Imino esters, enantioselective hydrogenation

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

Soon after these initial reports, the groups of Antilla [92] and You [93] indepen dently applied the chiral phosphoric acid catalysis to the enantioselective hydro genation of a imino esters. The method provides an alternative route to the enantioselective synthesis of a amino esters. Antilla and coworkers employed a new type of axially chiral phosphoric acid (9) derived from VAPOL originally developed by his research group (Scheme 3.42), whereas lg was used in You s case. In both cases, excellent enantioselectivities were achieved. You and coworkers further applied the method to the enantioselective reduction of a imino esters having an alkynyl substituent at the a position (Scheme 3.43) [94]. Both alkyne and imine moieties were reduced under transfer hydrogenation conditions with an excess amount of... 

Antilla and coworkers also developed asymmetric transfer hydrogenation reaction by means of 50, derived from VAPOL (Scheme 11.13) [24]. They realized the highly enantioselective transfer hydrogenation of acyclic a-imino ester 51 by the combination of 39 and 50 to furnish synthetically useful a-amino acid derivatives 52 in excellent enantioselectivities (94—99% ee). They also achieved reductive ami-nation of alkyl-substituted kettmines (R = alkyl) in the presence of dehydrating agent (4A MS). 

Palladium-catalyzed carboalkoxylation of imidoyl iodides 6 provides benzyl [9] and even te/t-butyl[10] esters 7. Asymmetric hydrogenation of the imino moiety of imono esters 7 in a Pd(OCOCF3)2 / (7 )-BINAP / CF3CH2OH system gives enantio-enriched amino esters 8 in 85-91% ee (see Scheme 9.2) [11].The enantioselectivity achieved by the hydrogenation was much better than that by Corey s hydride reduction [12] and was employed for the syntheses of enantiomerically pure A-Boc-(3,(3-difluoroproline benzyl ester 9 (see Scheme 9.3)[13] and enantiomerically enriched A-Boc-P -difluoroglutamic acid benzyl ester [13]. 

The chiral phosphoric acid (218)-catalysed enantioselective transfer hydrogenation of unprotected disubstituted 2-(imino (phenyl) methyl) phenol using a Hantzsch ester (2, R = BuO as the hydrogen source gave the corresponding chiral Af,0-unprotected amines in high yields with excellent ee. The presence of the ortho-OW group enabled conversion to medicinally relevant compounds. ... 

---