Aliphatic and aromatic methyl ethers have been easily cleaved on treatment with a hard acid, aluminum halide, and a soft nucleophile, EtSH, to give parent alcohols and phenols, respectively. With compounds possessing both aliphatic ,and aromatic methyl ether groups, simultaneous demethylation of both types of ethers occurred. The ethereal crubon-oxygen bond in compounds possessing both ether and ester groups was selectively cleaved under mild conditions by using dichloromethane as a cosolvent. Acetoxyl and N-acetyl groups were shown to be stable to this reagent system, except for easy hydrolysis of aromatic acetoxyl groups under conditions of workup after the reaction.
The introduction of a thiol group into a chiral alcohol reagent for asymmetric Meerwein-Ponndorf-Verley (MPV) reductions allows asymmetric reduction of R,β-unsaturated ketones to secondary alcohols and allylic alcohols via a novel tandem Michael addition/MPV reduction. The reaction of acyclic R,β-unsaturated ketones 1 and an optically active 1,3-mercapto alcohol (-)-2 using dimethylaluminum chloride afforded the MPV reduction products 3 diastereoselectively in very high yields (up to 96%). Mechanistic studies elucidated (1) the structure of the chelation complex D with (-)-2 and Me 2 AlCl, (2) an asymmetric 1,7-hydride shift (intramolecular MPV reduction), and (3) dynamic kinetic resolution via reversible Michael addition. Subsequent reductive desulfurization of the MPV products 3 with a modified Raney nickel system led to the highly enantioselective reduction of R,β-unsaturated ketones to saturated secondary alcohols in 96-98% ee. β-Elimination of the corresponding sulfoxides gave the allylic alcohols in 86-98% ee. Applications to the asymmetric reduction of a synthetic intermediate 1m of prostaglandins and to a new asymmetric synthesis of the (+)-Rove beetle pheromone 11 are described.
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