Decarbonylative Radical Coupling of α‐Aminoacyl Tellurides: Single‐Step Preparation of γ‐Amino and α,β‐Diamino Acids and Rapid Synthesis of Gabapentin and Manzacidin A

Abstract

A new radical-based coupling method has been developed for the single-step generation of various g-amino acids and a,b-diamino acids from a-aminoacyl tellurides. Upon activation by Et 3 B and O 2 at ambient temperature, a-aminoacyl tellurides were readily converted into a-amino carbon radicals through facile decarbonylation, which then reacted intermolecularly with acrylates or glyoxylic oxime ethers. This mild and powerful method was effectively incorporated into expeditious synthetic routes to the pharmaceutical agent gabapentin and the natural product (À)-manzacidin A.

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

“…Asymmetric synthesis of an α-AA derivative 63 by conjugate addition of radical to a chiral glyoxylic oxime ether 57 (Inoue, 2015). [149] Scheme 32. Asymmetric synthesis of the β-AA derivatives 65 by conjugate addition of carbon radicals to a chiral glyoxylic oxime ether 64 and the isolation of α,β-substituted β-AA derivative 66 .…”

“…[148] In 2015 Nagatomo et al found a practical application of the radical approach for the asymmetric synthesis of an α,β-diamino acid derivative 63 (Scheme 31). [149] The triethyl borane/O 2 mediated [137] decarbonylative radical coupling of α-aminoacyl telluride with an Oppolzer's camphor sultam derivative of glyoxylic oxime ether 57 at ambient temperature afforded the desired α,β-diamino acid derivative 63 in a 94% yield, albeit the dr was low (3.3:1) (Scheme 31). It was assumed that an α-aminoacyl telluride was readily converted into α-amino carbon radical through facile decarbonylation, which then reacted intermolecularly with a glyoxylic oxime ether 57 (Scheme 31).…”

“…It was assumed that an α-aminoacyl telluride was readily converted into α-amino carbon radical through facile decarbonylation, which then reacted intermolecularly with a glyoxylic oxime ether 57 (Scheme 31). [149] Scheme 50. Asymmetric synthesis of an γ-AA derivative 114 by the decomposition of a chiral Barton ester 112 under light irradiation and conjugate addition of radicals generated to an α,β-unsaturated ester 101 b (Pereira, 2007).…”

“…Asymmetric synthesis of an α-AA derivative 117 by conjugate addition of radical generated from a chiral 115 to an achiral α,β-unsaturated ester 116 (Inoue, 2015). [149] The interesting method for the diastereoselective synthesis of the non-proteinogenic β-AA derivatives 65 via the sequential conjugate radical addition/intramolecular cyclization/reduction processes were reported. [150] Using an aldoxime ether substrate 64 which was readily prepared from D-mannitol, the desired γ-butyrolactones 65 were isolated in moderate yields (64-70%) with good selectivities (12:1 dr) (Scheme 32).…”

“…[175] In 2015 Nagatomo et al employed a chiral telluride 115 for the diastereoselective synthesis of an unusual γ-quaternary α-AA derivative 117 (Scheme 51). [149] The triethyl borane/oxygen-initiated radical addition of 115 to an α-N-phthaloyl acrylate 116 provided the α-AA derivative 117 in an 83% yield, albeit no stereocontrol was observed (1:1 dr). Importantly, the obtained product 117 was used for the further synthesis of a purely natural product (À )-manzacidin A.…”