Total synthesis of (-)-cylindrocyclophanes A and F exploiting the reversible nature of the olefin cross metathesis reaction

Efficient total syntheses of the C-2-symmetric (-)-cylindrocyclophanes A an d F (1a and 1f) have been achieved. The initial strategy featured the use o f a common advanced intermediate to assemble in stepwise fashion the requir ed macrocycle of 1f, exploiting in turn a Myers reductive coupling followed by ring-closing metathesis. In a second-generation strategy, a remarkable cross olefin metathesis dimerization cascade was discovered and exploited t o assemble the requisite [7,7]-paracyclophane macrocycles of both 1a and 1f from dienyl monomers. The successful syntheses also featured the effective use of the Danheiser annulation to construct substrates for both the Myers reductive coupling and the metathesis dimerizations strategies. Finally, t he Kowalski two-step chain homologation of esters to siloxyalkynes proved s uperior over the original onestep protocol.