Highly Enantioselective Chlorination of beta-Keto Esters and Subsequent S(N)2 Displacement of Tertiary Chlorides: A Flexible Method for the Construction of Quaternary Stereogenic Centers

作者：Shibatomi Kazutaka^*; Soga Yoshinori; Narayama Akira; Fujisawa Ikuhide; Iwasa Seiji

来源：Journal of the American Chemical Society, 2012, 134(24): 9836-9839.

DOI：10.1021/ja304806j

Highly enantioselective chlorination of beta-oxo esters and subsequent stereospecific substitution of tertiary chlorides are described. Enantioselective chlorination of beta-keto esters and malonates was performed using a chiral Lewis acid catalyst prepared from Cu(OTf)(2) and the newly developed spirooxazoline ligand 2 to yield the desired a-chlorinated products with high enantioselectivity (up to 98% ee). Nucleophilic substitution of the resulting chlorides proceeded smoothly to afford a variety of chiral molecules such as alpha-amino, alpha-allcylthio, and alpha-fluoro esters, without loss of enantiopurity. The results of X-ray crystallographic analysis proved that Walden inversion occurs at the chlorinated tertiary carbon center. These results supported the fact that the substitution proceeds via an S(N)2 mechanism.

• 出版日期2012-6-20