Process for the hydroformylation of olefins using hydrocarbon and fluorinated solvents in the presence of a phospholane-phosphite ligand

Abstract

A process for the production of at least one aldehyde at hydroformylation temperature and pressure conditions comprising contacting at least one olefin with hydrogen and carbon monoxide in the presence of at least one hydrocarbon solvent or fluorinated solvent and a transition metal-based catalyst composition comprising a phospholane-phosphite ligand.

Description

[0001] This application is a divisional application of the invention application with application number "202180052218.X" and invention title "Method for Hydroformylation of Olefins Using Hydrocarbon Solvents and Fluorinated Solvents in the Presence of Phosphacyclopentane-Phosphine Ligands".

[0002] Parties involved in the joint research agreement The invention disclosed or claimed herein was made under a joint research agreement between Eastman Chemical Company and the University Court of the University of St. Andrews (a charity registered in Scotland). Technical Field

[0003] This application relates to a method for the hydroformylation of olefins using hydrocarbon solvents and fluorinated solvents in the presence of phosphopropentane-phosphite ligands. Background Technology

[0004] Hydroformylation, also known as carbonyl synthesis, is widely used in industrial processes to prepare aldehydes by reacting 1 mole of an olefin with 1 mole each of hydrogen and carbon monoxide. A particularly important application of this reaction is the preparation of n-(...) from propylene. n -) Butyraldehyde and isobutyraldehyde iso -) Butyraldehyde. Both of these products are key structural units in the synthesis of many chemical intermediates such as alcohols, carboxylic acids, esters, plasticizers, glycols, essential amino acids, flavorings, fragrances, polymers, pesticides, hydraulic fluids, and lubricants.

[0005] Currently, it is easier to achieve high orthoselectivity ( n- selectivity, while high heterogeneity selectivity iso- Achieving selectivity remains challenging. Various approaches have been attempted over the years to address this problem, including the use of various ligands (Phillips, Devon, Puckette, Stavinoha, Vanderbilt, (EastmanKodak Company), US Pat. No. 4,760,194) and reactions under aqueous conditions (Riisager, Eriksen, Hjorkjær, Fehrmann, J. Mol. Catal. A: Chem. 2003, 193, 259). Results are generally unsatisfactory, either due to unsatisfactory isomer selectivity and / or because the reaction requires undesirable temperatures. The highest reported isomer selectivity of 63% was achieved at 19 °C (Norman, Reek, Besset, (Eastman Chemical Company), US Pat. No. 8,710,275). However, this is undesirable in some cases because hydroformylation reactions at lower temperatures can lead to lower reaction rates; therefore, industrially, reactions are generally preferred at higher temperatures. In this case, when the reaction is carried out at 80°C, the isomer selectivity decreases to 38%.

[0006] Therefore, many Rh-based catalyst systems providing high n-butyraldehyde selectivity in propylene hydroformylation have been industrially implemented, while isomer selectivity remains challenging, and we recognize that there is no industrial method from propylene hydroformylation that yields greater than 50% isobutyraldehyde. We recently disclosed ligand systems capable of producing 64.7% isobutyraldehyde at 90 °C (US 10,144,751, US 10,183,961, US 10,351,583 and...). Angew Chem. Int. Ed 2019, 58, (2120). Despite our significant progress, the new ligand system exhibits thermal degradation at higher temperatures.

[0007] There is still a need for ligand and olefin hydroformylation methods that exhibit isomer selectivity and sufficient thermal stability. Summary of the Invention

[0008] In one aspect, the present invention relates to a method for preparing at least one aldehyde under hydroformylation temperature and pressure conditions. The method comprises contacting at least one olefin with hydrogen and carbon monoxide in the presence of at least one solvent and a transition metal-based catalyst composition, wherein the olefin may be propylene in some embodiments, and the transition metal-based catalyst composition may be rhodium-based in some embodiments, comprising a phosphacyclopentane-phosphite ligand having general formula I. I Wherein: R1 and R2 are independently selected from H, or substituted and unsubstituted aryl, alkyl, aryloxy or cycloalkyl containing 1 to 40 carbon atoms; R3, R4 and R5 are independently selected from H, F, Cl, Br, or substituted and unsubstituted aryl, alkyl, alkoxy, trialkylsilyl, triarylsilyl, aryldialkylsilyl, diarylalkylsilyl and cycloalkyl containing 1 to 20 carbon atoms, wherein the silicon atom of the alkylsilyl is at the α position of the substituent; and R6 and R7 are independently selected from H, F, Cl, Br, alkyl containing 1 to 10 carbon atoms, haloalkyl, or aryl containing 1 to 20 carbon atoms.

[0009] According to one aspect, the at least one solvent comprises a hydrocarbon solvent. In various aspects, the hydrocarbon solvent may comprise one or more of the following: n-nonane, n-decane, n-undecane, or n-dodecane.

[0010] In another aspect, the at least one solvent comprises a fluorinated solvent. In various aspects, the fluorinated solvent may comprise one or more of octafluorotoluene or perfluorophenyl octyl ether. In other aspects, the fluorinated solvent may comprise any solvent having 2 to 20 carbon atoms substituted with at least one fluorine atom.

[0011] The ligands of this invention exhibit good isomeric selectivity for the hydroformylation of propylene in the presence of rhodium metal. In fact, the hydroformylation of propylene using these novel catalyst systems can provide isobutyraldehyde selectivity exceeding 55% under industrially relevant conditions. Furthermore, we have found that isobutyraldehyde selectivity can be improved by using hydrocarbon solvents or fluorinated solvents. The ligands themselves are separately promoted in a co-pending application filed with common assignees.

[0012] Regardless of the ligand used, the hydroformylation method can use at least one solvent. In some embodiments, the aldehyde product of this method may have an isomer selectivity of about 55% to about 90%, about 60% to about 85%, about 60% to about 80%, or about 55% or higher, or 57% or higher.

[0013] Furthermore, in some embodiments, the hydroformylation method is operated in a pressure range of about 2 atm to about 80 atm, about 5 atm to about 70 atm, about 8 atm to about 20 atm, about 8 atm, or about 20 atm. In some embodiments, the method is also operated in a temperature range of about 40 to about 150 degrees Celsius, about 40 to about 120 degrees Celsius, about 40 to about 100 degrees Celsius, about 50 to about 90 degrees Celsius, about 50 degrees Celsius, about 75 degrees Celsius, or about 90 degrees Celsius.

[0014] Other aspects of the invention are as disclosed and claimed herein. Detailed Implementation

[0015] Therefore, in one aspect, the present invention relates to ligands that can be used in hydroformylation methods. Ligands according to the invention may have the general formula I: I in: R1 and R2 are independently selected from H, or substituted and unsubstituted aryl, alkyl, aryloxy or cycloalkyl groups containing 1 to 40 carbon atoms; R3, R4, and R5 are independently selected from H, F, Cl, Br, or substituted and unsubstituted aryl, alkyl, alkoxy, trialkylsilyl, triarylsilyl, aryldialkylsilyl, diarylalkylsilyl, and cycloalkyl groups containing 1 to 20 carbon atoms, wherein the silicon atom of the alkylsilyl group is at the α-position of the substituent; and R6 and R7 are independently selected from H, F, Cl, Br, alkyl groups containing 1 to 10 carbon atoms, haloalkyl groups, or aryl groups containing 1 to 20 carbon atoms.

[0016] Another aspect of the invention relates to the use of ligands of such formula I as further described herein in a hydroformylation process.

[0017] In a further aspect, the present invention relates to ligands represented by the following general formula II: II in: R3, R4, and R5 are independently selected from H, F, Cl, Br, or substituted and unsubstituted aryl, alkyl, alkoxy, trialkylsilyl, triarylsilyl, aryldialkylsilyl, diarylalkylsilyl, and cycloalkyl groups containing 1 to 20 carbon atoms, wherein the silicon atom of the alkylsilyl group is at the α-position of the substituent; and R6 and R7 are independently selected from H, F, Cl, Br, alkyl groups containing 1 to 10 carbon atoms, haloalkyl groups, or aryl groups containing 1 to 20 carbon atoms.

[0018] In other embodiments of Formula II, R3 may be independently tert-butyl, and R4 and / or R5 may be independently methyl. Similarly, R3 may be independently tert-butyl, and R4 may be independently methoxy.

[0019] Another aspect of the invention relates to the use of ligands of such formula II as further described herein in a hydroformylation process.

[0020] In a further aspect, the ligand can be represented by the following general formula III: III in: R3, R4, and R5 are independently selected from H, F, Cl, Br, or substituted and unsubstituted aryl, alkyl, alkoxy, trialkylsilyl, triarylsilyl, aryldialkylsilyl, diarylalkylsilyl, and cycloalkyl groups containing 1 to 20 carbon atoms, wherein the silicon atom of the alkylsilyl group is at the α-position of the substituent; and R6 is independently selected from H, F, Cl, Br, alkyl groups containing 1 to 10 carbon atoms, haloalkyl groups, or aryl groups containing 1 to 20 carbon atoms.

[0021] In another aspect, the present invention relates to a method for preparing at least one aldehyde, the method comprising contacting at least one olefin with hydrogen and carbon monoxide in the presence of at least one hydrocarbon solvent or fluorinated solvent and a transition metal-based catalyst composition, said transition metal-based catalyst composition comprising one or more of the phosphacene-phosphite ligands of any one or more of formulas I, II and III as just described or elsewhere herein.

[0022] In other respects, the phosphacyclopentane-phosphite ligand according to the invention corresponds to one or more of the following: Unless otherwise specified, all numerical values ​​used in the specification and claims to indicate the amount of an ingredient, properties such as molecular weight, reaction conditions, etc., are to be understood to be modified by the term "about" in all cases. Therefore, unless otherwise stated, the numerical parameters set forth in the following specification and appended claims are approximate values ​​that may vary according to the desired properties sought to be obtained according to the invention. At a minimum, each numerical parameter should be interpreted based at least on the reported significant figures and by applying common rounding techniques. Furthermore, the ranges described in this disclosure and claims are intended to specifically include the entire range, and not just one or more endpoints. For example, the range of 0 to 10 is intended to disclose all integers between 0 and 10, such as 1, 2, 3, 4, etc., all fractions between 0 and 10, such as 1.5, 2.3, 4.57, 6.1113, etc., and the endpoints 0 and 10.

[0023] Although the numerical ranges and parameters described in this invention are approximate, the values ​​set forth in the specific embodiments are intended to be reported precisely in light of the measurement methods. However, any numerical value inherently contains some error that is necessarily caused by the standard deviation present in their respective test measurements.

[0024] It should be understood that mentioning one or more method steps does not preclude the presence of additional method steps before or after the combined steps, or the insertion of method steps between those explicitly identified steps. Furthermore, the naming of other aspects of method steps, components, or information disclosed or claimed in this application using letters, numbers, etc., is a convenient means of identifying discrete activities or components, and unless otherwise specified, the letters may be arranged in any order.

[0025] As used herein, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. For example, referring to a type of C n Alcohol equivalences are intended to include multiple types of C n Alcohol equivalents. Therefore, the use of language such as "at least one / at least one" or "at least some" in one place does not imply that other uses of "a," "an," and "the" exclude plural pronouns unless the context clearly specifies otherwise. Similarly, the use of language such as "at least some" in one place does not imply that the absence of such language elsewhere implies "all," unless the context clearly specifies otherwise.

[0026] As used herein, the term “and / or” when used in a list of two or more items means that any one of the listed items may be used alone, or any combination of two or more of the listed items may be used. For example, if a composition is described as containing components A, B and / or C, the composition may contain A alone; B alone; C alone; a combination of A and B; a combination of A and C; a combination of B and C; or a combination of A, B and C.

[0027] As used herein, the term “catalyst” typically means to those skilled in the art as a substance that increases the rate of a chemical reaction without being consumed in real mass by the reaction.

[0028] As used herein, the term "alkyl" refers to a group containing one or more saturated carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, 2-ethylhexyl, n-octyl, n-decyl, dodecyl, n-octadecyl, and their various isomers. Unless otherwise expressly specified, "alkyl" includes straight-chain alkyl, branched-chain alkyl, and cycloalkyl. "Straight-chain alkyl" refers to an alkyl group without carbon atom branches. "Branched-chain alkyl" refers to an alkyl group with carbon atom branches, such that at least one carbon atom in the group is bonded to at least three other atoms, said other atoms being either carbon atoms within the group or atoms outside the group. Thus, "an alkyl group with a branch at the α-carbon" is a type of branched alkyl group in which the carbon atoms bonded to the two carbon atoms within the alkyl group are also bonded to a third (non-hydrogen) atom not located within the alkyl group. "Cycloalkyl" or "cyclic alkyl" groups are alkyl groups with alkyl carbons arranged in a ring, such as cyclopentyl or cyclohexyl.

[0029] As used herein, the term "aryl" refers to a group that is or contains a carbon-containing aromatic ring. Some examples of aryl groups include phenyl and naphthyl.

[0030] As used herein, the term "aryloxy group" refers to a group having the structure shown in the formula -O-Ar, where Ar is an aryl group as described above.

[0031] As used in this article, the term "aralkyl" refers to an aryl group in which an alkyl group is substituted with at least one hydrogen atom.

[0032] As used in this article, the term "alkylaryl" refers to an alkyl group in which an aryl group replaces at least one hydrogen atom.

[0033] The term "aryldialkylsilyl" refers to a group in which a single silicon atom is bonded to two alkyl groups and an aryl group.

[0034] The term "diarylalkylsilyl" refers to a group in which a single silicon atom is bonded to an alkyl group and two aryl groups.

[0035] The term "phenyl" refers to an aryl substituent having the formula C6H5, provided that the "substituted phenyl" has one or more groups that substitute for one or more hydrogen atoms.

[0036] The term "trialkylsilyl" refers to a group in which three alkyl groups are bonded to the same silicon atom.

[0037] The term "triarylsilyl" refers to a group in which three aryl groups are bonded to the same silicon atom.

[0038] According to the present invention, the hydroformylation method described herein relates to an olefin in contact with hydrogen and carbon monoxide in the presence of a transition metal catalyst and ligands. In one embodiment, the olefin is propylene. Other olefins, such as butene, pentene, hexene, hepten, and octene, are also contemplated to function in this method.

[0039] These ligands exhibit good isomer selectivity for the hydroformylation of propylene in the presence of Rh metal. Furthermore, these ligands demonstrate good stability at high temperatures.

[0040] Therefore, in one respect, the inventive ligands of the present invention can exhibit stability at temperatures of, for example, from about 50°C to about 120°C, or from 55°C to 110°C, or from 60°C to 100°C.

[0041] According to another aspect of the invention, selectivity can be altered by changing the ratio of the ligand to Rh. Thus, in one aspect, the ratio of the ligand to Rh can be from about 1:1 to about 50:1, or 2:1 to 40:1, or 3:1 to 30:1, or 4:1 to 20:1, in each case based on the molar ratio of the ligand to rhodium.

[0042] The catalyst composition obtained by this method contains a transition metal and ligands as described herein. In some embodiments, the transition metal catalyst contains rhodium.

[0043] Acceptable forms of rhodium include rhodium(II) or rhodium(III) salts of carboxylic acids, rhodium carbonylspecies, and rhodium organophosphine complexes. Some examples of rhodium(II) or rhodium(III) salts of carboxylic acids include dirhodium tetraacetate dihydrate, rhodium acetate (II), rhodium isobutyrate (II), rhodium (II) 2-ethylhexanoate, rhodium (II) benzoate, and rhodium (II) octanoate. Some examples of rhodium carbonylspecies include [Rh(acac)(CO)2] and Rh4(CO). 12 and Rh6(CO) 16 An example of a rhodium organophosphine complex that can be used is tris(triphenylphosphine)carbonyl rhodium.

[0044] The absolute concentration of the transition metal in the reaction mixture or solution can vary from about 1 mg / L to about 5000 mg / L; in some embodiments, it is higher than about 5000 mg / L. In some embodiments of the invention, the concentration of the transition metal in the reaction solution is in the range of about 20 to about 300 mg / L. The ratio of ligand moles to transition metal moles can vary over a wide range, for example, a ligand mole:transition metal mole ratio of about 0.1:1 to about 500:1 or about 0.5:1 to about 500:1. For rhodium-containing catalyst systems, in some embodiments, the ligand mole:rhodium mole ratio is in the range of about 0.1:1 to about 200:1, in some embodiments, the ratio is in the range of about 1:1 to about 100:1, or about 1:1 to about 10:1.

[0045] In some embodiments, the catalyst is formed in situ from a transition metal compound such as [Rh(acac)(CO)2] and ligands. Those skilled in the art will understand that a wide variety of Rh compounds will form the same active catalyst upon contact with ligands, hydrogen, and carbon monoxide; therefore, there is no limitation on the choice of Rh precatalyst.

[0046] According to the present invention, the method is carried out in the presence of at least one hydrocarbon solvent. Suitable hydrocarbon solvents include one or more of the following: n-nonane, n-decane, n-undecane, or n-dodecane. Other solvents are also contemplated for use in combination with one or more hydrocarbon solvents.

[0047] According to a further aspect, the at least one solvent comprises a fluorinated solvent. In various aspects, the fluorinated solvent may comprise one or more of octafluorotoluene or perfluorophenyl octyl ether. In other aspects, the fluorinated hydrocarbon solvent may comprise any solvent having 2 to 20 carbon atoms substituted with at least one fluorine atom.

[0048] In another embodiment, the method is carried out in the presence of at least one additional solvent. When present, one or more solvents can be any compound or combination of compounds that will not unacceptably affect the hydroformylation process and / or be inert to the catalyst, propylene, hydrogen and carbon monoxide feed, and the hydroformylation product. These solvents can be selected from a wide variety of compounds, combinations of compounds, or materials that are liquid under the reaction conditions in which the method is operated. Such compounds and materials include various alkanes, cycloalkanes, alkenes, cycloalkenes, carbocyclic aromatic compounds, alcohols, carboxylic acid esters, ketones, acetals, ethers, and water. Specific examples of such solvents include alkanes and cycloalkanes, such as dodecane, naphthane, hexane, octane, mixtures of isooctanes, cyclohexane, cyclooctane, cyclododecane, and methylcyclohexane; aromatic hydrocarbons, such as benzene, toluene, xylene isomers, tetrahydronaphthalene, cumene, alkyl-substituted aromatic compounds, such as isomers of diisopropylbenzene, triisopropylbenzene, and tert-butylbenzene; alkenes and cycloalkenes, such as 1,7-octadiene, dicyclopentadiene, 1,5-cyclooctadiene, octene-1, octene-2, 4-vinylcyclohexene, cyclohexene, 1,5,9-cyclododecanetriene, and 1-pentene; crude hydrocarbon mixtures, such as naphtha, mineral oil, and kerosene; carboxylic acid esters, such as ethyl acetate, and high-boiling esters, such as 2,2,4-trimethyl-1,3-pentanediol diisobutyrate, and trimeric aldehyde esters-alcohols. ester-alcohols), such as 2,2,4-trimethyl-1,3-pentanediol mono(2-methylpropionate). Aldehyde products obtained by hydroformylation can also be used.

[0049] In some embodiments, the solvent may include higher-boiling-point byproducts that naturally form during the hydroformylation reaction and subsequent steps (e.g., distillation) that can be used to separate the aldehyde product. In some embodiments involving more volatile aldehydes, the solvent has a sufficiently high boiling point to be retained, to the greatest extent possible, in the gas jet reactor. Some examples of solvents and solvent combinations that can be used in the production of less volatile and non-volatile aldehyde products include 1-methyl-2-pyrrolidone, dimethylformamide, perfluorinated solvents such as perfluorinated kerosene, sulfolane, water, and high-boiling-point hydrocarbon liquids, as well as combinations of these solvents.

[0050] In other respects, regardless of the ligand used, the method may use fluorinated solvents, such as octafluorotoluene or perfluorophenyl octyl ether, and / or hydrocarbon solvents, such as n-nonane, n-decane, n-undecane, or n-dodecane.

[0051] This disclosure further provides methods for the synthesis as generally described herein and specifically described in the embodiments below.

[0052] For the formulation of the catalyst system, the preparation of the catalyst system and solution of the present invention does not require special or unusual techniques, although in some embodiments, higher activity can be observed if all operations on the rhodium and ligand components are carried out under an inert atmosphere (e.g., nitrogen, argon, etc.). Furthermore, in some embodiments, it may be advantageous to dissolve the ligand and transition metal together in a solvent to allow the ligand and transition metal to coordinate, followed by crystallization of the metal ligand complex, as described in US Pat. No. 9,308,527, which is incorporated herein by reference in its entirety.

[0053] Suitable reaction conditions for effective hydroformylation, as detailed in this paragraph, can be used. In some embodiments, the method is carried out at temperatures of about 40 to about 150 degrees Celsius, about 40 to about 120 degrees Celsius, about 40 to about 100 degrees Celsius, about 50 to about 90 degrees Celsius, about 50 degrees Celsius, about 75 degrees Celsius, or about 90 degrees Celsius. In some embodiments, the total reaction pressure can be about 2 atm to about 80 atm, about 5 atm to about 70 atm, about 8 atm to about 20 atm, about 8 atm, or about 20 atm.

[0054] In some embodiments, the hydrogen:carbon monoxide molar ratio in the reactor can vary significantly from about 10:1 to about 1:10, and the sum of the absolute partial pressures of hydrogen and carbon monoxide can range from about 0.3 to about 36 atm. In some embodiments, the partial pressures of hydrogen and carbon monoxide in the reactor are maintained in the range of about 1 to about 14 atm for each gas. In some embodiments, the partial pressure of carbon monoxide in the reactor is maintained in the range of about 1 to about 14 atm and varies independently of the partial pressure of hydrogen. The hydrogen to carbon monoxide molar ratio can vary widely within these partial pressure ranges of hydrogen and carbon monoxide. The ratio of hydrogen to carbon monoxide in the syngas (syngas—carbon monoxide and hydrogen) and their respective partial pressures can be easily altered by adding hydrogen or carbon monoxide to the syngas stream.

[0055] The amount of olefins present in the reaction mixture is also not critical. In some embodiments of propylene hydroformylation, the partial pressure in the vapor space of the reactor is in the range of about 0.07 to about 35 atm. In some embodiments involving propylene hydroformylation, the partial pressure of propylene is greater than about 1.4 atm, for example, about 1.4 to about 10 atm. In some embodiments of propylene hydroformylation, the partial pressure of propylene in the reactor is greater than about 0.14 atm.

[0056] Any efficient hydroformylation reactor design or construction can be used to implement the methods provided by this invention. Therefore, gas jet, liquid overflow, or take-off reactor designs as disclosed in the embodiments set forth herein can be used. In some embodiments of this mode of operation, the catalyst dissolved in a high-boiling-point organic solvent under pressure does not leave the reaction zone with the aldehyde product carried off from the top by unreacted gas. The top gas is then chilled in a gas / liquid separator to condense the aldehyde product, and the gas can be recycled back to the reactor. The liquid product is reduced to atmospheric pressure for separation and purification using conventional techniques. This method can also be carried out batchwise by contacting propylene, hydrogen, and carbon monoxide with the catalyst of this invention in an autoclave.

[0057] A reactor design in which the catalyst and feedstock are pumped into the reactor and overflowed along with the product aldehyde, i.e., a liquid overflow reactor design, is also suitable. In some embodiments, the aldehyde product can be separated from the catalyst by conventional means (e.g., by distillation or extraction), and then the catalyst can be recycled back to the reactor. Water-soluble aldehyde products can be separated from the catalyst by extraction techniques. A trickle bed reactor design is also suitable for this method. It will be apparent to those skilled in the art that other reactor designs can be used in this invention.

[0058] For continuously operating reactors, it may be desirable to add replenishing amounts of ligands (compounds) over time to replace those materials lost due to oxidation or other processes. This can be done by dissolving the ligands in a solvent and pumping it into the reactor as needed. Solvents that can be used include compounds present in the process, such as alkenes, product aldehydes, condensation products derived from aldehydes, and other esters and alcohols that can be readily formed from product aldehydes. Examples of solvents include butyraldehyde, isobutyraldehyde, propionaldehyde, 2-ethylhexanal, 2-ethylhexanol, n-butanol, isobutanol, isobutyl isobutyrate, isobutyl acetate, butyl butyrate, butyl acetate, 2,2,4-trimethylpentane-1,3-diol diisobutyrate, and n-butyl 2-ethylhexanoate. Ketones such as cyclohexanone, methyl isobutyl ketone, methyl ethyl ketone, diisopropyl ketone and 2-octanone, as well as trialdehyde ester alcohols such as Texanol™ ester alcohol (2,2,4-trimethyl-1,3-pentanediol mono(2-methylpropionate)).

[0059] In some embodiments, the reagents used in the hydroformylation method of the present invention are substantially free of materials that could reduce catalyst activity or completely deactivate the catalyst. In some embodiments, the reaction does not include materials such as conjugated dienes, acetylenes, thiols, inorganic acids, halogenated organic compounds, and free oxygen.

[0060] The present invention can be further illustrated by the following embodiments of its implementation, but it should be understood that these embodiments are included for illustrative purposes only and are not intended to limit the scope of the invention, unless otherwise expressly stated. Example

[0061] Generally: NMR spectra are recorded on a Bruker Advance 300, 400, or 500 MHz instrument. Proton chemical shifts are referenced to the protons in the internal residual solvent. Carbon chemical shifts are referenced to the carbon signal in the deuterated solvent. Signal multiplicity is given as s (singleton), d (doublet), t (triplet), q (quartet), m (multiplet), br.s (broad singlet), or a combination thereof. Where appropriate, the coupling constant ( J Cited in Hz and reported as the nearest 0.1 Hz. All spectra were recorded at room temperature, and the solvents used for the spectra are given in parentheses. NMR of phosphorus-containing compounds was recorded under an inert atmosphere in anhydrous (dry) and degassed solvents. Gas chromatography was performed on an Agilent Technologies 7820A instrument.

[0062] Rapid column chromatography was performed under an inert atmosphere using anhydrous and degassed solvents with Merck Geduran Si 60 (40-63 μm) silica gel or Sigma Aldrich activated neutral Brockmann I alumina.

[0063] Thin-layer chromatography (TLC) analysis was performed using POLYGRAM SIL G / UV254 or POLYGRAM ALOX N / UV254 plastic plates. TLC plates were visualized using a UV visualizer or stained with potassium permanganate followed by gentle heating. Preparative TLC was performed on alumina glass plates with a 254 nm fluorescent indicator.

[0064] Synthesized ligands: The following ligands, as shown in Figure 1, were synthesized: Figure 1.

[0065] Ligand synthesis: Ligand 1 was synthesized according to the procedure described in the literature (Noonan, Fuentes, Cobley, Clarke, Angew. Chem. Int. Ed. 2012, 51, 2477), which is incorporated herein by reference in its entirety. Ligands 2 and 3 were synthesized according to the procedures described in US 10,144,751 and US 10,183,961 (which are incorporated herein by reference in their entirety).

[0066] Ligand synthesis: The reaction scheme is shown in Figure 2 below: Figure 2.

[0067] Synthesis of phosphine adduct precursors: (Raceous)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a): Adduct a was synthesized according to the literature procedure (Noonan, Fuentes, Cobley, Clarke, Angew. Chem. Int. Ed. 2012, 51, 2477), which is incorporated herein by reference in its entirety.

[0068] Borane-protected 2-(trans-2,5-diphenylphosphacyclopentan-1-yl)ethyl 4-methylbenzenesulfonic acid (b): At -78°C under a nitrogen atmosphere, 1.48 M of (racemic)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a) (4 g, 15.74 mmol) was slowly added via syringe to a stirred solution of (racemic)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (40 mL) in THF. n -BuLi hexane solution (10.64 mL, 15.74 mmol). After stirring for 2 hours, the reaction mixture was heated to -20°C, removed from the bath, and stirred for another 15 minutes. The solution was then added dropwise via a cannula to a solution of ethane-1,2-dimethylbis(4-methylbenzenesulfonate) (11.66 g, 31.48 mmol) in THF (100 mL). Once the addition was complete, the reaction was stirred at room temperature for 18 hours. The reaction was quenched at 0°C by the slow addition of 1M HCl aqueous solution (30 mL). The reactants were concentrated under vacuum, and the resulting solid was partitioned between water (60 mL) and dichloromethane (60 mL). The organic layer was separated, and the aqueous layer was extracted with dichloromethane (3 × 40 mL). The organic fractions were combined, dried (MgSO4), filtered, and concentrated under vacuum to give a white solid. Unreacted ethane-1,2-dimethylbis(4-methylbenzenesulfonate) (7.32 g) was recovered by grinding with hexane:EtOAc 1:1 (100 mL). The washings from the grinding were reduced under vacuum, and the resulting solid was purified by rapid chromatography on silica gel (6:1:0.5 hexane:EtOAc:DCM) to give the desired product as a white solid (4.46 g, 9.86 mmol, 63%). 1 H NMR (CDCl3, 500 MHz) δ 7.51 (2H, d, J =8.2 Hz), 7.40-7.25 (12H, m, ArH), 3.87-3.43(4H, m, CH2-O, 2 x P-CH), 2.65-2.47 (2H, m, CH-C H 2, CH-C H 2), 2.44 (3H, s,CH3), 2.23-2.14 (2H, m, CH-C H 2, CH-C H 2), 1.96-1.88 (1H, m, P-CH2), 1.60-1.53 ​​(1H, m, P-CH2), 0.27 (3H, br q, BH3). 31 P{ 1 H} NMR (CDCl3, 202 MHz) δ 40.6 (br d, J = 44.4 Hz). HRMS (ES + C 25 H 30 O3BNaPS [MNa] + m / z: 475.1635 (measured value), 475.1639 (required value).

[0069] Borane-protected 2-((trans)-2,5-diphenylphosphazenecyclopentan-1-yl)ethanol-1-ol (c): At -60 °C under a nitrogen atmosphere, a solution of freshly prepared 1 M naphthol in THF (30 mL, 30.0 mmol) was slowly added via syringe to a stirred solution of borane-protected 2-(trans-2,5-diphenylphosphazenecyclopentan-1-yl)ethyl 4-methylbenzenesulfonic acid (b) (4.45 g, 9.84 mmol) in THF (24 mL) (until the green color persisted). The reaction was then heated to room temperature after stirring for 0.5 hours and quenched by the slow addition of a saturated aqueous solution of NH4Cl (25 mL). The reactants were diluted with dichloromethane (30 mL). The organic layer was separated, and the aqueous layer was extracted with dichloromethane (3 × 20 mL). The organic fractions were combined, dried (MgSO4), filtered, and concentrated under vacuum to obtain a solid. The product was purified by rapid chromatography on silica gel (2:1 hexane:EtOAc) to give the desired product as a white solid (2.52 g, 8.45 mmol, 86%). 1H NMR(CDCl3, 500 MHz) δ 7.41-7.30 (10H, m, ArH), 3.75-3.70 (1H, m, P-CH), 3.54-3.40 (3H, m, CH2-O, P-CH), 2.63-2.47 (2H, m, CH-C H 2, CH-C H 2), 2.33-2.19 (2H,m, CH-C H 2, CH-C H 2), 1.83-1.75 (1H, m, P-CH2), 1.71 (1H, br t, OH), 1.54-1.47(1H, m, P-CH2), 0.48 (3H, br q, BH3). 31 P{ 1 H} NMR (CDCl3, 202 MHz) δ 39.1 (br d, J = 61.4 Hz). 13 C NMR (CDCl3, 126 MHz) δ 136.89 (ArC), 135.69 (d, J = 5.0 Hz ArC),128.93 (ArCH), 128.92 (ArCH), 128.77 (ArCH), 128.74 (ArCH), 128.46 (ArCH),128.45 (ArCH), 127.73 (ArCH), 127.70 (ArCH), 127.42 (d, J = 2.3 Hz ArCH),127.27 (d, J = 2.3 Hz ArCH), 57.20 (OCH2), 47.24 (d, 1 J C-P = 28.3 Hz, P-CH), 45.73(d, 1 J C-P = 31.4 Hz, P-CH), 34.08 (d, 2 J C-P = 4.7 Hz, CH- C H2), 30.59 (CH- C H2), 27.51(d, 1 JC-P = 26.4 Hz, P-CH2). HRMS (ES + C 18 H 24 OBNaP [MNa] + m / z: 321.1545 (measured value), 321.1550 (required value).

[0070] Borane-protected -( R )-1-(( 2R,5R Synthesis of the 2,5-diphenylphosphazenecyclopentan-1-yl)prop-2-ol adduct (d1): At -78°C, under a nitrogen atmosphere, the mixture was stirred ( R,R )-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a) (0.761 g, 3.00 mmol) was added dropwise via syringe to a solution of 1.55 M THF (20 mL). n -BuLi hexane solution (2.04 mL, 3.15 mmol). The reaction was then heated to -30°C and stirred for 2 hours, after which the solution was added dropwise via syringe. R A solution of propylene oxide (0.232 mL, 3.3 mmol) in THF (4 mL) was prepared. Once the addition was complete, the reaction was heated to room temperature and stirred for 2.5 hours. The reaction was quenched by the slow addition of saturated NaHCO3 (aqueous solution) (15 mL) and water (5 mL), and the organic layer was separated by dilution with diethyl ether (10 mL). The aqueous layer was extracted with diethyl ether (2 × 20 mL). The organic fractions were combined, dried (MgSO4), filtered, and concentrated under vacuum to give a white solid. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, CDCl₃) spectra showed only a broad doublet at 37.0 ppm, corresponding to the desired borane-protected adduct. No further purification was required. (0.885 g, 2.83 mmol, 94%) 1 H NMR (CDCl3, 500 MHz) δ 7.42-7.29 (10H,m, ArH), 3.94-3.86 (1H, m, CH-O), 3.75-3.70 (1H, m, P-CH), 3.49-3.42 (1H, m,P-CH), 2.65-2.48 (2H, m, CH-C H 2, CH-C H2), 2.32-2.21 (2H, m, CH-C H 2, CH-C H 2),2.11 (br s, OH), 1.65-1.59 (1H, m, P-CH2), 1.46-1.38 (1H, m, P-CH2), 1.09 (3H,dd, J = 6.2, 1.2 Hz, C H 3-CH), 0.55 (3H, br q, BH3). 31 P{ 1 H} NMR (CDCl3, 162 MHz) δ37.1 (br d, J = 59.8 Hz). 13 C NMR (CDCl3, 126 MHz) δ 136.97 (ArC), 135.78 (d, J = 5.0 Hz ArC), 128.95 (ArCH), 128.94 (ArCH), 128.71 (ArCH), 128.68 (ArCH),128.55 (ArCH), 128.54 (ArCH), 127.76 (ArCH), 127.73 (ArCH), 127.42 (d, J = 2.3Hz ArCH), 127.33 (d, J = 2.2 Hz ArCH), 63.21 (OCH), 47.22 (d, 1 J C-P = 28.4 Hz, P-CH), 45.90 (d, 1 J C-P = 31.9 Hz, P-CH), 34.03 (d, 2 J C-P = 5.5 Hz, CH- C H2), 33.91 (d, 1 J C-P = 25.9 Hz, P-CH2), 30.64 (P-CH- C H2), 25.03 (d, J C-P = 9.9 Hz, CH-C H3). HRMS (ES + C 19 H 23 ONaP [MNa-BH3] + m / z: 321.1369 (measured value), 321.1379 (required value).

[0071] Borane-protected -( R )-2-(( 2R,5R )-2,5-diphenylphosphacyclopentan-1-yl)-1-phenylethyl-1-ol and its enantiomers (main isomer e1) and borane-protected -( S )-2-(( 2R,5R Synthesis of 2,5-diphenylphosphacyclopentan-1-yl)-1-phenylethane-1-ol and its enantiomer (minor isomer e2): At -78°C under a nitrogen atmosphere, 1.55 M of (racemic)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a) (1.015 g, 4.00 mmol) was added dropwise via syringe to a stirred solution of (racemic)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a) in 25 mL of THF. n -BuLi hexane solution (2.71 mL, 4.2 mmol). The reaction was then heated to -25 °C and stirred for 1 hour. A solution of styrene oxide (0.479 mL, 4.2 mmol) in THF (5 mL) was added dropwise via syringe. Once the addition was complete, the reaction was heated to room temperature and stirred for 2 hours. The reaction was quenched by the slow addition of saturated NaHCO3 (aqueous solution) (15 mL) and water (10 mL). The organic layer was separated by dilution with diethyl ether (10 mL). The aqueous layer was extracted with diethyl ether (2 × 20 mL). The organic fractions were combined, dried (MgSO4), filtered, and concentrated under vacuum to give a white solid. Crude product. 31 P{ 1 ¹H NMR (202.4 MHz, CDCl₃) spectra showed two major broad doublets at 39.1 and 38.1 ppm, corresponding to two major diastereomeric adducts protected by borane (two other possible diastereomeric adducts obtained from attack on the most substituted carbon were also present as minor products). Purification by rapid chromatography on silica gel (3:1 hexane:Et₂O) yielded minor isomers (0.319 g, 0.852 mmol, 21%), a mixture of the two isomers (0.084 g, 0.224 mmol, 6%), and major isomers (0.568 g, 1.52 mmol, 38%) as white solids. Major isomer (e1):1 H NMR (CDCl3, 500 MHz) δ 7.43-7.26 (13H, m, ArH), 7.13 (2H, d, J = 6.7 Hz, ArH), 4.80-4.76 (1H, m, CH-O),3.84-3.75 (1H, m, P-CH), 3.69-3.52 (1H, m, P-CH), 2.65-2.51 (3H, m, CH-C H 2,CH-C H 2, OH), 2.35-2.23 (2H, m, CH-C H 2, CH-C H 2), 1.91-1.85 (1H, m, P-CH2), 1.78(1H, ddd, J = 15.9, 9.6, 6.8 Hz, P-CH2), 0.63 (3H, br q, BH3). 31 P{ 1 H} NMR (CDCl3,202 MHz) δ 38.1 (br d, J = 49.4 Hz). 13 C NMR (CDCl3, 126 MHz) δ 143.66 (d, J = 9.8Hz ArC), 136.96 (ArC), 135.89 (d, J = 5.2 Hz ArC), 129.01 (ArCH), 129.00(ArCH), 128.70-128.68 (m, 4 x ArCH), 128.54 (ArCH), 128.53 (ArCH), 127.93(ArCH), 127.79 (ArCH), 127.76 (ArCH), 127.42 (d, J = 2.2 Hz ArCH), 127.31 (d, J = 2.2 Hz ArCH), 125.48 (2 x ArCH), 69.26 (OCH), 46.58 (d, 1 J C-P = 28.3 Hz, P-CH),45.68 (d, 1 J C-P =31.5 Hz, P-CH), 34.43 (d, 1 J C-P = 23.4 Hz, P-CH2), 33.81 (d, 2 J C-P = 5.2Hz, CH- C H2), 30.69 (P-CH- C H2). HRMS (ES + C 24 H 28 OBNaP [MNa] + m / z: 397.1851 (measured value), 397.1863 (required value).

[0072] Minor isomer (e2) : 1 H NMR (CDCl3, 500 MHz) δ 7.45-7.21 (13H, m, ArH), 6.97(2H, d, J = 6.9 Hz, ArH), 4.41-4.38 (1H, m, CH-O), 3.82-3.76 (1H, m, P-CH), 3.56-3.49 (1H, m, P-CH), 2.69 (1H, br s, OH), 2.63-2.50 (2H, m, CH-C H 2, CH-C H 2), 2.32-2.18 (2H, m, CH-C H 2, CH-C H 2), 1.93 (1H, ddd, J = 14.7, 11.0, 8.6 Hz,P-CH2), 1.76-1.66 (1H, m, P-CH2), 0.65 (3H, br q, BH3). 31 P{ 1 H} NMR (CDCl3, 202MHz) δ 39.0 (br d, J = 56.5 Hz). 13 C NMR (CDCl3, 126 MHz) δ 143.77 (d, J = 11.8 HzArC), 136.95 (ArC), 135.70 (d, J =4.8 Hz ArC), 129.10 (ArCH), 129.09 (ArCH),128.92 (ArCH), 128.88 (ArCH), 128.44-128.36 (m, 4 x ArCH), 127.93 (ArCH),127.90 (ArCH), 127.56 (ArCH), 127.50 (d, J = 2.3 Hz ArCH), 127.24 (d, J = 2.2 HzArCH), 125.19 (2 x ArCH), 69.36 (OCH), 47.27 (d, 1 J C-P = 28.6 Hz, P-CH), 45.94 (d, 1 J C-P = 31.3 Hz, P-CH), 34.66 (d, 1 J C-P = 23.7 Hz, P-CH2), 34.06 (d, 2 J C-P = 4.4 Hz, CH- C H2), 30.64 (P-CH- C H2). HRMS (ES + C 24 H 28 OBNaP [MNa] + m / z: 397.1853 (measured value), 397.1863 (required value).

[0073] Borane-protected -( R )-3-(( 2R,5R )-2,5-diphenylphosphacyclopentan-1-yl)-1,1,1-trifluoroprop-2-ol and enantiomers (main isomer f1) and borane-protected -( S )-3-(( 2R,5R Synthesis of 2,5-diphenylphosphacyclopentan-1-yl)-1,1,1-trifluoroprop-2-ol and its enantiomer (minor isomer f2): At -78°C under a nitrogen atmosphere, 1.6 M of (racemic)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a) (1.269 g, 5.00 mmol) was added dropwise via syringe to a stirred solution of (racemic)-2,5-trans-diphenylphosphazenecyclopentane-borane adduct (a) in 25 mL of THF. n -BuLi hexane solution (3.44 mL, 5.5 mmol). The reaction was then heated to -30 °C and stirred for 2 hours. A solution of 2-(trifluoromethyl)ethylene oxide (0.474 mL, 5.5 mmol) in THF (9 mL) was added dropwise via syringe. Once the addition was complete, the reaction was heated to room temperature and stirred for 1.5 hours. The reaction was quenched by the slow addition of saturated NaHCO3 (aqueous solution) (5 mL) and water (20 mL). The organic layer was separated by dilution with diethyl ether (20 mL). The aqueous layer was extracted with diethyl ether (2 × 20 mL). The organic fractions were combined, dried (MgSO4), filtered, and concentrated under vacuum to give a white solid. Crude product. 31 P{ 1 ¹H NMR (202.4 MHz, CDCl₃) spectra showed two broad doublets at 39.3 and 40.9 ppm, corresponding to two diastereomeric borane-protected adducts with a ratio of 58:42. Purification by rapid chromatography on silica gel (3:1 hexane:Et₂O) yielded a minor isomer (0.642 g, 1.753 mmol, 35%) and a major isomer (0.795 g, 2.17 mmol, 43%) as white solids. Major isomer (f₁): 1 H NMR (CDCl3, 500 MHz) δ 7.45-7.32 (10H, m, ArH), 4.08-3.96 (1H, m, CH-O), 3.84-3.76 (1H, m, P-CH), 3.54-3.44 (1H, m, P-CH), 2.69-2.50 (3H, m, CH-C H 2, CH-C H 2, OH), 2.37-2.26 (2H, m, CH-C H 2, CH-C H 2),1.86-1.81 (1H, m, P-CH2), 1.60 (1H, ddd, J = 15.1, 10.7, 8.3 Hz, P-CH2), 0.54(3H, br q, BH3). 31 P{ 1 H} NMR (CDCl3, 202 MHz) δ 39.2 (br d, J =55.6 Hz). 19 F NMR (CDCl3, 470 MHz) δ –80.40 (d, J = 6.4 Hz). 13 C NMR (CDCl3, 126 MHz) δ 136.02(ArC), 135.26 (d, J = 5.7 Hz ArC), 129.22 (ArCH), 129.20 (ArCH), 128.78 (ArCH), 128.77 (ArCH), 128.50 (ArCH), 128.46 (ArCH), 127.83 (d, J = 2.3 Hz ArCH),127.72-127.69 (3 x ArCH), 124.11 (qd, 1 J C-F = 281 Hz, J = 15.1 Hz, CF3), 66.24 (q, 2 J C-F = 32.7 Hz (OCH), 47.09 (d, 1 J C-P = 28.8 Hz, P-CH), 45.34 (d, 1 J C-P = 31.6 Hz, P-CH), 33.37 (d, 2 J C-P = 6.4 Hz, CH- C H2), 30.76 (P-CH- C H2), 25.33 (d, 1 J C-P = 27.1 Hz, P-CH2). HRMS (ES) + C 19 H 23 OBF3NaP [MNa] + m / z: 389.1419 (measured value), 389.1424 (required value).

[0074] Minor isomer (f2): 1H NMR (CDCl3, 500 MHz) δ 7.44-7.28 (10H, m, ArH),3.89-3.74 (2H, m, CH-O, P-CH), 3.61-3.54 (1H, m, P-CH), 2.76 (br s, OH),2.69-2.51 (2H, m, CH-C H 2, CH-C H 2), 2.36-2.15 (2H, m, CH-C H 2, CH-C H 2), 1.86-1.78 (1H, m, P-CH2), 1.50-1.45 (1H, m, P-CH2), 0.50 (3H, br q, BH3). 31 P{ 1 H} NMR(CDCl3, 202 MHz) δ 40.7 (br d, J = 56.1 Hz). 19 F NMR (CDCl3, 470 MHz) δ –80.50(d, J = 6.4 Hz). 13 C NMR (CDCl3, 126 MHz) δ 136.94 (ArC), 134.88 (d, J = 5.0 HzArC), 129.15-129.10 (4 x ArCH), 128.36 (2 x ArCH), 127.74 (d, J = 2.3 Hz ArCH),127.64 (ArCH), 127.61 (ArCH), 127.27 (d, J = 2.2 Hz ArCH), 124.21 (qd, 1 J C-F = 282Hz, J = 15.8 Hz, CF3), 66.61 (q, 2 J C-F = 32.8 Hz, OCH), 47.44 (d, 1 J C-P = 28.2 Hz, P-CH), 45.92 (d, 1 J C-P= 32.1 Hz, P-CH), 34.98 (d, 2 J C-P = 4.4 Hz, CH- C H2), 30.42 (P-CH- C H2), 25.08 (d, 1 J C-P = 28.8 Hz, P-CH2). HRMS (ES + C 19 H 23 OBF3NaP [MNa] + m / z: 389.1417 (measured value), 389.1424 (required value).

[0075] Example 1: 4,8-Di-tert-butyl-6-(2-(( 2R,5R Synthesis of 2,5-diphenylphosphazenecyclopentan-1-yl)ethoxy)-1,2,10,11-tetramethyldibenzo[d,f][1,3,2]dioxaphosphazenecycloheptaadiene 4a: (Rax)-3,3'-di-tert-butyl-5,5',6,6'-tetramethylbiphenyl-2,2'-diol[( R ax [0.261 g, 0.737 mmol] of BIPHEN-H2 was placed in a Schlenk tube and dissolved in 2 mL of toluene. NEt3 (0.308 mL, 2.211 mmol) was added, and the resulting solution was cooled in an ice bath. PBr3 (0.105 mL, 1.106 mmol) was added dropwise to the reaction mixture, which was then removed from the ice bath and stirred for 16 hours. The suspension was filtered through a sleeve under an inert atmosphere, and the filtrate was evaporated using a Schlenk line and dried under vacuum to remove any residual PBr3, giving a white solid product that was used in the next step without further purification. Crude product. 31 P{ 1 The ¹H NMR (202.4 MHz, C6D6) spectrum showed a single peak at δ 181.3 ppm, corresponding to ( R ax )-BIPHEN bromophosphite. To the container containing (from the previous step) R axIn a Schlenk flask containing a solution of 2-((trans)-2,5-diphenylphosphazenecyclopentan-1-yl)ethanol-1-ol (c) adduct (0.199 g, 0.669 mmol) in toluene (3.1 mL), a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.75 g, 6.69 mmol, 10 eq.) in toluene (3.5 mL) was added.

[0076] The reaction mixture was then stirred overnight (21 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was compacted with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to obtain a white, foamy solid. This was achieved by recrystallization. R ax ,R,R Purification of 4a. Gently heat the flask containing the reaction mixture (0.294 g) using a heat gun. Add heptane (1 mL) to dissolve the foamy solid. Allow the resulting solution to stand in a refrigerator. Filter the resulting crystals to obtain pure 4a as a white solid. R ax ,R,R ))-4a (0.262 g, 0.393 mmol, 59%).

[0077] 1 H NMR (CDCl3, 400 MHz) δ 7.32-7.16 (11H, m, ArH), 7.08 (1H, s, ArH), 3.71-3.61 (2H, m, CH2-O, P-CH), 3.18-3.02 (2H, m, CH2-O, P-CH), 2.59-2.49(1H, m, CH-C H 2), 2.41-2.33 (1H, m, CH-C H 2), 2.26 (3H, s, CH3), 2.26-2.20 (4H,m, O-CH3, CH-C H 2), 1.95-1.83 (1H, m, CH-C H2), 1.82 (3H, s, CH3), 1.79 (3H, s,CH3), 1.72-1.63 (1H, m, P-CH2), 1.44 (9H, s, 3 x CH3), 1.39-1.32 (10H, m, P-CH2, 3 x CH3). 31 P{ 1 H} NMR (CDCl3), 162 MHz δ 130.4 (s); 6.4 (s). 13 C NMR (CDCl3,126 MHz) δ 145.34 (ArC), 144.62 (ArC), 144.49 (ArC), 138.44 (ArC), 137.97(ArC), 136.75 (ArC), 134.95 (ArC), 134.28 (ArC), 132.31 (ArC), 131.70 (ArC),131.45 (ArC), 130.45 (ArC), 128.52-125-83 (m, 12 x ArCH), 62.85 (dd, 2 J C-P = 30.0, 4.6 Hz, OCH2), 50.16 (d, 1 J C-P = 15.8 Hz, P-CH), 45.95 (d, 1 J C-P = 14.6 Hz, P-CH), 37.31 (CH- C H2), 34.59 (2 x C (CH3)3), 31.90 (d, 2 J C-P = 4.3 Hz, CH- C H2), 31.34(d, J C-P = 5.2 Hz, C( C H3)3), 31.06 (C( C H3)3), 27.99 (d, 1 J C-P =24.9 Hz, P-CH2), 20.45(CH3), 20.41 (CH3), 16.75 (CH3), 16.54 (CH3). HRMS (ES + C 42 H 53 O3P2[MH] + m / z: 667.3455 (measured value), 671.3464 (required value).

[0078] Example 2: 4,8-Di-tert-butyl-6-(2-((trans)-2,5-diphenylphosphazene-1-yl)ethoxy)-2,10-dimethoxydibenzo[d,f][1,3,2]dioxaphosphazene-heptadiene 4b: 3,3'-Di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diol (0.228 g, 0.637 mmol) was placed in a Schlenk tube and suspended in 3 mL of toluene. NEt3 (0.266 mL, 1.911 mmol) was added, and the resulting solution was cooled in an ice bath. PBr3 (0.091 mL, 0.956 mmol) was added dropwise to the reaction mixture, which was then removed from the ice bath and stirred for 16 hours. The suspension was filtered through a sleeve under an inert atmosphere, and the filtrate was evaporated using a Schlenk line and dried under vacuum to remove any residual PBr3. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed two peaks: a second peak at δ 189.4 ppm, corresponding to bromophosphite, and a second peak at δ 140.6 ppm, corresponding to the byproduct, in a ratio of 3:1. The product was used in the next step without further purification. To a Schlenk flask containing a solution of bromophosphite from the previous step in toluene (3 mL), a solution of borane-protected 2-((trans)-2,5-diphenylphosphacetacyclopentan-1-yl)ethanol-1-ol (c) adduct (0.161 g, 0.541 mmol) in toluene (4 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.607 g, 5.41 mmol, 10 eq.) in toluene (3 mL).

[0079] The reaction mixture was then stirred overnight (19 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to obtain a white, foamy solid. Recrystallization was then performed to achieve… tropos , trans , rac Purification of 4b: Heptane (1 mL) was added to a flask containing the reaction mixture, and the flask was then gently heated with a hot air gun to dissolve the solid. The resulting solution was allowed to stand in a refrigerator. The resulting crystals were filtered to give a pure 4b as a white solid. tropos , trans , rac )-4b (0.111 g, 0.166 mmol, 31%).

[0080] 1 H NMR (C6D6, 500 MHz) δ 7.21-7.02 (12H, m, ArH), 6.66 (2H, d, J = 2.9Hz, ArH), 3.94-3.86 (1H, m, CH2-O), 3.69-3.61 (1H, m, CH2-O), 3.42-3.36 (1H,m, P-CH), 3.31 (3H, s, OCH3), 3.30 (3H, s, OCH3), 3.12-3.07 (1H, m, P-CH),2.27-2.19 (1H, m, CH-C H 2), 2.00-1.88 (2H, m, CH-C H 2), 1.75-1.68 (1H, m, P-CH2), 1.64-1.55 (1H, m, CH-C H 2), 1.47 (9H, s, 3 x CH3), 1.44 (9H, s, 3 x CH3), 1.41-1.35 (1H, m, P-CH2). 31 P{ 1 H} NMR (C6D6, 202 MHz) δ 134.3 (s); 5.9 (s). 13CNMR (C6D6, 126 MHz) δ 155.96 (ArC), 155.93 (ArC), 144.87 (ArC), 144.73 (ArC), 142.59 (ArC), 142.19 (ArC), 142.12 (ArC), 138.72 (ArC), 133.93 (ArC), 133.80(ArC), 128.46-125-75 (m, 10 x ArCH), 114.60 (ArCH), 114.53 (ArCH), 112.94(ArCH), 112.88 (ArCH), 63.03 (d, 2 J C-P = 29.6 Hz, OCH2), 54.74 (OCH3), 54.72(OCH3), 50.66 (d, 1 J C-P = 17.0 Hz, P-CH), 45.98 (d, 1 J C-P = 15.6 Hz, P-CH), 37.61 (CH- C H2), 35.18 ( C (CH3)3), 35.15 ( C (CH3)3), 31.83 (d, 2 J C-P = 4.2 Hz, CH- C H2), 30.59 (C( C H3)3), 30.59 (C( C H3)3), 28.22 (d, 1 J C-P = 26.2 Hz, P-CH2). HRMS (ES + C 40 H 49 O5P2[MH] + m / z: 671.3041 (measured value), 671.3050 (required value).

[0081] Example 3: Synthesis of 4c-1 and 4c-2 as a mixture of diastereomers: 3,3'-Di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diol (2.8 g, 7.8 mmol) was placed in a Schlenk tube and dissolved in 24 mL of THF. The resulting solution was cooled to -78 °C, and PCl3 (1.02 mL, 11.7 mmol) was slowly added. NEt3 (3.27 mL, 23.4 mmol) was also added to the reaction mixture, which was then stirred and allowed to reach room temperature overnight, or 16 hours later. The suspension was filtered through a frit filter under an inert atmosphere, and the filtrate was evaporated using a Schlenk line and dried under vacuum to remove any residual PCl3. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed a single peak at δ 172.0 ppm, corresponding to chlorophosphite. The product was used in the next step without further purification. Borane-protected ⁻¹(H⁺) was added to a Schlenk flask containing a solution of chlorophosphite from the previous step in toluene (20 mL). R )-3-(( 2R,5R )-2,5-diphenylphosphacyclopentan-1-yl)-1,1,1-trifluoroprop-2-ol (and its enantiomers) and borane-protected -( S )-3-(( 2R,5R A solution of 2,5-diphenylphosphacyclopentan-1-yl)-1,1,1-trifluoroprop-2-ol (and its enantiomers) (f1 and f2) (58:42) (2.80 g, 7.70 mmol) in toluene (30 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (4.75 g, 42.3 mmol, 5.5 eq.) in toluene (30 mL).

[0082] The reaction mixture was then stirred overnight (19 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to give a white solid. Purification was achieved by column chromatography on silica gel (pre-dried overnight in an oven) using 20% ​​ethyl acetate in hexane as eluent, yielding the compound as a white solid. tropos , rac , trans )-4c-1 and ( tropos , rac , trans )-4c-2 (a 59:41 mixture of diastereomers) (4.21 g, 5.70 mmol, 74%). The individual diastereomers can be prepared using the same procedure but with a single diastereomer of the phosphacyclopentene adduct. 4,8-Di-tert-butyl-6-((( R )-3-(( 2R,5R )-2,5-diphenylphosphacyclopentane-1-yl)-1,1,1-trifluoroprop-2-yl)oxy)-2,10-dimethoxydibenzo[d,f][1,3,2]dioxaphosphacycloheptadecene and its enantiomer 4c-1: 1 H NMR (C6D6, 500 MHz) δ 7.20-7.01 (12H, m, ArH), 6.64 (1H, d, J = 3.0Hz, ArH), 6.62 (1H, d, J = 3.0 Hz, ArH), 4.55-4.45 (1H, m, CH-O), 3.45-3.35(1H, m, P-CH), 3.31 (3H, s, OCH3), 3.28 (3H, s, OCH3), 3.06-3.10 (1H, m, P-CH), 2.26-2.18 (1H, m, P-CH-C H 2), 1.98-1.92 (1H, m, P-CH-C H 2), 1.89-1.80 (2H,m, P-CH-C H 2, P-CH2), 1.63-1.53 ​​(2H, m, P-CH-C H 2, P-CH2), 1.45 (9H, s, 3 x CH3), 1.41 (9H, s, 3 x CH3). 31 P{ 1 H} NMR (C6D6), 202 MHz δ 143.9 (dq, J P-P = 32.6 Hz, J P-F = 7.0 Hz), 1.2 (br s). 19 F NMR (C6D6, 470 MHz) δ –77.32 (br s). 13 C NMR (C6D6, 126MHz) δ 156.25 (ArC), 156.03 (ArC), 144.15 (d, JC-P = 17.5 Hz, ArC), 142.75 (ArC),142.35 (ArC), 141.76 (d, J C-P = 7.9 Hz, ArC), 141.24 (ArC), 138.27 (ArC), 134.27(ArC), 133.72 (ArC), 128.50-127-50 (m, 8 x ArCH), 126.18 (ArCH), 125.90(ArCH), 124.41 (qm, 1 J C-F = 283 Hz,CF3), 114.55 (ArCH), 114.52 (ArCH), 113.07(ArCH), 112.92 (ArCH), 71.42-70.62 (m, OCH), 54.72 (2 x OCH3), 51.23 (d, 1 J C-P = 17.9 Hz, P-CH), 45.93 (d, 1 J C-P = 16.1 Hz, P-CH), 37.56 (P-CH- C H2), 35.24 ( C (CH3)3), 35.17 ( C (CH3)3), 31.89 (d, 2 J C-P = 3.7 Hz, P-CH- C H2), 31.04 (C( C H3)3),30.66 (d, J C-P = 2.7 Hz, C( C H3)3), 27.10 (d, 1 J C-P = 32.1 Hz, P-CH2). HRMS (ES + )C 41 H 48 O5F3P2[MH]+ m / z: 739.2908 (measured value), 739.2924 (required value).

[0083] 4,8-di-tert-butyl-6-(( S )-3-(( 2R,5R )-2,5-diphenylphosphacyclopentane-1-yl)-1,1,1-trifluoroprop-2-yl)oxy)-2,10-dimethoxydibenzo[d,f][1,3,2]dioxaphosphacycloheptadecene and its enantiomer 4c-2: 1 H NMR (C6D6, 500 MHz) δ 7.21-7.03 (12H, m, ArH), 6.67 (1H, d, J = 2.9 Hz (ArH), 6.60 (1H, d, J = 3.0 Hz, ArH), 3.48-3.41 (1H, m, P-CH), 3.36-3.29 (1H,m, CH-O), 3.30 (3H, s, OCH3), 3.27 (3H, s, OCH3), 2.68-2.63 (1H, m, P-CH),2.17-2.09 (1H, m, P-CH-C H 2), 1.93-1.83 (2H, m, P-CH-C H 2, P-CH2), 1.77-1.69(1H, m, P-CH-C H 2), 1.57-1.44 (2H, m, P-CH-C H 2, P-CH2), 1.44 (9H, s, 3 x CH3), 1.27 (9H, s, 3 x CH3). 31 P{ 1 H} NMR (C6D6), 202 MHz δ 142.5 (d, J P-P = 41.5 Hz), –3.8 (br s). 19 F NMR (C6D6, 471 MHz) δ –77.62 (s). 13C NMR (C6D6, 126 MHz) δ 156.44(ArC), 155.61 (ArC), 144.01 (ArC), 143.86 (ArC), 142.91 (ArC), 142.60 (ArC),140.67 (ArC), 137.36 (ArC), 135.00 (ArC), 132.85 (ArC), 128.84-127-50 (m, 8 xArCH), 126.17 (ArCH), 126.09 (ArCH), 124.15 (qm, 1 J C-F = 227 Hz,CF3), 114.75(ArCH), 114.45 (ArCH), 113.16 (ArCH), 112.40 (ArCH), 70.92-69.89 (m, OCH),54.71 (2 x OCH3), 51.37 (d, 1 J C-P = 16.7 Hz, P-CH), 46.02 (d, 1 J C-P = 16.7 Hz, P-CH),38.35 (P-CH- C H2), 35.25 ( C (CH3)3), 35.06 ( C (CH3)3), 31.15 (d, 2 J C-P = 3.6 Hz, P-CH- C H2), 30.72 (d, J C-P = 3.9 Hz, C( C H3)3), 30.42 (C( C H3)3), 27.19 (d, 1 J C-P = 30.2 Hz,P-CH2). HRMS (ES + ) C 41 H 48 O5F3P2[MH] +m / z: 739.2912 (measured value), 739.2924 (required value).

[0084] Example 4: 4,8-Di-tert-butyl-6-((( R )-1-(( 2R,5R )-2,5-diphenylphosphazene-1-yl)prop-2-yl)oxy)-2,10-dimethoxydibenzo[d,f][1,3,2]dioxaphosphazene-heptadiene 4d: 3,3'-Di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diol (0.315 g, 0.878 mmol) was placed in a Schlenk tube and dissolved in 3 mL of THF. The resulting solution was cooled to -78 °C, and PBr3 (0.1 mL, 1.053 mmol) was added dropwise. NEt3 (0.367 mL, 2.634 mmol) was also added dropwise to the reaction mixture, which was then stirred and allowed to reach room temperature overnight (16 hours). The suspension was filtered through a sleeve under an inert atmosphere, the filtrate was evaporated using a Schlenk line, and dried under vacuum to remove any residual PBr3. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed a single peak at δ 188.9 ppm, corresponding to bromophosphite. The product was used in the next step without further purification. Borane-protected -( R )-1-(( 2R,5R A solution of 2,5-diphenylphosphacyclopentan-1-yl)prop-2-ol adduct (d1) (0.250 g, 0.8 mmol) in toluene (7 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.538 g, 4.8 mmol, 6 eq.) in toluene (5 mL).

[0085] The reaction mixture was then stirred overnight (19 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to obtain a white, foamy solid. Recrystallization was then performed to achieve… tropos , R , R , RPurification of 4d-100g. Heptane (1 mL) was added to a flask containing the reaction mixture, and the flask was then gently heated with a hot air gun to dissolve the solid. The resulting solution was allowed to stand in a refrigerator. The resulting crystals were filtered to obtain a white solid. tropos , R , R , R )-4d (0.184 g, 0.269 mmol, 34%). 1 H NMR (C6D6, 500 MHz) δ 7.22-7.02 (12H, m, ArH), 6.66 (2H, d, J = 2.9 Hz, ArH), 4.16-4.07 (1H, m, CH-O), 3.48-3.41 (1H, m, P-CH), 3.31 (3H,s, OCH3), 3.30 (3H, s, OCH3), 3.27-3.18 (1H, m, P-CH), 2.31-2.24 (1H, m, P-CH-C H 2), 2.04-1.98 (2H, m, P-CH-C H 2), 1.75-1.65 (2H, m, P-CH2), 1.64-1.56 (1H, m,P-CH-C H 2), 1.53 (9H, s, 3 x CH3), 1.44 (9H, s, 3 x CH3), 1.22 (3H, d, J = 6.2Hz, C H 3-CH). 31 P{ 1 H} NMR (C6D6, 202 MHz) δ 148.6 (s), 4.5 (s). 13 C NMR (C6D6, 126MHz) δ 155.95 (ArC), 155.90 (ArC), 145.10 (ArC), 144.96 (ArC), 142.35-142.18(3 x ArC), 139.01 (ArC), 134.29 (ArC), 134.17 (ArC), 128.55-125-73 (m, 8 xArCH), 126.01 (ArCH), 125.73 (ArCH), 114.50 (ArCH), 114.47 (ArCH), 112.90 (2x ArCH), 72.01 (dd, J C-P= 22.1, 18.7 Hz, OCH), 54.77 (OCH3), 54.75 (OCH3), 51.03(d, 1 J C-P = 16.8 Hz, P-CH), 46.13 (d, 1 J C-P = 15.3 Hz, P-CH), 37.92 (P-CH- C H2), 35.31(dd, J C-P = 19.0, 3.9 Hz, P-CH2), 35.19 (2 x C (CH3)3), 31.99 (d, 2 J C-P = 4.0 Hz, CH- C H2), 31.09 (d, J C-P = 2.1 Hz, C( C H3)3), 30.89 (d, J C-P = 2.5 Hz, C( C H3)3), 23.14 (dd, J C-P = 9.8, 4.0 Hz, CH- C H3). HRMS (ES + C 41 H 51 O5P2[MH] + m / z: 685.3197 (measured value), 685.3206 (required value).

[0086] Example 5: 4,8-Di-tert-butyl-6-(( R )-2-(( 2R,5R )-2,5-diphenylphosphacyclopentane-1-yl)-1-phenylethoxy)-2,10-dimethoxydibenzo[d,f][1,3,2]dioxaphosphacycloheptaadiene and its enantiomer 4e-1: 3,3'-Di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diol (0.342 g, 0.955 mmol) was placed in a Schlenk tube and dissolved in 3 mL of THF. The resulting solution was cooled to -78 °C, and PCl3 (0.1 mL, 1.146 mmol) was added dropwise. NEt3 (0.4 mL, 2.865 mmol) was also added to the reaction mixture, which was then stirred and allowed to reach room temperature overnight, or 16 hours later. The suspension was filtered through a sleeve under an inert atmosphere, the filtrate was evaporated using a Schlenk line, and dried under vacuum to remove any residual PCl3. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed a single peak at δ 172.7 ppm, corresponding to chlorophosphite. The product was used in the next step without further purification. Borane-protected -( R )-2-(( 2R,5R A solution of 2,5-diphenylphosphacyclopentan-1-yl)-1-phenylethyl-1-ol and its enantiomer (e1) (0.311 g, 0.83 mmol) in toluene (7 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.559 g, 4.98 mmol, 6 eq.) in toluene (5 mL).

[0087] The reaction mixture was then stirred overnight (19 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to give a white solid. Recrystallization was then performed to achieve… tropos , rac , trans Purification of 4e-1. Add heptane (2 mL) to a flask containing the reaction mixture to dissolve the solid. Allow the resulting solution to stand in a refrigerator. While still cold, decant the resulting white precipitate and wash with cold heptane (1 mL) to give a white solid. tropos , rac , trans )-4e-1 (0.257 g, 0.344 mmol, 41%). 1 H NMR (C6D6, 500 MHz) δ 7.23-6.85 (17H, m, ArH),6.65 (1H, d, J = 3.0 Hz, ArH), 6.64 (1H, d,J = 3.0 Hz, ArH), 5.12-5.06 (1H, m, CH-O), 3.39-3.30 (1H, m, P-CH), 3.31 (3H, s, OCH3), 3.29 (3H, s, OCH3), 2.73-2.68 (1H, m, P-CH), 2.22-2.14 (1H, m, P-CH-C H 2), 2.09-1.95 (4H, m, P-CH2, P-CH-C H 2), 1.54-1.42 (1H, m, P-CH-C H 2), 1.42 (9H, s, 3 x CH3), 1.22 (9H, s, 3 x CH3). 31 P{ 1 H} NMR (C6D6), 202 MHz δ 148.6 (br s), 4.2 (s). 13 C NMR (C6D6, 126 MHz)δ 156.05 (ArC), 155.84 (ArC), 145.09 (ArC), 144.95 (ArC), 142.51-141.59 (4 xArC), 139.05 (ArC), 134.40 (d, J C-P = 3.7 Hz, ArC), 133.86 (d, J C-P = 3.3 Hz, ArC),128.59-127-50 (m, 13 x ArCH), 126.05 (ArCH), 125.52 (ArCH), 114.46 (ArCH),114.33 (ArCH), 112.82 (ArCH), 112.80 (ArCH), 78.21 (dd, J C-P = 30.6, 17.2 Hz,OCH), 54.78 (OCH3), 54.74 (OCH3), 50.07 (d, 1 J C-P = 17.2 Hz, P-CH), 46.35 (d, 1 J C-P =15.3 Hz, P-CH), 37.43 (P-CH- C H2), 35.41-34.92 (m, P-CH2, 2 x C (CH3)3), 32.07(d, 2 J C-P = 4.2 Hz, CH- C H2), 30.95 (C( C H3)3), 30.58 (d, J C-P = 3.6 Hz, C( C H3)3). HRMS(ES + C 46 H 52 O5NaP2[MNa] + m / z: 769.3165 (measured value), 769.3182 (required value).

[0088] Example 6: 4,8-Di-tert-butyl-6-(( S )-2-(( 2R,5R )-2,5-diphenylphosphacyclopentane-1-yl)-1-phenylethoxy)-2,10-dimethoxydibenzo[d,f][1,3,2]dioxaphosphacycloheptadecene and its enantiomer 4e-2: 3,3'-Di-tert-butyl-5,5'-dimethoxy-[1,1'-biphenyl]-2,2'-diol (0.158 g, 0.439 mmol) was placed in a Schlenk tube and dissolved in 2 mL of THF. The resulting solution was cooled to -78 °C, and PBr3 (0.05 mL, 0.527 mmol) was added. NEt3 (0.184 mL, 1.317 mmol) was also added to the reaction mixture, which was then stirred and allowed to reach room temperature overnight, or 16 hours later. The suspension was filtered through a sleeve under an inert atmosphere, the filtrate was evaporated using a Schlenk line, and dried under vacuum to remove any residual PBr3. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed a single peak at δ 189.5 ppm, corresponding to bromophosphite. The product was used in the next step without further purification. Borane-protected -( R )-2-(( 2R,5R A solution of 2,5-diphenylphosphacyclopentan-1-yl)-1-phenylethyl-1-ol and its enantiomer (e2) (0.090 g, 0.240 mmol) in toluene (3 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.162 g, 1.44 mmol, 6 eq.) in toluene (3 mL).

[0089] The reaction mixture was then stirred overnight (19 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to give a white solid. The solid was obtained by column chromatography on silica gel (pre-dried overnight in an oven) using 50% hexane in dichloromethane as eluent. tropos , rac , trans Purification of 4e-2 yielded a white solid compound ( ). tropos , rac , trans )-4e-2 (0.068 g, 0.091 mmol, 38%). 1 H NMR (C6D6, 500 MHz)δ 7.24-6.86 (17H, m, ArH), 6.75 (1H, d, J = 2.7 Hz (ArH), 6.70 (1H, d, J = 2.8Hz, ArH), 5.04-4.90 (1H, m, CH-O), 3.46-3.40 (1H, m, P-CH), 3.33 (3H, s,OCH3), 3.32 (3H, s, OCH3), 3.01-2.97 (1H, m, P-CH), 2.30-2.22 (1H, m, P-CH-C H 2), 2.01-1.91 (3H, m, P-CH2, P-CH-C H 2), 1.74-1.70 (1H, m, P-CH2), 1.61-1.50(1H, m, P-CH-C H 2), 1.40 (9H, s, 3 x CH3), 1.33 (9H, s, 3 x CH3). 31 P{ 1 H} NMR(C6D6), 202 MHz δ 142.9 (d, J P-P =12.6 Hz), 0.5 (d, J P-P = 12.6 Hz). 13 C NMR (C6D6, 126MHz) δ 156.11 (ArC), 155.82 (ArC), 144.82 (ArC), 144.68 (ArC), 142.80-141.85(4 x ArC), 138.82 (ArC), 134.60 (ArC), 133.57 (ArC), 128.52-126-76 (m, 13 xArCH), 125.85 (ArCH), 125.79 (ArCH), 114.52 (ArCH), 114.47 (ArCH), 113.19(ArCH), 112.74 (ArCH), 76.02 (dd, J C-P = 20.6, 7.3 Hz, OCH), 54.80 (OCH3), 54.71(OCH3), 51.26 (d, 1 J C-P = 18.0 Hz, P-CH), 45.83 (d, 1 J C-P = 16.6 Hz, P-CH), 38.40 (P-CH- C H2), 37.64 (d, J C-P = 27.4, P-CH2), 35.16 (2 x C (CH3)3), 30.80 (d, 2 J C-P = 3.1 Hz,CH- C H2), 30.80 (d, J C-P = 3.1 Hz, C( C H3)3), 30.67 (C( C H3)3). HRMS (ES + ) C 46 H 53 O5P2[MH] +m / z: 747.3344 (measured value), 747.3363 (required value).

[0090] Example 7: 2,4,8,10-Tetrachloro-6-(( R )-3-(( 2R,5R )-2,5-diphenylphosphazenecyclopentan-1-yl)-1,1,1-trifluoroprop-2-yl)oxy)dibenzo[d,f][1,3,2]dioxaphosphazenecycloheptadecene and its enantiomer 4f: 3,3',5,5'-Tetrachloro-[1,1'-biphenyl]-2,2'-diol (0.21 g, 0.65 mmol) was placed in a Schlenk tube and dissolved in 3 mL of THF. The resulting solution was cooled to -78 °C, and PCl3 (0.1 mL, 1.146 mmol) was slowly added. NEt3 (0.27 mL, 1.95 mmol) was also added to the reaction mixture, which was then stirred and allowed to reach room temperature overnight, or 18 hours later. The suspension was filtered through a glass frit filter under an inert atmosphere, and the filtrate was evaporated using a Schlenk line and dried under vacuum to remove any residual PCl3. Crude product 31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed a singlet at δ 184.5 ppm, corresponding to chlorophosphite. The product was used in the next step without further purification. Borane-protected -( R )-3-(( 2R,5R A solution of 2,5-diphenylphosphacyclopentan-1-yl)-1,1,1-trifluoroprop-2-ol and its enantiomer (f1) (0.190 g, 0.752 mmol) in toluene (4 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.350 g, 3.12 mmol, 6 eq.) in toluene (4 mL).

[0091] The reaction mixture was then stirred overnight (17 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to give 4f as a white solid, which was used without further purification. 1H NMR (CDCl3, 500 MHz) δ7.49-7.18 (14H, m, ArH), 4.13-4.04 (1H, m, CH-O), 3.82-3.75 (1H, m, P-CH),3.24-3.19 (1H, m, P-CH), 2.69-2.61 (1H, m, P-CH-C H 2), 2.50-2.43 (1H, m, P-CH-C H 2), 2.34-2.25 (1H, m, P-CH-C H 2), 1.99-1.85 (2H, m, P-CH-C H 2, P-CH2), 1.66-1.62 (1H, m, P-CH2). 31 P{ 1 H} NMR (CDCl3, 202 MHz) δ 151.45-151.20 (m), 1.95-1.59(m). 19 F NMR (CDCl3, 471 MHz) δ –76.53-–76.60 (m). 13 C NMR (CDCl3, 126 MHz) δ144.05 (d, J C-P = 6.3 Hz, ArC), 143.91-143.87 (m, 2 x ArC), 143.72 (ArC), 137.97(ArC), 132.01 (d, J C-P = 3.3 Hz, ArC), 131.84 (d, J C-P = 2.8 Hz, ArC), 130.59 (ArC),130.51 (ArC), 130.24 (ArCH), 130.15 (ArCH), 128.84 (2 x ArCH), 128.61 (2 xArCH), 128.41 (ArC), 127.95 (ArCH), 127.84 (ArCH), 127.83 (ArCH), 127.75(ArCH), 127.52 (ArCH), 127.49 (ArCH), 126.45 (ArCH), 126.12 (d, J C-P =1.6 Hz (ArCH), 123.49 (qm, 1 J C-F = 282 Hz,CF3), 72.60-71.51 (m, OCH), 51.30 (d, 1 J C-P = 17.0Hz, P-CH), 46.10 (d, 1 J C-P = 15.5 Hz, P-CH), 37.99 (P-CH- C H2), 31.99 (d, 2 J C-P = 3.9Hz, P-CH- C H2), 27.18 (d, 1 J C-P = 31.1 Hz, P-CH2). HRMS (ES + C 31 H 24 O3Cl4F3P2[MH] + m / z: 702.9891 (measured value), 702.9901 (required value).

[0092] Example 8: 2,4,8,10-Tetrabromo-6-(( R )-3-(( 2R,5R )-2,5-diphenylphosphazenecyclopentan-1-yl)-1,1,1-trifluoroprop-2-yl)oxy)dibenzo[d,f][1,3,2]dioxaphosphazenecycloheptadecene and enantiomers 4g: 3,3',5,5'-Tetrabromo-[1,1'-biphenyl]-2,2'-diol (0.126 g, 0.351 mmol) was placed in a Schlenk tube and dissolved in 2.5 mL of THF. The resulting solution was cooled to -78 °C, and PCl3 (0.046 mL, 0.527 mmol) was slowly added. NEt3 (0.147 mL, 1.053 mmol) was also added to the reaction mixture, which was then stirred and allowed to reach room temperature overnight, or 16 hours later. The suspension was filtered through a glass frit filter under an inert atmosphere, and the filtrate was evaporated using a Schlenk line and dried under vacuum to remove any residual PCl3. Crude product31 P{ 1 ¹H NMR (202.4 MHz, C6D6) spectra showed a single peak at δ 183.4 ppm, corresponding to chlorophosphite. The product was used in the next step without further purification. Borane-protected -( R )-3-(( 2R, 5R A solution of 2,5-diphenylphosphacyclopentan-1-yl)-1,1,1-trifluoroprop-2-ol and its enantiomer (f1) (0.116 g, 0.316 mmol) in toluene (3 mL) was added, followed by a solution of 1,4-diazabicyclo-[2,2,2]octane (DABCO) (0.213 g, 1.896 mmol, 6 eq) in toluene (3 mL).

[0093] The reaction mixture was then stirred overnight (20 hours) at room temperature. The resulting suspension was filtered through silica gel (pre-dried overnight in an oven) under an inert atmosphere, and the filtered solution was filled with anhydrous toluene and washed with SiO2. The resulting solution was evaporated under reduced pressure to give a white solid. The solid was obtained by column chromatography on silica gel (pre-dried overnight in an oven) using 12.5% ​​ethyl acetate in hexane as eluent. tropos , rac , trans Purification of 4g yielded a white solid compound ( ). tropos , rac , trans )-4g (0.095 g, 0.108 mmol, 34%). 1 H NMR (CDCl3, 400 MHz) δ7.79 (1H, d, J = 2.2 Hz (ArH), 7.76 (1H, d, J = 2.2 Hz, ArH), 7.44-7.19 (12H, m,ArH), 4.25-4.11 (1H, m, CH-O), 3.82-3.73 (1H, m, P-CH), 3.25-3.19 (1H, m, P-CH), 2.70-2.59 (1H, m, P-CH-C H 2), 2.50-2.43 (1H, m, P-CH-C H 2), 2.36-2.21 (1H,m, P-CH-C H 2), 1.99-1.87 (2H, m, P-CH-CH 2, P-CH2), 1.67-1.62 (1H, m, P-CH2). 31 P{ 1 H} NMR (CDCl3, 162 MHz) δ 150.53 (dq, J = 21.8, 10.9 Hz), 2.60-2.16 (m). 19 FNMR (CDCl3, 470 MHz) δ –76.59 (dd, J = 17.0, 11.2 Hz). 13 C NMR (CDCl3, 126 MHz) δ145.73 (d, J C-P = 6.8 Hz, ArC), 145.50 (d, J C-P = 5.4 Hz, ArC), 143.99 (ArC), 143.85(ArC), 138.03 (ArC), 132.30 (d, J C-P = 3.1 Hz, ArC), 131.95 (d, J C-P = 2.5 Hz, ArC),118.15-117.99 (3 x ArC), 135.87 (ArCH), 135.74 (ArCH), 131.59 (ArCH), 131.56(ArCH), 128.84 (2 x ArCH), 128.61 (2 x ArCH), 127.83 (ArCH), 127.76 (ArCH), 127.59 (ArCH), 127.56 (ArCH), 126.46 (ArCH), 126.10 (ArCH), 123.54 (qm, 1 J C-F = 282 Hz, CF3), 72.70-71.61 (m, OCH), 51.27 (d, 1 J C-P = 17.2 Hz, P-CH), 46.22 (d, 1 J C-P= 15.5 Hz, P-CH), 38.04 (P-CH- C H2), 32.09 (d, 2 J C-P = 3.9 Hz, P-CH- C H2), 27.07 (d, 1 J C-P = 31.9 Hz, P-CH2).

[0094] Example 9: Study on the hydroformylation of propylene using various solvents In this study, [Rh(acac)(CO)2] was used as the Rh source, and propylene was hydroformylated using the ligands shown in Figure 1 above. The synthesis of the ligands used is described above.

[0095] General: All operations are performed using standard Schlenk techniques under an inert atmosphere of nitrogen or argon. Anhydrous and degassed solvents are obtained from a solvent distiller or SPS solvent purification system. Toluene, octafluorotoluene, n-undecane, n-dodecane, and DOTP are degassed only before use. Unless otherwise specified, all chemicals are commercially purchased and used as is. Premixed CO / H2 (1:1) and propylene / CO / H2 (10:45:45) are obtained from BOC. Gas chromatography is performed on an Agilent Technologies 7820A system.

[0096] The general procedure for hydroformylation is as follows: The hydroformylation reaction is carried out in a Parr 4590 Micro Bench Top Reactor with a volumetric capacity of 0.1 L, a top-mounted stirrer (set to 1200 RPM) with a gas entrainment head, a temperature controller, a pressure gauge, and the ability to connect to a gas cylinder.

[0097] Follow the general procedure below in each experiment.

[0098] A stock solution of [Rh(acac)(CO)2] was prepared by dissolving 10.0 mg of [Rh(acac)(CO)2] in 5.0 mL of toluene.

[0099] In a Schlenk flask, under N2 (or argon) atmosphere, a suitable ligand (6.40 or 10.24 μmol) is dissolved in 19.35 mL of a suitable solvent along with 0.65 mL of a rhodium catalyst solution (containing 5.12 μmol of [Rh(acac)(CO)2] from the above stock solution) and an internal standard (1-methylnaphthalene) (0.1 mL), to obtain a molar ratio of 1:1.25 Rh:ligand or 2:ligand.

[0100] The empty autoclave was sealed and flushed three times with syngas (CO / H2 1:1) at 5–10 atm, releasing to 1 atm each time. Then, 20 mL of the solution from the Schlenk flask was added via the injection port. The resulting catalyst solution was activated by stirring with syngas at 20 bar for one hour at the reaction temperature and pressure specified in Table 1–2. The autoclave pressure was released and repressurized with a propylene / CO / H2 (10:45:45) gas mixture. The reactants were stirred at the reaction temperature for the time specified in the table. After the reaction was complete, the reactor was cooled to room temperature and the reactor pressure was released. The sample was then analyzed by gas chromatography (GC), with both isomers calibrated relative to 1-methylnaphthalene as an internal standard. The GC results were used to determine TON and isomer selectivity (the percentage of isobutyraldehyde in total butyraldehyde).

[0101] These hydroformylation experiments involve first activating a catalyst system ([Rh(acac)(CO)2] and ligands) with syngas in the presence of a solvent, followed by the addition of propylene to form butyraldehyde, as disclosed in US Patent No. 10,351,583, the relevant portions of which are incorporated herein by reference in their entirety. The ligands 1 to ( ) are used in undecane and dodecane solvents. tropos, trans The results of propylene hydroformylation of )-3 are shown in Table 1.

[0102] Table 1. Ligands 1 to ( tropos, trans The effect of )-3 on the selectivity of propylene hydroformylation using n-undecane and n-dodecane solvents. [a] From [Rh(acac)(CO)2] (5.12×10 -3 mmol) and ligand (6.40 × 10 -3 (L:Rh 1.25:1) or 10.24×10 -3The catalyst (mmol / L:Rh 2:1) was pre-formed by stirring for 1 hour at a syngas pressure of 20 bar and an activation temperature of 75 °C in the presence of a solvent (19.35 mL + 0.65 mL toluene). After 1 hour, a propylene / CO / H2 mixture with an initial pressure of 20 bar at a ratio of 1:4.5:4.5 was introduced and maintained for 1 hour. Rh concentration = 2.52 × 10⁻⁶ mmol / L (L:Rh 2:1) -4 mol dm -3 The product was determined by GC using 1-methylnaphthalene as an internal standard. [b] US ​​Patent No.: US 10,351,583 B2.

[0103] The results of propylene hydroformylation using ligands 4a to 4g in different solvents and under different reaction conditions are given in Table 2.

[0104] Table 2. Effect of ligands 4a to 4g on the selectivity of propylene hydroformylation. [a] From [Rh(acac)(CO)2] (5.12×10 -3 mmol) and ligand (10.24 × 10 -3 The catalyst was pre-formed by stirring in a solvent (19.35 mL + 0.65 mL toluene) at 20 bar CO / H2 at the activation temperature (1, 1 h; 4a and 4b 50 min; 4c, 4d and 4e 45 min; 4f and 4g, 20 min), followed by raising or lowering the temperature to the desired temperature, and then reacting at specified times with a propylene / CO / H2 ratio of 1:4.5:4.5 (20 bar initial pressure, unless otherwise specified). Rh concentration = 2.52 × 10 mmol (L:Rh 2:1) -4 mol dm -3 The product was determined by GC using 1-methylnaphthalene as an internal standard.

Claims

1. A method for preparing at least one aldehyde under hydroformylation temperature and pressure conditions, comprising contacting at least one olefin with hydrogen and carbon monoxide in the presence of at least one hydrocarbon solvent or fluorinated solvent and a transition metal-based catalyst composition, said transition metal-based catalyst composition comprising a phosphacyclopentane-phosphite ligand having general formula I: I， in: R1 and R2 are independently selected from H, or substituted and unsubstituted aryl, alkyl, aryloxy or cycloalkyl groups containing 1 to 40 carbon atoms; R3, R4, and R5 are independently selected from H, F, Cl, Br, or substituted and unsubstituted aryl, alkyl, alkoxy, trialkylsilyl, triarylsilyl, aryldialkylsilyl, diarylalkylsilyl, and cycloalkyl groups containing 1 to 20 carbon atoms, wherein the silicon atom of the alkylsilyl group is at the α-position of the substituent; and R6 and R7 are independently selected from H, F, Cl, Br, alkyl groups containing 1 to 10 carbon atoms, haloalkyl groups, or aryl groups containing 1 to 20 carbon atoms.

2. The method according to claim 1, wherein the phosphacyclopentane-phosphite ligand has general formula II: II, in: R3, R4, and R5 are independently selected from H, F, Cl, Br, or substituted and unsubstituted aryl, alkyl, alkoxy, trialkylsilyl, triarylsilyl, aryldialkylsilyl, diarylalkylsilyl, and cycloalkyl groups containing 1 to 20 carbon atoms, wherein the silicon atom of the alkylsilyl group is at the α-position of the substituent; and R6 and R7 are independently selected from H, F, Cl, Br, alkyl groups containing 1 to 10 carbon atoms, haloalkyl groups, or aryl groups containing 1 to 20 carbon atoms.

3. The method according to claim 2, wherein R3 is tert-butyl, and R4 and / or R5 is methyl.

4. The method according to claim 2, wherein R3 is tert-butyl and R4 is methoxy.

5. The method according to claim 1, wherein the phosphotene-phosphite ligand is selected from one or more of the following: 。 6. The method of claim 1, wherein the at least one hydrocarbon solvent is present, and the at least one hydrocarbon solvent comprises one or more of the following: n-nonane, n-decane, n-undecane, or n-dodecane.

7. The method of claim 1, wherein the at least one fluorinated solvent is present, and the at least one fluorinated solvent comprises one or more of the following: octafluorotoluene or perfluorophenyl octyl ether.

8. The method of claim 1, wherein the fluorinated solvent is present, and the fluorinated solvent comprises a solvent having 2 to 20 carbon atoms substituted with at least one fluorine atom.

9. The method of claim 1, wherein the product of the method has about 55% to about 90% isomer selectivity.

10. The method of claim 1, wherein the product of the method has 55% or higher heteroselectivity.

11. The method of claim 1, wherein the pressure is about 2 atm to about 80 atm.

12. The method of claim 1, wherein the temperature is about 40 to about 120 degrees Celsius.

13. The method of claim 1, wherein the olefin comprises propylene.

14. The method of claim 1, wherein the transition metal-based catalyst comprises a rhodium-based catalyst.

Images