A pericyclic cascade to the stereocontrolled synthesis of 9-cis-retinoids

A domino reaction that is pericyclic in nature is thought to be triggered u pon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comp rises an ordered sequence of sigmatropic rearrangements: a reversible [2,3] -allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl su lfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiatin g [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrenc e of the C7 to C11 hydrogen migration has been demonstrated by labeling exp eriments. The double diastereoselection of the [1,5]sigmatropic hydrogen sh ift to afford a single isomer of the final polyene 13 is thought to arise f rom a combination of the electronic effect of the sulfoxide at one terminus , and the steric effect imparted by the bulky trimethylcyclohexenyl substit uent at the other terminus. The overall process thus constitutes a stereose lective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in par ticular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoi ds, including labeled analogues, is straightforward.