Abstract
Currently, conventional reductive catalytic methodologies do not guarantee general access to enantioenriched β-branched β-trifluoromethyl α-amino acid derivatives. Herein, a one-pot approach to these important α-amino acids, grounded on the reduction – ring opening of Erlenmeyer–Plöchl azlactones, is presented. The configurations of the two chirality centers of the products are established during each of the two catalytic steps, enabling a stereodivergent process.
Highlights
Introduction bBranched a-amino acids (AAs) carrying different b-substituents – bearing two vicinal chirality centres, at the a- and bcarbons – are important yet challenging synthetic targets.[1]
A noncomprehensive list of examples includes enantioselective conjugate additions and alkylations of glycinate imines,[2] palladium catalysed b-C(sp3)–H alkylation and arylation of AAs,[3] aziridine ring-opening,[4] an engineered tryptophan synthase,[5] multi-enzymatic b-methylation of AAs,[6] and catalytic asymmetric hydrogenation of a,b-dehydro-amino acids (DHAAs), in its implementation with tetra-substituted substrates.[7]
The b-tri uoromethyl Z-DHAAs required for the target was found to be reluctant to asymmetric hydrogenation,9a preventing application of Turner's formal stereodivergent reduction of DHAAs.[10]
Summary
Introduction bBranched a-amino acids (AAs) carrying different b-substituents – bearing two vicinal chirality centres, at the a- and bcarbons – are important yet challenging synthetic targets.[1]. Scheme 2 Optimization of the alcoholytic ring-opening step: selected results (d.r. values refer to anti/syn ratios).
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