate that contains a base moiety. The carbamate and carbon dioxide can be further cleaved to provide a desired base compound. In addition, the cleaved base compound(s) may act as a catalyst(s) for formation of polyimide from a polyimide precursor.

[0027] The term “moiety” as used herein refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized as chemical entities embedded in or appended to a molecule.

[0028] The term “benzofuran” as used herein, refers to a chemical moiety with the following structure:

[0029] The term “benzodioxole” as used herein, refers to a chemical moiety with the following structure:

[0030] The term “benzoimidazole” as used herein, refers to a chemical moiety with the following structure: The term “benzodioxine” as used herein, refers to a chemical moiety with the following structure:

[0031] The term “benzooxazine” as used herein, refers to a chemical moiety with the following structure:

[0032] The term “benzene” as used herein, refers to a chemical moiety with the following structure:

[0033] In one embodiment, a photobase generator compound includes a cyclic derivative, a linker group, and a cyclic or acyclic amine derivative. In one form, the cyclic derivative may be a nitro-herteroaryl derivative. In one form, a photobase generator compound may include a visible light absorbing cyclic moiety (e.g., a nitro-substituted heteroaromatic moiety), a linker moiety including a functional group that can promote efficient cleavage of a base (e.g., the base moiety), and a separable base moiety.

[0034] In some forms, the photobase generator compound may include a substituted heteroaryl, such as benzofuran, benzodioxole, benzoimidazole, benzodioxine, dimethoxybenzene and a benzooxazine derivative, or an aryl such as a substituted benzene. By way of non-limiting example, the photobase generator compound may include a structure according to the following general formula:

[0035] In this formula, n is 0, 1 , or 2, X is C, O or N, Y is N or O, X and Y are optionally connected together to form a ring when n is 1 or 2, R1 is a hydrogen, nitro, phenyl, substituted phenyl, alkynyl, substituted alkynyl or methoxy; ; R2 is hydrogen, phenyl, substituted phenyl, alkynyl, substituted alkynyl, cyano ) or methoxy; R3is hydrogen, a C1-C6alkyl (e.g., methyl, cyclopropyl, cyclopentyl, or cyclohexyl), or a trihalomethyl group such as CF3; R4is a C3-C8alkyl and Rs is a C3-C8alkyl or wherein R4and Rs are connected together to form a nitrogen containing ring provided that when R4and Rs are connected together to form the nitrogen containing ring R3is hydrogen, a C3-C8alkyl, or a trihalomethyl group. In some forms, n is 1 or 2 and X and Y are connected to form one of the following rings In some forms, R3is In some forms, R4and Rs are connected together and the nitrogen containing ring connected ring is one of

[0036] While not intending to be bound by any particular theory, it is believed that Ra may stabilize a benzofuran, benzodioxole, benzoimidazole, benzodioxine, dimethoxybenzene and / or benzooxazine aci-nitro intermediate through inductive effect, thereby promoting the release of a base quickly.

[0037] The following are non-limiting examples of compounds according to the aforementioned formula:

[0038]

[0039] In a further embodiment, a method for measuring the base release efficiency of a photobase generator compound may include dissolving a photobase generator compound as described herein in a polar solvent. In some forms, the polar solvent may be acetonitrile. The method may further include measuring the pH of a solution including the photobase generator / dissolved in the polar solvent; exposing the solution to visible light (e.g., about 600 mJ / cm2although other variations are possible); and measuring the pH of the solution following exposure to visible light. The comparative change in pH before and after exposure to visible light may be indicative of the amount of basic moiety released and thus the base release efficiency.

[0040] The photobase generator compounds described herein may have a high photosensitivity or high quantum yield for release of the base moiety upon exposure to a desired wavelength radiation. The photosensitivity is demonstrated by a change in pH before and after exposure, and the pH change maybe greater than about 0.2, about 0.4, about 0.8, about 1.5, or about 2.2 In some forms, the release quantum yield can be greater than about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.8, about 0.9, about 1.0, about 1.5 or about 2.2. Base release efficiency may be measured by subtracting the pH of a photobase generator solution after exposure to light of certain energy vs the pH of the same solution before light exposure, which is equivalent to the release efficiency of the PBG moiety. In various embodiments, the PBG moiety may have a release efficiency greater than about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, about 1.0, about 1.25, about 1.5, about 2.0 or about 2.2. The pH change measurements in solution can be made with a mercury lamp such as a Dymax UV curing conveyor with 5000-EC lamps. In some forms, the photobase generator may absorb ultraviolet and visible light and may have a peak absorption maximum between about 370 nm to about 440 nm wavelength. In some forms, the peak absorption may be in the range of about 370 nm, about 375 nm, about 380 nm, about 390 nm, about 395 nm, about 400 nm, about 410 nm, about 420 nm, about 430 nm, or about 440 nm to about 410 nm, about 420 nm, about 430 nm, or about 440 nm, and / or any permutation of the aforementioned values, e.g., 365 nm, 405 nm, and or 436 nm.

[0041] In one embodiment, a photobase generator may include a spatial distance between an ultraviolet UV and a part of a visible light absorbing benzofuran, benzodioxole, benzoimidazole, benzodioxine, dimethoxybenzene or benzoxazine derivative, and a piperidine base derivative which may be optimized through a linker complex for formation of a carbamate anion, and to photo-release a piperidine or alkyl amine base.

[0042] In some aspects, a photobase generator may include an ultraviolet a part of a visible light absorbing benzofuran, benzodioxole, benzoimidazole, benzodioxine, dimethoxybenzene or benzoxazine derivative, a photo base-release activating substituent, and a nitrogen moiety such as an amino, nitro, or piperidine base moiety. In some forms, a benzofuran, benzodioxole, benzoimidazole, benzodioxine, dimethoxybenzene or benzooxazine derivative absorbs light energy of a first excitation wavelength which may be followed by intramolecular hydrogen abstraction by the nitro group to form an aci-nitro intermediate. The decay rate constant of the aci-nitro intermediate may depend on the substitution of the oNB group. An irreversible cyclization of the aci-nitro intermediate, and subsequent ring-opening may give a hemiacetal intermediate that may hydrolyze to release the carbamate. The carbamate may include a piperidine derivative or acyclic amine derivative, and an ester linkage, and may undergo photodecarboxylation to release a desired piperidine or acyclic amine base moiety. The released base pH change may be greater than zero, e.g., more basic, e.g. from about 0.2 to about 1.5. The released base compound may act as a catalyst for formation of polyimide from a polyimide precursor.

[0043] The linker complex covalently links the ultraviolet and a part of a visible light absorbing benzofuran, benzodioxole, benzoimidazole, benzodioxine, dimethoxybenzene or benzooxazine derivative with the nitrogen containing base moiety. The linker complex may be tuned to optimize the quick release of a nitrogen containing base moiety. By optimizing the linker complex, the efficiency of base release may be tuned.

[0044] The linker complex may include a stabilizing substitution, e.g., methyl, cyclopentyl, cyclohexyl, isopropyl, cyclopropyl, and trifloromethyl. In some forms, the photobase generator includes a linker complex (L), where the linker complex covalently links the UV- visible light absorbing o-nitro heteroaryl derivative to the piperidine or acyclic amine base moiety.

[0045] In some embodiments, the linker complex may include an unsubstituted ester group. When the linker complex includes an unsubstituted ester group, the linker complex may include one of the following structures:

[0046] In some forms, the linker complex may include an unsubstituted ester or substituted ester. In some more particular forms, the linker complex may include an optically substituted C2-C7 ester group. When the linker complex includes a substituted ester group, the linker complex can be selected from among one of the following

[0047] A method for making polyimide may include providing a photobase generator as described herein and a polyimide precursor dispersion. In some forms, the PBG and polyimide precursor may be dispersed within a solvent and / or a dispersant. In some forms, the polyimide precursor can be a polyamidic acid such as one of the following:

[0048] In some forms, the dispersant may be an aprotic / polar / non-polar solvent such as n-methyl pyrrolidone (NMP). The method may also include applying visible light to the PBG and polyimide precursor covered substrate, e.g., about 600 mJ / cm2, and heating the covered substrate to remove the dispersant from the covering, e.g., heating at about 120 °C for at least about 10 minutes. In some forms, the method includes heating the covered surface to cure, polymerize, and / or harden the covered substrate surface, e.g., at about 185 °C for about 5 minutes. The method may also include masking portions of the dispersant covered substrate to restrict, minimize or reduce the exposure of the precursor dispersant to the enabling visible light.

[0049] EXAMPLES

[0050] It has been discovered that photobase generators described herein have exhibited absorption over 400 nm and improved photobase release performance. These benefits are further demonstrated by the following examples, which are intended to be illustrative of the disclosure but are not intended to limit the scope or underlying principles in any way.

[0051] The following examples are procedures for the synthesis of cyclic (e.g., o-nitro heteroaryl) photobase generators as described herein:

[0052]

[0053] Synthesis of PBG1-1.1 (2-bromo-4-formyl-6-methoxyphenyl acetate):

[0054] A solution of 5-bromovanillin (14.6 g, 63.2 mmol, 1.0 equiv) and a catalytic amount of

[0055] / V, / V'-dimethylaminopyridine, DMAP (70 mg, 1 mol%) in dry tetrahydrofuran, and (THF)

[0056] (65 mL) was cooled in an ice bath. Acetic anhydride (8.96 mL, 94.8 mmol, 1.5 equiv) was added via syringe slowly. The yellow solution was stirred at room temperature (RT) for 3 h, and concentrated in a rotary evaporator. Flash chromatography (hexanes:ethyacetate

[0057] 2:1 to 100%ethylacetate) provided PBG1-1.1 as a white crystalline solid (17.9 g, 96% yield). MS (APCI): calculated for Chemical Formula: C8H6BrO3 ([M-Ac]-) = 229; found:

[0058] 229.1H NMR (400 MHz, CDCb) δ 9.89 (s, 1H), 7.69 (d, J = 1.8 Hz, 1H), 7.42 (d, J = 1.7

[0059] Hz, 1H), 3.91 (s, 3H), 2.39 (s, 3H).13C NMR (101 MHz, CDCb) δ 189.88, 167.29, 153.31,

[0060] 143.00, 135.38, 127.70, 118.16, 110.10, 56.55, 20.47.

[0061] Synthesis of PBG1-1.2 (6-bromo-4-formyl-2-methoxy-3-nitrophenyl acetate):

[0062] Fuming nitric acid (HNOa) (90%, 6 mL, 128 mmol) in a round bottom flask was cooled in an ice bath. PBG1-1.1 (2.50 g, 9.15 mmol) was added slowly in small portions. The solution was stirred in the ice bath for 1 h, and poured into ice (~ 100 g). The yellow precipitate was collected by filtration and washed with water. Purification by flash chromatography dichloromethane / ethylacetate (CH2Cl2EtOAc) provided PBG1-1.2 as a yellow solid (2.18 g, 71%). MS (APCI): calculated for Chemical Formula: C10H8BrNO6

[0063] ([M]-) = 317; found: 317.1H NMR (400 MHz, CDCb) 69.86 (s, 1H), 7.94 (s, 1H), 3.95 (s, 3H), 2.44 (s, 3H).13C NMR (101 MHz, CDCb) δ 184.57, 166.52, 147.92, 146.16, 129.20, 126.08, 121.46, 63.27, 20.49.

[0064] Synthesis ooff PBG1-1.3 (4-formyl-2-methoxy-3-nitro-6-

[0065] ((trimethylsilyl)ethynyl)phenyl acetate):

[0066] In a two-neck round bottom flask, a solution of PBG1-1.2 (2.10 g, 6.60 mmol, 1.0 equiv), bis(triphenylphosphine)palladium(ll) dichloride, Pd(PPh3)2Cb. (463 mg, 0.66 mmol, 10 mol%), copper(l)iodide, Cui, (251 mg, 1.32 mmol, 20 mol%) in toluene : N,N- diisopropylethylamine (DI PEA) (30 mL:6 mL) was degassed with argon sparging for 10 min. Trimethylsilylacetylene (1.88 mL, 13.2 mmol, 2.0 equiv) was added via syringe. The reaction was heated and stirred at 50 °C for 2 h, filtered through celite and concentrated to provide a brown oil. Purification by flash chromatography (hexanes to 1:1 hexanes: EtOAc) provided PBG1-1.3 as a brown oil (1.62 g, 73%). MS (APCI): calculated for Chemical Formula: C15H17NO6SI ([M]-) = 335; found: 335.1H NMR (400 MHz, CDCb) δ 9.85 (s, 1H), 7.78 (s, 1H), 3.94 (s, 3H), 2.41 (s, 3H), 0.27 (s, 9H).13C NMR (101 MHz, CDCb) δ 185.37, 166.93, 150.69, 145.57, 129.71, 125.71, 122.83, 105.71, 96.59, 63.29, 20.79, -0.18.

[0067] Synthesis of PBG1-1.4 (7-methoxy-6-nitrobenzofuran-5-carbaldehyde): PBG1-1.3 (1.62 g, 4.83 mmol, 1.0 equiv) was dissolved in dry methanol (MeOH) (24 mL). Potassium carbonate, K2CO3, (2.0 g, 3.0 equiv) was added. The reaction was stirred at room temperature (RT) for 1.5 h. Trifluoroacetic acid (TFA) (1.85 mL, 24.15 mmol, 5.0 equiv) was added, and the reaction was concentrated to provide a brown oil. The crude was diluted with ethylacetate (EtOAc) (100 mL), washed with water (50 mL x 2), brine (20 mL), dried over sodium sulfate, filtered and concentrated.1H NMR shows two products (the alkyne and the furan in a 2:1 ratio). The mixture was dissolved in tetrahydrofuran (THF, 24 mL). N,N-Diisopropylethylamine (DIPEA, 4.2 mL, 24.15 mmol, 5.0 equiv) and copper(l)iodide (920 mg, 4.83 mmol, 1.0 equiv) were added. The suspension was stirred at 50° C for 2 h, filtered and concentrated to provide a brown oil. Purification by flash chromatography (hexanes: EtOAc) provided PBG1-1.4 as an orange crystalline solid (510 mg, 48% yield). MS (APCI): calculated for Chemical Formula: C10H7NO5 ([M]-) = 221; found: 221.1H NMR (400 MHz, CDCb) δ 9.95 (s, 1H), 7.87 (d, J = 2.2 Hz, 1H), 7.82 (s, 1H), 6.98 (d, J = 2.2 Hz, 1H), 4.34 (s, 3H).13C NMR (101 MHz, CDCb) δ 187.02, 149.19, 147.13, 138.13, 138.08, 131.17, 124.45, 118.88, 107.92, 61.59. Synthesis of PBG1-1.5 (1-(7-methoxy-6-nitrobenzofuran-5-yl)ethan-1-ol): A solution of PBG1-1.4 (510 mg, 2.306 mmol, 1.0 equiv) in dry dichloromethane, CH2CI2. (23 mL) was cooled in an ice bath. Trimethylaluminum (AIMe3) (2.0 M in heptane, 2.3 mL, 4.612 mmol, 2.0 equiv) was added dropwise via syringe. The reaction was stirred in the ice bath for 1 h, and quenched with ice / water followed by 1 M MCI until a pH ~ 2. The organic layer was separated, and the aqueous layer was extracted with CH2CI2 (50 mL x3). The combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated to provide a yellow oil. Purification by flash chromatography (hexanes: EtOAc) provided PBG1-1.5 as a yellowish solid (242 mg, 44% yield). MS (APCI): calculated for Chemical Formula: C11H11NO5 ([M]— ) = 237; found: 237.1H NMR (400 MHz, CDCb) δ 7.75 (d, J = 2.2 Hz, 1H), 7.49 (s, 1H), 6.82 (d, J = 2.2 Hz, 1H), 4.97 (q, J = 6.4 Hz, 1 H), 4.28 (s, 3H), 2.46 - 2.06 (br s, 1 H), 1.53 (d, J = 6.4 Hz, 3H).13C NMR (101 MHz, CDCb) δ 147.97, 143.34, 138.60, 137.02, 133.84, 131.56, 111.60, 107.24, 65.60, 61.36, 24.72.

[0068] Synthesis of PBG 1-1 (1-(7-methoxy-6-nitrobenzofuran-5-yl)ethyl dihexylcarbamate): In a round bottom flask, PBG1-1.5 (240 mg, 1.012 mmol, 1.0 equiv) was dissolved in dry dichloromethane, CH2CI2. (10 mL). 4-Nitrophenyl chloroformate (306 mg, 1.518 mmol, 1.5 equiv) and N,N-dimethylaminopyridine, DMAP, (185 mg, 1.518 mmol, 1.5 equiv) were added. The reaction mixture was stirred at room temperature (RT) for 1 h, then dihexylamine (712 uL, 3.035 mmol, 3.0 equiv) was added. The reaction was stirred overnight (15 hrs) and concentrated. Purification by flash chromatography (4:1 hexanes: EtOAc) provided PBG1-1 as a yellowish liquid (348 mg, 77% yield). MS (APCI): calculated for Chemical Formula: C24H36N2O6 ([M]-) = 448; found: 448.1H NMR (400 MHz, CDCb) δ 7.74 (d, J = 2.1 Hz, 1H), 7.28 (s, 1H), 6.78 (d, J = 2.2 Hz, 1H), 5.81 (q, J = 6.6 Hz, 1H), 4.27 (s, 3H), 3.18 (br m + 1, J = 7.5 Hz, 4H), 1.60 (d, J = 6.6 Hz, 3H), 1.54 (br s, 4H), 1.27 (br m, 12H), 0.87 (brs, 6H).13C NMR (101 MHz, CDCb) 6 155.11, 147.98, 143.87, 138.89, 137.61, 131.70, 131.40, 111.99, 107.22, 69.52, 61.54, 47.60, 46.97, 31.73, 30.46, 28.83, 28.11, 23.01, 22.72, 14.13. Synthesis of 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dibutylcarbamate (PBG2-1)

[0069] 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-one (PBG2-1.1): A 500 mL 3-neck round bottom flask was charged with 1-(benzo[d][1,3]dioxol-5-yl)ethan-1-one, (16.4 g, 100 mmol), and nitromethane (120 mL). At room temperature (RT), nitric acid (42 mL, 70%) was added dropwise via an addition funnel over 45 min, and the reaction mixture was stirred for an additional 1 h at RT. Upon completion, the reaction mixture was slowly dropped into cold saturated sodium bicarbonate solution (100 mL) and extracted organic product into ethyl acetate, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 25-100% CH2CI2 in hexanes) to afford the product. Yield: 14.0 g, 67%. MS (LC / MS): calculated for Chemical Formula: C9H8NO5[M+H]+= 210; found: 210.1H NMR (400 MHz, CDCb) 67.54 (s, 1H), 6.75 (s, 1H), 6.17 (s, 2H), 2.48 (s, 3H).

[0070] 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol (PBG2-1.2): A 500 mL 3-neck round bottom flask was charged with tetrahydrofuran (110 mL) under Argon. Sodium borohydride (NaBH4) (4.34 g, 114.74) was added as solid portions and acetic acid (6.56 mL, 114.74) was added dropwise over 15 minutes. 1-(6-nitrobenzo[d][1,3]dioxol-5- yl)ethan-1-one (PBG2-1.1)(12.00 g, 57.37 mmol) was added into the reaction mixture as solid portions, and a further 50 mL of tetrahydrofuran and 50 mL of isopropanol were added. The reaction mixture was stirred for an additional 1 h at room temperature. Upon completion, the reaction mixture was slowly dropped into saturated ammonium chloride solution (300 mL), extracted organic product into diethyl ether, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 5-10% ethyl acetate in CH2CI2) to afford the product Yield: 11.4 g, 94.1%. MS (LC / MS): calculated for Chemical Formula: C9H10NO5 [M+H]+= 212; found: 212.1H NMR (400 MHz, CDCb) 67.46 (s, 1H), 7.27 (s, 1H), 6.15 - 6.07 (m, 2H), 5.46 (qd, J= 6.3, 3.7 Hz, 1H), 2.23 (s, 1H), 1.58 - 1.49 (m, 3H).

[0071] 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dibutylcarbamate (PBG2-1): A 100 mL 2- neck round bottom flask was charged with 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol (PBG2-1.2) (1.20 g, 5.68 mmol) and carbonyldiimidazole (1.10 g, 6.82 mmol) in 15 mL of dichloromethane (CH2CI2). Triethylamine (0.87 mL, 6.25 mmol) was added dropwise and the reaction mixture was stirred at reflux in the dark for 4 h. Then, N, / V-dibutylamine (2.90 mL, 17.06 mmol) was added, and the mixture was stirred in the dark for 14 h. Upon completion, the reaction mixture was washed with water and sodium chloride solution, extracted by CH2CI2. and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (5-20% ethyl acetate in hexanes) to afford the product Yield: 1.46 g, 70.2%. MS (LC / MS): calculated for Chemical Formula: C18H27N2O6 [M+HJ* = 367; found: 367.1H NMR (400 MHz, CDCb) 67.48 (s, 1H), 6.96 (s, 1H), 6.28 (q, J= 6.4 Hz, 1H), 6.17 - 6.01 (m, 2H), 3.36 - 3.04 (m, 4H), 1.59 (d, J = 6.4 Hz, 7H), 1.41 - 1.14 (m, 4H), 1.06 - 0.75 (m, 6H).

[0072] Synthesis of 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate (PBG2-2)

[0073] PBG2-2.1, 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-one: A 1000 mL 3-neck round bottom flask (RBF) was charged with 1-(benzo[d][1,3]dioxol-5-yl)ethan-1-one, (23.8 g, 144.94 mmol), and nitromethane (180 mL). At room temperature (RT), nitric acid (HNOa) (62 mL, 70%) was added dropwise via an addition funnel over 45 min, and the reaction mixture was stirred for an additional 1 h at RT. Upon completion, the reaction mixture was slowly dropped into cold saturated sodium bicarbonate (NaHCOa) solution (300 mL) and extracted organic product into ethyl acetate, washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (NaaSO4) After drying, the crude product was purified by flash chromatography (silica gel, 25-100% CH2CI2 in hexanes) to afford the product PBG2-2.1. Yield: 20.5 g, 67.6%. MS (LC / MS): calculated for Chemical Formula: C9H9NO5 [M+H]+= 210; found: 210.1H NMR (400 MHz, CDCb) δ 7.54 (s, 1H), 6.75 (s, 1H), 6.17 (s, 2H), 2.48 (s, 3H).

[0074] PBG2-2.2, 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol: A 1000 mL 3-neck round bottom flask (RBF) was charged with tetrahydrofuran (200 mL) under Ar. Sodium borohydride (NaBH4) (7.24 g, 191.25) was added as solid portions and acetic acid (5.4 mL, 95.62) was added dropwise over 20 minutes. 1-(6-nitrobenzo[d][1,3]dioxol-5- yl)ethan-1-one (PBG2-2.1), (20.0 g, 95.62 mmol) was added into the reaction mixture as solid portions, and a further 50 mL of tetrahydrofuran and 85 mL of isopropanol were added. The reaction mixture was stirred for an additional 75 minutes at RT. Upon completion, the reaction mixture was slowly dropped into saturated ammonium chloride (NH4CI) solution (300 mL), extracted organic product into diethyl ether, washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (NazSO4). After drying, the crude product was purified by flash chromatography (silica gel, 5-10% ethyl acetate in CH2CI2) to afford the product. Yield: 17.5 g, 87.1%. MS (LC / MS): calculated for Chemical Formula: C9H11NO5 [M+H]+= 212; found: 212.1H NMR (400 MHz, CDCb) 67.46 (s, 1H), 7.27 (s, 1H), 6.15 - 6.07 (m, 2H), 5.46 (qd, J = 6.3, 3.7 Hz, 1H), 2.23 (s, 1H), 1.58 - 1.49 (m, 3H).

[0075] PBG2-2, 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: A 500 mL 2-neck round bottom flask was charged with 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol, PBG2- 2.2, (12.50 g, 59.2 mmol) and carbonyldiimidazole (11.5 g, 71.09 mmol) in 125 mL dichloromethane (CH2CI2). Next, triethylamine (9.0 mL, 65.16 mmol) was added dropwise, and the reaction mixture was stirred at reflux in the dark for 4 h. Then, / V, / V-dihexylamine (41.0 mL, 177.72 mmol) was added, and the mixture was stirred in the dark for 14 h. Upon completion, the reaction mixture was washed with water and NaCI solution, extracted by CH2CI2. and dried over Na2SO4. After drying, the crude product was purified by flash chromatography (90% CH2CI2 in hexanes) to afford the product Yield: 17.3 g, 69.2%. MS (LC / MS): calculated for Chemical Formula: C22H36N2O6[M+H]+= 423; found: 423.1H NMR (400 MHz, CDCb) δ 7.48 (s, 1H), 6.96 (s, 1H), 6.27 (q, J = 6.4 Hz, 1H), 6.13 - 6.03 (m, 2H), 3.32 - 3.08 (m, 4H), 1.59 (d, J = 6.4 Hz, 7H), 1.39 - 1.15 (m, 12H), 0.88 (d, J= 16.7 Hz, 6H). Scheme of compound PBG2-3 synthesis

[0076] General procedure of compound PBG2-3.1 synthesis — (4,5-dimethoxy-2- nitrophenyl)methanol: A 100 mL flask was fitted with a stir bar and was equipped with a Dean-Stark apparatus. To the flask, compound 6-nitroveratraldehyde (2.1 g, 10.0 mmol) and isopropyl alcohol (25 mL) were added. Meanwhile, isopropyl alcohol (15 mL) was added into the Dean-Stark apparatus. To the solution, Aluminum isopropoxide (511.0 mg, 2.5 mmol) was added. After the addition, the reaction mixture was heated up to 110 °C and kept at this temperature for 4 hours. TLC and LCMS showed the completion of the reaction. The reaction mixture was poured into 0.2 N hydrochloric acid (100 mL) and extracted with chloroform (100mL*3). The combined organic phase was dried over anhydrous sodium sulfate and concentrated under rotavapor to provide PBG2-3.1 as a pale-yellow solid for the next step without further purification. 1.9 g, 87% yield. MS (APCI): calculated for Chemical Formula: C9H11NO5 ([M-H]”) = 213 found: 213.1H NMR (400 MHz, CDCb) 7.71 (s, 1H), 7.18 (s, 1H), 4.97 (d, J= 6.4 Hz, 2H), 4.01 (s, 3H), 3.96 (s, 3H), 2.61 (t, J = 6.4 Hz, 1H).

[0077] General procedure of compound PBG2-3.2 synthesis — (4,5-dimethoxy-2-nitrobenzyl (4-nitrophenyl) carbonate): A 100 mL flask was fitted with a stir bar. To the flask, compound PBG2-3.1 (6.4 g, 30.0 mmol) and dimethylacetamide (120 mL) were added, followed by the addition of trimethylamine (8.4 mL, 60.0 mmol). The reaction was cooled down to 0 °C and degassed under vacuum. To the solution, 4-nitrophenyl chloroformate (6.7 g, 33 mmol) was added. After the addition, the reaction mixture was warmed up gradually to room temperature and kept at room temperature for 18 hours. TLC and LCMS showed the completion of the reaction. The reaction mixture was poured into water (2 L) and the precipitate was collected by vacuum filtration. After drying, the precipitate was dissolved in dichloromethane and purified by silica gel flash chromatography to provide PBG2-3.2 as a pale-yellow solid using ethyl acetate in dichloromethane (0-10%) as the eluants. 4.5 g, 40% yield. MS (APCI): calculated for Chemical Formula: C16H14N2O9 ([M+H2OD = 396 found: 396.1H NMR (400 MHz, CDCb) 8.32 (ddd, J = 9.2 Hz, 3.2 Hz, 2.0 Hz, 2H), 7.80 (s, 1H), 7.44 (ddd, J= 9.2 Hz, 3.2 Hz, 2.0 Hz, 2H), 7.13 (s, 1H), 5.74 (s, 2H), 4.05 (s, 3H), 4.01 (s, 3H).

[0078] General procedure of compound PBG2-3synthesis — (6-nitrobenzo[d][1,3]dioxol-5- yljmethyl cyclohexylcarbamate: A 100 mL flask was fitted with a stir bar. To the flask, compound PBG2-3.2 (1.08 g, 3.0 mmol) and dimethylacetamide (18 mL) were added, followed by the addition of cyclohexylamine (1.4 mL, 10.8 mmol). The reaction was degassed under vacuum. To the solution, 1 -hydroxybenzotriazole hydrate (137.8 mg, 0.9 mmol) was added. After the addition, the reaction mixture was heated up to 90 °C and kept at this temperature for 6 hours. TLC and LCMS showed the completion of the reaction. The reaction mixture was poured into 1% sodium bicarbonate (100 mL) and the precipitate was collected by vacuum filtration and washed with water. The precipitate was dried over the vacuum oven at 90 °C for 3 hours to provide a light-yellow solid. 988.0 mg, Quantitative yield. MS (APCI): calculated for Chemical Formula: C15H18N2O6([M+H]+.) = 323 found: 323.1H NMR (400 MHz, CDCb) 7.62 (s, 1H), 7.00 (s, 1H), 6.12 (s, 2H), 5.44 (s, 2H), 3.58-3.41 (m, 1H), 2.01-1.92 (m, 2H), 1.76-1.67 (m, 2H), 1.65-1.58 (m, 2H), 1.41- 1.29 (m, 2H), 1.23-1.11 (m, 3H).

[0079] Synthesis Of PBG2-41 -(6-nitrobenzo[d][1 ,3]dioxol-5-yl)ethyl dicyclohexylcarbamate:

[0080] 1703-53, 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl (4-nitrophenyl) carbonate (PBG2- 4.1): A 100 mL 2-neck round bottom flask was charged with 1-(6-nitrobenzo[d][1,3]dioxol- 5-yl)ethan-1-ol, (PBG2-1.2) (2.40 g, 11.37 mmol), N. / V'-dimethylaminopyridine (2.08 g, 17.05 mmol), and dichloromethane (CH2CI2) (20 mL). At 0 °C, 4-nitrophenyl chloroformate (2.75 g, 13.64 mmol) was added. After the addition, the reaction mixture was allowed to warm to room temperature and stirred for 14 h. Upon completion, the reaction mixture was poured into water (200 mL), and the organic product extracted into CH2CI2, washed with sodium chloride solution, and dried over sodium sulfate. After concentrating, the residue was filtered, and the precipitate was rinsed with CH2CI2 to afford the product Yield: 2.90 g, 67.9%. MS (LC / MS): calculated for Chemical Formula: C16H12N2O9 [M]+= 376; found: 332 (M-44)+.1H NMR (400 MHz, CDCI3) 6 8.31 - 8.19 (m, 2H), 7.52 (s, 1H), 7.40 - 7.30 (m, 2H), 7.13 (s, 1H), 6.42 (q, J = 6.4 Hz, 1H), 6.15 (s, 2H), 1.75 (d, J = 6.4 Hz, 3H).

[0081] 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dicydohexylcarbamate (PBG2-4): A 100 mL 3-neck flask was charged with 1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl (4-nitrophenyl) carbonate, PBG2-4.1, (2.85 g, 7.58 mmol), / V, / V'-dimethylaminopyridine (0.19 g, 1.51 mmol) and / V, / V'-dimethylacetamide (32 mL) under Ar. At RT, 2,6-dimethylpiperidine (4.53 mL, 22.73 mmol) was added, and the reaction mixture was stirred at 90 °C in the dark for 7 h. Upon completion, the reaction mixture was poured into H2O (150 mL), and the organic product was extracted into diethyl ether, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 0-25% ethyl acetate in hexanes) to afford the product. Yield: 1.85 g, 60%. MS (LC / MS): calculated for Chemical Formula: C22H31N2O6 [M+H]+= 419; found: 419.1H NMR (400 MHz, CDCI3) 67.48 (s, 1H), 6.96 (s, 1H), 6.26 (q, J= 6.4 Hz, 1H), 6.09 (s, 2H), 3.78 - 3.10 (m, 2H), 1.79 (s, 6H), 1.61 (d, J = 6.4 Hz, 9H), 1.29 (s, 4H), 1.10 (d, J = 13.9 Hz, 2H).

[0082] Synthesis of cyclopropyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyldihexylcarbamate (PBG2-5) cyclopropyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methanol (PBG2-5.1): A 100 mL 2-neck round bottom flask was charged with 6-nitrobenzo[d][1 ,3]dioxole-5-carbaldehyde (4.60 g, 24.0 mmol), and cyclopropylzincbromide (60 mL, 30 mmol, 0.5 M). The reaction mixture was heated at 50 °C for 24 h. Upon completion, the reaction mixture was dropped slowly into saturated ammonium chloride (NH4CI) (100 mL), and the organic product was extracted into dichloromethane (CH2CI2), washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (silica gel, 20% ethyl acetate in hexanes) to afford the product. Yield: 3.11 g, 55.7%. MS (LC / MS): calculated for Chemical Formula: C11H13NO5 [M+HJ* = 238; found: 238.1H NMR (400 MHz, CDCb) δ 7.42 (s, 1H), 7.27 (s, 1H), 6.11 (s, 2H), 4.82 (dd, J = 7.1, 3.8 Hz, 1H), 2.51 (d, J = 3.8 Hz, 1H), 1.28 (dtd, J = 13.2, 7.4, 5.4 Hz, 1H), 0.72 - 0.34 (m, 4H).

[0083] PBG2-5, cyclopropyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl dihexylcarbamate: A 100 mL 2-neck flask was charged with cyclopropyl(6-nitrobenzo[d][1,3]dioxol-5- y I) methanol (1.40 g, 5.90 mmol) and carbonyldiimidazole (1.15 g, 7.08 mmol) in 20 mL of dichloromethane (CH2CI2). Next, triethylamine (0.90 mL, 6.49 mmol) was added dropwise, and the reaction mixture was stirred at reflux in the dark for 4 h. Then, / V, / V-dihexylamine (4.15 mL, 17.72 mmol) was added, and the mixture was stirred in the dark for 17 h. Upon completion, the reaction mixture was washed with water and sodium chloride (NaCI) solution, extracted by CH2CI2. and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (20% ethylacetate in hexanes) to afford the product Yield: 1.53 g, 58%. MS (LC / MS): calculated for Chemical Formula: C24H37N2O8 [M+H]+= 449; found: 449.1H NMR (400 MHz, CDCb) 67.43 (s, 1H), 6.96 (s, 1H), 6.15 - 6.05 (m, 2H), 6.01 (d, J= 6.7 Hz, 1H), 3.18 (dt, J= 14.8, 7.4 Hz, 4H), 1.48 (s, 2H), 1.42 - 1.12 (m, 13H), 1.00 - 0.76 (m, 6H), 0.68 - 0.47 (m, 4H).

[0084] Synthesis of PBG2-6, cyclopropyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl 4- methylpiperidine-1 -carboxylate

[0085] PBG2-6: A 100 mL 2-neck round bottom flask was charged with cyclopropyl(6- nitrobenzo[d][1,3]dioxol-5-yl)methanol (PBG2-5.1)(1.00 g, 4.21 mmol) and carbonyldiimidazole (0.82 g, 5.06 mmol) in 20 mL of dichloromethane (CH2CI2). Triethylamine (0.65 mL, 4.64 mmol) was added dropwise and the reaction mixture was stirred at reflux in the dark for 4 h. Then, 4-methylpiperidine (1.50 mL, 12.65 mmol) was added, and the mixture was stirred in the dark for 14 h. Upon completion, the reaction mixture was washed with water, and sodium chloride solution, extracted by dichloromethane (CH2CI2). and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (20% acetone in hexanes) to afford the product Yield: 1.05 g, 65.2%. MS (LC / MS): calculated for Chemical Formula: C18H23N2O6 [M+HJ* = 363; found: 363.1H NMR (400 MHz, CDCb) 67.42 (s, 1H), 6.96 (s, 1H), 6.09 (q, J = 1.3 Hz, 2H), 5.96 (d, J = 6.9 Hz, 1H), 4.06 (d, J = 13.1 Hz, 2H), 2.76 (s, 2H), 1.62 (d, J = 12.8 Hz, 2H), 1.53 (d, J = 4.0 Hz, 2H), 1.49 (dq, J = 10.2, 3.3 Hz, 1H), 1.42 - 1.28 (m, 1H), 1.08 (d, J = 13.1 Hz, 2H), 0.94 (d, J = 6.5 Hz, 3H), 0.68 - 0.47 (m, 4H).

[0086] Benzo[d][1,3]dioxol-5-yl(cyclopentyl)methanone (PBG2-7.1): A 250 mL 2-neck round bottom flask was charged with benzo[d][1,3]dioxol-5-ylboronic acid (10.0 g, 60.27 mmol), palladium(I l)acetate (0.56 g, 2.51 mmol), and 2,2'-bipyridyl (0.78 g, 5.02 mmol). The reaction flask was evacuated and refilled with Argon twice. Tetrahydrofuran (40 mL) and cyclopentanecarbonitrile (5.23 mL, 50.23 mmol) were added. To the reaction mixture, trifluoroacetic acid (38.5 mL, 10 eq.) and water (34.5 mL) were added, and the reaction mixture was heated at 70 °C for 24 h. Upon completion, the reaction mixture was dropped slowly into saturated sodium bicarbonate (100 mL), and the organic product was extracted into ethyl acetate, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 40-70% CH2CI2 in hexanes) to afford the product. Yield: 6.30 g, 58%. MS (LC / MS): calculated for Chemical Formula: C13H15O3 [M+H]+= 219; found: 219.1H NMR (400 MHz, CDCb) 67.58 (dd, J = 8.2, 1.7 Hz, 1H), 7.45 (d, J = 1.7 Hz, 1H), 6.84 (d, J = 8.2 Hz, 1H), 3.61 (p, J = 7.9 Hz, 1 H), 1.96 - 1.82 (m, 4H), 1.80 - 1.60 (m, 4H). Cyclopentyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methanone (PBG2-7.2): A 250 mL 3- neck round bottom flask was charged with benzo[d][1,3]dioxol-5- yl(cyclopentyl)methanone (PBG2-7.1) (5.65 g, 26.03 mmol), and nitromethane (46 mL). At room temperature (RT), nitric acid (17 mL, 70%) was added dropwise via an addition funnel over 15 min, and the reaction mixture was stirred for an additional 1 h at RT. Upon completion, the reaction mixture was slowly dropped into cold saturated sodium bicarbonate solution (100 mL) and extracted organic product into ethyl acetate, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 50 -60% CH2CI2 in hexanes) to afford the product. Yield: 4.60 g, 67.5%. MS (LC / MS): calculated for Chemical Formula: C13H14NO5 [M+H]+= 264; found: 264.1H NMR (400 MHz, CDCb) 6 7.57 (s, 1H), 6.71 (s, 1H), 6.17 (s, 2H), 3.13 (p, J = 8.1 Hz, 1H), 1.89 (q, J = 6.9 Hz, 4H), 1.77 (h, J = 6.6 Hz, 2H), 1.60 (dd, J= 10.8, 5.8 Hz, 2H).

[0087] Cyclopentyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methanol (PBG2-7.3): A 250 mL 3-neck round bottom flask was charged with tetrahydrofuran (30 mL) under Argon. Sodium borohydride (NaBH4) (1.30 g, 34.22) was added as solid portions and acetic acid (1.96 mL, 34.22) was added dropwise over 10 minutes. Cyclopentyl(6-nitrobenzo[d][1,3]dioxol- 5-y I) methanone (PBG2-7.2) (4.50 g, 17.11 mmol) was added into the reaction mixture as solid portions, and a further 15 mL of tetrahydrofuran and 15 mL of isopropanol were added. The reaction mixture was stirred for 16 h at room temperature. Upon completion, the reaction mixture was slowly dropped into saturated ammonium chloride solution (150 mL), extracted organic product into diethyl ether, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 90% CH2CI2 in hexanes) to afford the product. Yield: 4.20 g, 92.7%. MS (LC / MS): calculated for Chemical Formula: CI3HI6NO5[M+H]+= 266; found: 266.1H NMR (400 MHz, CDCb) δ 7.39 (s, 1H), 7.16 (s, 1H), 6.10 (s, 2H), 5.11 (dd, J = 7.3, 4.1 Hz, 1H), 2.38 (d, J = 4.1 Hz, 1H), 2.35 - 2.21 (m, 1H), 1.83 - 1.71 (m, 1H), 1.71 - 1.46 (m, 6H), 1.30 - 1.12 (m, 1H).

[0088] Cyclopentyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl (4-nitrophenyl) carbonate PBG2-7.4). A 100 mL 2-neck round bottom flask was charged with cyclopentyl(6- nitrobenzo[d][1,3]dioxol-5-yl)methanol (PBG2-7.3) (1.50 g, 5.66 mmol), N,N- dimethylaminopyridine (1.03 g, 8.49 mmol), and dichloromethane (CH2CI2) (30 mL). At 0 °C, 4-nitrophenyl chloroformate (1.37 g, 6.79 mmol) was added. After the addition, the reaction mixture was allowed to warm to room temperature and stirred for 13 h. Upon completion, the reaction mixture was transferred to a 100 mL single-neck flash, and the solvent was concentrated. The crude product was purified by flash chromatography (silica gel, 50-80% CH2CI2 in hexanes) to afford the product Yield: 1.61 g, 65.2%. MS (LC / MS): calculated for Chemical Formula: [M]+= 430; found: 386 (M-44)*.1H NMR (400 MHz, CDCb) δ 8.23 (d, J = 8.8 Hz, 2H), 7.48 (s, 1H), 7.34 (d, J = 8.7 Hz, 2H), 7.07 (s, 1H), 6.36 (d, J = 7.4 Hz, 1H), 6.14 (s, 2H), 2.48 (p, J = 8.0 Hz, 1H), 1.95 - 1.55 (m, 7H), 1.48 (dt, J= 11.7, 8.0 Hz, 1H).

[0089] Cyclopentyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl (2R,6S)-2,6-dimethylpiperidine- 1-carboxylate (PBG2-7): A 100 mL 3-neck round bottom flask was charged with cyclopentyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl (4-nitrophenyl) carbonate, 6d, (1.40 g, 3.25 mmol), / V, / V'-dimethylaminopyridine (0.08 g, 0.65 mmol) and / V, / V'-dimethylacetamide (16 mL) under Ar. At room temperature, 2,6-dimethylpiperidine (1.32 mL, 9.76 mmol) was added, and the reaction mixture was stirred at 90 °C in the dark for 6 h. Upon completion, the reaction mixture was poured into water (100 mL), and the organic product was extracted into diethyl ether, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 10-30% ethyl acetate in hexanes) to afford the product. Yield: 0.53 g, 41%. MS (LC / MS): calculated for Chemical Formula: found: 405.

[0090] Benzo[d][1,3]dioxol-5-yl(cyclohexyl)methanone (PBG2-8.1): A 250 mL 2-neck round bottom flask was charged with benzo[d][1,3]dioxol-5-ylboronic acid (9.12 g, 54.94 mmol), palladiumfl l)acetate (0.42 g, 1.83 mmol), 2,2'-bipyridyl (0.43 g, 2.74 mmol), and Cesium fluoride (CsF) (13.0 g, 85.6 mmol). The reaction flask was evacuated and refilled with Argon twice and cyclohexanecarbonitrile (5.45 mL, 45.78 mmol). To the mixture, 1:3 (v / v) trifluoroacetic acid (11.5 mL) and water (34.5 mL) were added, and the reaction mixture was heated at 60 °C for 90 minutes. Upon completion, the reaction mixture was dropped slowly into saturated sodium bicarbonate (NaHCOa) (100 mL), and the organic product was extracted into CH2CI2, washed with NaCI solution, and dried over Na2SO4After drying, the crude product was purified by flash chromatography (silica gel, 50-60% CH2CI2 in hexanes) to afford the product. Yield: 5.66 g, 55.4%. MS (LC / MS): calculated for Chemical Formula: C14H17O3 [M+H]+= 233; found: 233.1H NMR (400 MHz, CDCb) 67.55 (d, J = 8.1 Hz, 1H), 7.43 (s, 1H), 6.85 (d, J = 8.2 Hz, 1H), 6.03 (s, 2H), 3.16 (tt, J = 11.9, 3.2 Hz, 1H), 1.94 - 1.78 (m, 4H), 1.73 (d, J= 12.7 Hz, 1H), 1.53 - 1.15 (m, 5H). Cyclohexyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methanone (PBG2-8.2): A 250 mL 3-neck RBF was charged with benzo[d][1,3]dioxol-5-yl(cyclohexyl)methanone, PBG2-8.1, (5.50 g, 23.70 mmol), and nitromethane (42 mL). At room temperature (RT), nitric acid (15 mL, 70%) was added dropwise via an addition funnel over 20 min, and the reaction mixture was stirred for 15 h at RT. Upon completion, the reaction mixture was slowly dropped into cold saturated sodium bicarbonate (NaHCOa) solution (100 mL) and extracted organic product into ethyl acetate, washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (silica gel, 25 -100% CH2CI2 in hexanes) to afford the product. Yield: 4.92 g, 75%. MS (LC / MS): calculated for Chemical Formula: found: 278.1H NMR (400 MHz, CDCb) δ 7.59 (s, 1H), 6.67 (s, 1H), 6.17 (s, 2H), 2.59 (tt, J = 11.7, 3.5 Hz, 1H), 1.95 (d, J = 12.9 Hz, 2H), 1.88 - 1.59 (m, 3H), 1.54 - 1.35 (m, 2H), 1.35 - 1.08 (m, 3H).

[0091] Cyclohexyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methanol (PBG2.8.3): A 250 mL 3-neck round bottom flask was charged with tetrahydrofuran (30 mL) under Ar. Sodium borohydride (NaBH4) (1.34 g, 35.37) was added as solid portions and acetic acid (2.02 mL, 35.37) was added dropwise over 10 minutes. Cyclohexyl(6-nitrobenzo[d][1,3]dioxol- 5-y I) methanone (PBG2-8.2) (4.90 g, 17.69 mmol) was added into the reaction mixture as solid portions, and a further 15 mL of tetrahydrofuran and 16 mL of isopropanol were added. The reaction mixture was stirred for an additional 1 h at room temperature. Upon completion, the reaction mixture was slowly dropped into saturated ammonium chloride (NH4CI) solution (150 mL), extracted organic product into diethyl ether, washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (NazSO4). After drying, the crude product was purified by flash chromatography (silica gel, 80% CH2CI2 in hexanes) to afford the product. Yield: 1.60 g. MS (LC / MS): calculated for Chemical Formula: C14H17NO5 [M+H]+= 280; found: 280.1H NMR (400 MHz, CDCb) 6 7.43 (s, 1H), 7.16 (s, 1H), 6.10 (t, J = 0.9 Hz, 2H), 5.13 (dd, J= 6.0, 4.2 Hz, 1H), 2.14 (d, J= 4.3 Hz, 1H), 1.86 - 1.58 (m, 5H), 1.52 - 1.43 (m, 1 H), 1.25 - 1.06 (m, 5H).

[0092] Cyclohexyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl (4-nitrophenyl) carbonate (PBG2-8.4): A 100 mL 2-neck flask was charged with cyclohexyl(6- nitrobenzo[d][1,3]dioxol-5-yl)methanol (PBG2-8.3), (1.40 g, 5.01 mmol), N,N- dimethylaminopyridine (0.92 g, 7.52 mmol), and dichloromethane (CH2CI2) (30 mL). At 0 °C, 4-nitrophenyl orthochloroformate (1.21 g, 6.01 mmol) was added. After the addition, the reaction mixture was allowed to warm to room temperature (RT) and stirred for 14 h. Upon completion, the reaction mixture was transferred to a 100 mL single-neck flash, and the solvent was concentrated. The crude product was purified by flash chromatography (silica gel, 40-80% CH2CI2 in hexanes) to afford the product. Yield: 1.6 g, 72%. MS (LC / MS): calculated for Chemical Formula: C21H20N2O9[M]+= 444; found: 400 (M-44)+.1H NMR (400 MHz, CDCb) δ 8.24 (d, J = 8.7 Hz, 2H), 7.52 (s, 1H), 7.34 (d, J = 8.7 Hz, 2H), 7.02 (s, 1H), 6.26 (d, J = 6.3 Hz, 1H), 6.14 (s, 2H), 1.92 (d, J = 10.5 Hz, 2H), 1.87 - 1.73 (m, 2H), 1.70 (s, 1H), 1.59-1.56 (m, 1H) 1.40 - 1.12 (m, 5H).

[0093] Cyclohexyl(6-nitrobenzo[d][1,3]dioxol-5-yl)methyl (2R,6S)-2,6-dimethylpiperidine- 1-carboxylate (PBG2-8): A 100 mL 3-neck flask was charged with cyclohexyl(6- nitrobenzo[d][1,3]dioxol-5-yl)methyl (4-nitrophenyl) carbonate (PBG2-8.4), (1.40 g, 3.153 mmol), / V, / V'-dimethylaminopyridine (0.08 g, 0.63 mmol) and / V, / V -dimethylacetamide (15 mL) under Argon. At room temperature, 2,6-dimethylpiperidine (1.27 mL, 9.46 mmol) was added, and the reaction mixture was stirred at 90 °C in the dark for 6 h. Upon completion, the reaction mixture was poured into water (100 mL), and the organic product was extracted into diethyl ether, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 0-5% ethyl acetate in dichloromethane) to afford the product. Yield: 0.66 g, 50%. MS (LC / MS): calculated for Chemical Formula: C22H31N2O6 [M]+= 419; found: 419.1H NMR (400 MHz, CDCb) 67.50 (s, 1H), 6.86 (s, 1H), 6.17 (d, J= 5.0 Hz, 1H), 6.09 (s, 2H), 4.47 - 4.22 (m, 2H), 1.75 (t, J = 9.8 Hz, 5H), 1.71 - 1.57 (m, 4H), 1.47 (d, J = 12.0 Hz, 1H), 1.22 (q, J= 16.1 Hz, 12H).

[0094] Scheme of compound PBG2-9 and PBG2-11 synthesis

[0095] General procedure of compound PBG2-9.1 synthesis 6- nitro -4- ((trimethylsilyl)ethynyl)benzo[d][1,3]dioxole-5-carbaldehyde: A 25 mL flask was fitted with a stir bar. To the flask, PBG2-14.1 (274.0 mg, 1.0 mmol), trimethylsilylacetylene (0.2 mL, 1.4 mmol), copper iodide (19.0 mg, 0.1 mmol), bis(triphenylphosphine)palladium (II) chloride (7.0 mg, 0.01 mmol), triethylamine (1.4 mL) and tetrahydrofuran (4.2 mL) were added. The mixture was degassed at room temperature. Then it was heated up to 60 °C and kept at this temperature for 4 hours. LCMS showed the completion of the reaction. The mixture was cooled down to room temperature and was filtered through a celite pad. The filtrate was concentrated and purified by silica gel chromatography to provide a yellow-brown solid using 0-20%-40% ethyl acetate in Hexane as the eluants. 175.0 mg, 60% yield. MS (APCI): calculated for Chemical Formula: CnHnNOsSi ([M-H]") = 291 found: 291.1H NMR (400 MHz, CDCb) 10.23 (s, 1H), 7.35 (s, 1H), 6.26 (s, 2H), 0.27 (s, 9H).

[0096] General procedure of compound PBG2-9.2 synthesis — 1-(6-nitro-4- ((trimethylsilyl)ethynyl)benzo[d][1,3]dioxol-5-yl)ethan-1-ol: A 50 mL flask was fitted with a stir bar. To the flask, compound PBG2-9.1 (150.0 mg, 0.5 mmol) was suspended in anhydrous dichloromethane (8 mL). The solution was cooled down to 0 °C with an icewater bath. Trimethylaluminium (2.0 in Hexane, 0.5 mL) was added dropwise to the solution. The reaction was slowly warmed up to room temperature after the completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed the completion of the reaction. Then it was cooled down to 0 °C and worked-up by the addition of water and sodium hydroxide (1 N) solution, 30 mL for each. The mixture was extracted with dichloromethane (3* with 30 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-9.2 as a light-yellow oil using 0- 20%-40% ethyl acetate in Hexane as the eluants. 17.0 mg, 11% yield. MS (APCI): calculated for Chemical Formula: C14H17NOsSi ([M-H]") = 307 found: 307.1H NMR (400 MHz, CDCb) 7.19 (s, 1H), 6.16 (s, 2H), 5.29-5.23 (m, 1H), 3.31 (d, J = 6.4 Hz, 1H), 1.75 (d, J= 6.4 Hz, 3H), 0.29 (s, 9H).

[0097] General procedure of compound PBG2-9 and PBG2-11 synthesis — For PBG2-9: 1- (4-ethynyl-6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate; For PBG2-11: 1- (6-nitro-4-((trimethylsilyl)ethynyl)benzo[d][1 ,3]dioxol-5-yl)ethyl dihexylcarbamate: A mixture of PBG2-9.2 (150.0 mg, 0.5 mmol) and carbonyl diimidazole (152.0 mg, 0.9 mmol) was degassed at room temperature. Then dichloromethane (5 mL) and triethylamine (75 pL, 0.6 mmol) were added sequentially. The solution was heated up to 50 °C and kept at this temperature for 4 hours. LCMS showed the consumption of the starting material. Then dihexylamine (342 pL, 1.5 mmol) was added. The reaction was kept at 50 °C 3 hours, and another portion of dihexylamine (342 pL, 1.5 mmol) was added. The reaction was kept at 50 °C overnight. LCMS showed the completion of the reaction. After cooling down to room temperature, the crude solution was purified by silica gel flash chromatography to provide PBG2-9 as a yellow oil and PBG2-11 as a light-yellow oil using 0-20%-40% ethyl acetate in Hexane as the eluants. For PBG2-9, 63.0 mg, 29% yield. MS (APCI): calculated for Chemical Formula: C24H34N2O6 ([M+H]) = 447 found: 447.1H NMR (400 MHz, CDCb) 7.10 (s, 1H), 6.19 (dd, J= 6.8 Hz, 6.8 Hz, 1H), 6.16-6.12 (m, 2H), 3.61 (s, 1H), 3.36-2.96 (m, 4H), 1,78 (d, J = 6.8 Hz, 3H), 1.53-1.41 (m, 4H), 1.34-1.16 (m, 12H), 0.93-0.82 (m, 6H). For PBG2-11, 78.0 mg, 31% yield. MS (APCI): calculated for Chemical Formula: C27H42N2O6Si ([M+H]) = 519 found: 519.1H NMR (400 MHz, CDCb) 7.03 (s, 1H), 6.17 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 6.14-6.11 (m, 2H), 3.40-2.92 (m, 4H), 1,78 (d, J = 6.8 Hz, 3H), 1.52-1.38 (m, 4H), 1.35-1.17 (m, 12H), 0.93-0.82 (m, 6H), 0.28 (s, 9H). Scheme of compound PBG2-10 synthesis

[0098] General procedure of compound PBG2-10.1 synthesis — 4-(3,3-dimethylbut-1-yn- 1-yl)-6-nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 25 mL flask was fitted with a stir bar. To the flask, PBG2-14.1 (274.0 mg, 1.0 mmol), trimethylsilylacetylene (0.2 mL, 1.4 mmol), copper iodide (19.0 mg, 0.1 mmol), bis(triphenylphosphine)palladium (II) chloride (7.0 mg, 0.01 mmol), triethylamine (1.4 mL) and tetrahydrofuran (4.2 mL) were added. The mixture was degassed at room temperature. Then it was heated up to 60 °C and kept at this temperature overnight. LCMS showed the completion of the reaction. The mixture was cooled down to room temperature and was filtered through a celite pad. The filtrate was concentrated and was purified by silica gel chromatography to provide PBG2-10.1 as a brown solid using 0-20%-40% ethyl acetate in Hexane as the eluants. 212.0 mg, 77% yield. MS (APCI): calculated for Chemical Formula: C14H13NO5 ([M-H]-) = 276 found: 276.1H NMR (400 MHz, CDCb) 10.22 (s, 1H), 7.31 (s, 1H), 6.23 (s, 2H), 1.33 (s, 9H).

[0099] General procedure of compound PBG2-10.2 synthesis — 1-(4-(3,3-dimethylbut-1- yn-1-yl)-6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol: A 250 mL flask was fitted with a stir bar. In the flask, compound PBG2-10.1 (1.46 g, 5.3 mmol) was suspended in anhydrous dichloromethane (73 mL). The solution was cooled down to 0 °C with an ice-water bath. Trimethylaluminium (2.0 in Hexane, 5.3 mL) was added dropwise to the solution. The reaction was slowly warmed up to room temperature after the completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed the completion of the reaction. It was then cooled down to 0 °C and worked-up by the addition of water and hydrochloric acid (1 N) solution, 150 mL for each. The mixture was extracted with dichloromethane (3* 150 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-10.2 as a brown solid using 0-20%-40% ethyl acetate in Hexane as the eluants. 561.0 mg, 38% yield. MS (APCI): calculated for Chemical Formula: C15H17NO5 ([M-H]-) = 291 found: 291.1H NMR (400 MHz, CDCb) 7.16 (s, 1H), 6.13 (s, 2H), 5.29-5.23 (m, 1H), 3.29 (d, J = 10.4 Hz, 1H), 1.74 (d, J = 6.4 Hz, 3H), 1.36 (s, 9H). General procedure of compound PBG2-10synthesis — 1-(4-(3,3-dimethylbut-1-yn-

[0100] 1-yl)-6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: A mixture of PBG2-10.2

[0101] (561.0 mg, 1.9 mmol) and 4-nitrophenyl chloroformate (583.0 mg, 2.9 mmol) was degassed at room temperature. Then 1,2-dichloroethane (16 mL) was added. The reaction was cooled down to 0 °C by ice-water bath. Then 4-(dimethylamino)pyridine

[0102] (353.8 mg, 2.9 mmol) was added sequentially, followed by degassing of the reaction. The reaction was warmed up to room temperature and kept at this temperature for 3 hours.

[0103] LCMS showed the consumption of the starting material. Dihexylamine (1.3 mL, 5.7 mmol) was then added. The reaction was kept at room temperature for 1 hour. LCMS showed the completion of the reaction. The crude was purified by silica gel flash chromatography to provide PBG2-10 as a yellow oil using 0-20%-40% ethyl acetate in Hexane as the eluants. 786.0 mg, 82% yield. MS (APCI): calculated for Chemical Formula: ([M+HD = 503 found: 503.1H NMR (400 MHz, CDCb) 6.97 (s, 1H), 6.21 (dd, J= 6.4 Hz,

[0104] 6.4 Hz, 1 H). 6.12-6.08 (m, 2H), 3.36-2.94 (m, 4H), 1,76 (d, J= 6.8 Hz, 3H), 1.51-1.40 (m,

[0105] 4H), 1.36 (s, 9H), 1.33-1.24 (m, 12H), 0.91-0.84 (m, 6H).

[0106] Scheme of compound PBG2-12 synthesis General procedure of compound PBG2-12.1 synthesis — 7-bromo-6- nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 100 mL flask was fitted with a stir bar. To the flask, 6-nitropiperonal (9.8 g, 50.0 mmol) was dissolved in sulfuric acid (75 mL), followed by the addition of N-Bromosuccinimide (NBS) (14.2 g, 80.0 mmol). The mixture was kept at room temperature for 4 hours and then poured into crushed ice (1000 g). The reaction was extracted with ethyl acetate (500 mL*3). The combined organic phase was washed by brine and was dried over anhydrous sodium sulfate. After being concentrated under rotavapor, the mixture was triturated with hot methanol. The solid, which is PBG2- 12.1, was collected via vacuum filtration. The filtrate was purified by silica gel chromatography to provide a mixture of PBG2-14.1, PBG2-12.1 and 6-nitropiperonal with 1:1:1 molar ratio as a yellow solid using 0-20% ethyl acetate in Hexane as the eluants. 6.6 g, 15% yield. MS (APCI): calculated for Chemical Formula: C8H4BrNO5([M-H]-) = 274, 276 found: 274, 276.1H NMR (400 MHz, CDCb) 9.76 (s, 1H), 7.31 (s, 1H), 6.27 (s, 2H).

[0107] General procedure of compound PBG2-12.2 synthesis— 4-bromo-6-(1, 3-dioxolan-2- yl)-5-nitrobenzo[d][1,3]dioxole: A 250 mL flask was fitted with a stir bar and set up with a Dean-Stark apparatus. To the flask, a mixture of compounds PBG2-14.1, PBG2-12.1 and 6-nitropiperonal with 1:1:1 molar ratio (4.1 g, 15.0 mmol) and toluene (150 mL) were added, followed by the addition of ethylene glycol (5.4 mL) and p-toluenesulfonic acid monohydrate (570.0 mg, 3.0 mmol). The mixture was purged with Argon and was warmed up to 150 °C and kept at this temperature for 2 hours. Both TLC and LCMS showed the completion of the reaction. The mixture was cooled down to room temperature and then poured into saturated sodium bicarbonate solution (180 mL). The mixture was extracted with ethyl acetate (3* 150 mL). The combined organic phase was washed with water (100 mL), and brine (100 mL) sequentially and was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-12.2 as a yellow solid using 0-40% ethyl acetate in Hexane as the eluants. 91% yield. MS (APCI): calculated for Chemical Formula: CwH8BrNO8([M-H]-) = 318, 320 found: 318, 320.1H NMR (400 MHz, CDCb) 7.03 (s, 1H), 6.16 (s, 2H), 5.94 (s, 1H), 4.01 (s, 4H).

[0108] General procedure of compound PBG2-12.3synthesis — 6-(1,3-dioxolan-2-yl)-5- nitrobenzo[d][1,3]dioxole-4-carbonitrile: In a 20 mL microwave vial, compound PBG2- 12.2 (1.2 g, 3.8 mmol) and copper cyanide (1.0 g, 11.3 mmol) were suspended in anhydrous dimethylformamide (12 mL). The mixture was degassed by bubbling of nitrogen gas and was heated up to 200 °C. The reaction was kept at this temperature for 1 hour. Both TLC and LCMS showed the completion of the reaction. The mixture was filtered through a pat of celite and washed by ethyl acetate (20 mL). The filtrate was concentrated under rotavapor and was purified by silica gel chromatography to provide PBG2-12.3 as a yellow solid using 0-20%-40% ethyl acetate in Hexane as the eluants. 415.0 mg, 42% yield. MS (APCI): calculated for Chemical Formula: CnH8N2O8([M-H]") = 264 found: 264.1H NMR (400 MHz, CDCb) 7.27 (s, 1H), 6.27 (s, 2H), 6.12 (s, 1H), 3.99 (s, 4H).

[0109] General procedure of compound PBG2-12.4synthesis — 6-formyl-5- nitrobenzo[d][1,3]dioxole-4-carbonitrile: In a 10 mL microwave vial, compound PBG2- 12.3 (335 mg, 1.3 mmol) and Indium(lll) trifluoromethanesulfonate (56.2 mg, 0.1 mmol) were suspended in acetone (4 mL). The mixture was heated up to 100 °C. The reaction was kept at this temperature for 2 hours. LCMS showed ~88% conversion of the reaction. Then it was purified by silica gel chromatography to provide PBG2-12.4 as a light yellow solid using 0-20%-40% ethyl acetate in Hexane as the eluants. 298.0 mg, 64% yield. MS (APCI): calculated for Chemical Formula: C8H4N2O5([M-H]") = 220 found: 220.1H NMR (400 MHz, CDCb) 10.02 (s, 1H), 7.49 (s, 1H), 6.40 (s, 2H).

[0110] General procedure of compound PBG2-12.5 synthesis — 6-(1-hydroxyethyl)-5- nitrobenzo[d][1,3]dioxole-4-carbonitrile: A 50 mL flask was fitted with a stir bar. To the flask, compound PBG2-12.4 (298.0 mg, 1.4 mmol) was suspended in anhydrous dichloromethane (20 mL). The solution was cooled down to 0 °C with an ice-water bath. Trimethylaluminium (2.0 in Hexane, 1.4 mL) was added dropwise to the solution. The reaction was slowly warmed up to room temperature after the completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed the completion of the reaction. It was then cooled down to 0 °C and worked-up by the addition of water and a sodium hydroxide (1 N) solution, 60 mL for each. The mixture was extracted with dichloromethane (3* 50 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-12.5 as a light-yellow solid using 0-10%-20% ethyl acetate in dichloromethane as the eluants. 178.0 mg, 50% yield. MS (APCI): calculated for Chemical Formula: C10H8N205([M-H] ) = 236 found: 236.1H NMR (400 MHz, CDCb) 7.39 (s, 1H), 6.32-6.23 (m, 2H), 5.24 (dd, J = 12.8 Hz, 6.4 Hz, 1H), 1.51 (d, J = 6.4 Hz, 3H). General procedure of compound PBG2-12.61715-69 synthesis — 1-(7-cyano-6- nitrobenzo[d][1,3]dioxol-5-yl)ethyl (4-nitrophenyl) carbonate: To a solution of PBG2-

[0111] 12.5 (178.0 mg, 0.8 mmol) in 1 ,2-dichloroethane (5 mL), 4-nitrophenyl chloroformate (227.9 mg, 1.1 mmol) was added, followed by the addition of triethylamine (0.3 mL). The reaction was kept at room temperature for 1 hour. LCMS showed the completion of the reaction. The crude has been purified by silica gel flash chromatography to provide PBG2-

[0112] 12.6 as a yellow solid using 0-20%-40%-60% ethyl acetate in Hexane as the eluants. 100.0 mg, 39% yield. MS (APCI): calculated for Chemical Formula: C17H11N3O9 ([M-CO2- H]-) = 357 found: 357.1H NMR (400 MHz, CDCb) 8.29-8.23 (m, 2H), 7.37-7.31 (m, 2H), 7.25 (s, 1H), 7.35-7.30 (m, 2H), 6.01 (dd, J = 12.8 Hz, 6.4 Hz, 1H), 1.75 (d, J = 6.4 Hz, 3H).

[0113] General procedure of compound PBG2-12 synthesis — 1-(7-cyano-6- nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: To a solution of PBG2-12.6 (100.0 mg, 0.25 mmol) in 1 ,2-dichloroethane (2 mL), dihexylamine (116.6 pL, 0.50 mmol) was added. The reaction was kept at room temperature for 2 hours. LCMS showed the completion of the reaction. The crude was purified by silica gel flash chromatography to provide PBG2-12 as a light-yellow oil using 0-20%-40%-60% ethyl acetate in Hexane as the eluants. 63.0 mg, 56% yield. MS (APCI): calculated for Chemical Formula: C23H33N3O6 ([M+HD = 448 found: 448.1H NMR (400 MHz, CDCb) 7.05 (s, 1H), 6.26 (dd, J= 7.6 Hz, 0.8 Hz, 2H), 5.85 (dd, J= 12.8 Hz, 6.4 Hz, 1H), 3.26-3.18 (m, 2H), 3.18-3.06 (m, 2H), 1.59 (d, J= 6.4 Hz, 3H), 1.53-1.18 (m, 16H), 0.94-0.82 (m, 6H).

[0114] Scheme of compound PBG2-13 synthesis General procedure of compound PBG2-13.1 synthesis — 6-(1,3-dioxolan-2-yl)-4-(4- methoxyphenyl)-5-nitrobenzo[d][1,3]dioxole: A 100 mL flask was fitted with a stir bar. To the flask, PBG2-12.2 (800.0 mg, 2.5 mmol), 4-methoxyphenylboronic acid (764.6 mg, 5.0 mmol), [1,T-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (204.2 mg, 0.25 mmol), sodium bicarbonate (630.0 mg, 7.5 mmol), and tetrahydrofuran (43 mL) and water (7 mL) were added. The mixture was degassed at room temperature. It was then heated up to 85 °C and kept at this temperature for 24 hours. LCMS showed almost completion of the reaction. The mixture was cooled down to room temperature and was filtered through a celite pad. The filtrate was concentrated and was purified by silica gel chromatography to provide PBG2-13.1 as an orange solid using dichloromethane as the eluant 607.0 mg, 70% yield. MS (APCI): calculated for Chemical Formula: C17H15NO7 ([M+Hf) = 346 found: 346.1H NMR (400 MHz, CDCb) 7.33-7.28 (m, 2H), 7.07 (s, 1H), 6.97-6.92 (m, 2H), 6.06 (s, 2H), 5.97 (s, 1H), 4.08-4.04 (m, 2H), 4.04- 4.00 (m, 2H), 3.82 (s, 3H).

[0115] General procedure of compound PBG2-13.2 synthesis — 7-(4-methoxyphenyl)- 6- nitrobenzo[d][1,3] dioxole-5-carbaldehyde: In a 25 mL microwave vial, compound PBG2-13.1 (607.0 mg, 1.8 mmol) and lithium tetrafluoroborate (164.7 mg, 1.8 mmol) were suspended in acetonitrile (16 mL) and water (320 pL). The mixture was heated up to 60 °C. The reaction was kept at this temperature for 8 hours. LCMS showed almost completion of the reaction. The reaction was cooled to room temperature and was concentrated. Then it was purified by silica gel chromatography to provide PBG2-13.2 as a yellow solid using 0-10% ethyl acetate in dichloromethane as the eluants. 211.0 mg, 40% yield. MS (APCI): calculated for Chemical Formula: found: 301.1H NMR (400 MHz, CDCb) 9.82 (s, 1H), 7.37-7.30 (m, 3H), 7.01-6.96 (m, 2H), 6.17 (s, 2H), 3.84 (s, 3H).

[0116] General procedure of compound PBG2-13.3 synthesis — 1-(7-(4-methoxyphenyl)- 6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol: A 50 mL flask was fitted with a stir bar. In the flask, compound PBG2-13.2 (211.0 mg, 0.7 mmol) was suspended in anhydrous dichloromethane (11 mL). The solution was cooled down to 0 °C with ice-water bath. Trimethylaluminium (2.0 in Hexane, 0.7 mL) was added dropwise to the solution. The reaction was slowly warmed up to room temperature after the completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed the completion of the reaction. It was then cooled down to 0 °C and worked-up by the addition of water and a hydrogen chloride (1 N) solution, 50 mL for each. The mixture was extracted with dichloromethane (3* 50 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-13.3 as an orange-brown oil using 0-20%-40% ethyl acetate in Hexane as the eluants. 74.0 mg, 33% yield. MS (APCI): calculated for Chemical Formula: C16H15NO6([M-H]-) = 317 found: 317.1H NMR (400 MHz, CDCb) 7.33-7.28 (m, 2H), 7.09 (s, 1H), 7.98-7.93 (m, 2H), 6.07-6.03 (m, 2H), 4.90 (dd, J= 6.0 Hz, 6.0 Hz, 1H), 3.83 (s, 3H), 1.52 (d, J= 6.0 Hz, 3H), 1.02 (d, J= 7.6 Hz, 1H).

[0117] General procedure of compound PBG2-13 synthesis — 1 -(7-( 4-methoxy phenyl )-6- nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: To a solution of PBG2-13.3 (74.0 mg, 0.2 mmol) in 1,2-dichloroethane (2 mL), 4-nitrophenyl chloroformate (70.6 mg, 0.4 mmol) was added, followed by the addition of 4-(dimethylamino)pyridine (42.7 mg, 0.4 mmol). The reaction was kept at room temperature for 20 minutes. TLC showed the completion of the reaction. Dihexylamine (160.0 pL, 0.7 mmol) was then added. The reaction was kept at room temperature overnight. LCMS showed the completion of the reaction. The crude was purified by silica gel flash chromatography to provide PBG2-13 as a light-yellow oil using 0-20%-40%-60% ethyl acetate in Hexane as the eluants. 48.0 mg, 21% yield. MS (APCI): calculated for Chemical Formula: C29H40N2O7([M+H] = 529 found: 529.1H NMR (400 MHz, CDCb) 7.34-7.27 (m, 2H), 6.96-6.91 (m, 2H), 6.84 (s, 1H), 6.06-6.01 (m, 2H), 5.69 (dd, J= 6.4 Hz, 6.4 Hz, 1H), 3.81 (s, 3H), 3.30-3.10 (m, 4H), 1.57 (s, 3H), 1.55-1.48 (m, 4H), 1.34-1.27 (m, 12H), 0.87-0.84 (m, 6H).

[0118] Scheme of compound PBG2-14 synthesis

[0119] General procedure ooff compound PBG2-14.1 synthesis 4-bromo-6- nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 100 mL flask was fitted with a stir bar. In the flask, 6-nitropiperonal (9.8 g, 50.0 mmol) was dissolved in sulfuric acid (75 mL), followed by the addition of N-bromosuccinimide (14.2 g, 80.0 mmol). The mixture was kept at room temperature for 4 hours. The mixture was poured into crushed ice (1000 g). The reaction was extracted with ethyl acetate (500 mL*3). The combined organic phase was washed by brine and was dried over anhydrous sodium sulfate. It was then concentrated under rotavapor, and the mixture was triturated with hot methanol. The solid, which is PBG2-14.1, was collected via vacuum filtration. The filtrate was purified by silica gel chromatography to provide a mixture of PBG2-14.1, PBG2-12.1 and 6-nitropiperonal with 1:1:1 molar ratio as a yellow solid using 0-20% ethyl acetate in Hexane as the eluants. 6.6 g, 15% yield. MS (APCI): calculated for Chemical Formula: C8H4BrNOs ([M- H]-) = 274, 276 found: 274, 276.1H NMR (400 MHz, CDCb) 10.1 (s, 1H), 7.50 (s, 1H), 6.28 (s, 2H).

[0120] General procedure of compound PBG2-14.2 synthesis — 4-(4-methoxyphenyl)-6- nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 25 mL flask was fitted with a stir bar. In the flask, PBG2-14.1 (274.0 mg, 1.0 mmol), 4-methoxyphenylboronic acid (182.4 mg, 2.0 mmol), [1,T-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (81.7 mg, 0.1 mmol), sodium bicarbonate (252.0 mg, 3.0 mmol), and tetrahydrofuran (17 mL) and water (3 mL) were added. The mixture was degassed at room temperature. Then it was heated up to 85 °C and kept at this temperature for 24 hours. LCMS showed almost completion of the reaction. The mixture was cooled down to room temperature and was filtered through a celite pad. The filtrate was concentrated and was purified by silica gel chromatography to provide PBG2-14.2 as a yellow solid using dichloromethane as the eluant 168.0 mg, 56% yield. MS (APCI): calculated for Chemical Formula: CisHnNOs ([M-H]"') = 301 found: 301.1H NMR (400 MHz, CDCb) 10.09 (s, 1H), 7.44 (s, 1H), 7.39-7.33 (m, 1H), 7.07-7.01 (m, 1H), 6.99-6.96 (m, 2H), 6.17 (s, 2H), 3.85 (s, 3H).

[0121] General procedure of compound PBG2-14.3synthesis — 1-(4-(4-methoxyphenyl)-6- n it robenzo[d][1,3]dioxol-5-yl)et han-1 -ol: A 100 mL flask was fitted with a stir bar. In the flask, compound PBG2-14.2 (773.0 mg, 2.6 mmol) was suspended in anhydrous dichloromethane (40 mL). The solution was cooled down to 0 °C with an ice-water bath. Trimethylaluminium (2.0 in Hexane, 2.7 mL) was added dropwise to the solution. The reaction was slowly warmed up to room temperature after the completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed the completion of the reaction. It was then cooled down to 0 °C and worked-up by the addition of water and hydrochloric acid(1N) solution, 30 mL for each. The mixture was extracted with dichloromethane (3* 100 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-14.3 as a brown oil using 0-10% ethyl acetate in dichloromethane as the eluants. 336.0 mg, 41% yield. MS (APCI): calculated for Chemical Formula: CI6HI5NO6([M-H]-) = 317 found: 317.1H NMR (400 MHz, CDCb) 7.28 (s, 1H), 7.03-6.97 (m, 4H), 6.04 (dd, J = 10.4 Hz, 1.2 Hz, 2H), 4.95-4.84 (m, 1H), 3.86 (s, 3H), 3.28 (d, J = 10.4 Hz, 1H), 1.42 (d, J = 6.8 Hz, 3H).

[0122] General procedure of compound PBG2-14 synthesis — 1 -(4-( 4-methoxy phenyl )-6- nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: A mixture of PBG2-14.3 (336.0 mg, 1.1 mmol) and carbonyl diimidazole (342.5 mg, 2.1 mmol) was degassed at room temperature. Then dichloromethane (16 mL) and triethylamine (169 pL, 1.2 mmol) were added sequentially. The solution was heated up to 50 °C and kept at this temperature for 3 hours. LCMS showed the consumption of the starting material. Then dihexylamine (770 pL, 3.3 mmol) was added. The reaction was kept at 50 °C overnight, and another portion of dihexylamine (342 μL, 1.5 mmol) and 1 -hydroxybenzotriazole hydrate (51.0 mg), and dimethylacetamide (12 mL) were added. The reaction was heated up to 90 °C and kept at 90 °C overnight. LCMS showed 50% conversion of the reaction. After cooling down to room temperature, the crude solution was added to 1% sodium bicarbonate (200 mL). The crude was collected via vacuum filtration and re-dissolved in dichloromethane and was purified by silica gel flash chromatography to provide PBG2-14 as a yellow oil, 104.0 mg, 18% yield. MS (APCI): calculated for Chemical Formula: found: 529.1H NMR (400 MHz, CDCb) 7.43-7.27 (m, 2H), 7.06-6.98 (m, 3H), 6.02-5.94 (m, 2H), 5.78 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 3.04 (s, 3H), 3.31-3.17 (m, 2H), 3.04-2.80 (m, 2H), 1.55 (d, J = 6.8 Hz, 3H), 1.49-1.38 (m, 4H), 1.30-1.21 (m, 12H), 0.91-0.83 (m, 6H).

[0123] Scheme of compound PBG2-15 synthesis

[0124] General procedure of compound PBG2-15.1 synthesis — 4,7-dibromo-6- nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 100 mL flask was fitted with a stir bar. In the flask, 6-nitropiperonal (9.8 g, 50.0 mmol) was dissolved in sulfuric acid (75 mL), followed by the addition of N-bromosuccinimide (14.2 g, 80.0 mmol). The mixture was heated to 45 °C and kept at this temperature for 4 hours. The mixture was poured into crushed ice (1000 g). The reaction was extracted with ethyl acetate (500 mL*3). The combined organic phase was washed by brine and was dried over anhydrous sodium sulfate. After being concentrated under rotavapor, the mixture was triturated with hot methanol. The solid, which is PBG2-15.1, was collected via vacuum filtration. The filtrate was purified by silica gel chromatography to provide a mixture of PBG2-14.1, PBG2-15.1 and 6-nitropiperonal with a 10:1:1 molar ratio as a yellow solid using 0-20% ethyl acetate in Hexane as the eluants. 660.0 mg, 1.5% yield. MS (APCI): calculated for Chemical Formula: ([M-H]”) = 350, 352, 354 found: 350, 352, 354.1H NMR (400 MHz, CDCb) 10.3 (s, 1H), 6.27 (s, 2H).

[0125] General procedure ooff compound PBG2-15.2 synthesis — 4,7-bis(4- methoxyphenyl)-6-nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 25 mL flask was fitted with a stir bar. In the flask, PBG2-15.1 (27.4 mg, 0.1 mmol), 4-methoxyphenylboronic acid (18.2 mg, 0.2 mmol), [1,T-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (8.2 mg, 0.01 mmol), sodium bicarbonate (25.2 mg, 0.3 mmol), and tetrahydrofuran (1.7 mL) and water (0.3 mL) were added. The mixture was degassed at room temperature. Then it was heated to 85 °C and kept at this temperature for 24 hours. LCMS showed almost completion of the reaction. The mixture was cooled down to room temperature and was filtered through a celite pad. The filtrate was concentrated and was purified by silica gel chromatography to provide PBG2-15.2 as a light-yellow solid using 70%-80%-100% dichloromethane in Hexane as the eluants. 34.5 mg, 85% yield. MS (APCI): calculated for Chemical Formula: C22H17NO7 ([M-H]") = 407 found: 407.1H NMR (400 MHz, CDCb) 9.74 (s, 1H), 7.41-7.31 (m, 4H), 7.07-6.94 (m, 4H), 6.14 (s, 2H), 3.88 (s, 3H), 3.84 (s, 3H).

[0126] General procedure of compound PBG2-15.3 synthesis — 1-(4,7-bis(4- methoxyphenyl)-6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol: A 50 mL flask was fitted with a stir bar. In the flask, compound PBG2-15.2 (96.4 mg, 0.2 mmol) was suspended in anhydrous dichloromethane (4 mL). The solution was cooled to 0 °C with an ice-water bath. Trimethylaluminium (2.0 in Hexane, 0.2 mL) was added dropwise to the solution. The reaction was slowly warmed to room temperature after the completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed completion of the reaction. It was then cooled down to 0 °C and worked-up by the addition of water and hydrochloric acid (1N) solution, 5 mL for each. The mixture was extracted with dichloromethane (3* 10 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, the crude was purified by silica gel chromatography to provide PBG2-15.3 as a brown oil using 0-20%-40% ethyl acetate in dichloromethane as the eluants. 57.0 mg, 57% yield. MS (APCI): calculated for Chemical Formula: C23H21NO7 ([M-H]") = 423 found: 423.1H NMR (400 MHz, CDCb) 7.37-7.28 (m, 4H), 7.04-6.94 (m, 4H), 6.00-5.95 (m, 2H), 4.95-4.85 (m, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 2.28 (d, J= 6.0 Hz, 1H), 1.44 (d, J = 6.8 Hz, 3H).

[0127] General procedure of compound PBG2-15 synthesis — 1-(4,7-bis(4- methoxyphenyl)-6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: A mixture of PBG2-15.3 (57.0 mg, 0.1 mmol) and carbonyl diimidazole (41.9 mg, 0.2 mmol) was degassed at room temperature. Then dichloromethane (2 mL) and triethylamine (20 pL, 0.1 mmol) were added sequentially. The solution was heated to 50 °C and was kept at this temperature for 4 hours. LCMS showed the consumption of the starting material. Then dihexylamine (91 pL, 0.4 mmol) was added. The reaction was kept at 50 °C overnight, and another portion of dihexylamine (91 pL, 0.4 mmol) and 1 -hydroxybenzotriazole hydrate (0.6 mg), and dimethylacetamide (3 mL) were added. The reaction was heated to 90 °C and kept at 90 °C overnight LCMS showed completion of the reaction. After cooling down to room temperature, the crude solution was added to 1% sodium bicarbonate (200 mL). The crude was collected via vacuum filtration and re-dissolved in dichloromethane and was purified by silica gel flash chromatography to provide PBG2-15 as a light-yellow oil, 19.0 mg, 23% yield. MS (APCI): calculated for Chemical Formula: C36H46N2O8 ([M+HH = 635 found: 635.1H NMR (400 MHz, CDCb) 7.69-7.28 (m, 4H), 7.10-7.00 (m, 2H), 7.00-6.92 (m, 2H), 5.95 (s, 2H), 5.78 (dd, J= 6.8 Hz, 6.8 Hz, 1H), 3.85 (s, 3H), 3.82 (s, 3H), 3.39-3.27 (m, 2H), 2.99-2.88 (m,1H), 2.82-2.71 (m, 1H), 1.48 (d, J = 6.8 Hz, 3H), 1.46-1.36 (m, 4H), 1.31-1.19 (m, 12H), 0.88-0.81 (m, 6H).

[0128] Synthesis of 2,2,2-trifluoro-1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl (2S,6R)-2,6- dimethylpiperidine-1 -carboxylate (PBG2-16).

[0129] 2,2,2-trifluoro-1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol (PBG2-16.1): A 250 mL2- neck round bottom flask was charged with 6-nitrobenzo[d][1,3]dioxole-5-carbaldehyde (4.00 g, 20.49 mmol), and potassium carbonate (K2CO3) (0.56 g, 4.05 mmol). Under Argon, / V, / V-dimethylformamide (50 mL) and trimethyl(trifluoromethyl)silane (6.10 mL, 40.99 mmol) were added, and the reaction mixture was stirred for 2 h at room temperature. Upon completion, the reaction mixture was poured into 0.1 N MCI (100 mL) and extracted organic product into dichloromethane (CH2CI2), washed with NaCI solution, and dried over Na2SO4. After drying, the crude product was purified by flash chromatography (silica gel, 0-2% ethyl acetate in CH2CI2) to afford the product Yield: 4.60 g, 84.7%. MS (LC / MS): calculated for Chemical Formula: C9H7F3NO5 [M+H]+= 266; found: 266.1H NMR (400 MHz, CDCb) δ1H NMR (400 MHz, CDCb) 67.54 (s, 1H), 7.33 (s, 1H), 6.21 (q, J = 6.1 Hz, 1H), 6.19 - 6.13 (m, 2H), 3.03 (s, 1H). 4-nitrophenyl (2,2,2-trifluoro-1 -(6-nitrobenzo[d][1 ,3]dioxol-5-yl)ethyl) carbonate (PBG2-16.2): A 250 mL 3-neck flask was charged with 2,2,2-trifluoro-1-(6- nitrobenzo[d][1,3]dioxol-5-yl)ethan-1-ol, (PBG2.16.1)(3.26 g, 12.30 mmol), and N.N*- dimethylformamide (50 mL). At 0 °C, triethylamine (2.60 mL, 18.45 mmol) and 4- nitrophenyl chloroformate (2.97 g, 14.76 mmol) were added. After the addition, the reaction mixture was allowed to warm to room temperature (RT) and stirred for 14 h. Upon completion, the reaction mixture was poured into water (200 mL), and the organic product was extracted into dichloromethane (CH2CI2), washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 60% CH2CI2 in hexanes) to afford the product Yield: 3.33 g, 63%. MS (LC / MS): calculated for Chemical Formula: C16H9F3N2O9[M]+= 430; found: 386 [M-44]+.1H NMR (400 MHz, CDCb) 6 8.34 - 8.24 (m, 2H), 7.64 (d, J = 1.0 Hz, 1H), 7.46 - 7.37 (m, 2H), 7.26 - 7.20 (m, 1H), 6.21 (q, J= 1.1 Hz, 2H), 6.17 (q, J = 1.2 Hz, 1H).

[0130] 2,2,2-trifluoro-1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl (2S,6R)-2,6- dimethylpiperidine-1-carboxylate (PBG2-16): A 100 mL 3-neck flask was charged with 4-nitrophenyl (2,2,2-trifluoro-1-(6-nitrobenzo[d][1,3]dioxol-5-yl)ethyl) carbonate (2.0 g, 4.65 mmol), Hydroxybenzotriazole (0.19 g, 1.39 mmol) and N,N -dimethylacetamide (15 mL) under Argon at room temperature. 2,6-dimethylpiperidine (2.50 mL, 18.60 mmol) was added, and the reaction mixture was stirred at 90 °C in the dark for 6 h. Upon completion, the reaction mixture was poured into a 1% sodium bicarbonate (NaHCOs) solution (100 mL), and the organic product was extracted into ethyl acetate, washed with sodium chloride solution, and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 0-15% ethyl acetate in CH2CI2) to afford the product Yield: 0.46 g, 34%. MS (LC / MS): calculated for Chemical Formula: C17H20F3N2O8 [M+H]+= 430; found: 386.1H NMR (400 MHz, CDCb) 6 7.59 (s, 1H), 7.22 (q, J = 6.3 Hz, 1H), 7.09 - 7.05 (m, 1H), 6.16 (s, 2H), 4.42 - 4.25 (m, 2H), 1.85 - 1.57 (m, 5H), 1.50 (dq, J = 12.2, 3.5 Hz, 1H), 1.25 (t, J = 6.5 Hz, 6H). Synthesis of 1-(7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethyl dihexylcarbamate

[0131] 1-(7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one (PBG3-1): A 250 mL 3- neck round bottom flask (RBF) was charged with 1-(2,3-dihydrobenzo[b][1,4]dioxin-6- yl)ethan-1-one, (4.5 g, 25.25 mmol). At 0 °C, nitric acid (90 mL, 70%) was added dropwise via an addition funnel over 20 min, and the reaction mixture was allowed to warm to room temperature (RT) and stirred at RT for an additional 2 h. Upon completion, the reaction mixture was slowly dropped into a cold saturated sodium bicarbonate (NaHCOa) solution (200 mL) and extracted organic product into ethyl acetate, washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (NaaSO^. After drying, the crude product was purified by flash chromatography (silica gel, 0-100% CH2CI2 in hexanes) to afford the product (PBG3-1.1). Yield: 3.60 g, 69%. MS (LC / MS): calculated for Chemical Formula: C10H10NO5 [M+H]+= 224; found: 224.1H NMR (400 MHz, CDCI3) 6 7.65 (s, 1H), 6.85 (s, 1H), 4.39 - 4.31 (m, 4H), 2.48 (s, 3H).

[0132] 1-(7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-ol (PBG3-1.2): A 250 mL 2- neck round bottom flask (RBF) was charged with 1-(7-nitro-2,3- dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one (3.50 g, 15.69 mmol), and tetrahydrofuran (THF) (70 mL) under Ar. Sodium borohydride (NaBH4) (0.89 g, 23.53) was added as solid portions and the reaction mixture was stirred at RT for 30 minutes. 30 mL of ethanol was added and the reaction mixture was stirred for an additional 60 minutes at room temperature (RT). Upon completion, the reaction mixture was slowly dropped into saturated ammonium chloride (NH4CI) solution (100 mL), extracted organic product into ethylacetate, washed with sodium chloride (NaCI) solution, and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (silica gel, 5-15% ethyl acetate in CH2CI2) to afford the product (PBG3-1.2). Yield: 2.4 g, 71%. MS (LC / MS): calculated for Chemical Formula: C10H12NO5 [M+H]+= 226; found: 226.1H NMR (400 MHz, CDCb) 6 7.60 (s, 1H), 7.27 (s, 1H), 5.42 (qd, J= 6.3, 3.9 Hz, 1H), 4.39 - 4.26 (m, 4H), 2.43 (d, J = 3.9 Hz, 1H), 1.52 (d, J= 6.3 Hz, 3H).

[0133] 1-(7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethyl dihexylcarbamate (PBG3-1): A 100 mL 2-neck round bottom flask was charged with 1-(7-nitro-2,3- dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-ol (1.43 g, 6.35 mmol) (PBG3-1.2) and carbonyldiimidazole (1.24 g, 7.62 mmol) in 30 mL of dichloromethane (CH2CI2). Next, triethylamine (0.97 mL, 6.99 mmol) was added dropwise, and the reaction mixture was stirred at reflux in the dark for 4 h. Then, / V, / V-dihexylamine (4.44 mL, 19.06 mmol) was added, and the mixture was stirred in the dark for 16 h. Upon completion, the reaction mixture was washed with water, and sodium chloride (NaCI) solution, extracted by CH2CI2. and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (80% CH2CI2 in hexanes) to afford the product Yield: 1.61 g, 59.4%. MS (LC / MS): calculated for Chemical Formula: C23H37N2O6 [M+Hp = 437; found: 437.1H NMR (400 MHz, CDCb) 67.62 (s, 1H), 7.01 (s, 1H), 6.29 (q, J= 6.4 Hz, 1H), 4.38

[0134] - 4.22 (m, 4H), 3.33 - 3.05 (m, 4H), 1.57 (d, J = 6.4 Hz, 7H), 1.40 - 1.14 (m, 12H), 0.96

[0135] - 0.77 (m, 6H).

[0136] Synthesis of 1-(7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethyl dihexylcarbamate

[0137] 1-(5,7-dinitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one (PBG3-2.1): A 250 mil-neck round bottom flask (RBF) was charged with fuming nitric acid (35 mL, 90%). At 0 °C, 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one, (5.0 g, 28.0 mmol) was added as solid portions, and the reaction mixture was allowed to warm to room temperature (RT) and stirred at RT for an additional 1 h. Upon completion, the reaction mixture was slowly dropped into cold H2O (200 mL) and the precipitate was filtered, washed with water, and rinsed with methanol (MeOH). After drying, the crude product was purified by flash chromatography (silica gel, 0-100% CH2CI2 in hexanes) to afford the product (PBG3-2.1). Yield: 3.45 g, 46%. MS (LC / MS): calculated for Chemical Formula: CI0H8N2O7[M+H]+= 269; found: 269.1H NMR (400 MHz, CDCI3) 67.15 (s, 1H), 4.46 (s, 4H), 2.52 (s, 3H).

[0138] 1-(5,7-dinitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-ol (PBG3-2.2): A 100 mL

[0139] 2-neck round bottom flask was charged with 1 -(5,7-dinitro-2,3-dihydrobenzo[b][1 ,4]dioxin- 6-yl)ethan-1-one (PBG3-2.1)(1.00 g, 3.73 mmol), and tetrahydrofuran (15 mL) under Ar. Sodium borohydride (NaBH4) (0.22 g, 5.81 mmol) was added as solid portions and the reaction mixture was stirred at room temperature (RT) for 15 minutes. 5 mL of ethanol was added and the reaction mixture was stirred for an additional 45 minutes at RT. Upon completion, the reaction mixture was slowly dropped into a saturated ammonium chloride (NH4CI) solution (100 mL), extracted organic product into ethylacetate, washed with NaCI solution, and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (silica gel, 5-15% ethyl acetate in CH2CI2) to afford the product Yield: 0.72 g, 70%. MS (LC / MS): calculated for Chemical Formula: C10H11N2O7 [M+H]+= 271; found: 271. 1H NMR (400 MHz, CDCI3) 67.38 (s, 1H), 5.09 (q, J = 6.3 Hz, 1H), 4.48 - 4.31 (m, 4H), 1.51 (d, J = 6.4 Hz, 3H).

[0140] 1-(5,7-dinitro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethyl dihexylcarbamate (PBG3- 2): A 100 mL 2-neck round bottom flask was charged with 1 -(5,7-dinitro-2,3- dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-ol (0.72 g, 2.66 mmol)(PBG3-2.2), and N,N'- dimethylaminopyridine (DMAP) (0.49 g, 3.99 mmol) in 20 mL 1 ,2-dichloroethane. At 0 °C, 4-nitro orthochloroformate (0.81 g, 3.99 mmol) was added as a solid, and the reaction mixture was stirred for 1 h. Then, / V, / V-dihexylamine (1.25 mL, 5.33 mmol) was added, and the mixture was stirred at room temperature for 4 h. Upon completion, the reaction mixture was washed with water, and sodium chloride (NaCI) solution, extracted organic product by CH2CI2. and dried over sodium sulfate (Na2SO4). After drying, the crude product was purified by flash chromatography (50-80% CH2CI2 in hexanes) to afford the product. Yield: 0.95 g, 74.2%. MS (LC / MS): calculated for Chemical Formula: C23H36N3O8 [M+H]+= 482; found: 482.1H NMR (400 MHz, CDCI3) δ 7.09 (s, 1H), 5.83 (q, J = 6.5 Hz, 1H), 4.50 - 4.26 (m, 4H), 3.28 - 3.03 (m, 4H), 1.59 (d, J = 6.5 Hz, 3H), 1.56 - 1.38 (m, 4H), 1.41 - 1.11 (m, 12H), 0.97 - 0.79 (m, 6H). Synthesis of Compound PBG4-1

[0141] PBG4-1: To a solution of PBG4-2.2 (446 mg, 1.0 mmol), hydroxybenzotriazole (HOBt) (46 mg, 0.3 mmol) in anhydrous N,N -dimethylacetamide (DMAc) (10 mL), 2,6- dimethylpiperidine (453 mg, 4 mmol) was added. The mixture was heated at 90 °C overnight, then worked up with brine, extracted with dichloromethane (100 mL x 3), dried over sodium sulfate, loaded on silica gel, and purified by flash chromatography using eluents of hexeanes / ethyl acetate (0% to 40% ethyl acetate). A white solid (100 mg, in 23.8% yield) was obtained after removal of solvents.1H NMR (400 MHz, TCE) 6 7.59 (s, 1H), 7.22 (d, J = 6.3 Hz, 1H), 6.98 (s, 1H), 4.25 (bs, 2H), 3.87 (d, J = 1.6 Hz, 6H), 1.54 (m, 5H), 1.47 - 1.37 (m, 1H), 1.16 (dd, J = 16.0, 7.0 Hz, 6H).

[0142] Synthesis of Compound PBG4-2

[0143] Compound PBG4-2.1 : To a mixture of 6-nitroveratraldehyde (4.22 g, 20 mmol), anhydrous potassium carbonate, K2CO3, (0.552 g, 4 mmol) in anhydrous N,N- dimethylformamide (DMF) (25 mL) (trifluoromethyl)trimethylsilane (5.688g, 6 mL, 40 mmol) was added at room temperature under argon. The whole was stirred for 2 hours. To the resulting mixture, 1N MCI aqueous solution (4 mL) was added and stirred for one hour at room temperature. The mixture was worked up with brine, and extracted with ethyl acetate (150 mL x 3). The organic phase was collected, dried over sodium sulfate, concentrated, then diluted with dichloromethane and loaded on silica gel, and purified by flash chromatography using eluents of hexanes / ethyl acetate (0% to 60% ethyl acetate). The main peak was collected, and removal of solvents gave a light-yellow solid (4.9 g, in 87% yield). LCMS (APCI-): Calcd for C10H10F3N05 = 281.05; Found: 281.1H NMR (400 MHz, TCE) δ 7.54 (s, 1 H), 7.24 (s, 1 H), 6.23 (p, J = 6.0 Hz, 1 H), 3.91 (s, 3H), 3.87 (s, 3H), 3.08 (d, J = 5.4 Hz, 1H).

[0144] CompoundPBG4-2.2: To a mixture of compound PBG4-2.1 (1.0 g, 3.56 mmol), 4- nitrophenyl-chloroformate (1 ,0g, 5 mmol), / V, / V-dimethylaminopyridine (DMAP) (0.61 g, 5 mmol), dichloroethane (25 mL) at 0 °C was added. The mixture was stirred at 0 °C for 30 min, then at room temperature for 2 hours. The resulting mixture was diluted with dichloromethane (DCM) (50 mL), washed with 1 N HCI aqueous solution (50 mL x 2) and brine (150 mL), dried over sodium sulfate, loaded on silica gel and purified by flash chromatography using eluents of hexanes / ethyl acetate (0% to 20% ethyl acetate). The main fraction was collected, and removal of solvents gave a light-yellow solid, which was reprecipitated in DCM / MeOH to give an off-white solid (1.06 g, in 66.8% yield).1H NMR (400 MHz, TCE) 6 8.24 - 8.16 (m, 2H), 7.62 (s, 1H), 7.39 - 7.32 (m, 2H), 7.29 (q, J= 5.8 Hz, 1H), 7.10 (s, 1H), 3.94 (s, 3H), 3.89 (s, 3H).

[0145] Compound PBG4-2: To a solution of compound PBG4-2.2 (446 mg, 1 mmol), hydroxybenzotriazole (HOBt) (46 mg, 0.3 mmol) in anhydrous / V, / V'-dimethylacetamide (DMAc) (10 mL), piperidine (340 mg, 4 mmol) was added. The whole was heated at 90 °C for 2 hours. TLC showed the reaction completed. The mixture was poured into water (50 mL), 10 mL brine was added, and extracted with dichloromethane (100 mL x 3). The organic phase was collected, dried over sodium sulfate, loaded on silica gel, and purified by flash chromatography using eluents of hexanes / ethyl acetate (10% to 40% ethyl acetate). The main peak was collected, concentrated, and precipitated with MeOH / HzO (10:1) to give a white solid (270 mg, in 69% yield).1H NMR (400 MHz, TCE) δ 7.58 (s, 1H), 7.17 (q, J = 6.2 Hz, 1H), 6.96 (s, 1H), 3.87 (d, J = 2.5 Hz, 6H), 3.47 (s, 2H), 3.31 (s, 2H), 1.46 (s, 2H).

[0146] Synthesis of PBG5-1 Compound PBG5-1.1: A mixture of 6-acetyl-2H-1,4-benzoxazin-3(4H)-one (0.956g, 5 mmol), potassium carbonate, K2CO3, (0.76 g, 5.5 mmol), and iodomethane (0.85 g, 6 mmol) in / V, / V -dimethylformamide (10 mL) was stirred at 50 °C overnight. The reaction mixture was worked up with brine and ethyl acetate (80 mL x 3). The organic phase was collected, and dried over magnesium sulfate. After removal of solvent, the solid was redissolved in dichloromethane (DCM) and loaded on silica gel, then purified by flash chromatography using eluents of DCM / ethyl acetate (0% to 40% ethyl acetate). The main fraction was collected, and removal of solvents gave a white solid (0.90 g, in 88% yield).1H NMR (400 MHz, CDCb) 67.63 (d, J = 8.1 Hz, 2H), 7.02 (dd, J= 7.9, 0.7 Hz, 1H), 4.69 (s, 2H), 3.42 (s, 3H), 2.59 (s, 3H). LCMS (APCI+): calcd for M+H = 206; found: 206

[0147] Compound PBG5-1.2: To a solution of compound PBG5-1.1 (0.83 g) in 10 mL nitromethane, 5mL of 70% nitric acid and 5 mL of 90% nitric acid were added. The mixture was stirred at room temperature for 20 min, then 50 mL of distilled water was added slowly. Yellow precipitate formed immediately, which was filtered and washed with water, and dried in air to give the desired product as yellow solid (0.99 g, in 90% yield).1H NMR (400 MHz, CDCb) δ 7.74 (s, 1H), 6.91 (s, 1H), 4.75 (s, 2H), 3.42 (s, 3H), 2.51 (s, 3H). LCMS (APCI+): calcd for M+H = 251; found 251.

[0148] Compound PBG5-1.3: To a suspension of compound PBG5-1.2 (1.1 g, 4.4 mmol), in tetrahydrofuran / ethanol (THF / EtOH) (30 mL / 30 mL), sodium borohydride (NaBH4) (0.18 g, 4.8 mmol) was added. The mixture was stirred for one hour and turned into a clear solution. The solution was diluted with 100 mL ethyl acetate, and washed with brine (100 mL). The organic phase was collected, dried over magnesium sulfate, loaded on silica gel and purified by flash chromatography using eluents of dichloromethane / ethyl acetate (0% to 40% ethyl acetate). The main peak was collected, and removal of the solvents gave a yellow solid (0.85 g, in 76% yield).1H NMR (400 MHz, CDCb) 67.66 (s, 1H), 7.44 (s, 1H), 5.56 (dt, J= 6.3, 3.2 Hz, 1H), 4.70 (s, 2H), 3.45 (s, 3H), 2.25 (d, J = 3.7 Hz, 1H), 1.57 (d, J = 6.3 Hz, 3H). LCMS (APCI-): calcd for M- = 252; found: 252.

[0149] Compound PBG5-1 : To a solution of compound PBG5-1.3 (0.45 g, 1.78 mmol) in 20 mL 1 ,2-dichloroethane, 4-nitrophenyl-chloroformate (0.54g, 2.68 mmol) in N,N- dimethylaminopyridine (0.327g, 2.68 mmol) was added. The mixture was stirred at room temperature for 20 min. TLC showed the reaction was completed. To the resulting solution, N,N-dihexylamine (1.24 mL, 5.34 mmol) was added, and it was then stirred at room temperature overnight. The solution was washed with 20% sodium chloride solution (50 mL), then 5% sodium bicarbonate solution (50 mL x 2). It was loaded on silica gel, and purified by flash chromatography using eluents of dichloromethane / ethyl acetate (0% to 10% ethyl acetate). The 2ndmain peak was collected as desired product. Removal of solvents gave an oily liquid (0.56 g, in 70% yield).1H NMR (400 MHz, CDCb) δ 7.71 (s, 1H), 7.11 (s, 1H), 6.35 (q, J= 6.4 Hz, 1H), 4.71 (s, 2H), 3.41 (s, 3H), 3.38 - 3.04 (m, 4H), 1.65 (m, J = 6.5 Hz, 5H), 1.52 (s, 2H), 1.44 - 1.13 (m, 12H), 1.05 - 0.77 (m, 6H). LCMS (APCI+): calcd for M+H = 464; found:

[0150] Synthesis of 1 -(4-methyl-5,7-dinitro-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)ethyl dihexylcarbamate (PBG5-2)

[0151] 6-bromo-4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine (PBG5-2.1): 6-bromo-3,4- dihydro-2H-benzo[b][1,4]oxazine, (10.00 g, 46.70 mmol), and potassium carbonate (K2CO3) (12.89 g, 93.41) were stirred in Acetonitrile (70 mL) for 15 minutes. 1- iodomethane (Mel) (5.81 mL, 93.41 mmol) was added, and the reaction mixture was heated at 50 °C for 16 h. Upon completion, the reaction mixture was filtered, and filtrates were concentrated. After drying, the crude product was purified by flash chromatography (silica gel, 0-70% CH2CI2 in hexanes) to afford the product. Yield: 6.39 g, 62.9%. MS (LC / MS): calculated for Chemical Formula: C9H11BrNO [M+H]+= 229; found: 229.1H NMR (400 MHz, CDCb) δ 6.72 (s, 2H), 6.65 - 6.36 (m, 1H), 4.25 (s, 2H), 3.26 (s, 2H), 2.87 (s, 3H).

[0152] 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde (PBG5-2.2): A 250 mL 3-neck round bottom flask was charged with 6-bromo-4-methyl-3,4-dihydro-2H- benzo[b][1 ,4]oxazine (PBG5-2.1), (5.20 g, 22.80 mmol), and tetrahydrofuran (THE) (46 mL). The reaction flask was placed under a dry ice / acetone bath. At -65 °C, n-butyllithium (nBuLi) (13.70 mL, 34.21 mmol) was added drop wise over 20 minutes. The reaction mixture was stirred for 30 minutes, and N-methylformanilide (4.20 mL, 34.21 mmol) was added, and the mixture was further stirred for 1 h. Upon completion, the reaction mixture was allowed to warm to room temperature and quenched with saturated ammonium chloride (50 mL). The reaction mixture was washed with water (200 mL), and the organic product was extracted into ethylacetate. The organic phase was washed with sodium chloride solution and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 80% CH2CI2 in hexanes) to afford the product Yield: 2.47 g, 61%. MS (LC / MS): calculated for Chemical Formula: C10H12NO2 [M+HJ* = 178; found: 178.1H NMR (400 MHz, CDCb) 69.79 (d, J = 1.4 Hz, 1H), 7.18 (dd, J = 6.6, 1.8 Hz, 2H), 6.86 (dd, J = 8.2, 1.8 Hz, 1 H), 4.40 - 4.31 (m, 2H), 3.32 - 3.26 (m, 2H), 2.94 (d, J = 1.5 Hz, 3H).

[0153] 4-methyl-5,7-dinitro-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde (PBG5- 2.3): 4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde, (2.00 g, 11.23 mmol) was dissolved in Nitromethane (20 mL). The reaction flask was placed under an ice bath. Nitric acid (HNO3) (2.86 mL, 44.94 mmol) was added slowly. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. Upon completion, the reaction mixture was dropped into sat. sodium bicarbonate solution, and the organic product was extracted into dichloromethane (CH2CI2). The organic phase was washed with sodium chloride solution and dried over sodium sulfate. After drying, the crude product was dissolved in CH2CI2 and precipitated from methanol. The precipitate was filtered and dried under vacuum. Yield: 1.90 g, 70%. MS (LC / MS): calculated for Chemical Formula: C10H10N3O6[M+H]+= 268; found: 268.1H NMR (400 MHz, CDCb) δ 10.35 (s, 1H), 7.67 (s, 1H), 4.32 (t, J = 4.7 Hz, 2H), 3.64 (t, J = 4.7 Hz, 2H), 2.94 (s, 3H).

[0154] 1-(4-methyl-5,7-dinitro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)ethan-1-ol (PBG5- 2.4): A 250 mL 3-neck round bottom flask was charged with 4-methyl-5,7-dinitro-3,4- dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde (PBG5-2.3), (1.75 g, 6.55 mmol), and dichloromethane (CH2CI2) (100 mL). The reaction flask was placed in an ice bath. At 0 °C, trimethylaluminum (6.5 mL, 13.1 mmol, 2M) was added drop wise over 20 minutes. The reaction mixture was allowed to warm to room temperature (RT) and stirred at RT for 14 h. Upon completion, the reaction mixture was cooled to 0 °C, and 1 N sodium hydroxide (NaOH) (50 mL) was added drop wise. The reaction mixture was washed with H2O (200 mL), and the organic product was extracted into CH2CI2. The organic phase was washed with a sodium chloride solution and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (silica gel, 0-15% ethylacetate in CH2CI2) to afford the product. Yield: 1.1 g, 59.4%. MS (LC / MS): calculated for Chemical Formula: C11H14N3O6 [M+H]+= 284; found: 284.1H NMR (400 MHz, CDCI3) 67.49 (s, 1H), 5.05 (p, J = 6.6 Hz, 1H), 4.29 - 4.16 (m, 2H), 3.49 - 3.38 (m, 2H), 2.93 (s, 3H), 2.62 (d, J = 6.7 Hz, 1H), 1.78 (d, J = 6.7 Hz, 3H).

[0155] 1-(4-methyl-5,7-dinitro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)ethyl dihexylcarbamate (PBG5-2): A 100 mL 2-neck flask was charged with 1-(4-methyl-5,7- dinitro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)ethan-1-ol (0.50 g, 1.76 mmol) (PBG5- 2.4), and N. / V'-dimethylaminopyridine (DMAP) (0.32 g, 2.65 mmol) in 17 mL of 1,2- dichloroethane. At 0 °C, 4-nitrophenyl chloroformate (0.53 g, 2.65 mmol) was added as a solid, and the reaction mixture was stirred for 1 h. Then, / V, / V-dihexylamine (0.83 mL, 3.53 mmol) was added, and the mixture was stirred at room temperature for 3 h. Upon completion, the reaction mixture was washed with water, and a sodium chloride solution, organic product was extracted by CH2CI2. and dried over sodium sulfate. After drying, the crude product was purified by flash chromatography (0-50% ethylacetate in hexanes) to afford the product Yield: 0.55 g, 64%. MS (LC / MS): calculated for Chemical Formula: C24H39N4O7 [M+H]+= 495; found: 495. 1H NMR (400 MHz, CDCI3) δ 7.44 (s, 1H), 5.95 (q, J = 6.7 Hz, 1H), 4.22 (t, J = 4.6 Hz, 2H), 3.38 (td, J = 4.3, 1.3 Hz, 2H), 3.35 - 3.18 (m, 2H), 2.99 (ddd, J = 14.0, 12.3, 6.1 Hz, 2H), 2.90 (s, 3H), 1.84 (d, J = 6.8 Hz, 3H), 1.46 (h, J = 6.3 Hz, 4H), 1.38 - 1.13 (m, 12H), 0.97 - 0.79 (m, 6H).

[0156] Compound PBG6-1.1: To a solution of 1,3-dimethyl-1,3-dihydro-2h-benzimidazol-2-one (0.905 g, 5.6 mmol), in 10 mL of 1,2-dichloroethane aluminum trichloride (AlCb) (1.60 g, 12 mmol) was added, then acetyl chloride (0.94 g, 12 mmol) was added at 0 °C. The mixture was stirred at room temperature overnight. The mixture was poured into ice-water (100 mL) and extracted with dichloromethane (DCM) (100 mL x 2). The organic phase was collected and dried over magnesium sulfate, concentrated, then loaded on silica gel and purified by flash chromatography using eluents of DCM / ethyl acetate (0% to 60% ethyl acetate). The main peak was collected, and removal of solvents gave a white solid (0.85 g, in 75% yield).1H NMR (400 MHz, CDCb) δ 7.80 (dd, J = 8.2, 1.6 Hz, 1H), 7.66 (d, J= 1.6 Hz, 1H), 7.02 (d, J= 8.2 Hz, 1H), 3.49 (d, J= 3.1 Hz, 6H), 2.66 (s, 3H). LCMS (APCI+): calcd for M+H = 205; found: 205.

[0157] Compound PBG6-1.2: To a solution of compound PBG6-1.1 (0.75 g, 4.2 mmol) in 10 mL nitromethane, 5 mL of 70% nitric acid and 5 mL of 90% nitric acid were added. The solution was then stirred at room temperature for 10 min. To the solution, 50 mL water was added, and a precipitate formed. After filtration, the solid was washed with water, dried in air, then redissolved in dichloromethane (DCM), loaded on silica gel, and purified by flash chromatography using eluents of DCM / ethyl acetate (0% to 5% ethyl acetate). The 2ndpeak was collected as the desired product. Removal of solvents gave a yellow solid (0.95 g, in 91% yield).1H NMR (400 MHz, CDCb) 6 7.78 (s, 1H), 6.92 (s, 1H), 3.53 (s, 3H), 3.51 (s, 3H), 2.56 (s, 3H). LCMS (APCI+): calcd for M+H = 250; found: 250.

[0158] Compound PBG6-1.3: To a solution of compound PBG6-1.2 (0.95 g, 3.82 mmol) in tetrahydrofuran / ethanol (THF / EtOH) (15 mL / 15 mL) sodium borohydride (NaBH4) (0.158 g, 4.2 mmol) was added. The solution was then stirred at room temperature for 1.5 hours. The resulting mixture was worked up with brine and ethyl acetate (100 mL x2). The organic phase was collected, dried over sodium sulfate, and removal of solvents gave a yellow solid (0.95 g, in quantitative yield).1H NMR (400 MHz, CDCb) 67.70 (s, 1H), 7.45 (s, 1H), 5.64 (q, J= 6.2 Hz, 1H), 3.50 (d, J= 8.9 Hz, 6H), 1.62 (d, J= 6.3 Hz, 3H). LCMS (APCI+): calcd for M+H = 252; found 252.

[0159] Compound PBG6-1 : To a solution of compound PBG6-1.3 (0.95 g, 3.8 mmol) in 25 mL of 1 ,2-dichloroethane, 4-nitrophenyl chloroformate (1.145 g, 5.67 mmol), N,N- dimethylaminopyridine, DMAP, (0.69 g, 5.67 mmol) was added. The mixture was stirred at room temperature for 2 hours, then N,N-dihexylamine (1.85 g, 10 mmol) was added. The mixture was then stirred at room temperature overnight. The resulting solution was washed with water, then 5% sodium bicarbonate, NaHCOa, (3 x 50 mL), dried over magnesium sulfate, loaded on silica gel and purified by flash chromatography using eluents of dichloromethane / ethyl acetate (0% to 10% ethyl acetate). The 3rdpeak was collected as the desired product Removal of solvents gave a pale yellow solid (0.38 g, in 22% yield).1H NMR (400 MHz, CDCb) δ 7.73 (s, 1H), 7.10 (s, 1H), 6.42 (q, J = 6.4 Hz, 1H), 3.48 (s, 3H), 3.47 (s, 3H), 3.39 - 3.10 (m, 4H), 1.68 (d, J = 6.4 Hz, 3H), 1.62-1.50 (m, 4H), 1.43 - 1.16 (m, 12H), 1.00 - 0.79 (m, 6H). LCMS (APCI+): Calcd for M+H = 463;

[0160] Found: 463.

[0161] Synthesis of PBG6-2

[0162] General procedure of compound 6-2.1 synthesis — benzo[d][1,3]dioxol-4-ol: A 100 mL flask was fitted with a stir bar. In the flask, compound 2,3-

[0163] (methylenedioxy)benzaldehyde (540.4 mg, 3.6 mmol) was dissolved in DCM (30 mL), followed by the addition of m-CPBA (722.0 mg, 4.3 mmol). The mixture was heated up to reflux and kept refluxing for 6 hours. A 50% conversion was observed. Another portion of m-CPBA (722.0 mg, 4.3 mmol) was added. The reaction was kept refluxing for another 6 hours. LCMS showed completion of the reaction. The reaction was cooled down to room temperature. The mixture was concentrated under rotavapor. The residue was redissolved in EtOH (20 mL), followed by the addition of KOH (605.0 mg, 10.8 mmol). The mixture was kept stirring at room temperature for 5 minutes. LCMS showed the completion of the reaction. MCI (6 mL, 1M) was added to neutralize the solution. The crude was extracted with EtOAc (3* 50 mL). The combined organic phase was dried over anhydrous Na2SO4After filtration and concentration, the crude was purified by silica gel chromatography to provide 6-2.1 as a pale-yellow solid using 30%-40%-100% DCM in hexane as the eluants. 305.0 mg, 61% yield. MS (APCI): calculated for Chemical Formula: C7H6O3([M+H]*’) = 139 found: 139.1H NMR (400 MHz, CDCb) 6.76-6.68 (m, 1H), 6.52- 6.45 (m, 2H), 5.95 (s, 2H), 5.05 (bs, 1H).

[0164] General procedure of compound 6-2.2 synthesis — 4-hydroxybenzo[d][1,3]dioxole- 5-carbaldehyde: A 100 mL flask was fitted with a stir bar. In the flask, compound 6-2.1 (305.0 mg, 2.2 mmol) was dissolved in THF (22mL), followed by the addition of paraformaldehyde (264.0 mg, 8.8 mmol), MgCb (419.0 mg, 4.4 mmol) and EtaN (0.6 mL, 4.4 mmol). The mixture was heated to 85 °C and kept at this temperature for 6 hrs. LCMS showed completion of the reaction. The reaction was cooled down to room temperature. The reaction was worked up by MCI (15 mL). The crude was extracted with EtOAc (3* 50 mL). The combined organic phase was dried over anhydrous NazSO4. After filtration and concentration, the crude was purified by silica gel chromatography to provide 6-2.2 as a white solid using 0-40% EtOAc in hexane as the eluants. 226.0 mg, 62% yield. MS (APCI): calculated for Chemical Formula: C8H6O4([M+H]) = 167 found: 167.1H NMR (400 MHz, CDCb) 11.0 (s, 1H), 9.74 (s, 1H), 7.16 (d, J = 8.4 Hz, 1H), 6.59 (d, J = 8.4 Hz, 1H), 6.11 (s, 2H).

[0165] General procedure of compound 6-2.3 synthesis — 4-methoxybenzo[d][1,3]dioxole- 5-carbaldehyde: A 25 mL flask was fitted with a stir bar. In the flask, compound 6-2.2 (226.0 mg, 1.4 mmol) and iodomethane (0.2 mL, 2.8 mmol) were dissolved in acetone (5 mL), followed by the addition of K2CO3 (234.9 mg, 1.7 mmol). The mixture was heated to 75 °C and kept at this temperature for 24 hrs. LCMS showed completion of the reaction. The reaction was cooled down to room temperature. The mixture was filtered through a celite pad via vacuum filtration. After filtration and concentration, the crude was purified by silica gel chromatography to provide 6-2.3 as a white solid using 0-40% EtOAc in hexane as the eluants. 206.0 mg, 82% yield. MS (APCI): calculated for Chemical Formula: C9H8O4 ([M+HH = 181 found: 181.1H NMR (400 MHz, CDCb) 10.23 (d, J= 0.8 Hz, 1H), 7.47 (d, J= 8.4 Hz, 1H), 6.60 (dd, J= 8.4 Hz, 0.8 Hz, 1H), 6.04 (s, 2H), 4.13 (s, 3H).

[0166] General procedure of compound 6-2.4 synthesis — 4-methoxy-6- nitrobenzo[d][1,3]dioxole-5-carbaldehyde: A 25 mL flask was fitted with a stir bar. In the flask, compound 6-2.3 (206.0 mg, 1.1 mmol) was dissolved in CH3NO2 (4 mL), followed by the addition of HNO3 (300.0 pL, 4.6 mmol, 90% cone.). The reaction was kept at room temperature for 1 hr. LCMS showed completion of the reaction. It was worked up by the addition of NaHCOs (5 mL). After separation, the aqueous phase was further extracted with EtOAc (3* 10 mL). The combined organic phase was dried over anhydrous Na2SO4. After filtration and concentration, the crude was purified by silica gel chromatography to provide 6-2.4 as a pale-yellow solid using 0-40% EtOAc in hexane as the eluants. 149.0 mg, 58% yield. MS (APCI): calculated for Chemical Formula: C9H7NO8([M+HD = 226 found: 226.1H NMR (400 MHz, CDCb) 10.20 (s, 1H), 7.18 (s, 1H), 6.17 (s, 2H), 4.08 (s, 3H).

[0167] General procedure of compound 6-2.5 synthesis — 1-(4-methoxy-6- n it robenzo[d][1,3]dioxol-5-yl)et han-1 -ol: A 250 mL flask was fitted with a stir bar. In the flask, compound 6-2.4 (1.6 g, 7.0 mmol) was suspended in anhydrous DCM (84 mL). The solution was cooled down to 0 °C with an ice-water bath. MeaAl (2.0 in Hexane, 7.0 mL) was added dropwise to the solution. The reaction was slowly warmed up to room temperature after completion of the addition. The reaction was kept at room temperature for 2 hours. Both TLC and LCMS showed completion of the reaction. It was then cooled down to 0 °C and worked-up by the addition of water and HCI (1 N) solution, 20 mL for each. The mixture was extracted with DCM (3* 150 mL). The combined organic phase was dried over anhydrous Na2SO4. After filtration and concentration, the crude was purified by silica gel chromatography to provide 6-2.5 as a yellow solid using 0-40% EtOAc in hexane as the eluants. 1.4 g, 80% yield. MS (APCI): calculated for Chemical Formula: = 241 found: 241.1H NMR (400 MHz, CDCb) 7.03 (s, 1H), 6.10-6.05 (m, 2H), 5.18-5.08 (m, 1H), 4.12 (s, 3H), 3.38 (d, J= 7.2 Hz, 1H), 1.66 (d, J= 7.2 Hz, 3H).

[0168] General procedure Ooff compound 6-2 synthesis — 1-(4-methoxy-6- nitrobenzo[d][1,3]dioxol-5-yl)ethyl dihexylcarbamate: A 100 mL flask was fitted with a stir bar. In the flask, compound 6-2.5 (700.0 mg, 2.9 mmol) was dissolved in DCE (25 mL) and it was cooled down to 0 °C. To the solution, 4-nitrophenyl chloroformate (887.0 mg, 4.4 mmol) and DMAP (536.8 mg, 4.4 mmol) were added. The reaction was warmed to room temperature and kept at room temperature for 3 hrs. LCMS showed completion of the reaction. Then, dihexylamine (2.0 mL, 8.7 mmol) was added. The reaction was kept at room temperature overnight. LCMS showed completion of the reaction. The crude reaction solution was purified by silica gel chromatography to provide 6-2 as a yellow oil using 0-40% EtOAc in hexane as the eluants. 1.2 g, 88% yield. MS (APCI): calculated for Chemical Formula: = 453 found: 453.1H NMR (400 MHz, CDCb) 6.82 (s, 1H), 6.15 (dd, J = 6.8 Hz, 6.8 Hz, 1H), 6.03 (dd, J= 6.4 Hz, 1.2 Hz, 2H), 4.05 (s, 3H), 3.31-3.16 (m, 2H), 3.11-2.92 (m, 2H), 1.67 (d, J = 6.8 Hz, 3H), 1.52-1.40 (m, 4H), 1.33-1.23 (m, 12 H), 0.92-0.84 (m, 6H).

[0169]

[0170] Compound 6-3.1 :

[0171] A mixture of 6-acetyl-2H-1 ,4-benzoxazin-3(4H)-one (1.9 g, 10 mmol), K2CO3 (1.518 g, 11 mmol), and iodoethane (1.716 g, 11 mmol) in DMF (20 mL) was stirred at 50 °C overnight. The reaction mixture was worked up with brine and ethyl acetate (100 mL x 3). The organic phase was collected, and dried over MgSO4. After removal of solvent, the solid was redissolved in DCM and loaded on silica gel, then purified by flash chromatography using eluents of DCM / ethyl acetate (0% to 20% ethyl acetate). The main fraction was collected, and removal of solvents gave a white solid (1.90 g, in 87% yield).

[0172] 1H NMR (400 MHz, CDCb) δ 7.69 (d, J = 1.9 Hz, 1H), 7.63 (dd, J= 8.3, 1.9 Hz, 1H), 7.05 (d, J= 8.3 Hz, 1H), 4.69 (s, 2H), 4.08 (q, J= 7.2 Hz, 2H), 2.61 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H).

[0173] Compound 6-3.2:

[0174] To a solution of compound 6-3.1 (1.90 g, 8.68 mmol) in 20 mL nitromethane, 10mL of 70% nitric acid and 10 mL of 90% nitric acid were added. The mixture was stirred at room temperature for 20 min, then 200 mL of distilled water was added slowly. Yellow precipitate formed immediately, which was filtered and washed with water, and dried in air to give the desired product as yellow solid (2.01 g, in 70.6% yield).

[0175] 1H NMR (400 MHz, CDCb) 6 7.76 (s, 1H), 6.94 (s, 1H), 4.74 (s, 2H), 4.05 (q, J = 7.2 Hz, 2H), 2.54 (s, 3H), 1.32 (t, J = 7.2 Hz, 3H). Compound 6-3.3:

[0176] To a suspension of compound 6-3.2 (2.01 g, 7.56 mmol), in THF / EtOH (25 mL / 25 mL), NaBH4 (0.343 g, 9.07 mmol) was added. The mixture was stirred for one hour and turned into a clear solution. The solution was diluted with 200 mL ethyl acetate, and washed with brine (100 mL). The organic phase was collected, dried over MgSO4, loaded on silica gel and purified by flash chromatography using eluents of DCM / ethyl acetate (0% to 20% ethyl acetate). The main peak was collected, and removal of the solvents gave a yellow solid (1.1 g, in 54% yield).

[0177] 1H NMR (400 MHz, CDCb) 6 7.70 (s, 1H), 7.49 (s, 1H), 5.60 (qd, J = 6.3, 3.7 Hz, 1H), 4.70 (s, 2H), 4.10 (q, J = 7.2 Hz, 2H), 2.28 (d, J= 3.7 Hz, 1H), 1.60 (s, 2H), 1.58 (s, 2H), 1.34 (t, J = 7.2 Hz, 3H).

[0178] Compound 6-3:

[0179] To a solution of compound 6-3.3 (0.519 g, 1.95 mmol) in 25 mL of DCE, 4-nitrophenol- chloroformate (0.588 g, 2.9 mmol) and DMAP (0.354 g, 2.9 mmol) were added. The mixture was stirred at room temperature for 1.5 hr. TLC showed completion of the reaction.

[0180] To the resulting solution, N,N-dihexylamine (0.67 mL, 2.9 mmol) was added, and it was then stirred at room temperature overnight. The solution was washed with a 20% NaCI solution (50 mL), then a 5% NaHCO3 solution (50 mL x 2). It was loaded on silica gel, and purified by flash chromatography using eluents of hexanes / DCM (0% to 10% DCM to DCM with 3% EA). The 2ndmain peak was collected as the desired product. Removal of solvents gave a pale-yellow solid (0.70 g, in 75% yield).

[0181] LCMS (APCI+): Calcd for C25H40N3O6 (M+H) = 478.28; Found: 478.

[0182] 1H NMR (400 MHz, CDCb) 6 7.72 (s, 1H), 7.13 (s, 1H), 6.35 (q, J = 6.4 Hz, 1H), 4.69 (s, 2H), 4.22 - 3.93 (m, 2H), 3.46 - 3.07 (m, 4H), 1.65 (d, J = 6.5 Hz, 3H), 1.51 (m, 2H), 1.41 - 1.18 (m, 17H), 1.01 - 0.78 (m, 6H).

[0183] 1.1. PBG base release efficiency measurements pH change studies of o-nitro heteroaryl-based PBGs were performed in acetonitrile (MeCN) solvent with a 1 mg / mL concentration. In an amber vial, ~6 mg of corresponding PBG compound and then ~6 mL acetonitrile was added to dissolve it The initial pH (before exposure) was measured using a pH meter (after 3 pH Calibrations at pH 4.0, 7.0 and 10.0). Then, the solution containing o-nitro heteroaryl-based PBGs was exposed to -600 mJ / cm2mercury lamp using a Dymax UV curing conveyor. The pH after exposure was then measured using the same pH meter. The pH change was calculated by subtracting the pH after exposure with the initial pH. The pH Change results are shown in Table 1.

[0184] Solution base release experiments of o-nitro heteroaryl-based PBGs were performed in MeCN solvent with a 1 mg / mL concentration. In a transparent glass vial, -1 mg of the corresponding PBG compound was added and then -1 mL acetonitrile was added to dissolve it. Then, the solution containing the o-nitro heteroaryl-based PBG was exposed to -600 mJ / cm2 mercury lamp using a Dymax UV curing conveyor. Analysis of photo products, and efficiency was carried out using Shimadzu LC / MS.

[0185] 1.2. TGA Data of o-nitro heteroaryl-based PBGs

[0186] TGA measurements were taken from 25 °C to 450 °C under nitrogen with a flow rate of 25 ml / min using a method with a ramp rate of 10 °C / min by TA instrument TGA550. The TGA data of the o-nitro heteroaryl-based PBGs are presented in Table 1.

[0187] Table 1. Efficiency of base-release under light, and TGA of PBG compounds

[0188]

[0189] 1.3. Standard Polyimide formation method

[0190] A selected PBG (e.g., PBG2-2, PBG2-8, and or PBG2-7) and a polyimide precursor (e.g., a polyamidic acid such as PAA-55 and / or PAA-56 identified above) were weighed into a container / jar ( / .e. 30 mg of PBG in 3 g PI Varnish), then mixed by using Thinky (2000 rpm for 3 min, added more mixing time as needed until all fully dissolved). The mixed solution was spin-coated on Steel Use Stainless (SUS) 304 substrates taped on a rigid glass plate

[0191] (main spin-coating rate: 1100 rpm for 30 sec). SUS304 is a Japanese JIS Standard and one of the most frequently used stainless steels, comprising 18% Cr and 8% Ni. The substrates were then baked at 120 °C for 10 min to remove N-methyl-2-pyrrolidone (NMP) solvent. Thereafter, 600 mJ / cm2of mercury lamp was then exposed on the sample with a mask (using Dymax UV curing conveyor). Afterwards, the post-exposure baking was conducted at 185 °C for 5 min. As the final step, FT-IR (Thermo Nicolet i860) measurements of the exposed and the unexposed area of the sample were performed to obtain an imidization contrast ratio (Imidization rate% = Corrected height of imide peak (1777 cm*1) / Corrected height of benzene peak (1489 cm*1) x 100). The imidization contrast ratio is the ratio of imidization rate% of exposed area to the imidization rate% of the unexposed area. See Figure 1. PBG2-2, PBG2-8 and PBG2-7 showed good imidization contrast ratio of 1.50, 1.62, and 1.33, respectively, as shown in Figure 1.

[0192] 1.4. Optical Measurements of PBGs

[0193] Additional optical properties of PBG3-1, PBG2-2, PBG3-2, PBG6-1, and PBG5-2 are graphically illustrated in FIG. 2. Absorbance spectra of the PBGs were measured in N- methylpyrrolidone (NMP) solvent (~ 0.001 mmol / ml concentration) using Shimadzu UV3600 spectrometer. The normalized absorption spectra of the PBGs are graphically illustrated in FIG. 2.

[0194] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties, such as, molecular weight, reaction conditions, and so forth used in the specifications and embodiments are to be understood as being modified in all instances by the term “about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached embodiments are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents, to the scope of the embodiments, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying conventional and ordinary rounding techniques.

[0195] For the processes and / or methods disclosed, the functions performed in the process and methods may be implemented in differing order, as may be indicated by context Furthermore, the outlined steps and operations are only provided as examples and some of the steps and operations may be optional, combined into fewer steps and operations, or expanded into additional steps and operations.

[0196] This disclosure may sometimes illustrate different components contained within, or connected with, other different components. Such depicted architectures are merely examples, and many other architectures can be implemented to achieve the same or similar functionality.

[0197] The terms used in this disclosure and in the appended embodiment, (e.g., bodies of the appended embodiments) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including, but not limited to,” the term “having” should be interpreted to “having at least”, the term “includes” should be interpreted as “includes, but not limited to,” etc. in addition, if a specific number of elements is introduced, this may be interpreted to mean at least the recited number, as may be indicated by context (e.g., the bare recitation of “two recitations”, without other modifiers, means at least two recitations or two or more recitations). As used in this disclosure, any disjunctive word and / or phrase presenting two or more alternative terms should be understood to contemplate the possibilities of including one of those terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of A” or “B” or “A and B”. Similarly, the phrase “A and / or B” will be understood to include the possibilities of A” or “B” or “A and B”.

[0198] The terms “a”, “an”, “the”, and similar referents used in the context of describing the present disclosure (especially in the context of the following embodiments) are to construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context The use of any and all examples, or representative language (e.g., “such as” or “for instance”) provided herein is intended merely to better illustrate the present disclosure and does not pose a limitation on the scope of any embodiments. No language in this specification herein shall be construed as indicating any non-embodied element essential to the practice of the present disclosure.

[0199] Groupings of alternative elements or embodiments disclosed herein are not to be construed as limitations. Each group member may be referred to and embodied individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified, thus fulfilling the written description of all Markush groups used in the appended embodiments.

[0200] Certain embodiments are described herein, including the best mode known to the inventors for carrying out the present disclosure. Of course, variations on these described embodiments, will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the present disclosure to be practiced otherwise than specifically described herein. Accordingly, the embodiments are permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is contemplated unless otherwise indicated herein or otherwise clearly contradicted by context In closing, it is to be understood that the embodiments disclosed herein are illustrative of the principles of the embodiments. Therefore, by way of example, but not of limitation, alternative embodiments may be utilized in accordance with the teachings herein. Henceforth, the embodiments are not limited to the embodiments precisely as shown and described herein.

Claims

CLAIMSWhat is claimed is:

1. A compound according to formula (1):wherein: n is 0, 1, or 2;X is C, O or N,Y is O or N,X and Y are optionally connected together to form a ring when n is 1 or 2,R1 is a hydrogen, nitro, phenyl, substituted phenyl, alkynyl, substituted alkynyl or methoxy;R2 is hydrogen, cyano ) phenyl, substituted phenyl or methoxy,R3is hydrogen, a C1-C6alkyl, or a trihalomethyl group;R4is a C3-C8alkyl andRs is a C3-C8alkyl, or R4and Rs are connected together to form a nitrogen containing ring provided that when R4and Rs are connected together to form the nitrogen containing ring R3is hydrogen, a C3-C8alkyl, or a trihalomethyl group.

2. The compound of claim 1, wherein n is 1 or 2 and X and Y are connected together to form one of the following rings:

3. The compound of claim 1, wherein Ri is4. The compound of claim 1, wherein R2 is5. The compound of claim 1 , wherein R3 is6. The compound of claim 1, wherein each of R4and Rs is a C3-C8alkyl.

7. The compound of claim 1 , wherein R4and Rs are connected together and the nitrogen containing ring connected ring is one of and8. The compound of claim 1, having the following structure:

9. The compound of claim 1, having one of the following structures:

511. The compound of embodiment 1, having one of the following structures:

12. The compound of claim 1, having one of the following structures:

13. The compound of claim 1, having one of the following structures:

14. A method for making a polyimide, comprising: providing a compound according to any one of claims 1-13 and a polyimide precursor dispersion in a dispersant; applying the compound and the polyimide precursor to a substrate; applying visible light to the compound and polyimide precursor on the substrate; and heating the substrate to accomplish at least one of removing the dispersant and curing the covered substrate.

15. The method of claim 14, further comprising masking portions of the substrate to selectively apply visible light to unmasked portions of the substrate.

16. A method for measuring the base release efficiency of a photobase generator compound, comprising: dissolving a compound according to any one of claims 1-14 in acetonitrile; measuring the pH of a solution including the compound dissolved in the acetonitrile; exposing the solution to visible light; and measuring the pH of the solution following exposure to visible light.