A comprehensive new strategy for stereocontrolled construction of carbocycles via [m+n] annulation is outlined. For the first time, a unified approach to five-, six- and seven-membered rings will be accessible through common intermediates. In addition to allowing generation of several different ring sizes, this entry to carbocycles comprises several other advantageous features. Procedures outlined are anticipated to be highly chemoselective. Enhanced stereoselectivity is also expected, and incorporation of quaternary centers on carbocycles is possible with complete stereochemical control. Isolated rings as well as fused rings (either linearly fused or spirocyclic systems) are accessible. Most acyclic substrates we propose to utilize can be readily accessed in chiral, non-racemic form, allowing synthesis of optically active carbocyclic ring systems. Few other synthetic methods boast the flexibility and scope of application that we envision for these synthetic methods. As a demonstration of the methods described, syntheses of (-)-aristeromycin, pentenomycin, chokol A, and methylenomycin analogs are proposed.
| Molander, Gary A; Czako, Barbara; St Jean Jr, David J (2006) A general route toward the synthesis of the cladiellin skeleton utilizing a SmI2-mediated cyclization. J Org Chem 71:1172-80 |
