Ir-Catalyzed Synthesis of Functionalized Pyrrolidines and Piperidines Using the Borrowing Hydrogen Methodology

Abstract

The Ir(III)-catalyzed synthesis of 3-pyrrolidinols and 4-piperidinols combining 1,2,4-butanetriol or 1,3,5-pentanetriol with primary amines was carried out. This borrowing hydrogen methodology was further extended to the sequential diamination of triols leading to amino-pyrrolidines and aminopiperidines.

Borrowing hydrogen C-alkylation with secondary saturated heterocyclic alcohols

“…In order to extend the scope of N -heterocyclic compounds we took advantage of our recent work on the cyclization of triols (1,2,4-butanetriol and 1,3,5-pentanetriol) with various benzylic and aliphatic amines. 34 By leveraging the cyclization chemistry of triols with benzylic and aliphatic amines, we could efficiently access a diverse range of N -heterocycles with tailored structural and functional properties. Indeed, the direct annulation of triols using the BH methodology is a very attractive strategy to access N -protected heterocycles 4 bearing a free hydroxyl group.…”

“…The sequential triol annulation with amines followed by C -alkylation was thus envisioned (Scheme 4). The first attempt was carried out under previously reported conditions 34 using benzylamine (1.0 eq. ), 1,2,4-butanetriol (1.2 eq.…”

Access to Saturated Aza‐Heterocycles using the Borrowing Hydrogen Methodology

“…Taking advantage of the third hydroxyl group, the methodology was further extended to the sequential diamination of triols affording 3‐aminopyrrolidines and 4‐aminopiperidines (Scheme 4). [26] …”