Volume 13, Issue 26 p. 7280-7286
Concept

Enantioselective Radical Cyclizations: A New Approach to Stereocontrol of Cascade Reactions

Hideto Miyabe Prof.

Hideto Miyabe Prof.

School of Pharmacy, Hyogo University of Health Sciences, Minatojima, Kobe 650-8530, Japan, Fax: (+81) 78-304-2794

Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan, Fax: (+81) 75-753-4569

Search for more papers by this author
Yoshiji Takemoto Dr.

Yoshiji Takemoto Dr.

Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan, Fax: (+81) 75-753-4569

Search for more papers by this author
First published: 29 August 2007
Citations: 66

Graphical Abstract

Stereocontrol of radical reactions: The role of hydroxamate ester as a coordination site in enantioselective radical cyclization is described. Stereocontrol in cascade radical addition–cyclization was achieved by this new approach, which involves a chiral Lewis acid coordinating to a tether between two radical acceptors.

Abstract

Stereocontrol in a cascade radical addition–cyclization–trapping reaction was achieved by a new approach, which utilizes a hydroxamate ester moiety as a coordinating chiral Lewis acid tether between two radical acceptors. A remarkable feature of this reaction is the construction of three bonds and tertiary and quaternary stereogenic centers through both inter- and intramolecular carbon–carbon bond-forming processes. The chiral Lewis acid mediated reaction of oxime ethers also proceeded smoothly with good enantio- and diastereoselectivities, indicating the usefulness of the cascade approach for the asymmetric synthesis of various γ-lactams.