Catalyst-Controlled Divergent Reactions of 2,3-Disubstituted Indoles with Propargylic Alcohols: Synthesis of 3H-Benzo[b]azepines and Axially Chiral Tetrasubstituted Allenes

Abstract

Catalyst-controlled divergent reactions of 2,3-disubstituted indoles with propargylic alcohols were developed for the first time. In the presence of TsOH or B(C 6 F 5 ) 3 as catalyst, 2,3-disubstituted indoles reacted smoothly with 3-alkynyl-3hydroxyisoindolinones to afford 3H-benzo[b]azepines by selective C2(sp 2 )−C3(sp 2 ) ring expansion of indoles. In contrast, decreasing the catalyst strength (e.g., with chiral phosphoric acid) interrupted the cascade reactions, affording axially chiral tetrasubstituted allenes bearing an adjacent chiral quaternary carbon stereocenter. Control experiments provided insights into the reaction mechanism.

Design and Organocatalytic Asymmetric Synthesis of Indolyl-Pyrroloindoles Bearing Both Axial and Central Chirality

“…To solve these challenging issues, we considered isoindolinone-derived propargylic alcohols might be able to act as a class of suitable 1,3-dielectrophiles to undergo (2 + 3) cycloadditions with 3,3′-bisindoles under the catalysis of chiral phosphoric acid (CPA) (Scheme b). The selection of propargylic alcohols as 1,3-dielectrophiles is based on their high reactivity in catalytic asymmetric (3 + n ) cycloadditions as 1,3-dielectrophiles. , In our design, isoindolinone-derived propargylic alcohols can readily transform into alkynyliminium cation A via dehydration in the presence of CPA. So, 3,3′-bisindole and intermediate A can be simultaneously activated by CPA via hydrogen-bonding and ion-pairing interactions, thereby facilitating the enantioselective 1,4-addition to generate allene intermediate B , which can further transform into alkenyliminium cation C .…”

Recent Progress in Application of Propargylic Alcohols in Organic Syntheses

“…[25] Differ- ). [26] By replacing the acid catalyst with a weaker one containing chiral phosphoric acid moiety, functionalization on the C3 position of the indole ring occurred through access to axially chiral tetrasubstituted allenes. According to the mechanism, The dehydration of alcohol 1 and 1,4-addition was reversible.…”

“…found a new procedure for the synthesis of 3 H ‐benzo[ b ]azepines 36 by ring expansion of indole ring in 2,3‐disubstituted indoles 34 in the reaction with propargyl alcohol derivatives 1 in the presence of Brønsted/Lewis acid catalysts like p ‐toluenesulfonic acid ( p ‐TSA) and B(C 6 F 5 ) 3 (Scheme 18). [26] By replacing the acid catalyst with a weaker one containing chiral phosphoric acid moiety, functionalization on the C3 position of the indole ring occurred through access to axially chiral tetrasubstituted allenes. According to the mechanism, The dehydration of alcohol 1 and 1,4‐addition was reversible.…”

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.…”