A new asymmetric synthesis of both enantiomers of P-substituted ketones is described.
Our recent investigation on the chemistry of activating a chiral protecting group by organometallic reagents' has prompted us to report a stereoselective conjugate addition of organoaluminum compounds to chiral o, P-unsaturated ketals, which, complementary to hitherto existing methodologies, provides a useful synthetic tool for preparation of optically active P-substituted ketones.
2
The starting cy, @-unsaturated ketal 1 was readily prepared by transacetalization of 2-cyclohexenone dimethyl keta13 with (S, S)-(-)-N, N, N', N'-tetramethyltartaric acid diamide ( 2)4 in 85-90% yield. Treatment of &, in toluene with trimethylaluminum (5 equiv) at 25°C for 3 h furnished after acetylation the conjugate adduct 3_ exclusively in 94% yield. The optical pirity of 3 was established to be 77% ee by GC analysis after converting to the acetal 4, of (-)-(2R,4R)-2,4-pentanediol (5J (cat. TsOH, toluene reflux, 90% yield). Hydrolysis of g (6N HCl-Dioxane) gave rise to (S)-3-metbylcyclohexanone ( c)5 in 85% yield. The choice of the tartaric acid diamide 2 as a chiral auxiliary is crucial for obtaining the high diastereoselection : Attempted reaction of P-cyclohexenone ketal derived from (-)-(2R_, 3R_)-2,3butanediol (1) with Me3A1 under the comparable conditions resulted in formation of the conjugate adduct (91% yield) with a low level of asymmetric induction (-23% ee). '