Palladium‐Catalyzed Enantioselective Allylic Phosphination

Abstract

Chiral phosphines are pre-eminent ligands in asymmetric catalysis and are utilized in applications ranging from laboratory syntheses to industrial processes.[1] Despite their wide-spread use in enantioselective catalysis, there are surprisingly few syntheses of chiral phosphines by enantioselective methods. Thus, it is of interest to develop such reactions because catalytic asymmetric transformations in which the P À C bond and stereogenic centers are simultaneously formed might allow access to new chiral motifs, give more efficient syntheses of valuable chiral ligands, and stimulate the development of new enantioselective processes.Recently, a few strategies for catalytic PÀC bond formations have emerged that give enantiomerically enriched phosphines.[2] It is noteworthy that these systems frequently find close parallels in N À C bond formations. For example, organolanthanide compounds catalyze both intramolecular hydroaminations and hydrophosphinations, apparently through analogous mechanisms.[3] Also, our group has described a nickel(II) catalyst which is active for asymmetric hydroamination and hydrophosphination of vinyl nitriles. [4] Finally, of particular relevance are palladium-catalyzed aryl-X/E-H (E = N, P) coupling reactions, which have shown tremendous synthetic utility.[5] Thus, new catalytic asymmetric phosphine synthesis might be guided by examples from the corresponding amine chemistry. In this context, it is of interest to note that although asymmetric allylic amination is a prominent method for the preparation of chiral amines, [6] there are no reports of asymmetric allylic phosphination (Scheme 1). Additionally, a pendant allylic group would offer the possibility of further functionalizations, and allylic alkylations and aminations have been shown to be useful in synthesis. [7] There are, however, several examples of non-enantioselective catalytic syntheses of allylic phosphonates, which all involve Pd 0 -or Ni 0 -catalyzed coupling of phosphonates and allylic substrates.[8] Furthermore, Moreno Maaeas and coworkers have synthesized allylic phosphonium salts by the reaction of allylic pyridinium salts and triphenylphosphine in the presence of [Pd(PPh 3 ) 4 ].[9] Most notably, this complex was shown 25 years ago by Fiaud to catalyze the reaction of lithium diphenylphosphide with aliphatic allylic acetate derivatives to afford the corresponding substitution products.[10] However, to our knowledge these transition-metalcatalyzed reactions do not appear to have ever been attempted in the presence of chiral ligands. Finally, the advent of organocatalytic processes in recent years has led to the development of an enantioselective 1,4-addition of secondary phosphines to a,b-unsaturated aldehydes, giving products in up to 98 % ee.[11]Based on previous work in the area of asymmetric allylic substitutions [12] and on our hydroamination/hydrophosphination chemistry, [4] we began to pursue asymmetric allylic phosphination. We initially examined reactions of 1,3-diphenylallyl ethyl carbonate (1 a; Sche...

Secondary Phosphine Sulfide‐Enabled Iridium‐Catalyzed Asymmetric Allylic Substitution

“…In asymmetric catalytic reactions, diarylphosphines and secondary phosphine oxides are commonly used as reactants [2a,b] . For asymmetric allylic substitution reactions, these two types of phosphine nucleophiles have been used in reactions with allylic alcohol derivates to construct symmetric or linear chiral phosphorus compounds, and the strongly coordinated chiral bisphosphine ligands Josiphos [9a] and BDPP [9c] have been used to avoid deactivating metal catalysts. However, when synthesizing chiral phosphorus‐containing branched allylic substitution products in AAS reactions, it is challenging to simultaneously control the stereoselectivity and regioselectivity of the reaction.…”

Pd‐Catalyzed Reaction of Allyl Carbonate with Polyols: The Role of CO2 in Transesterification versus Etherification of Glycerol

“…General procedure: In a 25 mL Schlenk tube, a mixture of diallyl carbonate (2, 0.145 mL, 1.00 mmol), glycerol (1 g, 92.1 mg, 1.0 mmol) and 5 mL of degassed THF were stirred under atmosphere of N 2 (g) at room temperature for 5 min. After addition of triphenylphosphine (10.49 mg, 40.0 mmol) and [Pd 2 A C H T U N G T R E N N U N G (dba) 3 ·dba] (11.50 mg, 10.0 mmol), the reaction mixture was stirred at 25 8C. The reaction was sampled by withdrawing 0.1 mL aliquots and quenching into a GC vial containing 3.0 mg of 1,3bis(diphenylphosphino)propane (DPPP).…”

“…After the contents of the Schlenk tube had been frozen in N 2 (l) and kept in vacuo for 5 s, 13 CO 2 was transferred directly from a glass flask containing 250 mL (11.2 mmol) of gas at 1 bar of pressure. Then, triphenylphosphine (10.49 mg, 40.0 mmol) and [Pd 2 A C H T U N G T R E N N U N G (dba) 3 ·dba] (11.50 mg, 10.0 mmol) were added and the reaction mixture warmed rapidly to 25 8C and stirred magnetically. The reaction was sampled by withdrawing 0.1 mL aliquots, quenching these with 3.0 mg of 1,3-bis(diphenylphosphino)propane (DPPP), and then removing the solvent in vacuo.…”

“…General procedure for the synthesis of cyclic carbonates 4 g, 4 h and 4 i: In a 25 mL Schlenk tube, a mixture of diallyl carbonate (2) (0.14-0.43 mL, 1.0-3.0 mmol), alcohol (1 g-i, 1.00 mmol) and 2-5 mL of degassed DMSO or DMF or THF were stirred under an atmosphere of N 2 (g) at room temperature for 5 min. After addition of triphenylphosphine (40.0-160.0 mmol) and [Pd 2 A C H T U N G T R E N N U N G (dba) 3 Reaction with meso-erythritol (1 i): a mixture of diallyl carbonate (2, 0.22 mL, 1.50 mmol), meso-erythritol (1 i, 123.3 mg, 1.0 mmol), triphenylphosphine (20.98 mg, 80.0 mmol), [Pd 2 A C H T U N G T R E N N U N G (dba) 3 ·dba] (23.00 mg, 20.0 mmol) and degassed DMF (2 mL) was stirred at 25 8C for 24 h. The reaction mixture was then analysed by 1 H NMR spectroscopy (82 % rac-4 i, 5% meso-4 i). Purification by flash chromatography (dichloromethane/ethanol/triethylamine 100:2:2, R f < 0.1) on silica gel to give rac-4 i as a colorless oil.…”

“…Allyl carbonates are widely employed in Tsuji–Trost allylation, efficiently generating carbanion,1 boronate,2 phosphide,3 amide,4 and alkoxide5 nucleophiles in situ, and providing about 10 2 ‐rate enhancements over allyl acetate 6. 7 Allyl carbonates are also of considerable current interest for intramolecular decarboxylative asymmetric couplings 8.…”