Efficient asymmetric synthesis of P-chiral phosphine oxides via properly designed and activated benzoxazaphosphinine-2-oxide agents.

Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., 900 Old Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877, USA. steve.han@boehringer-ingelheim.com

Journal of the American Chemical Society 2013 Feb 20

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A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.

Citation

Zhengxu S Han, Navneet Goyal, Melissa A Herbage, Joshua D Sieber, Bo Qu, Yibo Xu, Zhibin Li, Jonathan T Reeves, Jean-Nicolas Desrosiers, Shengli Ma, Nelu Grinberg, Heewon Lee, Hari P R Mangunuru, Yongda Zhang, Dhileep Krishnamurthy, Bruce Z Lu, Jinhua J Song, Guijun Wang, Chris H Senanayake. Efficient asymmetric synthesis of P-chiral phosphine oxides via properly designed and activated benzoxazaphosphinine-2-oxide agents. Journal of the American Chemical Society. 2013 Feb 20;135(7):2474-7