Nucleophilic displacement routes to P-chiral phosphines; the introduction of sterically encumbered groups

Article abstract of DOI:10.1016/S0022-328X(96)06660-0

Methods for the asymmetric synthesis of P-chiral monophosphines carrying a bulky residue have been appraised. Reaction of 2-adamantylmagnesium bromide with P-chlorooxazaphospholidine 1 gives two diastereomeric products after oxidation with t-BuOOH; the S_P isomer was characterised by X-ray and the R_P isomer through a detailed NMR analysis. Although ring opening of either isomer 2 or 3 on reaction with o-anisylmagnesium bromide occurred satisfactorily, continuation of the desired reaction sequence through acid-catalysed methanolysis of the phosphinamide 4 and further with PhMgBr led to diminution of the enantiomeric purity in each step because of the more forcing conditions brought about by the steric demands of the 2-adamantyl residue. Similar difficulties were experienced when following the P-borane route of Juge and Genet, where the 2-adamantyl group was introduced in the initial step. More success was achieved by the borane route when the bulky residue was introduced last by reaction of RLi with the phosphinite complex 13. In this way the ferrocenyl, 1-adamantyl and t-butylphosphines carrying both phenyl and o-anisyl residues, were formed as borane complexes. Deboronation proceeded smoothly in the first two cases to give the tertiary phosphines in greater than 92% e.e.