Organocatalysis With Carbon-Nucleophiles And Phosphonium Salts

Organocatalysis is currently being vigorously pursued because of its attractive features such as the metal-free conditions,experimental simplicity and the ease to recover the organocatalysts.We have examined a number of nucleophilic organic compounds for their catalytic activities in the cyanation of carbonyl compounds and/or the Henry reaction,and found that silyl ketene acetals,phosphonium ylides, phosphonium salts and a dual-reagent system of a phosphine and electron-deficient alkene can all serve as useful organocatalysts.These studies demonstrate a new concept to the development of synthetically useful organocatalysis.Several readily available neutralÏ€-nucleophiles were first examined,and a silyl ketene acetal was found to be able to efficiently catalyze the cyanation of carbonyl compounds.The mild reaction condition,excellent functional group tolerance, excellent to quantitative yield and the simple protocol for product purification illustrate the practically attractive features of this catalysis.This is the first illustration of using neutralÏ€-nucleophiles as efficient organocatalysts for organic synthesis.In contrast to silyl ketene acetals,nucleophilic phosphonium ylides are ready to undergo the Wittig reaction with carbonyl compounds.However,the catalytic activity of stablized phosphonium ylides toward the cyanation reaction was observed to override their reactivity toward the Wittig reaction,and Ph₃P=CHCO₂Me was found to be able to efficiently catalyze the cyanosilylation of various aldehydes and ketones. This is the first illustration of using a phosphonium ylide to catalyze a synthetically important reaction.Furthermore,a phosphonium salt was identified to be an efficient catalyst for the cyanosilylation of ketones.The basic and nucleophilic zwitterions,generated by the Michael-type addition of phosphines to electron-deficient alkenes,were explored as conceptually new catalysts in the Henry reaction.Although neither triphenylphosphine nor methyl acrylate could catalyze the Henry reaction,they together could transform a wide range of aldehydes andα-keto esters into the correspondingβ-nitroalkanols in good to excellent yields.In addition,a catalytic cycle was proposed for this reaction according to the deuterium labeling experiments.This dual-reagent catalyst system was further successfully applied to the cyanosilylation of carbonyl compounds.Several chiral carbon-nucleophiles and phosphonium salts were synthesized and applied to the catalytic asymmetric cyanosilylation of carbonyl compounds and/or Henry reaction,and a chiral phosphonium ylide was found to catalyze the asymmetric cyanosilylation of ketones to give the corresponding chiral cyanohydrin silyl ethers with up to 50%ee.