Enantioselectivity azodicarboxylate esters

Amide enolates mirror ester enolates in their amination reactions. Secondary amides can be used by employing two equivalents of the base, but yields in the only example found in the literature are low to fair.212 Ketene aminals react with azodicarboxylic esters at room temperature, but yields are low (Eq. 125).251 Eq. 126 shows the application of the copper-catalyzed enantioselective addition of mixed ketene acetal/aminals to azodicarboxylic esters previously described for silyl enol ethers in Eq. 94.252 Increasing bulk of the R substituent in the substrate causes partial or complete amination on the pyrrole, as evidenced by the yields of products 60 and 61 as R is varied. 

Nitrogen-containing reagents electrophilic at the N atom such as azodicarboxylate esters, tosyl and nosyl azides, and nitrosobenzene have been successfiilly applied to a variety of organocatalyzed enantioselective amination reactions of carbonyl compounds and other related pronucleophiles. Early work in this area has been covered in previous reviews [1 ], and here the most representative examples are presented. 

Aza-P-lactams may be prepared by the Staudinger reaction of a ketene with an azodicarboxylate ester under catalysis by a planar chiral nucleophile. Dimethyl azodicarboxylate and diethyl azodicarboxylate performed well in this reaction. Higher azodicarboxylate esters afforded lower yields and lower enantioselectivities, while an azodicarboxamide failed to undergo reaction. 

Scheme 6.80 Typical products obtained from the 64-catalyzed enantioselective addition of a-substituted (J-keto esters to di-tert-butyl azodicarboxylate (a-hydrazination).

Direct Asymmetric a-Amination Reaction of 2-Keto Esters. The cir-DiPh-Box copper complex catalyzes highly enantioselective direct a-amination reaction of 2-keto esters with dialkyl azodicarboxylates and thus provides convenient access to optically active jyn-3-amino-a-hydroxy esters (eq 2). This enantioselective, direct a-amination is applicable to a range of 2-keto esters when dibenzyl azodicarboxylate is used as the nitrogen source. The immediate product of the amination reaction is prone to racemization. Stereoselective reduction of the keto functionality by L-selectride enables further synthetic operations to be carried out without loss of enantiopurity. 

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