A convenient synthesis of substituted pyrazolidines and azaproline derivatives through highly regio- and diastereoselective reduction of 2-pyrazolines

J Org Chem. 2008 Jan 18;73(2):550-7. doi: 10.1021/jo702050t. Epub 2007 Dec 18.

Abstract

The synthesis of substituted N-acetyl- and N-aroyl-2-pyrazolines via intramolecular Michael addition of alpha,beta-unsaturated hydrazones generated through olefination of phosphinyl and phosphonyl hydrazones with carbonyl compounds is reported. The regioselective reduction of the C-N double bond in these 2-pyrazolines using Superhydride (Et3BHLi) gives pirazolidine derivatives with excellent levels of cis-diastereoselectivity. These 2-pyrazolines can also be obtained in one-pot reaction from allenes, hydrazides, and aldehydes; and pyrazolidines, after reduction, from allenes, hydrazides, and aldehydes. This synthetic route was developed to provide a new approach to substituted azaproline derivatives in a diastereoselective fashion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Cyclization
  • Molecular Structure
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis*
  • Proline / chemistry
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry*
  • Stereoisomerism

Substances

  • Aza Compounds
  • Pyrazoles
  • Proline