ZIRCONIUM-CATALYZED ETHYLMAGNESATION OF HYDROXYLATED TERMINAL ALKENES - A CATALYTIC AND DIASTEREOSELECTIVE CARBON-CARBON BOND-FORMING REACTION

Zirconocene dichloride catalyzes the addition of ethylmagnesium halides to chiral allylic and homoallylic alcohols and ethers in an efficient manner. These transformations proceed with high levels of regio- and stereocontrol; with the appropriate choice of the neighboring heteroatom substituent (alcohol vs ether), either of the two diastereotopic faces of a chiral alkene can be selectively functionalized. Experimental data described indicate that the regio- and stereoselective outcomes of catalytic carbomagnesation of acyclic substrates are unique. Simple addition of zirconacyclopropanes to unsaturated alcohols and ethers proceeds without stereoselection and affords the derived metallacyclopentanes either with no regiocontrol or with a completely opposite sense of regiochemistry compared to that obtained under the catalytic conditions. A detailed mechanistic scheme is provided that accounts for all the characteristics of a zirconium-catalyzed ethylmagnesation reaction. The proposed paradigm includes a biszirconocene complex as its centerpiece; intermediacy of the bimetallic complex is supported by rate studies and readily accounts for the observed selectivities. The proposed mechanistic hypothesis rationalizes (i) the requirement for excess EtMgCl, (ii) the necessity for the presence of a Lewis basic heteroatom, and (iii) the reason for the highly regioselective rupture of the intermediate metallacyclopentane.