I₂-DMSO-Mediated N–H/α-C(sp³)–H Difunctionalization of Tetrahydroisoquinoline: Formal [2 + 2 + 1] Annulation for the Construction of Pyrrolo[2,1-a]isoquinoline Derivatives

Abstract

An I 2 -DMSO-mediated cascade reaction using methyl ketones and 1,2,3,4-tetrahydroisoquinolines (THIQs) as commercially available substrates has been developed for the construction of pyrrolo[2,1-a]isoquinoline derivatives. This metalfree process involves N−H/α-C(sp 3 )−H difunctionalization of THIQ. Two C−C bonds and one C−N bond are formed in one pot under mild conditions. Besides, a quaternary carbon center has been constructed in this transformation efficiently.

Water as an oxygen source in I2-mediated construction of highly functionalized maleimide-fused phenols

“…According to the above studies and related literature precedents, 18 a plausible mechanism was proposed (Scheme 6). At first, self-condensation of acetophenone promoted by Lewis acid generated dypnone ( A ), which subsequently reacted with iodine to give iododypnone ( B ).…”

Review of application of the I2 and dimethyl sulfoxide combined reagent system to aryl methyl ketones for diverse transformations

“…To synthesize similar skeletons, in 2022, our group reported N-H/α-C(sp 3 )-H difunctionalization of tetrahydroisoquinolines (THIQ) under the mediation of the I 2 -DMSO combined reagent. 55 We synthesized pyrrolo[2,1-a]isoquinoline derivatives with a tertiary alcohol quaternary carbon center via Deuterated compounds have important application value in the pharmaceutical industry, organic synthesis, and material science. Recently, our group proposed the one-pot synthesis of fully substituted pyrroles starting from methyl ketones, anilines, ethyl benzoyl acetate, and CD 3 OD through multicomponent cascade cyclization under the mediation of the I 2 -DMSO combined reagent.…”

“…To synthesize similar skeletons, in 2022, our group reported N–H/α-C(sp 3 )–H difunctionalization of tetrahydroisoquinolines (THIQ) under the mediation of the I 2 –DMSO combined reagent. 55 We synthesized pyrrolo[2,1- a ]isoquinoline derivatives with a tertiary alcohol quaternary carbon center via formal [2 + 2 + 1] cyclization (Scheme 45A). Investigation of the possible mechanism showed that the ketoaldehyde is captured by the THIQ to generate imine ion 45-1 , which is then deprotonated to generate imine ylide intermediate 45-2 .…”