Directed hydrozirconation of propargylic alcohols.

Hydrozirconation of alkynes with Cp2ZrH(Cl) (Schwartz reagent) generates vinyl zirconium species reliably, stereospecifically, and regioselectively. These organometallic reagents can participate in cross-coupling reactions, conjugate and nucleophilic additions, and can undergo carbonylation and halogenation.1 Hydrozirconation of terminal alkynes often proceeds with >50:1 selectivity to form the terminal vinyl zirconium product. Addition to internal alkynes often displays lower selectivity, but the initial kinetic distribution of products can reach equilibrium via â-hydride elimination from a dizirconium intermediate.2 The least hindered product is always observed. For these reasons, hydrozirconation has become a staple of modern synthetic chemistry. It was thus of interest to determine if the regioselectivity of hydrometalation could be reversed. While unprecedented, such an accomplishment would provide access to synthetically valuable reagents and might reveal fundamental aspects of organozirconium chemistry. As part of a program to exploit directing groups in alkyne functionalization reactions,3,4 we explored the hydrozirconation of propargylic alcohols.5 We initiated our studies with the most challenging class of propargylic alcohols, namely, terminal alkynes. Thus, consistent with literature reports, terminal alkyne 1a provided, after iodination, the terminal vinyl iodide 2a as a single regioisomer (Table 1, entry 1).6 In contrast, hydrozirconation of the lithium alkoxide of 1a yielded an equal distribution of regioisomers (entry 2). We hypothesized that an (alkoxy) zirconium hydride species Cp2Zr(OR)H might be formed under the reaction conditions through chloride displacement by lithium alkoxide. However, when prepared independently, such complexes were not competent intermediates in the hydrozirconation. While failing to support our original hypothesis, these experiments did suggest that chloride was important for the hydrozirconation reactions. Accordingly, we evaluated the effect of exogenous chloride sources. Additional lithium chloride proved marginally beneficial with respect to regioselectivity (entry 3), and zinc chloride yielded substantial improvements. Thus, in the presence of 6 equiv of ZnCl2, only the