U311546.pdf (6.81 MB)
Some aspects of the preparation of optically-active alcohols.
thesisposted on 2015-11-19, 08:46 authored by Andrew James. Macpherson
The rhodium(I)-catalysed asymmetric hydrogenation of adrenalone hydrochloride, and several analogues, was investigated under a variety of conditions, using a specially modified apparatus. Several phosphine ligands were used, one of these was the new compound di-(2-methoxyphenyl)menthylphosphine. This ligand did catalyse the required reaction, but only very slowly. A new route to dialkyl- and diarylmenthylphosphines via the novel compound menthylphosphonous dichloride was devised. The two new phosphines dimethylmenthylphosphine and di-(2-methoxyphenyl)phosphine were prepared using this route. Menthylphosphonous dichloride did not, however, undergo facile McCormack-type reactions with isoprene. Anomalies in the reported asymmetric reduction of 1-phenyl, 3- methyl, 2-phospholene, 1-oxide by aluminium hydride reagents were pointed out, and alternative explanations offered. The asymmetric reduction of 1-phenyl, 3-methyl, 2-phospholene, 1-oxide and benzyl- methylphenylphosphine oxide using the reagent derived from lithium aluminium hydride and (S)-2-(anilinomethyl)pyrrolidine was carried out to give phosphines with modest enantiomeric excesses. The chlorination of less than half a mol equivalent of a racemic mixture of 1-phenylethanol by diphenylmenthylphosphine oxide and carbon tetrachloride was shown to proceed to give optically-active 1-chloroethylbenzene and optically-active 1-phenylethanol via a kinetic resolution. Both 1-chloroethylbenzene and 1-phenylethanol were obtained in ∼12% ee. Chlorination using (+)- or (-)-2,3-0-iso-propylidene-2,3-dihydroxy-l ,4-bis (diphenylphosphino)butane and carbon tetrachloride gave products with very much inferior optical yields. Chlorination of diphenylmenthylphosphine in the absence of carbon tetrachloride produced a species which brought about the chlorination and kinetic resolution of 1-phenylethanol in a similar manner. This yielded 1-phenylethanol in ∼12% ee and 1-chloroethylbenzene in ∼20% ee. The reduction of adrenalone hydrochloride, and several analogues, by the action of actively fermenting yeast was investigated. Under a variety of conditions adrenalone hydrochloride was not reduced. Adrenalone hydrochloride was not reduced by the enzymes from disrupted yeast cells, and neither was it reduced by commercially available Yeast Alcohol Dehydrogenase. The reduction of adrenalone hydrochloride using sodium borohydride under a variety of conditions was studied. The reduction was easily carried out in water, but the product could only be isolated by employing conditions calculated to destroy borate esters which, in theory, could be formed.
Date of award1980-01-01
Awarding institutionUniversity of Leicester