MECHANISTIC AND SYNTHETIC ASPECTS OF STEREOSELECTIVE REACTIONS OF LITHIUM DERIVATIVES OF CHIRAL PHOSPHINE OXIDES - X-RAY CRYSTAL-STRUCTURE OF L-2'-PHENYLPROPYL)-2-PHENYLSULFANYLCYCLOHEXAN-1-OL

Lithiation of four different chiral phosphine oxides and reaction with seven different electrophiles has been carried out in order to discov er what factors govern the sense and degree of asymmetric induction im parted by the resident chiral centre. Provided the groups at the chira l centre are significantly different in steric size (e.g. Ph and Me) a nd ketones, esters or Me3SiCl are used as the electrophile, surprising ly high levels of syn-diastereoselectivity are observed. Reactions wit h benzaldehyde or methyl iodide proved to be rather unselective. The s tereochemistry of the reaction of lithiated 1-diphenylphosphinoyl-2-ph enylpropane 9 with cyclohexanone was elucidated by conversion into l-2 '-phenylpropyl)-2-phenylsulfanylcyclohexan-1-ol syn,syn,anti-39 and su bsequent X-ray crystal structure analysis; The stereochemistry of the remainder of the compounds were determined by analogy and by using a r eliable C-13 NMR spectroscopy (3)J(PC) coupling constant correlation. A detailed (and potentially general) mechanistic interpretation of the results which combines knowledge of the structure and configurational stability of lithiated phosphine oxides is discussed. In particular, it is suggested that a dynamic kinetic diastereoselection of rapidly e quilibrating diastereomeric lithiated phosphine oxides explains the ob served high levels of stereocontrol; a tentative transition state mode l is proposed to explain the syn-selectivity. Finally, the use of one of the addition products in the concise and stereoselective synthesis of an alkene with 1,4-disposed chiral centres is described.