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Synlett 2004(7): 1140-1157  
DOI: 10.1055/s-2004-822889
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© Georg Thieme Verlag Stuttgart · New York

Carbon-Carbon Bond Construction Based on Radical Addition to C=N Bond

Hideto Miyabea,b, Masafumi Uedaa, Takeaki Naito*a
a Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan
b Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Fax: +81(78)4417556; e-Mail: taknaito@kobepharma-u.ac.jp;
Further Information

Publication History

Received 13 December 2003
Publication Date:
25 March 2004 (online)

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Abstract

We have studied the carbon radical addition to imine derivatives as an effective carbon-carbon bond forming method for the synthesis of a variety of amines. The reaction of oxime ethers proceeded smoothly in the presence of BF3·OEt2 to give the alkylated products in high yields via the free radical-mediated carbon-carbon bond forming process. Intermolecular radical addition to oxime ethers was effectively improved by using alkyl iodides and triethylborane, which acts multiply as a Lewis acid, a radical initiator and a terminator. The asymmetric synthesis of α-amino acids based on a diastereoselective radical addition to glyoxylic imine derivatives was achieved. Highly diastereoselective alkyl radical addition to Oppolzer’s camphorsultam derivatives of oxime ether provided a convenient method for preparing the enantiomerically pure α,β-dialkyl-β-amino acids. We have demonstrated that imine derivatives such as oxime ethers, hydrazones, and nitrones are excellent radical acceptors for the radical reactions in aqueous medium. The radical addition to imine derivatives in aqueous medium was also studied by using indium or zinc as a single-electron transfer radical initiator. We have found that triethylborane can be applied to solid-phase radical reactions. The solid-phase tandem carbon-carbon bond forming reaction of oxime ethers connected with an α,β-unsaturated carbonyl group proceeded effectively to give the azacycles or chiral oxacycles after cleavage from the resin.

  • 1 Introduction

  • 2 Intermolecular Radical Addition to Imine Derivatives

  • 2.1 Addition to Oxime Ethers

  • 2.2 Reactivity of Imine Derivatives

  • 2.3 Iodine Atom-Transfer Reaction

  • 3 Stereocontrol in Radical Addition to Imine Derivatives

  • 3.1 Addition to Chiral Glyoxylic Oxime Ether

  • 3.2 Addition to Chiral Unactivated Oxime Ether

  • 3.3 Addition to Chiral Nitrone

  • 4 Radical Reaction of Imine Derivatives in Aqueous Media

  • 4.1 One-Pot Reaction

  • 4.2 Triethylborane-Mediated Reaction in Aqueous Media

  • 4.3 Zinc-Mediated Reaction in Aqueous Media

  • 5 Solid-Phase Radical Reaction

  • 5.1 Intermolecular Radical Reaction

  • 5.2 Intramolecular Radical Reaction

  • 5.3 Tandem Radical Addition-Cyclization

  • 5.4 Solid-Phase Radical Reaction in Aqueous Media

  • 6 Conclusion

Key words

radical - imine - oxime ether - amino acid - water - solid-phase - hydrazone - nitrone

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Wang and TentaGel OH resins purchased from Novabiochem were used in all experiments.