ASYMMETRIC INDUCTION IN THE MICHAEL INITIATED RING-CLOSURE REACTION

The Michael Initiated Ring Closure reaction has been explored with an eye toward achieving asymmetric induction. The formation of three, fiv e and six-membered rings was examined using compounds 1-7 as substrate s. In the case of cyclopropane formation, diastereoselectivity was stu died over a range of temperatures, the best results being obtained bet ween -68 and -72 degrees C using lithium 1-buthylthiolate as the nucle ophile and a 10-dicyclohexylsulfamoyl-D-isoborneol-derived auxiliary ( 72-78% yield, 50-56% de; note equation 5). An isokinetic point is beli eved to occur between -41 and -68 degrees C. 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 (2-6% de). Five and six-membered rings were formed in good to excellent yields (62-97%) with diastereometric excesses reaching as high as 95% in the case of cyclohexyl ester forma tion, using lithium diisopropylamide as the nucleophile and the 10-dic yclohexylsulamoyl-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 condu cting both reactions at low temperature, one can use this rate differe nce to assess the diastereomeric excess obtained in the conjugate addi tion of LDA to the six-membered ring precursor 7. The de obtained in t his manner (ca 95%) agreed within experimental error with that obtaine d when the reaction was conducted at a low temperature where cyclizati on occurred.