Esters conjugate reductions, sodium borohydride

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

Toward that end, the Stetter product (21) from our earlier campaign was selectively reduced to aldehyde 34 (Scheme 8) and subjected to a HWE homologation reaction to provide conjugated ester 35. Following reduction of the benzylic ketone with sodium borohydride, we were ready to test the... 

Thiol esters are reduced to primary alcohols by sodium borohydride in ethanol without significant transesterification.These conditions do not affect oxygen esters whereas sodium borohydride used either in polyethylene glycols such as PEG-400 at 65 or in DMSO containing methanesulphonic acid, has been shown to reduce esters to primary alcohols the borohydride-acidic DMSO system also reduces carboxylic acids, other than conjugated aromatic acids, to alcohols. An improved procedure for rapid reduction of esters to alcohols with borane-dimethylsulphide involves using THF as solvent at reflux, with an aqueous alkaline work-up. 

Cyclopropanecarboxylic esters have been prepared, in 75—86 % yield, by intramolecular alkylation of 4-chloroalkyl esters, using phase-transfer catalysis. Monoalkylation of nitro-alkenes by acrylic esters occurs in a controlled manner if a two-phase system is used, to give products of Michael addition in 45—65 % yield for five examples. An interesting variant on this reaction involves the generation of the a-nitro-carbanion by conjugate reduction of a nitroalkene with sodium borohydride followed by its conjugate addition to methyl acrylate yields of 62—95% are reported for five cases (Scheme 39). ... 

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