Pd-Catalyzed Asymmetric Hydrogenation of α-Fluorinated Iminoesters in Fluorinated Alcohol:  A New and Catalytic Enantioselective Synthesis of Fluoro α-Amino Acid Derivatives

Abstract

[figure: see text] Under hydrogen pressure, a catalytic amount of palladium(II) trifluoroacetate and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) promoted asymmetric hydrogenation of alpha-fluorinated iminoesters to afford highly enantioenriched beta-fluorinated alpha-amino esters. The yield and ee were much improved by employing fluorinated alcohols such as 2,2,2-trifluoroethanol (up to 91% ee).

Enolate-Based Strategies to Construct <i>gem</i>-Difluoromethylene Compounds

“…When 24 was subjected to reduction with hydrogen under pressure in the presence of a small amount of Pd(OCOCF 3 ) 2 and (R) BINAP in 2,2,2 tri uoroethanol (TFE), 31 catalytic asymmetric hydrogenation of 24 proceeded smoothly at room temperature to yield aminoester (R) 25 in 88% ee. Upon treatment with allyltributyltin and a catalytic amount of AIBN as a radical initiator, (R) 25 underwent radical allylation to afford C allylated aminoester (R) 26.…”

Homogeneous palladium-catalyzed asymmetric hydrogenation

“…16 A dramatic solvent effect was observed in the asymmetric hydrogenation of a-fluorinated iminoesters. Ordinary solvents (toluene, AcOH, Scheme 1 Asymmetric hydrogenation of fluorinated iminoesters.…”

“…However, the homogeneous palladium-catalyzed asymmetric hydrogenation has been in silence as a ''sleeping beauty'' for a long time until 2001. 1, 16 Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts. In addition, palladium is cheaper than rhodium and iridium, so from an industrial perspective this is also highly useful.…”

New Approaches to Stereoselective Synthesis of Fluorinated Amino Acids.

“…We have reported the first successful, conceptually new example of asymmetric hydrogenation of fluorinated iminoesters 28 catalyzed by Pd(OCOCF3)2-BINAP complex to afford enantiomerically enriched fluorinated amino acid derivatives 31, which involves a dramatic improvement in both product yield and enantioselectivity by the use of fluorinated alcohol solvents. 32 In ordinary (non-fluorinated) solvents, when a-iminoester 28a was subjected to hydrogenation in the presence of a small amount of a chiral palladium complex, a-aminoester 31a formed in low to moderate ee. Surprisingly, in 2,2,2-trifluoroethanol (TFE), both the yield and ee of 31a were dramatically improved (Table 1).…”