Wong Marie L J, Mousseau James J, Mansfield Steven J, Anderson Edward A
Chemistry Research Laboratory , University of Oxford , 12 Mansfield Road , Oxford OX1 3TA , U.K.
Pfizer Worldwide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.
Org Lett. 2019 Apr 5;21(7):2408-2411. doi: 10.1021/acs.orglett.9b00691. Epub 2019 Mar 14.
Bicyclo[1.1.1]pentanes (BCPs), useful surrogates for para-substituted arenes, alkynes, and tert-butyl groups in medicinal chemistry, are challenging to prepare when featuring stereogenic centers adjacent to the BCP. We report the development of an efficient route to α-chiral BCPs, via highly diastereoselective asymmetric enolate functionalization. We also describe the application of this chemistry to the synthesis of BCP analogues of phenylglycine and tarenflurbil, the single enantiomer of the NSAID flurbiprofen.
双环[1.1.1]戊烷（BCPs）是药物化学中对位取代芳烃、炔烃和叔丁基的有用替代物，当在BCP相邻位置具有立体中心时，其制备具有挑战性。我们报告了一种通过高度非对映选择性不对称烯醇盐官能化制备α-手性BCPs的有效路线。我们还描述了该化学方法在合成苯甘氨酸和他仑氟比（非甾体抗炎药氟比洛芬的单一异构体）的BCP类似物中的应用。
