Kinetic resolution of sec-alcohols by a new class of pyridine catalysts having a conformation switch system Shinji Yamada, * Tomoko Misono and Yuko Iwai Department of Chemistry, Ochanomizu University, Bunkyo-ku, Tokyo 112-8610, Japan Received 27 December 2004; revised 1 February 2005; accepted 3 February 2005 Abstract—The catalysts having a conformation switch system induced by acylation and deacylation serve as asymmetric acylating catalysts of sec-alcohols. The kinetic resolution of various sec-alcohols resulted in good to excellent selectivities in the presence of 0.5 to 0.05 mol % of catalyst 1a. The conformation switch system plays a key role to attain both good selectivity and high catalytic activity. Ó 2005 Elsevier Ltd. All rights reserved. Kinetic resolution is an effective method for obtaining chiral sec-alcohols. Various types of non-enzymatic acyl-transfer organocatalysts 1 such as chiral phos- phines, 2,3 diamines, 4 4-aminopyridine analogues, 5 pep- tide-based catalysts, 6,7 dihydroimidazopyridines, 8 and N-heterocyclic carbenes 9 have extensively been explored, and the catalytic acylations are achieved by them in high enantioselectivities. Nevertheless, further development of a new class of acylating catalysts has continued to be an important challenge in synthetic organic chemistry. We have recently found a new type of cation–p interac- tion 10 between a pyridinium ring and a thiocarbonyl group. 11 This interaction was utilized for the selective shielding of the pyridinium face by the thiocarbonyl group, which enabled nucleophiles to attack the oppo- site side to give chiral 1,4-dihydropyridines. 12 This result suggests a new conformation switch system based on the interconversion between uncomplexed form I and self- complexed form II induced by N-acylation and deacyla- tion steps as shown in Scheme 1. We planned to develop new asymmetric acylating catalysts having this confor- mation switch system because this system would play a key role to attain both high catalytic activity and selec- tivity in the kinetic resolution; the formation of cation–p complex II enables discrimination of enantiomeric sec- alcohols and the uncomplexed form I causes smooth N-acylation for the next catalytic cycle. This concept seems to be related to an induced-fit process proposed by Kawabata et al. 13 Recently, several groups have extensively developedpyri- dine catalysts for asymmetric acylation of alcohols. The key feature of the catalytic reactions is selective blocking of the pyridinium ring by an aromatic moiety such as pentaphenylcyclopentadienyl, 14 naphthyl, 13 binaph- thyl, 15 biaryl, 16 and substituted aryl 17 group; however, a non-aromatic system has not yet been reported. In this letter, we report a new class of pyridine catalysts having a conformation switch system, which serve as practical asymmetric acylating catalysts for sec-alcohols. We prepared 4-dimethylaminopyridine (DMAP) and 4- pyrrolidinopyridine (PPY) analogues 1–4 possessing chiral thiazolidine-2-thione, oxazolidine-2-thione or oxazolidine-2-one. These catalysts can be readily pre- pared from 4-aminonicotinic acid obtained from com- mercially available 4-chloropyridine with the chiral auxiliary. 18 Acylation of 1-(2-naphthyl)ethanol (8) with 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.02.019 Keywords: Kinetic resolution; Cation–p interaction; Asymmetric acyl- ation; Organocatalyst; Conformation switch system. * Corresponding author. Tel.: +81 3 5978 5349; fax: +81 3 5978 5715; e-mail: yamada@cc.ocha.ac.jp Scheme 1. Tetrahedron Letters 46 (2005) 2239–2242 Tetrahedron Letters