Mechanistic investigations of silylcarbinol rearrangements and use of a sigmatropic rearrangement for the stereoselective synthesis of polypropionates.

Abstract

Silylcarbinols generated from the 1,2-addition of dimethyl(phenyl)silyllithium to cyclic $\alpha,\beta$-unsaturated ketones were found to undergo acid or base catalyzed rearrangements, depending upon the substitution pattern of the substrate. The $\alpha,\beta$-unsaturated silylcarbinols which contain an alkoxy group at the $\alpha$ carbon, have been shown to undergo silicon rearrangement under mildly acidic conditions to provide cyclic $\alpha$-alkoxyenol silyl ethers. The mechanism of this novel rearrangement has been proposed to be an acid-catalyzed 1,2-silyl group migration, followed by a thermal rearrangement of the resulting $\beta$-ketosilanes to give the $\alpha$-alkoxyenol silyl ethers, based on the isolation of intermediates, and on kinetic data. On the other hand, cyclic $\alpha,\beta$-unsaturated silylcarbinols which have an alkyl substituent at the $\alpha$ carbon, follow a base-catalyzed rearrangement to the corresponding silyl enol ethers. This Brook rearrangement has been shown to be an efficient method for the regiospecific generation of cyclic silyl enol ethers. The second part of the thesis describes a concise and highly stereoselective method for the generation of polypropionates, many of which are naturally occurring substances with biological and medicinal importance. The conjugate addition of lithium dimethylcuprate to 2-(2-buten-1-yloxy)-5-methyl-2-cyclopenten-1-one in the presence of trimethylsilyl trifluoromethanesulfonate, and a subsequent Claisen rearrangement of the resulting silyl enol ether, followed by desilylation provides (2R\sp*,2\sp\prime R\sp*,3S\sp*,5R\sp*)-2-(3-buten-2-yl)-3,5-dimethyl-2-hydroxycyclopentanone in high yield. This cyclic hydroxyketone intermediate was then efficiently transformed into the syn,syn-trimethyl-substituted carbon chain, (2R\sp*,4S\sp*,6R\sp*)-5-oxo-2,4,6-trimethyl-7-octen-1-al. Thus, this highly stereoselective method for the generation of a syn,syn-trimethyl-substituted polypropionate has been applied to the total synthesis of ($\pm$)-siphonarienone, which contains identical relative stereochemistry. ($\pm$)-Siphonarienone, which was isolated from Siphonaria grisea in 1990, has been synthesized stereoselectively from (2R\sp*,4S\sp*,6R\sp*)-5-oxo-2,4,6-trimethyl-7-octen-1-al in 6 steps in 17% overall yield.Ph.D.ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/103096/1/9303762.pdfDescription of 9303762.pdf : Restricted to UM users only