Department of Chemistry, Florida Atlantic University, Boca Raton, Florida 33431, United States.
J Org Chem. 2013 Mar 1;78(5):2118-27. doi: 10.1021/jo3023439. Epub 2013 Jan 23.
A mild chlorination reaction of alcohols was developed using the classical thionyl chloride reagent but with added catalytic titanium(IV) chloride. These reactions proceeded rapidly to afford chlorination products in excellent yields and with preference for retention of configuration. Stereoselectivities were high for a variety of chiral cyclic secondary substrates including sterically hindered systems. Chlorosulfites were first generated in situ and converted to alkyl chlorides by the action of titanium tetrachloride which is thought to chelate the chlorosulfite leaving group and deliver the halogen nucleophile from the front face. To better understand this novel reaction pathway, an ab initio study was undertaken at the DFT level of theory using two different computational approaches. This computational evidence suggests that while the reaction proceeds through a carbocation intermediate, this charged species likely retains pyramidal geometry existing as a conformational isomer stabilized through hyperconjugation (hyperconjomers). These carbocations are then essentially "frozen" in their original configurations at the time of nucleophilic capture.
醇的温和氯化反应是使用经典的亚硫酰氯试剂开发的，但添加了催化四氯化钛。这些反应迅速进行，以优异的收率得到氯化产物，并优先保留构型。对于包括空间位阻系统在内的各种手性环状次级底物，立体选择性都很高。氯亚硫酸盐首先在原位生成，并通过四氯化钛的作用转化为烷基氯化物，据认为四氯化钛螯合氯亚硫酸盐离去基团，并从正面提供卤素亲核试剂。为了更好地理解这种新的反应途径，我们在 DFT 理论水平上使用两种不同的计算方法进行了从头算研究。这一计算证据表明，虽然反应通过碳正离子中间体进行，但这种带电物种可能保留了通过超共轭（超共轭物）稳定的金字塔几何形状的构象异构体。这些碳正离子在亲核捕获时基本上以其原始构型“冻结”。
