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. 2014 Nov 19;136(46):16148-51.
doi: 10.1021/ja510135t. Epub 2014 Nov 7.

Synthesis of α-amino acid derivatives and peptides via enantioselective addition of masked acyl cyanides to imines

Kin S Yang  1 , Viresh H Rawal
Affiliations

Synthesis of α-amino acid derivatives and peptides via enantioselective addition of masked acyl cyanides to imines

Kin S Yang et al. J Am Chem Soc. .

Abstract

A general, asymmetric synthesis of amino acid derivatives is reported. Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective additions to N-Boc-aldimines. The reactions are catalyzed by a modified cinchona alkaloid, which can function as a bifunctional, hydrogen bonding catalyst, and afford adducts in excellent yields (90-98%) and high enantioselectivities (up to 97.5:2.5 er). Unmasking the addition products gives acyl cyanide intermediates that are intercepted by a variety of nucleophiles to afford α-amino acid derivatives. Notably, the methodology provides an alternative method for peptide bond formation.

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Figures

Scheme 1
Scheme 1. Synthesis of α-Amino Acid Derivatives via Addition of Masked Acyl Cyanides (MAC)
Scheme 2
Scheme 2. Unmasking of MAC adducts
Scheme 3
Scheme 3. Unmasking of MAC Adducts to Dipeptides
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