Catalyst-Controlled Diastereoselective Synthesis of Cyclic Amines via C-H Functionalization

Abstract

Reliable regio- and stereochemical techniques applicable to nonactivated aliphatic systems remain largely elusive due to the challenges of discriminating between multiple, relatively strong sp C-H bonds whose chemical behavior often differ only subtly. Nevertheless, approaches that employ directing groups and/or auxiliaries have emerged, but impose practical restrictions, especially in complex molecule synthesis. This report describes a catalyst-controlled regio- and diastereoselective synthesis of N-unprotected pyrrolidines via dirhodium catalyzed intramolecular nitrene insertion into sp C-H bonds. The reaction proceeds at rt without external oxidants, nitrene stabilizing groups, or directing functionality. The insights that emerged from the conformational/stereoselectivity relationships (CSR) between catalysts and substrates provide a framework for rational catalyst design that can accommodate a broader range of aliphatic C-H chemistry.

Dirhodium(II,II) Paddlewheel Complexes

“… Dirhodium(II,II) complexes containing O , O' ‐bridging ligands with structural motive OOCCR 1 R 2 R 3 : O1 , [189] O2 , [190] O3 , [190] O4 , [191] O5 , [185] O6 , [192] O7 , [193] O8 , [191] O9 , [194] O10 , [194] O11 , [194] O12, [194] O13 : R=H, [195] R=Me, [196] O14 , [197] O15 , [197] O16 , [197] O17 , [197] O18 , [41] O19 , [41] O20 , [41] O21 , [41] O22 , [41] O23 , [41] O24 , [41] O25 , [41] O26 , [41] O27 , [41] O28 , [41] O29 , [41] O30 , [41] O31 , [41] O32 , [42] O33 , [42] O34 , [42] O35 , [42] O36 , [42] O37 , [42] O38 [182] …”

Directed C–H Functionalization of the Adamantane Framework

“…The stability of Rh 2 (esp) 2 in acidic media enabled the preparation of cyclic amines via an intramolecular nitrenoid insertion reaction into the C-H bond (Scheme 9). 21 Pyrrolidine derivative 15 was prepared in two steps from the primary alcohol 13. Boc-protected hydroxylamine derivative 14 was prepared by Mitsunobu reaction, which in the next step underwent acidic decomposition to generate a rhodium nitrenoid intermediate; insertion of this species into the C-H bond generates a five-membered ring.…”

Hydroxylamines as One-Atom Nitrogen Sources for Metal-Catalyzed Cycloadditions

“…At the same time, nitrogen is relatively electron positive com-Scheme 15 Rh-catalyzed stereoselective intermolecular synthesis of N-heterocycles. 30 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.…”

“…At the same time, nitrogen is relatively electron positive com-Scheme 15 Rh-catalyzed stereoselective intermolecular synthesis of N-heterocycles. 30…”

“…In 2017, Falck and co-workers discovered the catalystcontrolled diastereoselective synthesis of cyclic amines via C-H functionalization with Rh catalysts (Scheme 15). 30 Using a bulky ligand (such as S-tertPTTL) usually led to the cis product, which might be due to the lower steric hinder between the ligand and two substituent groups. When the ligand on Rh catalyst was a small one like OAc, the steric effect between the two substituent groups might be the dominate effect for the stereochemistry of the product.…”