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Synthesis Without Metals

Part 7. Green Synthesis

  1. Takahiko Akiyama

Published Online: 15 APR 2012

DOI: 10.1002/9783527628698.hgc081

Handbook of Green Chemistry

Handbook of Green Chemistry

How to Cite

Akiyama, T. 2012. Synthesis Without Metals. Handbook of Green Chemistry. 7:301–328.

Author Information

  1. Gakushuin University, Department of Chemistry, Tokyo, Japan

Publication History

  1. Published Online: 15 APR 2012


The enantioselective synthesis of organic compounds is one of the key issues to be resolved in the field of synthetic organic chemistry because chiral organic compounds are important as pharmaceutical products, agrochemicals, and fine chemicals. Until fairly recently, transition metal complexes and enzymes had been utilized primarily as catalysts for enantioselective synthesis. List, Lerner, and Barbas reported an aldol reaction catalyzed by (S)-proline, and MacMillan reported MacMillan's catalyst for the Diels–Alder reaction. Following these two seminal reports, organocatalysis has emerged as a novel asymmetric methodology viable for a number of transformations. Metal-based catalysts, which are sensitive to oxygen and water, are therefore prepared in situ from a metal salt and a chiral ligand and employed directly. In contrast, asymmetric organocatalysts are generally stable and thus easy to handle. Recently, chiral organocatalysts were found to complement metal-based catalysts. In this chapter, an overview of chiral organocatalysts, including the seminal work, is presented, focusing on the recently developed chiral Brønsted acid catalysts. The catalysts discussed include proline and derivatives, MacMillan's catalyst, peptide catalysts, ketone catalysts, phase-transfer catalysts, amine catalysts, guanidinium salt catalysts, hydrogen-bond catalysts, and Brønsted acid catalysts.


  • non-metal catalysts;
  • chiral organocatalysts;
  • chiral Brønsted acid catalysts;
  • organic synthesis;
  • enantioselective synthesis;
  • green chemistry