Simple and inexpensive threonine-based organocatalysts as highly active and recoverable catalysts for large-scale asymmetric direct stoichiometric aldol reactions on water

Nine O-acylated threonines were screened as catalysts at loadings of 0.5-5 mol % for the direct asymmetric stoichiometric aldol reaction on water by using variable amounts of water. These threonine-based organocatalyst were simple, inexpensive, highly active and could be synthesized on a large-scale. Among them, the threonine-based organocatalyst 1a is applicable to the stoichiometric reactions of a wide range of aromatic and heteroaromatic aldehydes with ketones, with the aldol products being obtained with up to 99:1 anti/syn ratios and >99% ee. The threonine-based organocatalyst 1a can be easily recovered and reused, and only a slight decrease in the enantioselectivities was observed after six cycles. This novel threonine-based organocatalyst 1a can be efficiently used in large-scale reactions with the enantioselectivities being maintained at the same level, which offers great possibility for application in industry. (C) 2012 Elsevier Ltd. All rights reserved.