Salvi Luca, Jeon Sang-Jin, Fisher Ethan L, Carroll Patrick J, Walsh Patrick J
P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, USA.
J Am Chem Soc. 2007 Dec 26;129(51):16119-25. doi: 10.1021/ja0762285. Epub 2007 Dec 4.
A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetalation with dialkylzinc reagents generate (Z)-disubstituted vinylzinc intermediates. In situ reaction of these reagents with aldehydes in the presence of a catalyst derived from (-)-MIB generates (Z)-disubstituted allylic alcohols. It was found that the resulting allylic alcohols were racemic, most likely due to a rapid addition reaction promoted by LiX (X = Br and Cl). To suppress the LiX-promoted reaction, a series of inhibitors were screened. It was found that 20-30 mol % tetraethylethylenediamine inhibited LiCl without inhibiting the chiral zinc-based Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem diastereoselective epoxidation reactions to provide epoxy alcohols and allylic epoxy alcohols with up to three contiguous stereogenic centers, enabling the rapid construction of complex building blocks with high levels of enantio- and diastereoselectivity.
介绍了一种直接制备对映体富集的(Z)-二取代烯丙醇的一锅法。1-卤代-1-炔烃与二环己基硼烷进行硼氢化反应，与叔丁基锂反应，再与二烷基锌试剂进行金属转移反应，生成(Z)-二取代乙烯基锌中间体。这些试剂在由(-)-MIB衍生的催化剂存在下与醛原位反应，生成(Z)-二取代烯丙醇。结果发现，所得烯丙醇是外消旋的，这很可能是由于LiX（X = Br和Cl）促进的快速加成反应。为了抑制LiX促进的反应，筛选了一系列抑制剂。发现20-30 mol%的四乙基乙二胺能抑制LiCl，而不抑制手性锌基路易斯酸。通过这种方式，获得了ee值高达98%的(Z)-二取代烯丙醇。不对称(Z)-乙烯基化反应可以与串联非对映选择性环氧化反应相结合，提供具有多达三个相邻立体中心的环氧化醇和烯丙基环氧化醇，从而能够以高对映选择性和非对映选择性快速构建复杂的结构单元。
