Synthesis of (1R,4S,6R)-5,5,6-trimethyl-2-phosphabicyclo[2.2.2]octane and derivatives

Abstract

The novel primary phosphine (1R,3S)-[1,2,2-trimethyl-3-(phosphinomethyl)cyclopentyl]methyl methanesulfonate 3a (or tosylate 3b) has been prepared in three steps from (1R,3S)-camphoric acid with a view to utilising it as a synthon for the preparation of polycyclic phosphines. Efforts to prepare a [3.2.1] bicyclic product by internal cyclisation of 3a or 3b under various conditions were unsuccessful, but heating the neat compound at 140 °C for several hours gave the new asymmetric, bicyclic secondary phosphine, (1R,4S,6R)-5,5,6-trimethyl-2-phosphabicyclo[2.2.2]octane (PBO) as its methanesulfonic acid 5a (or p-toluenesulfonic acid 5b) salt. The cyclisation involves a skeletal rearrangement and occurs with high stereoselectivity to generate two new stereogenic carbon centres and a chiral phosphorus atom. The secondary phosphine was obtained after base treatment of 5a/b and several derivatives of the phosphine have been synthesised and characterised. Reaction of two mol equivalents of the borane adduct of PBO with α,α′-dichloro-ortho-xylene gave the bidentate derivative, o-C₆H₄(CH₂PBO)₂.2BH₃, 12, and ultimately o-C₆H₄(CH₂PBO)₂, 13. Complexes of 13 with Pd(II), Pt(II), Pt(0) and Mo(0) have been prepared and characterised by spectroscopic and analytical methods including single-crystal X-ray structure determinations of cis-Pd{o-C₆H₄(CH₂PBO)₂}Cl₂, 14, cis-Pt{o-C₆H₄(CH₂PBO)₂}Cl₂, 15 and Mo(CO)₄{o-C₆H₄(CH₂PBO)₂} 17.