Access to Enantioenriched α-Amino Esters via Rhodium-Catalyzed 1,4-Addition/Enantioselective Protonation
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- 作者：Laure Navarre ; Ré ; mi Martinez ; Jean-Pierre Genet ; Sylvain Darses
- 刊名：Journal of the American Chemical Society
- 出版年：2008
- 出版时间：May 14, 2008
- 年：2008
- 卷：130
- 期：19
- 页码：6159 - 6169
- 全文大小：773K
- 年卷期：v.130,no.19(May 14, 2008)
- ISSN：1520-5126
文摘
Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected α-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the α carbon explaining the high levels of enantioselectivity attained in controlling this α chiral center.