Highly Efficient Route for Enantioselective Preparation of Chlorohydrins via Dynamic Kinetic Resolution

Abstract

Dynamic kinetic resolution (DKR) of various aromatic chlorohydrins with the use of Pseudomonas cepacia lipase (PS-C "Amano" II) and ruthenium catalyst 1 afforded chlorohydrin acetates in high yields and high enantiomeric excesses. These optically pure chlorohydrin acetates are useful synthetic intermediates and can be transformed to a range of important chiral compounds.

Tuning of the Electronic Properties of a Cyclopentadienylruthenium Catalyst to Match Racemization of Electron‐Rich and Electron‐Deficient Alcohols

“…[18] The rate-determining step for the racemization of electron-deficient alcohols by 4 is thought to be the b-hydride elimination (dehydrogenation) step, since these substrates are less prone to undergo oxidation to the corresponding ketone. The theory of a rate-determining b-hydride elimination for electron-deficient alcohols is supported by previous results from our group, [19] in which elevated temperatures and extended reaction times were required for the racemization of these substrates, when employing catalyst 4. An electron-deficient catalyst would speed up the rate of the b-hydride elimination from the alkoxide intermediate of these electron-deficient alcohols, and result in a more efficient overall racemization.…”

“…The corresponding chloromethyl aryl ketone of substrate 14 was obtained from the chlorination reaction of the methyl aryl ketone (Sigma) with Nchlorosuccinimide (NCS). [21] Subsequent reduction by NaBH 4 and kinetic resolution employing PS-C lipase (Amano), [19] afforded the substrate 14 in excellent ee. Substrate 15 was prepared from (S)-oxiranylanisole (Sigma), in a nucleophilic epoxide-opening reaction, using Li 2 CuCl 4 .…”

Tandem Reactions Combining Biocatalysts and Chemical Catalysts for Asymmetric Synthesis

“…Monomeric ruthenium pentamethylcyclopentadiene complex 1 developed by Bäckvall and co-workers [17] has been widely used in tandem with different enzymes to deracemize a wide range of functionalized secondary alcohols, including aliphatic alcohols [18,19], allylic alcohols [20][21][22], chlorohydins [23], diols [24,25], homoallylic alcohols [26], and N-heterocyclic 1,2-aminos alcohols [27] with excellent yields and enantiomeric excess (ee). Recently, complex 1 has been employed to synthesize biologically active 5,6-dihydropyran-2-ones and the corresponding δ-lactones [26].…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…Kim et al, 2013;S. Kim et al, 2013;Ko et al, 2007;Koh et al, 1999;Krumlinde et al, 2009;Larsson et al, 1997;Lee et al, 2000;Leijondahl et al, 2009;Lihammar et al, 2011;Mangas-Sánchez et al, 2009;Martín-Matute et al, 2004, 2006Mavrynsky et al, 2009Mavrynsky et al, , 2013Merabet-Khelassi et al, 2011;Norinder et al, 2007;Päiviö et al, 2011;Riermeier et al, 2005;Träff et al, 2008Träff et al, , 2011Warner et al, 2012). These catalysts are homogeneous under the conditions employed in DKR reactions and present differences regarding scope, mode of activation, requirement of additives, compatibility with acyl donors, stability, efficiency and cost.…”