Flexibilene synthesis

Here is an example from the McMurry flexibilene synthesis quoted in chapter 1. An alkyne 127 with a protected aldehyde group reacts with Cp2ZrHCl to give a vinyl zirconium complex 128 which is coupled to a palladium-allyl complex in the next step. The double bond so produced is present with the same E configuration in the final product. It is marked 129 with an arrow in the diagram.28... 

The effects on coupling efficiency and regiochemical control in nonsymmetrical allyl complexes as a function of added ligand in these reactions has been determined155,156 (vide infra) and applied in the synthesis of flexibilene and humulene.157... 

Cyeloalkenes (8, 483). The last step in a synthesis of flexibilene (2), a 15-membered-ring diterpene, involved cyclization of the keto-aldehyde 1, catalyzed with the active titanium metal prepared by reduction of TiClj with Zn-Cu in DME. A mixture of two cyclized products is formed, in which 2 is the major constituent.1... 

Figure 14.2 shows a synthesis of the diterpene, flexibilene, which uses metal-based reagents in almost every step one of the key steps is nucleophilic attack of a vinylzirconium species on an allylpalladium complex. 

McMurry, J., Matz, J.R., Kees, K.L., and Bock, P.A. (1982) Synthesis of flexibilene, a naturally occuring 15-membered-ring diterpene. Tetrahedron Lett., 23,1777-1780. 

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