Asymmetric hydrozirconation

Treatment of the optically active gem-borazirconocene alkanes with deuterium oxide followed by alkaline oxidation affords the corresponding optically active 1-deuterio primary alcohols. The enantiomeric excess of the resulting primary alcohols represents the diaster-eoselectivity of the asymmetric hydrozirconation (Scheme 7.13). Based on the cost and availability of optically active ligands, three types were explored monoterpenes, 1,2-diols, and 1,2-amino alcohols. Hydrozirconation of optically pure 1-alkenyl boranes 39 provided optically active 1,1-bimetallics 40. 

Wipf P, Kendall C (2005) Hydrozirconation and Its Applications. 8 1-25 Wu GG, Huang M (2004) Organolithium in Asymmetric Process. 6 1-36 Wu YT, de Meijere A (2004) Versatile Chemistry Arising from Unsaturated Metal Carbenes. 13 21-58... 

For the asymmetric 1,4-addition of alkenyl groups in aprotic media, alkenyl zirconium reagents can be used, which are generated by hydrozirconation of terminal alkynes (Figure 3.30). Under these conditions, alkenyl groups derived from alkylacetylenes are efficiently installed, but those from arylacetylenes are not as effective (entry 3). 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

Catalytic asymmetric vinylation of ketones has been achieved. Vinylzinc reagents have been generated by hydrozirconation of terminal alkynes which are then transmet- allated with zinc.199 A titanium(IV) complex of a tims-cyclohexane-bis(sulfonamide) provides chiral catalysis it also facilitates dienylation of ketones, with ees also >90% in this case. 

Walsh developed an efficient protocol for the asymmetric catalytic vinylation of a variety of aldehydes and ketones, using the vinylzinc species generated in situ by treatment of terminal alkynes with Schwartz s reagent for hydrozirconation, followed by transmetallation to zinc via reaction with Me2Zn. Under the catalysis of titanium complex of the chiral dihydroxyl bis (sulfonamide) ligand, the reaction provides access to the corresponding secondary or tertiary allylic alcohols in high yields and excellent enantiomeric excesses [65] (Scheme 14.13). 

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