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Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study
Author(s) -
Laurell Nash Anna,
Hertzberg Robin,
Wen YeQian,
Dahlgren Björn,
Brinck Tore,
Moberg Christina
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201503782
Subject(s) - lewis acids and bases , chemistry , cyanide , cyanohydrin , acylation , catalysis , aldehyde , catalytic cycle , lewis acid catalysis , trimethylsilyl cyanide , organic chemistry , polymer chemistry , medicinal chemistry
A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low‐temperature NMR spectroscopy studies, of the Lewis acid–Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O‐Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate‐determining step, whereas, for more reactive, electron‐deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate‐limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product.