Formal (3 + 4)-Annulation of Propargylic p-Quinone Methides with 2-Indolylmethanols: Synthesis of Polysubstituted Indole-Fused Oxepines

Abstract

A novel Brønsted acid catalyzed 1,8-addition mediated (3 + 4)-annulation of in situ generated propargylic p-quinone methides with 2-indolylmethanols is described. This method provides a convenient and mild approach to structurally interesting and synthetically important polysubstituted indole-fused oxepines in high yields. Moreover, 2-indolylmethanols as four-atom synthons in the (3 + 4)-annulations under Brønsted acid conditions have been explored for the first time.

Selective construction of spiro[indoline-3,5′-pyrrolo[3,4-b]azepines] and spiro[indoline-3,3′-pyrroles] via a [4 + 3]/[3 + 2] cycloaddition reaction of α,β-unsaturated aldimines and MBH adducts of isatins

“…11 However, the more challenging [4 + 3] cycloaddition with MBH adducts of isatins has been less developed, probably due to the lack of suitable electrophilic diene components. 12 In this respect, Chen and coworkers successfully developed several elegant [4 + 3] cycloaddition reactions for the efficient construction of various spiro[azepine-4,3′-indoline] derivatives. 13 For example, in 2015, Chen and co-workers reported the efficient construction of the spiro[azepine-4,3′-indoline] scaffold through a [4 + 3] cycloaddition reaction of bromosubstituted MBH adducts of isatins and N -( ortho -chloromethyl)aryl amides, in which both reactive intermediates of allylic phosphonium ylides and aza- o -quinone methides were in situ generated (eqn (1) in Scheme 1).…”

Dearomatization of 2,3-Disubstituted Indoles via 1,8-Addition of Propargylic (Aza)-para-Quinone Methides

“…However, the reaction of C3-functionalization of 2,3-disubstituted indoles with (aza)- p- QMs has not been achieved. Recently, propargylic p -QMs with additional alkynyl groups have been demonstrated to be a class of useful organic synthon because of the 1,6- and 1,8-addition sites. − The 1,8-addition and 1,8-addtion-mediated annulation of propargylic (aza)- p -QMs with different nucleophiles such as thiazolones, azlactones, 1,3-dicarbonyl compounds, and naphthols have been studied. − In 2019, Wang’s group reported the asymmetric catalytic tandem 1,8-addtion/Diels–Alder reaction of propargylic p -QMs involving the process of dearomatization of 2-naphthols. This is the only case of the application of propargylic p -QMs in dearomatization chemistry.…”

“…Accordingly, much effort has been devoted to exploring efficient methodologies for the construction of the allenic compounds . With the ongoing interest in (aza)- p -QM chemistry, , functionalization of indoles, and synthesis of tetrasubstituted allenes, we developed the dearomatization of 2,3-disubstituted indoles via 1,8-addition of propargylic p -QMs (Scheme b). As shown in Scheme , the main challenges of this protocol include: (1) the regioselectivities of 1,6-addtion , and 1,8-addtion of propargylic (aza)- p -QMs; (2) the regioselectivities of N1-, C3-, or C6-nucleophilicity of 2,3-disubstituted indoles (paths i–iii).…”

Bismuth(III)-Catalyzed 1,8-Addition/Cyclization/Rearrangement of Propargylic para-Quinone Methides with 2-Vinylphenol: Synthesis of Indeno[2,1-c]chromenes

“…In 2019, a 1,8-addition/Diels–Alder cascade reaction of propargylic p -QMs to access chiral polycyclic compounds was reported . Recently, propargylic p -QMs have been explored as a C3 synthon in (3+ n )-annulation reactions with dinucleophiles occurring at C6 and C8, which provide effective methods to produce synthetically important five- to seven-member cyclic compounds (Scheme a) . Despite this progress, exploration of innovative chemical transformations of propargylic p -QMs to synthesize high-value-added products remains in high demand.…”