Asymmetric Induction in the Michael Initiated Ring Closure Reaction

Article abstract of DOI:10.1016/S0040-4020(01)85631-3

The Michael Initiated Ring Closure reaction has been explored with an eye toward achieving asymmetric induction.The formation of three, five and six-membered rings was examined using compounds 1-7 as substrates.In the case of cyclopropane formation, diastereoselectivity was studied over a range of temperatures, the best results being obtained between -68 and -72 degC using lithium t-butylthiolate as the nucleophile and a 10-dicyclohexylsulfamoyl-D-isoborneol-derived auxiliary (72-78percent yield, 50-56percent de; note equation 5).An isokinetic point is believed to occur between -41 and -68 degC.No improvement in de was observed when the Oppolzer sultam was used instead (compound 18).The use of (-)-menthol and (-)-8-phenylmenthol derived auxiliaries led to substantially inferior results (2-6percent de).Five and six-membered rings were formed in good to excellent yields (62-97percent) with diastereomeric excesses reaching as high as 95percent in the case of cyclohexyl ester formation, using lithium diisopropylamide as the nucleophile and the 10-dicyclohexylsulfamoyl-D-isoborneol-derived auxiliary.Note equations 7 and 8.As expected, cyclization affording the five-membered ring adducts proceeded substantially faster than those leading to the six.By conducting both reactions at low temperature, one can use this rate difference to assess the diastrereomeric excess obtained in the conjugate addition of LDA to the six-membered ring precursor 7.The de obtained in this manner (ca. 95percent) agreed within experimental error with that obtained when the reaction was conducted at a temperature where cyclization occurred.