Iridium-Catalyzed Enantioselective Direct α-C–H Alkylation of Saturated Cyclic Amines with Alkenes

Abstract

Enantioselective direct α-C­(sp3)–H alkylation of saturated cyclic amines having N-methylbenzimidazolyl as a directing group was realized by using a cationic iridium/chiral diphosphine catalyst. The alkylation of pyrrolidine derivatives with various terminal alkenes proceeded to give α-alkylated products in high yields with high enantioselectivities. Chiral α,α′-dialkylated pyrrolidine derivatives were also synthesized by using an excess of alkenes or by stepwise alkylation.

Iridium‐Catalyzed Branch‐Selective and Enantioselective C2‐Alkylation of N‐Benzimidazolyl Indoles

“…Recently, we reported iridium‐catalyzed enantioselective α‐C( sp 3 )−H alkylation of saturated cyclic amines with terminal alkenes (Scheme 2a) [11] . When attempting the α−C−H alkylation of an indoline derivative, the formation of an alkylated indole was observed instead of the desired indoline derivative.…”

“…[8b,c] Recently, we reported iridium-catalyzed enantioselective α-C(sp 3 )À H alkylation of saturated cyclic amines with terminal alkenes (Scheme 2a). [11] When attempting the αÀ CÀ H alkylation of an indoline derivative, the formation of an alkylated indole was observed instead of the desired indoline derivative. Under the catalytic conditions, indoline underwent dehydrogenation to give the corresponding indole, and subsequent C2-alkylation led to the formation of the alkylated indole product (Scheme 2b).…”

Arylethanolamines in Ritter reaction: Synthesis of 2,4‐Diarylimidazole Core

“…Imidazoles and imidazolines represent an azaheterocyclic core which is widespread in nature, [1][2][3] medicine and pharmaceutical chemistry. [4][5][6][7][8][9][10] These heterocycles were also applied as ligands [11,12] and directing groups [13] in synthetic organic chemistry. A significant number of articles concerns the synthesis of 2,4-diaryl substituted imidazolines [14] and imidazoles.…”

Iridium-Catalyzed Tandem Dehydrogenation/Hydroarylation Approach to Synthetically Versatile C2-Alkenyl N–H Indoles

“…Therefore, and despite the well-known ability of Ir(I) complexes to oxidatively insert into C(sp 2 )−H bonds, tandem processes involving oxidative additions of in situ generated alkenyl C−H bonds to this metal center have never been described. 7 Herein, we demonstrate that iridium catalysts can promote one-pot, intermolecular reactions entailing a tandem sequence that involves a dehydrogenation, a C−H activation, and an alkyne (or alkene) addition step. Specifically, we show that this cascade process can be leveraged to transform N-carbamoyl indolines into 2-alkenyl and 2-alkyl N−H indoles (Scheme 1, eq 4).…”