Dearomatization of arenechromium tricarbonyl complexes provides a mild and rapid entry into functionalized carbocycles. Chiral auxiliary directed nucleophilic addition provides synthetically useful enantio enriched substituted cyclohexenones. The present studies were aimed at understanding the origin of diastereoselection and develop systems giving both enantiomers. Chiral auxiliaries derived from camphor attached to arenes with trimethylsilyl group as the para substituent gave both enantiomers in very high diastereoselectivity with lithio tert-butyl acetate nucleophile. The chiral auxiliaries are retrievable in most of the cases. The origin of diastereoselectivity is proposed to be due to charge control as reflected in the orientation of the Cr(CO)3 tripod with respect to the chiral auxiliary.
The chiral auxiliary directed lithio methyl phenyl sulphone addition was performed in an effort to asymmetrically synthesize, the cyclohexyl sub-unit of the immunosuppressant FK-506. Preliminary results indicate a moderate diastereoselectivity with the lithio methyl phenyl sulphone nucleophile.
X-ray crystal structure analysis and conformational analysis of the chiral arenechromium tricarbonyl complexes by NOE studies revealed a cis-endo conformation of the Cr(CO)3 tripod with respect to the camphyl framework. A possible preference of tripod orientation in solution was also proposed from the 13C NMR chemical shifts. In this context, conformational analysis of the chromium tricarbonyl tripod rotamers was thoroughly reinvestigated and the proposition that 13C NMR chemical shifts of the arene manifesting its electron charge densities is presented.
Addition of the pro-chiral nucleophiles to arenechromium tricarbonyl complexes was performed to study the vicinal stereocontrol during nucleophilic addition. The excellent erythro vicinal stereocontrol obtained on lithio tert-butyl propionate addition to para trimethylsilylanisolechromium tricarbonyl has been applied to a racemic formal synthesis of the sex pheromone Juvabione.