Premium
Hydrogen Bonding‐Assisted Enhancement of the Reaction Rate and Selectivity in the Kinetic Resolution of d,l ‐1,2‐Diols with Chiral Nucleophilic Catalysts
Author(s) -
Fujii Kazuki,
Mitsudo Koichi,
Mandai Hiroki,
Suga Seiji
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201700057
Subject(s) - chemistry , kinetic resolution , selectivity , catalysis , nucleophile , substrate (aquarium) , hydrogen bond , diol , reaction rate , alcohol , medicinal chemistry , combinatorial chemistry , organic chemistry , enantioselective synthesis , molecule , oceanography , geology
An extremely efficient acylative kinetic resolution of d,l ‐1,2‐diols in the presence of only 0.5 mol% of binaphthyl‐based chiral N , N ‐4‐dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert ‐alcohol unit(s) of the catalyst and the 1,2‐diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2‐diols with high selectivity factors. The kinetic resolution of d,l ‐hydrobenzoin and trans ‐1,2‐cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 °C); (iii) high substrate concentration (1.0 M); and (iv) short reaction time (30 min).