title: Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study.
abstract: 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.
authors.affiliation: KTH Royal Institute of Technology, Department of Chemistry, Organic Chemistry, 10044, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Laurell Nash
authors.affiliation: KTH Royal Institute of Technology, Department of Chemistry, Organic Chemistry, 10044, Stockholm, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Hertzberg
authors.affiliation: KTH Royal Institute of Technology, Department of Chemistry, Organic Chemistry, 10044, Stockholm, Sweden.
authors.forename: Ye-Qian
authors.initials: YQ
authors.lastname: Wen
authors.affiliation: KTH Royal Institute of Technology, Department of Chemistry, Applied Physical Chemistry, 10044, Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlgren
authors.affiliation: KTH Royal Institute of Technology, Department of Chemistry, Applied Physical Chemistry, 10044, Stockholm, Sweden.
authors.forename: Tore
authors.identifier: http://orcid.org/0000-0003-2673-075X
authors.initials: T
authors.lastname: Brinck
authors.affiliation: KTH Royal Institute of Technology, Department of Chemistry, Organic Chemistry, 10044, Stockholm, Sweden.
authors.forename: Christina
authors.identifier: http://orcid.org/0000-0002-1743-7650
authors.initials: C
authors.lastname: Moberg
keywords: Lewis acids; Lewis bases; asymmetric catalysis; reaction mechanisms; titanium