Iridium-Catalyzed Intermolecular Amidation of sp³ C–H Bonds: Late-Stage Functionalization of an Unactivated Methyl Group

Abstract

Reported herein is the iridium-catalyzed direct amidation of unactivated sp(3) C-H bonds. With sulfonyl and acyl azides as the amino source, the amidation occurs efficiently under mild conditions over a wide range of unactivated methyl groups with high functional group tolerance. This procedure can be successfully applied for the direct introduction of an amino group into complex compounds and thus can serve as a powerful synthetic tool for late-stage C-H functionalization.

A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp3)–H amination

“…iridium) via organometallic intermediates have a steric preference for functionalizing 1° methyl groups 42 , electrophilic high valent metal-heteroatom species (i.e. oxos and nitrenes) typically display poor reactivity of with 1° methyl C—H bonds due to their high BDEs and low basicity.…”

2.9 C—N Bond Formation by C—H Functionalization via Metal-Catalyzed Nitrene Insertion

“…Impressively, unactivated primary sp 3 -bonds are aminated selectively in good yields and with excellent tolerance of functional groups (Scheme 15). [31] This transformation is particularly useful for late-stage functionalization of complex natural products.…”

“…Scheme 15 Intermolecular Primary Amidation Using Sulfonyl Azides [31] 48 ( 3 4-Tol 87 [31] CH(iPr)(CH 2 ) 2 4-Tol 84 [31] Pr Me 4-Tol 73 [31] (CH 2 ) 3 Ph 90 [31] (CH 2 ) 3 Me 74 [31] N-[3-(Methoxyimino)alkyl]sulfonamides 50; General Procedure: [31] CAUTION: Care should be taken in working with organic azides as they can be explosive. It is recommended that azide-transfer reactions and workups be performed behind a blast shield, and azides should be stored in a freezer at -33 8C.…”

Efficient synthesis of 2-arylquinazolines via copper-catalyzed dual oxidative benzylic CH aminations of methylarenes

“…In these syntheses, the key step is to construct C-N bonds of the cyclization. Recently, transition-metal-catalyzed oxidative aminations of sp 3 C-H bond have emerged as important methods for C-N bond formations because of short steps and atom-economical advantages [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. In particular, copper as an inexpensive and lowly toxic metal catalyst, has been employed to catalyze the formation of C-N bond via a sp 3 C-H amination [39][40][41][42][43][44][45][46][47][48][49].…”