The Use of Chiro-Inositols in Asymmetric Synthesis

Abstract

D- and L- chiro-inositols are readily and inexpensively available as their O-methyl ethers pinitol and quebrachitol. To date the use of the choro-inositols in synthesis has not been exploited as fully as that of the more common isomer myo-inositol. The chiro-inositols were protected as either the di-isopropylidene or the di-cyclohexylidene systems to give them more steric bulk and were subsequently evaluated in the three areas of asymmetric synthesis; • as chiral reagents • as chiral auxiliaries • as chiral ligands. Outside of these areas was the successful application of methodology for the mono esterification of C-2 symmetric diols to these inositol systems. This allowed a series of molecules to be generated that proved useful in the areas outlined above. For the use of chiro-inositols as chiral reagents, two reagents were investigated. The first was a hydroboration reagent similar to pinenyl borane. The second was the generation of a strained silacycle for use as a reagent in the enantioselective allylation of aldehydes. In the area of chiral auxiliaries, these inositols were successfully used to give selectivity in the Michael reaction. Unfortunately this success was not repeatable in the aldol reaction. Investigations into the development of chiral ligands were unsuccessful in that we were unable to synthesize either a diamine or an amino alcohol from this system. A diol and an amino ether were trialed in asymmetric reactions but failed to provide any catalytic effect. This section of the project did lead to some interesting chemistry and a better understanding of this system that can be applied to future work.