Organocatalytic Enantioselective Construction of Axially Chiral Tetrasubstituted Allenes via 1,6‐Addition of Alkynyl Indole Imine Methides with 2‐Substituted Indoles

Abstract

An organocatalytic construction of axially chiral tetrasubstituted allenes featuring indole skeletons has been established. With the aid of chiral phosphoric acid, alkynyl indole imine methides were formed in situ from α-(3-indolyl)propargylic alcohols, followed by the asymmetric 1,6-conjugate addition with 2-substituted indoles, furnishing axially chiral indole-containing tetrasubstituted allenes in generally high yields and enantioselectivities.

Organocatalytic Asymmetric 3‐Allenylation of Indoles via Remote Stereocontrolled 1,10‐Additions of Alkynyl Indole Imine Methides

“…Very recently, we achieved an organocatalytic 1,10‐conjugate addition of alkynyl indole imine methides formed in situ from α‐(6‐indolyl) propargylic alcohols with thiazolones, affording axially chiral tetrasubstituted allenes featuring sulfur‐containing quaternary carbon stereocenters [11] . To continue our ongoing interest in the field of organocatalytic asymmetric reactions of propargylic alcohols, [7b–c,8d−e,12] here we disclosed a chiral phosphoric acid (CPA) catalyzed reactions between α‐(6‐indolyl)propargylic alcohols and 2‐arylindoles (Scheme 1C). In the presence of CPA, α‐(6‐indolyl)propargylic alcohols dehydrated to form alkynyl indole imine methide intermediates, followed by stereoselective 1,10‐conjugate addition of 2‐arylindole, affording axially chiral tetrasubstituted allenes bearing two indole motifs.…”

Recent Advances in Organocatalytic Enantioselective Synthesis of Axially Chiral Allenes

“…Pleasingly, 2-substituted indoles 82 were found to be suitable to react with alkynyl indole imine methides generated in situ from α-(3indolyl) propargylic alcohols 81 in the presence of C28, furnishing axially chiral indole-containing tetrasubstituted allenoates 83 in generally high yields and enantioselectivities (Scheme 23). [35] It should be noted that the substituent R 3 affected the reaction obviously, which was limited to aryl groups. For example, the reaction of 2-t-Bu-indole afforded the allenoate in 96% yield with 49% ee.…”

Organocatalytic enantioselective reaction of tertiary α-(7-indolyl)methanols with tryptamines

“…9 Notably, functionalized propargylic alcohols have been successfully applied to in situ formation of conjugate systems under acidic conditions, followed by asymmetric organocatalytic additions for the enantioselective construction of axially chiral tetrasubstituted allenes and related products. 6 d , e ,10–13 As a part of our continued interest in the field of organocatalytic asymmetric reactions of functionalized propargylic alcohols, 6 d , e ,10 a ,12 b , c ,13 a , c here we report a CPA-catalyzed enantioselective reaction of alkynyl 7-methylene-7 H -indoles generated in situ from α-(7-indolyl)propargylic alcohols with tryptamines for the asymmetric construction of axially chiral tetrasubstituted allenes bearing indole and hexahydropyrrolo[2,3- b ]indole units (Scheme 1BIV). Importantly, this protocol not only enriches the chemistry of α-(7-indolyl)methanols but also provides an efficient means for the preparation of structurally diverse axially chiral tetrasubstituted allenes.…”