Enantiomer‐Selective Carbamoylation of Racemic α‐Hydroxy γ‐Lactones with Chiral Cu^II Catalysts: An Example of a Highly Active Lewis Acid Catalyzed Reaction

Abstract

Enantiomer-selective carbamoylation of racemic alpha-hydroxy gamma-lactones with half equivalents of isocyanates in the presence of chiral Cu(II) catalysts was studied. Among a series of catalyst bearing chiral bis(oxazoline) (box) and pyridine(bisoxazoline) ligands, [Cu(tBu-box)]X(2) [X=OSO(2)CF(3) (3 a), SbF(6) (3 b)] showed the highest enantioselectivity in the reaction of pantolactone (1 a). Use of n-C(3)H(7)NCO, a small alkyl isocyanate, in CH(2)Cl(2) solution was important to achieve a high level of enantiomer selection. The tBu-box-Cu(II) catalyst efficiently differentiated two enantiomers of beta-substituted alpha-hydroxy gamma-lactones under the optimized reaction conditions, resulting in a stereoselectivity factor (s=k(fast)/k(slow)) of up to 209. Furthermore, this catalyst is highly active, so that the carbamoylation can be conducted with a substrate-to-catalyst molar ratio of 2000-3000. A catalytic cycle of this reaction is also proposed.

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

“…An efficient kinetic resolution of racemic α-hydroxy-γ-butyrolactones involving enantioselective carbamoylation with isocyanates in the presence of chiral Cu(II) bis(oxazoline) catalysts was first studied by the group of Ohkuma. 376 More recently, Shiina and co-workers reported the kinetic resolution of racemic 2-hydroxy-γ-butyrolactones through asymmetric esterification, providing an efficient method to access various optically enriched 2-hydroxy-γ-butyrolactone derivatives 238 and 239 ( Scheme 133 ). 377 Promoted by pivalic anhydride and C103 in the presence of diphenylacetic acid, this kinetic resolution smoothly proceeds to afford the corresponding esters and the recovered alcohols with excellent stereoinduction and high S -values up to 1000 ( Scheme 133 ).…”

“…An efficient kinetic resolution of racemic α-hydroxy-γ-butyrolactones involving enantioselective carbamoylation with isocyanates in the presence of chiral Cu­(II) bis­(oxazoline) catalysts was first studied by the group of Ohkuma . More recently, Shiina and co-workers reported the kinetic resolution of racemic 2-hydroxy-γ-butyrolactones through asymmetric esterification, providing an efficient method to access various optically enriched 2-hydroxy-γ-butyrolactone derivatives 238 and 239 (Scheme ).…”

Silylation-Based Kinetic Resolution of α-Hydroxy Lactones and Lactams

“…While a number of asymmetric synthetic methods , have been developed to produce these compounds, including enzymatic kinetic resolutions, until recently there has been very little work with nonenzymatic kinetic resolutions of these substrates. Currently, there are two examples of nonenzymatic kinetic resolutions of lactones which include a Cu-catalyzed carbamoylation and an isothiourea-catalyzed acylation . However, to the best of our knowledge, a successful nonenzymatic resolution of α-hydroxy lactams remains unreported.…”

Kinetic Resolution of Racemic 2-Hydroxy-γ-butyrolactones by Asymmetric Esterification Using Diphenylacetic Acid with Pivalic Anhydride and a Chiral Acyl-Transfer Catalyst

“…To the best of our knowledge, however, a general method for the kinetic resolution (KR) of racemic 2-hydroxy-γ-butyrolactones has not been reported until recently. A pioneering efficient KR of racemic 2-hydroxy-γ-butyrolactones was achieved by Ohkuma using the Matsumura protocol, which involves the asymmetric carbamoylation of racemic 2-hydroxy-γ-butyrolactones catalyzed by copper(II)–bis(oxazoline) . Previously, we demonstrated the first kinetic resolution of racemic alcohols with achiral carboxylic acids or racemic carboxylic acids with achiral alcohols by asymmetric esterification , via the in situ formation of a mixed anhydride using carboxylic anhydrides as coupling reagents in combination with chiral acyl-transfer catalysts.…”