Ambiphilic reduction of cyclohexanones with methylaluminum bis(2,6-di-tert-butyl-4methylphenoxide) and tert-butylmagnesium chloride provides the corresponding equatorial alcohols with high stereoselectivity.
. In connection with our recent project on the utility of ambiphilic systems in organic synthesis, 1
we wish to report a conceptually new, ambiphilic reduction of cyclohexanones leading to the highly stereocontrolled synthesis of equatorial alcohols. 2 This method is based on the stereoselective activation of carbonyl moiety using methylaluminum bis(2, 6-di-tert-butyl-4-methylphenoxide)3
(abbreviated to MAD) and subsequent reduction of the resulting ketone-MAD complex with tert-alkylmagnesium halide.
t -BuMgCI a8 ox
Treatment of 4-tert-butylcyclohexanone with MAD in toluene' at 0Β°C followed by addition of tert-butylmagnesium chloride in ether at this temperature gave rise to a mixture of axial and equatorial alcohols, L and 2, in 88% yield. GC analysis indicated the ratio of the ax/es alcohol to be 1: 99.
' Isolated yield.
' Determined by GC analysis.
f. Initial treatment of MAD with t-BuMgCl at 0Β°C for 30 min and subsequent addition of the ketone at 0Β°C.
' MAD was prepared in CH2C12.