Stereoselective reductive amination

The enantiospecific synthesis of natural and unnatural a-amino acids has been reviewed. Some of the most successful approaches involve the stereoselective hydrogenation of chiral dehydroamino acid derivatives. Many of these transformations are equivalent to the stereoselective reductive amination of a-keto acids (eq 2). For example, catalytic reduction of the imines of a-keto acids with chiral a-methylbenzylamine gives a-substituted a-amino acids with 12-80% ee (eq 3). ... 

Stereoselective Reductive Amination with Chiral Ketones... 

Table 7.2 Raney Ni substrate classes and optimal acid catalysts for stereoselective reductive amination with phenylethylamine (Scheme 7.10 Step 1).

The tert-Butylsulfinamide Auxiliary and Stereoselective Reductive Amination... 

Mono- and bimetallic Rh catalysts were evaluated for the stereoselective reductive amination of alkylphenols to the corresponding alkylcyclohexylaniines. Rhodium catalysts as well as bimetallic catalyst formulations with platinum were found to be the most suitable for this one-step hydrogenation. Both the chemo- and the stereoselectivity of that reaction depend on the amoimt of base added and other parameters such as kind of solvent and/or support. 

The synthesis of optically pure L-phenylglycine via the deracemization of mandelic acid was reported via three steps (racemization, enantioselective oxidation and stereoselective reductive amination). Racemization by mandelate racemase combined with simultaneous oxidation and reduction reactions with cofactor recycling gave the amino acid in 97% ee and 94% yield (Scheme 4.43) [96]. 

Scheme 8.94). Reduction of the alkene 8.339 and removal of the two protecting groups enabled stereoselective reductive amination to give the alkaloid 8.340. 

Figure 13.37 Stereoselective reductive amination of methyl isobutyl ketone to (R)-4-methyl-2-butylamine by engineered LeuDH (AmDH).

Another example, from the Pfizer portfolio, of successful incorporation of biocatalysis to make functional group interconversions (FGIs) more efficient in API synthesis is in a program for a smoothened (SMO) receptor inhibitor [17], Introduction of a transaminase-catalyzed stereoselective reductive amination of a 4-piperidone 4 with concurrent dynamic kinetic resolution (DKR) gave amine 5 (Scheme 7.2), resulting in the highly efficient incorporation of two chiral centers in a single step. 

Stereoselective Reductive Amination Using Chiral Amines as Auxiliary In 2004, Alexakis and coworkers reported on the diastereoselective synthesis of... 

C2-symmetrical secondary amines by applying the stereoselective reductive amination protocol using chiral amines as the source of chirality. In 2005, Nugent et al. published a novel method for the asymmetric reductive amination of prochiral aliphatic ketones116 where the (/ )- or (5)-a-methylbenzylamine (MBA) were employed as the cheap chiral ammonia equivalent. Ti(0 Pr)4/Raney Ni/H2 were employed as the catalyst system for the one-pot conversion of the prochiral ketones 116a-e to the corresponding chiral amines 117a-e with excellent dia-stereoselectivity (Scheme 39.33). 

Stereoselective Reductive Amination Using Chiral Ketones as Auxiliary The first report of asymmetric reductive amination using chiral ketone was published by Nugent and co-workers in 2004. The current methodology includes dynamic kinetic resolution of a racemic ketone 128 producing a chiral ketone 129,... 

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