Halocyclopropanation Process

Abstract

The present disclosure relates to halocyclopropanation processes useful for forming molecules with insecticidal utility against pests of the phyla Arthropoda, Mollusca, and Nematoda.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 185,399, filed May 7, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to halocyclopropanation processes useful for forming molecules with insecticidal utility against pests of the phyla Arthropoda, Mollusca, and Nematoda. [Background technology]

[0003] Halocyclopropanation processes are disclosed in WO 2016 / 168056, WO 2016 / 168058, WO 2016 / 168059, WO 2018 / 071320, and WO 2018 / 071327.

[0004] Definitions used in this disclosure The examples given in these definitions are non-exhaustive. It is understood that a substituent must comply with the chemical bonding rules and steric compatibility constraints for the particular molecule to which it is attached. These definitions are used solely for the purposes of this disclosure.

[0005] The term "alkoxy" means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, and tert-butoxy.

[0006] The term "alkyl" means an acyclic saturated branched or unbranched substituent composed of carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, and tert-butyl.

[0007] The term "aryl" means a cyclic aromatic substituent composed of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

[0008] The term "halo" means fluoro, chloro, bromo and iodo.

[0009] The term "haloalkoxy" means alkoxy further consisting of one to the maximum possible number of the same or different halo, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy and pentafluoroethoxy.

[0010] The term "haloalkyl" means alkyl further consisting of one to the maximum possible number of the same or different halo, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichloromethyl and 1,1,2,2-tetrafluoroethyl. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Scheme 1 is shown below. [ka]

[0012] In Scheme 1: (a) R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, or (C1-C4) haloalkoxy; (b) Each R n are independently (C1-C4) alkyl, or both R n The substituents together form a (C2-C6) alkyl bond connecting the two oxygen atoms, and (c) each X is independently F, Cl, Br, or I.

[0013] In one embodiment, R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl, or (C1-C4)haloalkoxy, provided that at least one of R2, R3, and R4 is not H.

[0014] In another embodiment, each X is independently Cl or Br.

[0015] In another embodiment of S1a, R2 and R4 are CF3, R1, R3, and R5 are H, and each R n is C2H5. This molecule is (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene, hereafter referred to as ("S1a-1"). [ka]

[0016] The reaction of Scheme 1 is carried out in the presence of a halocyclopropanation reagent that reacts with S1a to produce S1b. In other words, functionally, the halocyclopropanation reagent serves as a source of dihalocarbene. Examples of such halocyclopropanation reagents are carbon tetrachloride (CCl4), tetrachloroethylene (Cl2C-CCl2), chloroform (CHCl3), salts of trichloroacetic acid (metals including but not limited to lithium, sodium, potassium, and quaternary ammonium cations), alkyl esters of trichloroacetic acid, hexafluoroacetone ((F3C)2CO), hexachloroacetone (also known as 1,1,1,3,3,3-hexachloropropan-2-one, (Cl3C)2CO), and hexabromoacetone ((Br3C)2CO). In general, the amount that can be used depends on the particular reagent, but a range of about 0.5 moles to about 100 moles of reagent per mole of S1a can be used. For example, when chloroform is the reagent, a range of about 5 moles to about 100 moles may be used, but in some cases, a range of about 30 moles to about 60 moles may be used. As another example, when hexachloroacetone is the reagent, a range of about 0.5 moles to about 100 moles may be used, but in some cases, a range of about 1 mole to about 5 moles may be used. A mixture of halocyclopropanation agents may also be used.

[0017] The reaction of Scheme 1 is carried out in the presence of a lithium salt of a tertiary alkoxide. For example, lithium tert-butoxide (LiOC(CH3)3, also known as lithium 2-methylpropan-2-olate) and lithium 2-methyl-2-butoxide (also known as lithium tert-amoxide or lithium tert-amylate) can be used. In general, an amount ranging from about 1 mole to about 20 moles per mole of S1a can be used, and also from about 1 mole to about 15 moles can be used. Optionally, a mixture of such lithium salts can be used.

[0018] The reaction of Scheme 1 may be carried out in the presence of a co-solvent. Such co-solvents may be selected, for example, from one or more of the following: heptane, hexane, toluene, diglyme, tetrahydrofuran ("THF"), dimethyl carbonate, dimethoxyethane, ethylene glycol methyl ether, tert-butanol ("t-BuOH"), nitrobenzene, chlorobenzene, methyl tert-butyl ether ("MTBE"), 2-methyldecane, and anisole (also known as methoxybenzene). Optionally, mixtures of such co-solvents may be used, for example, C9-C 12 Mixtures of isoalkanes may be used.

[0019] Optionally, the reaction of scheme 1 can be carried out in the presence of a phase transfer catalyst. Such phase transfer catalysts are, for example, benzyltributylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hexachlorophosphate, N-benzylcinchonidium chloride, (-)-N-dodecyl-N-methylephedrinium bromide, Aliquat® 336 (trioctylmethylammonium chloride). Optionally, a mixture of phase transfer catalysts can be used.

[0020] The reaction of Scheme 1 may be carried out at ambient temperature and pressure. However, higher and lower temperatures and pressures may be used. Currently, temperatures of about 0°C to about 100°C may be used. However, other ranges may be used depending on the reagent used. For example, when chloroform is the reagent, a range of about 0°C to about 60°C may be used, in some circumstances a range of about 20°C to about 50°C may be used, and in other circumstances a range of about 25°C to about 40°C may be used. As another example, when hexachloroacetone is the reagent, a range of about 0°C to about 40°C may be used, but in some cases a range of about 0°C to about 25°C may be used. Pressures of about 10 kilopascals (kPa) to about 1000 kPa may be used, and in some circumstances a pressure of about 50 kPa to about 150 kPa may be used.

[0021] Scheme 2 is shown below. [ka]

[0022] In Scheme 2: (a) R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, or (C1-C4) haloalkoxy; (b) each Y is independently OH, OSi((C1-C4)alkyl)3, OSi((C1-C4)alkyl)2((C1-C4)alkyl-aryl), OSi((C1-C4)alkyl)2(aryl), OSi((C1-C4)alkyl)(aryl), OC(O)(C1-C4)alkyl, OC(O)O(C1-C4)alkyl, OC(O)NH(C1-C4)alkyl, O(C1-C4)alkyl-aryl, O-aryl, tetrahydropyranyl, or 1,3-dioxolanyl; and (c) each X is independently F, Cl, Br, or I.

[0023] In one embodiment, R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl, or (C1-C4)haloalkoxy, provided that at least one of R2, R3, and R4 is not H.

[0024] In another embodiment, Y is independently OSi(CH3)3, OSi(CH2CH3)3, OSi(CH(CH3)2)3, OSi(CH3)2phenyl, Obenzyl, O(C(O)NH-tert-butyl), OSi(CH3)2-(tert-butyl).

[0025] In another embodiment, each X is independently Cl or Br.

[0026] In another embodiment of S2a: R2 and R4 are CF3, R1, R3, and R5 are H, and Y is OSi(CH3)2 (tert-butyl). This molecule is (5R,6R)-5,6-bis((E)-3,5-bis(trifluoromethyl)styryl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane, hereafter referred to as ("S2a-1"). [ka]

[0027] The reaction of Scheme 2 is carried out in the presence of a halocyclopropanation reagent that converts S2a to the S2b main product. In other words, functionally, the halocyclopropanation reagent serves as a source of dihalocarbene. Examples of such halocyclopropanation reagents are carbon tetrachloride (CCl4), tetrachloroethylene (Cl2C-CCl2), chloroform (CHCl3), salts of trichloroacetic acid (metals including but not limited to lithium, sodium, potassium, and quaternary ammonium cations), alkyl esters of trichloroacetic acid, hexafluoroacetone ((F3C)2CO), hexachloroacetone (also known as 1,1,1,3,3,3-hexachloropropan-2-one, (Cl3C)2CO), and hexabromoacetone ((Br3C)2CO). In general, the amount that can be used depends on the particular reagent, but a range of about 0.5 moles to about 100 moles of reagent per mole of S2a can be used. For example, when chloroform is the reagent, a range of about 5 moles to about 100 moles may be used, but in some cases, a range of about 30 moles to about 60 moles may be used. As another example, when hexachloroacetone is the reagent, a range of about 0.5 moles to about 100 moles may be used, but in some cases, a range of about 1 mole to about 5 moles may be used. A mixture of halocyclopropanation agents may also be used.

[0028] The reaction of Scheme 2 is carried out in the presence of a lithium salt of a tertiary alkoxide. For example, lithium tert-butoxide ((LiOC(CH3)3, also known as lithium 2-methylpropan-2-olate) and lithium 2-methyl-2-butoxide (also known as lithium tert-amoxide or lithium tert-amylate) can be used. In general, an amount ranging from about 1 mole to about 20 moles per mole of S2a can be used, and an amount of about 1 mole to 15 moles can also be used. Optionally, a mixture of such lithium salts can be used.

[0029] The reaction of Scheme 2 may be carried out in the presence of a co-solvent. Such co-solvents may be selected, for example, from one or more of the following: heptane, hexane, toluene, diglyme, tetrahydrofuran ("THF"), dimethyl carbonate, dimethoxyethane, ethylene glycol methyl ether, tert-butanol ("t-BuOH"), nitrobenzene, chlorobenzene, methyl tert-butyl ether ("MTBE"), 2-methyldecane, and anisole (also known as methoxybenzene). Optionally, mixtures of such co-solvents may be used, for example, C9-C 12 Mixtures of isoalkanes may be used.

[0030] Optionally, the reaction of scheme 2 can be carried out in the presence of a phase transfer catalyst. Such phase transfer catalysts are, for example, benzyltributylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hexachlorophosphate, N-benzylcinchonidium chloride, (-)-N-dodecyl-N-methylephedrinium bromide, Aliquat® 336 (trioctylmethylammonium chloride). Optionally, a mixture of phase transfer catalysts can be used.

[0031] The reaction of Scheme 2 may be carried out at ambient temperature and pressure. However, higher and lower temperatures and pressures may be used. Currently, temperatures of about 0°C to about 100°C may be used. However, other ranges may be used depending on the reagent used. For example, when chloroform is the reagent, a range of about 0°C to about 60°C may be used, in some circumstances a range of about 20°C to about 50°C may be used, and in other circumstances a range of about 25°C to about 40°C may be used. As another example, when hexachloroacetone is the reagent, a range of about 0°C to about 40°C may be used, but in some cases a range of about 0°C to about 25°C may be used. Pressures of about 10 kilopascals (kPa) to about 1000 kPa may be used, and in some cases a pressure of about 50 kPa to about 150 kPa may be used. EXAMPLES

[0032] These examples are for illustrative purposes and should not be construed as limiting the disclosure to only the embodiments disclosed in these examples.

[0033] Starting materials, reagents, and solvents obtained from commercial sources were used without further purification. Anhydrous solvents were purchased from Aldrich as Sure / Seal™ and used as received. Bases and other reagents were kept in a nitrogen (N2) filled glove box unless otherwise noted. Examples using "ambient temperature" were performed in a climate-controlled laboratory where temperatures ranged from about 20°C to about 24°C. Molecules are given their known names and named according to naming programs within ChemDraw. If such programs are unable to name the molecule, such molecules are named using conventional IUPAC naming conventions. Unless otherwise noted, 1 H NMR spectral data are in ppm (δ) and were recorded at 400 and 500 MHz. 13 C NMR spectral data are in ppm (δ) and were recorded at 75, 100, or 150 MHz. 19 F NMR spectral data are in ppm (δ) and were recorded at 471 MHz.

[0034] Example 1a: Synthesis of trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a 250 milliliter (mL) three-neck round bottom flask equipped with a magnetic stir bar and temperature probe, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (5 grams (g), 14.61 millimoles (mmol)) was dissolved in chloroform (47.1 mL, 584 mmol). Lithium 2-methylpropan-2-olate (11.69 g, 146 mmol) was added to the solution in one portion. The mixture was heated to 40° C. and stirred vigorously for 24 hours. After cooling to ambient temperature, the reaction mixture was washed twice with water (50 mL) and then with brine. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum on a rotary evaporator to give the resulting oil containing the desired product (72% conversion to product). The starting material and product could not be separated by silica gel column chromatography (hexane-ethyl acetate eluent): 1 H NMR(400MHz,CDCl3)δ 7.83(s,1H),7.71(s,2H),4.64(d,J=6.1Hz,1H),3.82-3.55(m,4H),2.94(d,J=8.4 Hz,1H),2.35(dd,J=8.5,6.1Hz,1H),1.32(t,J=7.0Hz,3H),1.21(t,J=7.1Hz,3H); 19 F NMR(471MHz, CDCl3)δ -62.87.

[0035] Example 1b: Synthesis of trans-rac-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene [ka] In a vial, (E)-(3,3-diethoxyprop-1-en-1-yl)benzene (200 milligrams (mg), 0.97 mmol) was dissolved in chloroform (3.128 mL, 38.8 mmol). The solution was added to another vial containing lithium tert-butoxide (776 mg, 9.70 mmol, 10 equivalents relative to starting material) and weighed in a glove box. The reaction was heated to 40° C. and stirred vigorously for 24 hours. After cooling to ambient temperature, the reaction mixture was washed twice with water (2 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum on a rotary evaporator. The resulting oil was purified using 1,4-dinitrobenzene as an internal standard. 1 Analyzed by H NMR spectroscopy 1 H-NMR yield was obtained (82% yield): 1 H NMR(500MHz,CDCl3)δ 7.40-7.26(m,5H),4.61(d,J=6.5Hz,1H),3.90-3.53(m,4H),2.84(d,J=8.6Hz, 1H),2.31(dd,J=8.6,6.5Hz,1H),1.31(t,J=7.1Hz,3H),1.19(t,J=7.0Hz,3H).

[0036] Example 1c: Synthesis of trans-rac-1,3-dichloro-5-(2,2-dichloro-3-diethoxymethyl)cyclopropyl)benzene [ka] In a vial, (E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (200 mg, 0.727 mmol, 97 weight percent (wt%)) was dissolved in chloroform (2.345 mL, 29.1 mmol). The solution was added to another vial containing lithium tert-butoxide (582 mg, 7.27 mmol, 10 equivalents relative to starting material) and weighed in a glove box. The reaction mixture was heated to 40° C. and vigorously stirred for 24 hours. After cooling to ambient temperature, the reaction mixture was washed twice with water (2 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum on a rotary evaporator. The resulting oil was analyzed using 1,4-dinitrobenzene as an internal standard. 1 Analyzed by H NMR spectroscopy 1 H-NMR yield was obtained (71% yield): 1 H NMR(500MHz,CDCl3)δ 7.31(t,J=1.9Hz,1H),7.16-7.14(m,2H),4.59(d,J=6.1Hz,1H),3.80-3.47(m,4H),2.77( d,J=8.5Hz,1H),2.25(dd,J=8.5,6.2Hz,1H),1.30(t,J=7.1Hz,3H),1.20(t,J=7.0Hz,3H).

[0037] Example 2a: Synthesis of trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] A one-neck 50 mL round bottom flask equipped with a nitrogen inlet and a magnetic stir bar was charged with (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (5.00 g, 14.61 mmol, 1 equiv). Hexachloroacetone (19.34 g, 13.43 mL, 73.0 mmol, 5 equiv) was added to the flask. Lithium tert-butoxide (3.51 g, 43.8 mmol, 3 equiv) was added in one portion at 23° C. The reaction mixture was stirred at 23° C. under nitrogen atmosphere for 24 h. Heptane (20 mL) was added. The mixture was washed three times with water (10 mL). The heptane layer was concentrated. Purification by flash column chromatography on silica gel (eluent: 0-50% ethyl acetate in hexanes) afforded the title compound as a yellow solid (5.28 g, 85% yield): 1 H NMR(500MHz,CDCl3)δ 7.83(s,1H),7.71(d,J=1.6Hz,2H),4.64(d,J=6.1Hz,1H),3.81-3.67(m,3H),3.66-3.57(m,1H), 2.93(d,J=8.5Hz,1H),2.35(dd,J=8.5,6.0Hz,1H),1.32(t,J=7.1Hz,3H),1.21(t,J=7.1Hz,3H); 19 F NMR(471MHz, CDCl3)δ -62.89.

[0038] Example 2b: Synthesis of rac-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)benzene [ka] In a vial, (E)-(3,3-diethoxyprop-1-en-1-yl)benzene (0.200 g, 0.970 mmol) was dissolved in hexachloroacetone (0.738 mL, 4.85 mmol, 5 equivalents relative to starting material). This solution was added to another vial containing lithium tert-butoxide (0.233 g, 2.91 mmol, 3 equivalents relative to starting material) and weighed in a glove box. The reaction mixture was stirred vigorously for 24 h at 23 °C. 1,3,5-Trimethoxybenzene was added to the reaction mixture and used as an internal standard.1 The yield was calculated by 1 H NMR spectroscopy (91% yield).

[0039] Example 2c: Synthesis of trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1,3-dichloro-5-(3,3-diethoxyprop-1-en-1-yl)benzene (200 mg, 0.727 mmol, 97 wt%) was dissolved in hexachloroacetone (0.553 mL, 3.63 mmol). The solution was added to another vial containing lithium tert-butoxide (175 mg, 2.18 mmol, 3 equivalents relative to starting material) and weighed in a glove box. The reaction mixture was stirred vigorously for 24 h at 23 °C. 1,3,5-Trimethoxybenzene was added to the reaction mixture and used as an internal standard. 1 The yield was calculated by H NMR spectroscopy (98% yield): 1 H NMR(500MHz,CDCl3)δ 7.31(t,J=1.9Hz,1H),7.16-7.14(m,2H),4.59(d,J=6.2Hz,1H),3.81-3.56(m,4H),2.77( d,J=8.5Hz,1H),2.25(dd,J=8.5,6.2Hz,1H),1.30(t,J=7.0Hz,3H),1.20(t,J=7.1Hz,3H).

[0040] Example 2d: Synthesis of trans-rac-1-(2,2-dichloro-3-(diisopropoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1-(3,3-diisopropoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (200 mg, 0.540 mmol, 90 wt%) was dissolved in hexachloroacetone (0.411 mL, 2.70 mmol). The solution was added to another vial containing lithium tert-butoxide (130 mg, 1.62 mmol, 3 equivalents relative to starting material) and weighed in a glove box. The reaction was stirred vigorously for 24 h at 23 °C. 1,3,5-Trimethoxybenzene was added to the reaction mixture and used as an internal standard. 1 The yield was calculated by H NMR spectroscopy (71% yield): 1 H NMR(500MHz,CDCl3)δ 7.83(s,1H),7.73(s,2H),4.68(d,J=6.5Hz,1H),4.12-4.07(m,1H),4.00-3.94(m,1H),2.85(d,J=8.5Hz,1H),2.34 (dd,J=8.5,6.4Hz,1H),1.31(d,J=6.2Hz,3H),1.28(d,J=4.9Hz,3H),1.19(d,J=6.4Hz,3H),1.14(d,J=6.1Hz,3H); 19 F NMR(471MHz, CDCl3)δ -62.89.

[0041] Example 3a: Comparison of bases used in the reaction to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene from (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene [ka] The following general procedure was used: Base (5.84 mmol, 10 equiv.) was weighed into a scintillation vial in a glove box. In a separate vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.20 g, 0.584 mmol, 1 equiv.) and chloroform (1.885 mL, 23.37 mmol, 40 equiv.) were mixed and then added to the base via syringe at 23 °C. The mixture was stirred at 23 °C for 24 h. 1,4-Dinitrobenzene was added to the reaction mixture and used as an internal standard. 1 The yields were calculated by H NMR spectroscopy and the results are reported in the table below.

[0042] [Table 1]

[0043] Example 3b: Comparison of bases used in the reaction to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene from (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene [ka] The base (1.753, 3 equiv.) was weighed into a scintillation vial in a glove box. In a separate vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.20 g, 0.584 mmol, 1 equiv.) and hexachloroacetone (0.445 mL, 2.92 mmol, 5 equiv.) were mixed and then added to the solid base via syringe at 23 °C. The mixture was stirred at 23 °C for 24 h. 1,3,5-Trimethoxybenzene was added to the reaction mixture and used as an internal standard. 1 The yields were calculated by H NMR spectroscopy and the results are reported in the table below.

[0044] [Table 2]

[0045] Example 4a: Comparison of the amount of base used in the reaction of (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (200 mg, 0.584 mmol) was dissolved in chloroform (1.9 mL, 23.37 mmol). Lithium tert-butoxide (5-15 equiv.) was added to the solution in one portion. The mixture was heated to 40° C. and stirred vigorously for 24 h. After cooling to ambient temperature, the reaction mixture was washed twice with water (2 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum on a rotary evaporator. The resulting oil was analyzed using 1,4-dinitrobenzene as an internal standard. 1 Analyzed by H NMR spectroscopy 1 H NMR yields were obtained and the results are reported in the table below.

[0046] [Table 3]

[0047] Example 4b: Comparison of the amount of base used in the reaction of (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] Lithium tert-butoxide was weighed into a scintillation vial in a glove box. In a separate vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.20 g, 0.584 mmol, 1 eq.) and hexachloroacetone (0.445 mL, 2.92 mmol, 5 eq.) were mixed and then added to the solid base via syringe at 23° C. The mixture was stirred at 23° C. for 24 h. 1,3,5-trimethoxybenzene was added to the reaction mixture and used as an internal standard to determine the solubility of the base. 1 The yields were calculated by H NMR spectroscopy and the results are reported in the table below.

[0048] [Table 4]

[0049] Example 5a: Comparison of bases and temperatures used in the reaction of (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.25 g, 0.730 mmol) was dissolved in chloroform (2.356 mL, 29.2 mmol). The mixture was brought to the specified temperature and base (6-10 equiv.) was added. The mixture was stirred for 18 h. The conversion was 1 It was analyzed by 1 H NMR spectroscopy.

[0050] [Table 5]

[0051] Example 5b: Comparison of bases used in the reaction of (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.20 g, 0.584 mmol) was dissolved in hexachloroacetone (0.356 mL, 2.337 mmol, 4 equiv.) at 23 °C. Base (1.5-3 equiv.) was added. The mixture was stirred for 24 h. The conversion was 1 It was analyzed by 1 H NMR spectroscopy.

[0052] [Table 6]

[0053] Example 6a: Comparison of co-solvents and bases used in the reaction of (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.25 g, 0.730 mmol) was dissolved in chloroform (2.356 mL, 29.2 mmol). The mixture was brought to the specified temperature and the base (6-10 equiv.) was added as a solid or as a suspension with the specified co-solvent. The mixture was stirred for 18 h. The conversion was 1 It was analyzed by 1 H NMR spectroscopy.

[0054] [Table 7]

[0055] Example 6b: Comparison of co-solvents used in the reaction of (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene to form trans-rac-1-(2,2-dichloro-3-(diethoxymethyl)cyclopropyl)-3,5-bis(trifluoromethyl)benzene [ka] In a vial, (E)-1-(3,3-diethoxyprop-1-en-1-yl)-3,5-bis(trifluoromethyl)benzene (0.20 g, 0.584 mmol) was dissolved in hexachloroacetone (0.445 mL, 2.92 mmol, 5 equiv.) and the specified co-solvent. The mixture was brought to the specified temperature and lithium tert-butoxide (0.234 g, 2.92 mmol) was added. The mixture was stirred for 18 h. The conversion was 1 It was analyzed by 1 H NMR spectroscopy.

[0056] [Table 8]

[0057] Example 7: Synthesis of (5R,6R)-5,6-bis((1R,3R)-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane [ka] In a vial, (5R,6R)-5,6-bis((E)-3,5-bis(trifluoromethyl)styryl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane (0.25 g, 0.326 mmol) was mixed with hexachloroacetone (0.495 mL, 3.26 mmol). Lithium 2-methylpropan-2-olate (0.130 g, 1.630 mmol) was added in one portion. The mixture was stirred at ambient temperature overnight. After 18 h, 1 Analysis by H NMR spectroscopy showed >99% conversion of starting material to desired product with a diastereoselectivity ratio (dr) of approximately 5.5:1 in favor of the desired product. The reaction was quenched with water and the organic layer was separated, dried and concentrated to give an oil. No isolated yield was obtained.

[0058] Example 8: Synthesis of (5R,6R)-5,6-bis((1R,3R)-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane [ka] In a vial, (5R,6R)-5,6-bis((E)-3,5-bis(trifluoromethyl)styryl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane (0.25 g, 0.326 mmol) and lithium 2-methylpropan-2-olate (0.391 g, 4.89 mmol) were added. To the solid was added chloroform (1.841 mL, 22.82 mmol). The mixture was heated to 40° C. and stirred for 18 hours to give the desired product with a large amount of monocyclopropanated material. An additional 5 equivalents of lithium 2-methylpropan-2-olate were added (0.13 g) and the mixture was stirred for an additional day. After 40 hours, 1H NMR analysis showed about 15% alkene monocyclopropanated species and about 85% conversion to the desired product (dr not determined). The reaction was quenched with water and the organic layer was separated, dried and concentrated to give an oil. No isolated yield was obtained.

[0059] Example M1: Synthesis of (5R,6R)-2,2,3,3,8,8,9,9-octamethyl-5,6-divinyl-4,7-dioxa-3,8-disiladecane [ka] In a four-necked reactor equipped with a mechanical stirrer, condenser, nitrogen inlet, and temperature probe, (3R,4R)-hexa-1,5-diene-3,4-diol (60 g, 526 mmol) was stirred in anhydrous N,N-dimethylformamide (DMF, 394 mL) (note that DMF could be replaced with acetonitrile or a mixture of acetonitrile and DMF could be used). The mixture was cooled to 0-5 °C. Imidazole (140 g, 2050 mmol) was added. A solution of tert-butylchlorodimethylsilane (158 g, 1051 mmol, 2 equiv.) in heptane (131 mL) was added via an addition funnel (temperature <5 °C). The mixture was warmed to ambient temperature and stirred for 20 min. Methanol (15.95 mL, 394 mmol, 0.75 equiv.) was added with stirring at ambient temperature. After 1 h, the mixture was charged with heptane (1.5 L) and stirred vigorously for 10-15 min. Stirring was stopped and the layers were separated. The heptane portion (top layer) was collected and washed / partitioned with acetonitrile (2×100 mL). The heptane portion was concentrated to give the title compound as a colorless oil which was used without further manipulation (178 g, 95% yield, 96% purity): 1 H NMR(400MHz, CDCl3)δ 6.28-5.60(m,2H),5.26-5.04(m,4H),4.17-4.06(m,2H),0.91(s,18H),0.07(s,6H).0.05(s,6H).

[0060] Example M2: Synthesis of (5R,6R)-5,6-bis((E)-3,5-bis(trifluoromethyl)styryl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane [ka] The reaction was carried out under nitrogen in a four-necked 1 L jacketed reactor equipped with a mechanical stirrer, temperature probe, nitrogen inlet and baffles. 1-Bromo-3,5-bis(trifluoromethyl)benzene (115 g, 394 mmol) and (5R,6R)-2,2,3,3,8,8,9,9-octamethyl-5,6-divinyl-4,7-dioxa-3,8-disiladecane (50 g, 146 mmol) were stirred in DMF (365 mL). Potassium carbonate (38.3 g, 277 mmol), sodium acetate (15.56 g, 190 mmol) and diacetoxypalladium (1.31 g, 5.84 mmol, 4 mol%) were added. The mixture was heated to an internal temperature of 66° C. After 24 h, the heat was removed. While the reaction was warm, acetonitrile (500 mL) and heptane (1 L) were added with stirring. Upon cooling to ambient temperature, stirring was stopped and the layers were separated. The DMF portion (bottom layer) was drained from the reactor along with the solid salts. The heptane portion (top layer) was collected. The bottom layer was back extracted with heptane (500 mL). The heptane layers were combined, washed with acetonitrile (2×200 mL) and concentrated to give the title compound as an off-white solid (99.3 g, 84% yield): 1 H NMR(400MHz,CDCl3)δ 7.70(s,6H),6.62(dd,J=16.0,1.1Hz,2H),6.43(ddd,J=16.0,3.3,1.2Hz,2H),4.66-4.21(m,2H),0.98(s,18H),0.15(s,6H),0.12(s,6H); 19 F NMR(376MHz, CDCl3)δ -63.09.

[0061] As a result, in light of the above, the following additional, non-exhaustive disclosure detail (d) is provided.

[0062] Further details relating to Scheme 1 1d. A process comprising halocyclopropanating S1a to produce S1b in the presence of a halocyclopropanation reagent and a lithium salt of a tertiary alkoxide. [ka] (In the formula, (a) R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, or (C1-C4) haloalkoxy; (b) Each R n are independently (C1-C4) alkyl, or both R n The substituents together form a (C2-C6) alkyl bond between the two oxygen atoms, and (c) each X is independently F, Cl, Br, or I.

[0063] 2d. The process as detailed above, wherein R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl, or (C1-C4)haloalkoxy, with the proviso that at least one of R2, R3, and R4 is not H.

[0064] 3d.Each R n is independently (C1-C4) alkyl.

[0065] 4d. The process according to any of the preceding details, wherein each X is independently Cl or Br.

[0066] 5d. The process of any of the preceding details, wherein each X is Cl.

[0067] 6d. S1a has R2, R4 is CF3, R1, R3, and R5 are H, and each Rn is C2H5.

[0068] 7d. The process as detailed in any of the preceding, wherein said halocyclopropanation reagent is carbon tetrachloride (CCl4), tetrachloroethylene (Cl2C-CCl2), chloroform (CHCl3), salts of trichloroacetic acid (metals including but not limited to lithium, sodium, potassium, and quaternary ammonium cations), alkyl esters of trichloroacetic acid, hexafluoroacetone ((F3C)2CO), hexachloroacetone (also known as 1,1,1,3,3,3-hexachloropropan-2-one, (Cl3C)2CO), hexabromoacetone ((Br3C)2CO), and mixtures of said halocyclopropanation reagents.

[0069] 8d. The process of any of the preceding details, wherein said halocyclopropanation reagent is hexachloroacetone.

[0070] 9d. The process as described in any of the preceding details, wherein the amount of halocyclopropanation reagent present during halocyclopropanation is from about 0.5 moles to about 100 moles of reagent per mole of S1a.

[0071] 10d. The process as detailed in any of the preceding, wherein said halocyclopropanation agent is chloroform and the amount of chloroform present during the halocyclopropanation is from about 5 moles to about 100 moles of reagent per mole of S1a.

[0072] 11d. The process as described in any of the preceding details, wherein said halocyclopropanation agent is chloroform and the amount of chloroform present during the halocyclopropanation is from about 30 moles to about 60 moles of reagent per mole of S1a.

[0073] 12d. The process as described in any of the preceding details, wherein said halocyclopropanation agent is hexachloroacetone and the amount of hexachloroacetone present during the halocyclopropanation is from about 0.5 moles to about 100 moles of reagent per mole of S1a.

[0074] 13d. The process as described in any of the preceding details, wherein said halocyclopropanation agent is hexachloroacetone and the amount of hexachloroacetone present during the halocyclopropanation is from about 1 mole to about 5 moles of reagent per mole of S1a.

[0075] 14d. The process of any of the preceding details, wherein said halocyclopropanating agent is a mixture of hexachloroacetone and chloroform, the chloroform being in a molar amount less than the molar amount of hexachloroacetone.

[0076] 15d. The process as recited in any of the preceding details, wherein the lithium salt of the tertiary alkoxide is lithium tert-butoxide (LiOC(CH3)3, also known as lithium 2-methylpropan-2-olate) or lithium 2-methyl-2-butoxide (also known as lithium tert-amoxide or lithium tert-amylate), or a mixture thereof.

[0077] 16d. The process as described in any of the preceding details, wherein said lithium salt of a tertiary alkoxide is lithium tert-butoxide (LiOC(CH3).

[0078] 17d. The process as described in any of the preceding details, wherein the amount of lithium salt of the tertiary alkoxide present during the halocyclopropanation is from about 1 mole to about 20 moles of lithium salt of the tertiary alkoxide per mole of S1a.

[0079] 18d. The process as described in any of the preceding details, wherein the amount of lithium salt of the tertiary alkoxide present during the halocyclopropanation is from about 1 mole to about 15 moles of lithium salt of the tertiary alkoxide per mole of S1a.

[0080] 19d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a co-solvent.

[0081] 20d. The process as recited in any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a co-solvent selected from one or more of the following: heptane, hexane, toluene, diglyme, tetrahydrofuran ("THF"), dimethyl carbonate, dimethoxyethane, ethylene glycol methyl ether, tert-butanol ("t-BuOH"), nitrobenzene, chlorobenzene, methyl tert-butyl ether ("MTBE"), 2-methyldecane, anisole (also known as methoxybenzene), and C9-C6 12 A mixture of isoalkanes.

[0082] 21d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a phase transfer catalyst.

[0083] 22d. The process as described in any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a phase transfer catalyst selected from benzyltributylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hexachlorophosphate, N-benzylcinchonidium chloride, (-)-N-dodecyl-N-methylephedrinium bromide, trioctylmethylammonium chloride, and mixtures thereof.

[0084] 23d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at ambient temperature and pressure.

[0085] 24d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of from about 0° C. to about 100° C.

[0086] 25d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature between about 0° C. and about 60° C., and said halocyclopropanation reagent is chloroform.

[0087] 26d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of about 20° C. to about 50° C. and said halocyclopropanation reagent is chloroform.

[0088] 27d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of about 25° C. to about 40° C. and said halocyclopropanation reagent is chloroform.

[0089] 28d. The process as recited in any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of from about 0° C. to about 40° C. and said halocyclopropanation reagent is hexachloroacetone.

[0090] 29d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of about 20° C. to about 25° C. and said halocyclopropanation reagent is hexachloroacetone.

[0091] 30d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a pressure of from about 10 kilopascals (kPa) to about 1000 kPa, or from about 50 kPa to about 150 kPa.

[0092] Further details regarding Scheme 2 1d. A process comprising halocyclopropanating S2a in the presence of a halocyclopropanation reagent and a lithium salt of a tertiary alkoxide to produce a major product S2b. [ka] (In the formula, (a) R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, or (C1-C4) haloalkoxy; (b) each Y is independently OH, OSi((C1-C4)alkyl)3, OSi((C1-C4)alkyl)2((C1-C4)alkyl-aryl), OSi((C1-C4)alkyl)2(aryl), OSi((C1-C4)alkyl)(aryl), OC(O)(C1-C4)alkyl, OC(O)O(C1-C4)alkyl, OC(O)NH(C1-C4)alkyl, O(C1-C4)alkyl-aryl, O-aryl, tetrahydropyranyl, or 1,3-dioxolanyl; and (c) each X is independently F, Cl, Br, or I.

[0093] 2d. The process as detailed above, wherein R1, R2, R3, R4, and R5 are each independently H, F, Cl, Br, I, CN, NH2, NO2, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)haloalkyl, or (C1-C4)haloalkoxy, with the proviso that at least one of R2, R3, and R4 is not H.

[0094] 3d. The process of any of the preceding details, wherein each Y is independently OSi(CH3)3, OSi(CH2CH3)3, OSi(CH(CH3)2)3, OSi(CH3)2phenyl, Obenzyl, O(C(O)NH-tert-butyl), OSi(CH3)2-(tert-butyl).

[0095] 4d. The process according to any of the preceding details, wherein each Y is OSi(CH3)2-(tert-butyl).

[0096] 5d. The process according to any of the preceding details, wherein each X is independently Cl or Br.

[0097] 6d. The process of any of the preceding details, wherein each X is Cl.

[0098] 7d.S2a: The process according to any of the preceding details, wherein R2 and R4 are CF3, R1, R3 and R5 are H and Y is OSi(CH3)2(tert-butyl).

[0099] 8d. The process as detailed in any of the preceding, wherein said halocyclopropanation reagent is carbon tetrachloride (CCl4), tetrachloroethylene (Cl2C-CCl2), chloroform (CHCl3), salts of trichloroacetic acid (metals including but not limited to lithium, sodium, potassium, and quaternary ammonium cations), alkyl esters of trichloroacetic acid, hexafluoroacetone ((F3C)2CO), hexachloroacetone (also known as 1,1,1,3,3,3-hexachloropropan-2-one, (Cl3C)2CO), hexabromoacetone ((Br3C)2CO), and mixtures of said halocyclopropanation reagents.

[0100] 9d. The process of any of the preceding details, wherein said halocyclopropanation reagent is hexachloroacetone.

[0101] 10d. The process as described in any of the preceding details, wherein the amount of halocyclopropanation reagent present during halocyclopropanation is from about 0.5 moles to about 100 moles of reagent per mole of S1a.

[0102] 11d. The process as detailed in any of the preceding, wherein said halocyclopropanation agent is chloroform and the amount of chloroform present during the halocyclopropanation is from about 5 moles to about 100 moles of reagent per mole of S1a.

[0103] 12d. The process as detailed in any of the preceding, wherein said halocyclopropanation agent is chloroform and the amount of chloroform present during the halocyclopropanation is from about 30 moles to about 60 moles of reagent per mole of S1a.

[0104] 13d. The process as described in any of the preceding details, wherein said halocyclopropanation agent is hexachloroacetone and the amount of hexachloroacetone present during the halocyclopropanation is from about 0.5 moles to about 100 moles of reagent per mole of S1a.

[0105] 14d. The process as described in any of the preceding details, wherein said halocyclopropanation agent is hexachloroacetone and the amount of hexachloroacetone present during the halocyclopropanation is from about 1 mole to about 5 moles of reagent per mole of S1a.

[0106] 15d. The process of any of the preceding details, wherein said halocyclopropanating agent is a mixture of hexachloroacetone and chloroform, the chloroform being in a molar amount less than the molar amount of hexachloroacetone.

[0107] 16d. The process as recited in any of the preceding details, wherein the lithium salt of the tertiary alkoxide is lithium tert-butoxide (LiOC(CH3)3, also known as lithium 2-methylpropan-2-olate) or lithium 2-methyl-2-butoxide (also known as lithium tert-amoxide or lithium tert-amylate), or a mixture thereof.

[0108] 17d. The process as described in any of the preceding details, wherein said lithium salt of a tertiary alkoxide is lithium tert-butoxide (LiOC(CH3).

[0109] 18d. The process as described in any of the preceding details, wherein the amount of lithium salt of said tertiary alkoxide present during halocyclopropanation is from about 1 mole to about 20 moles of lithium salt of a tertiary alkoxide per mole of S1a.

[0110] 19d. The process as described in any of the preceding details, wherein the amount of lithium salt of the tertiary alkoxide present during the halocyclopropanation is from about 1 mole to about 15 moles of lithium salt of the tertiary alkoxide per mole of S1a.

[0111] 20d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a co-solvent.

[0112] 21d. The process as recited in any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a co-solvent selected from one or more of the following: heptane, hexane, toluene, diglyme, tetrahydrofuran ("THF"), dimethyl carbonate, dimethoxyethane, ethylene glycol methyl ether, tert-butanol ("t-BuOH"), nitrobenzene, chlorobenzene, methyl tert-butyl ether ("MTBE"), 2-methyldecane, anisole (also known as methoxybenzene), and C9-C 12 A mixture of isoalkanes.

[0113] 22d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a phase transfer catalyst.

[0114] 23d. The process as described in any of the preceding details, wherein said halocyclopropanation is carried out in the presence of a phase transfer catalyst selected from benzyltributylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hexachlorophosphate, N-benzylcinchonidium chloride, (-)-N-dodecyl-N-methylephedrinium bromide, trioctylmethylammonium chloride, and mixtures thereof.

[0115] 24d. The process as described in any of the preceding details, wherein said halocyclopropanation is carried out at ambient temperature and pressure.

[0116] 25d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of from about 0° C. to about 100° C.

[0117] 26d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature between about 0° C. and about 60° C., and said halocyclopropanation reagent is chloroform.

[0118] 27d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of about 20° C. to about 50° C. and said halocyclopropanation reagent is chloroform.

[0119] 28d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of about 25° C. to about 40° C. and said halocyclopropanation reagent is chloroform.

[0120] 29d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of from about 0° C. to about 40° C. and said halocyclopropanation reagent is hexachloroacetone.

[0121] 30d. The process as recited in any of the preceding details, wherein said halocyclopropanation is carried out at a temperature of about 20° C. to about 25° C. and said halocyclopropanation reagent is hexachloroacetone.

[0122] 31d. The process according to any of the preceding details, wherein said halocyclopropanation is carried out at a pressure of from about 10 kilopascals (kPa) to about 1000 kPa, or from about 50 kPa to about 150 kPa.

[0123] More about molecules 1d. A composition comprising one or more of the following molecules: [ka]

[0124] 2d. A molecule with the following structure: [ka]

[0125] 3d. A molecule with the following structure: [ka]

[0126] End of details

Claims

1. A process comprising halocyclopropanating S1a in the presence of hexachloroacetone and lithium tert-butoxide to produce S1b. 【Chemistry 1】 (In the formula, (a) R １ , R ２ , R ３ , R ４ , and R ５ are each independently H, F, Cl, Br, I, CN, or NH ２ , NO ２ , (C １ ~C ４ ) alkyl, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkyl, or (C １ ~C ４ ) haloalkoxy; (b) Each R ｎ are independently (C １ ~C ４ ) alkyl, or both R ｎ The substituents together form a link between the two oxygen atoms (C ２ ~C ６ ) forming an alkyl bond, and (c) each X is independently F, Cl, Br, or I.

2. A process comprising halocyclopropanating S2a in the presence of hexachloroacetone and lithium tert-butoxide to produce major product S2b. 【Chemistry 2】 (In the formula, (a) R １ , R ２ , R ３ , R ４ , and R ５ are each independently H, F, Cl, Br, I, CN, or NH ２ , NO ２ , (C １ ~C ４ ) alkyl, (C １ ~C ４ ) alkoxy, (C １ ~C ４ ) haloalkyl, or (C １ ~C ４ ) haloalkoxy; (b) each Y is independently OH, OSi((C １ ~C ４ ) alkyl) ３ , OSi((C １ ~C ４ ) alkyl) ２ ((C １ ~C ４ ) alkyl-aryl), OSi((C １ ~C ４ ) alkyl) ２ (aryl), OSi((C １ ~C ４ ) alkyl) (aryl) ２ , O C (O) (C １ ~C ４ ) alkyl, OC(O)O(C １ ~C ４ ) alkyl, OC(O)NH(C １ ~C ４ ) alkyl, O(C １ ~C ４ ) alkyl-aryl, O-aryl, tetrahydropyranyl, or 1,3-dioxolanyl; and (c) each X is independently F, Cl, Br, or I.

3. A molecule with the structure 【Chemistry 4】

4. A molecule with the structure 【Chemistry 5】

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