Aldehyde enantioselective hydrazidation

Maruoka and co-workers reported the first catalytic asymmetric three-component 1,3-dipolar cycloaddition of terminal alkynes with acyclic azomethine imines generated in situ from the corresponding aldehydes and hydrazides, which was realized using CuOAc/Ph-pybox and axially chiral dicarboxylic acid cocatalysts (Scheme 27) [48]. This transformation has abroad tolerance with regard to the substrates, affording diverse chiral 3,4-disubstituted pyrazolines with high enantioselectivities. The role of the axially chiral dicarboxylic acid is to generate the protonated acyclic azomethine imine, which then reacts with chiral Cu-acetylide. 

List [86] and Jorgensen [87] have recently independently described a novel application of L-proline (107) for catalysis of enantioselective hydrazidation of aldehydes [88]. For example, when aldehyde 106 is allowed to react with di-tert-butyl azodicarboxylate (95) in the presence of 10 mol% 107, adduct 108 is isolated in > 90% yield and 93% ee (Scheme 10.18) [87]. The product hydra-zides can be transformed into protected amino acid derivatives through a sequence that involves oxidation of the aldehyde to the corresponding carboxylic acid, esterification, deprotection, and N-N bond cleavage with Raney-Ni [86, 87]. The observed selectivity has been attributed to the intervention of transition state 111 [86]. This structure incorporates a hydrogen bond between proline s carboxyl group and the azodicarboxylate as a key organizing feature. The transition state structure has parallels to that proposed for the proline-cata-lyzed aldol addition reactions and is supported by quantum mechanical studies by Houk [89]. 

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