Organocatalytic Cascade β-Functionalization/Aromatization of Pyrrolidines via Double Hydride Transfer

Abstract

An unprecedented cascade β-functionalization/aromatization reaction of N-arylpyrrolidines was established. A series of β-substituted arylpyrroles embedded with trifluoromethyl groups are provided directly from N-arylpyrrolidines. The deuteriumlabeling experiments indicate that sequential double hydride transfer processes serve as the key steps in this transformation.Letter pubs.acs.org/OrgLett

Access to Polycyclic Indole-3,4-Fused Nine-Membered Ring via Cascade 1,6-Hydride Transfer/Cyclization

“…This speculation was further verified by the formation of [D]- 3a ′. On the basis of the above investigation and our precedent works, − the following mechanism is proposed for the construction of indole-3,4-fused 3a (Scheme ). Initially, the condensation of secondary amine with aldehyde produced the iminium ion I , which induced the subsequent 1,3-HT between the two benzylic C–H bonds to furnish the isomerized iminium ion II .…”

“…As a continuous interest in one-step assembly of molecular complexity via HT strategy, − recently, we reported the construction of spiro-indoles and indole-1,2-fused seven-membered indolodiazepines through rational design of the indole-based cascade 1,5-HT/cyclization. On the basis of that, herein, we report a novel cascade aldimine condensation/1,6-HT/Mannich-type cyclization for one-step construction of indole-3,4-fused nine-membered rings.…”

Recent approaches in the organocatalytic synthesis of pyrroles

“…In 2020, Zhou and his co-workers demonstrated an unprecedented cascade b-functionalization/aromatization reaction of N-aryl pyrrolidines for the synthesis of diverse b-substituted aryl pyrroles embedded with triuoromethyl groups by using 20 mol% of 1,1&-binaphthyl-2,2-diyl hydrogen phosphate 19 as the Brønsted acid catalyst in 1,2-dichloroethane (DCE) as the solvent at 100 C. The reaction of N-aryl pyrrolidines 148 with ketoesters 149 provided the corresponding b-functionalized pyrroles 150 in 35-78% yields (Scheme 43). 59 This reaction proceeded through the intramolecular [1,5]-hydride transfer (HT) initiated cascade reaction sequence. It is pertinent to note that various halogens present on the aromatic rings and other aromatic rings, such as naphthalene, acenaphthene, biphenyl, furan, and thiophene, were well tolerated with this transformation.…”

“…The reaction of N -aryl pyrrolidines 148 with ketoesters 149 provided the corresponding β-functionalized pyrroles 150 in 35–78% yields ( Scheme 43 ). 59 This reaction proceeded through the intramolecular [1,5]-hydride transfer (HT) initiated cascade reaction sequence. It is pertinent to note that various halogens present on the aromatic rings and other aromatic rings, such as naphthalene, acenaphthene, biphenyl, furan, and thiophene, were well tolerated with this transformation.…”

Non-Directed β- or γ-C(sp3)–H Functionalization of Saturated Nitrogen-Containing Heterocycles

“…In 2020, Xiao reported the phosphoric acid catalyzed -C(sp 3 )-H functionalization of an N-substituted pyrrolidine (Scheme 9). 18 Starting from 23 and ester 24, this reaction yielded the -functionalized pyrrole 25 via an intramolecular double hydride transfer.…”