Nozaki-Hiyama Coupling
Nozaki-Hiyama-Kishi Reaction

This coupling between halides and aldehydes is a chromium-induced redox reaction. A key advantage is the high chemoselectivity toward aldehydes. A disadvantage is the use of excess toxic chromium salts.

Newer methods allow the use of catalytic amounts chromium(II), which is regenerated by reduction with manganese or via electrochemical reduction.

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Mechanism of the Nozaki-Hiyama-Kishi Coupling

Catalyzed Reaction:

Recent Literature

Asymmetric Catalysis of Nozaki-Hiyama Allylation and Methallylation with A New Tridentate Bis(oxazolinyl)carbazole Ligand
M. Inoue, T. Suzuki, M. Nakada, J. Am. Chem. Soc., 2003, 125, 1140-1141.

A Highly Enantioselective Catalyst for the Asymmetric Nozaki-Hiyama-Kishi Reaction of Allylic and Vinylic Halides
A. Berkessel, D. Menche, C. A. Sklorz, M. Schroeder, I. Paterson, Angew. Chem. Int. Ed., 2003, 42, 1032-1035.

Stereochemical Diversity in Chiral Ligand Design: Discovery and Optimization of Catalysts for the Enantioselective Addition of Allylic Halides to Aldehydes
J.-Y. Lee, J. J. Miller, S. S: Hamilton, M. S. Sigman, Org. Lett., 2005, 7, 1837-1839.

Electrochemical Nozaki-Hiyama-Kishi Coupling: Scope, Applications, and Mechanism
Y. Gao, D. E. Hill, W. Hao, B. J. McNicholas, J. C. Vantourout, R. G. Hadt, S. E. Reisman, D. G. Blackmond, P. S. Baran, J. Am. Chem. Soc., 2021, 143, 9478-9488.

Design and Synthesis of Modular Oxazoline Ligands for the Enantioselective Chromium-Catalyzed Addition of Allyl Bromide to Ketones
J. J. Miller, M. S. Sigman, J. Am. Chem. Soc., 2007, 129, 2752-2753.

Chromium-Catalyzed Homoaldol Equivalent Reaction Employing a Nucleophilic Propenyl Acetate
J. Y. Kang, B. T. Connell, J. Am. Chem. Soc., 2010, 132, 7826-7827.

Enantioselective Synthesis of α-exo-Methylene γ-Butyrolactones via Chromium Catalysis
W. Chen, Q. Yang, T. Zhou, Q. Tian, G. Zhang, Org. Lett., 2015, 17, 5236-5239.