Organocatalytic Asymmetric Michael Addition of Oxazolones to Arylsulfonyl Indoles: Facile Access to syn‐Configured α,β‐Disubstituted Tryptophan Derivatives

Abstract

Enantioselective Michael addition of oxazolones to in situ generated vinylogous imine intermediates is reported. A series of optically active 3-alkylindole derivatives with adjacent quaternary and tertiary stereocenters was obtained. The[a] Chemical Synthesis and Pollution 456 resulting adducts can readily be converted into syn-configured α,β-disubstituted tryptophan derivatives without compromising the stereoselectivities.

Arenesulfonyl indole: new precursor for diversification of C-3 functionalized indoles

“…The asymmetric Michael addition of oxazolones (49) to arenesulfonyl indoles 11 catalysed by cinchonine derived thiourea catalyst VI under mild conditions was reported by Jing and co-workers 39 in 2012 to yield syn selective C-3 alkyl substituted indole derivative (10 R ,11 S )-50 containing adjacent quaternary and tertiary stereocenters in 45–88% yields and high dr as well as ee up to 90 : 10 and 98% respectively ( Scheme 14 ). The synthetic utility of the protocol was studied by transforming the Michael adduct-50 to syn -selective α,β-disubstituted tryptophan derivative 51 in 88% yield by ring opening of the oxazolone subunit with sodium methoxide while increasing ee from 96% to 98%.…”

Recent applications of <em>Cinchona</em> alkaloid-based catalysts in asymmetric addition reactions

“…Later on, the catalyst 40b was used by Cai et al in the Michael-addition reaction of oxazolones to vinylogous imine intermediates generated in situ from arylsulfonyl indoles. 46…”

Asymmetric Synthesis of Quaternary α‐Amino Acids and Their Phosphonate Analogues

“…The Jing group have reported the enantioselective synthesis of C-3-alkylated indole derivatives 74 by the Michael addition of azlactones 28 to vinyl imine intermediates 75, which were generated in situ from arylsulfonyl indoles 73 with the elimination of tolylsulfinic acid (Scheme 19). [36] Cinchonine-thiourea C21 (20 mol %) in the presence of K 3 PO 4 catalyzed the reaction between 28 and 73, which afforded 74 in moderate to good yields and diastereoselectivities, and with good enantioselectivities. Alkaline methanolysis of 74 (R 1 = Me, Ar = p-Br-C 6 H 4 ) provided the tryptophan derivative 76 with contiguous quaternary and tertiary stereocenters in good yield, enantio-and diastereoselectivities.…”