Tetrahedron Letters,Vol.29,No.37,pp 4653-4656,1988 0040-4039/88 $3.00 + .OO Printed in Great Britain Pergamon Press plc zyxwvutsrqponm A RAPID AND EFFICIENT CYCLOADDITION OF SIMPLE IMINES WITH ACTIVATED DIENES LEADING TO AMINO SUGARS; UNUSUALLY HIGH “CHELATION-CONTROLLED”DIASTEREOSELECTIVITY IN THE ADDITION TO AN a,S-DIHYDROXY IMINE PROTECTEDAS A RETAL. M. Mark Midland* and Jim I McLaughlin Department of Chemistry, University of CaliEornia, Riverside, CA 92521, USA Abstract: The addition of a ketal-protected imine to an activated diene using diethylaluminum chloride as a catalyst leads to an unexpected “chelation-controlled” product. The Lewis acid-mediated cycloadditton of activated silyloxy and alkoxy dienes with alde- hydes has been known for some time and has recently gained attention as a powerful method for the convergent construction of complex structures in a single step.l The extension of these reactions to include ketones has also been recently reported.la The reaction of imines, how- ever, has proven more difficult. Typically, imino Diels-Alder additions are successful only if the imine is activated lk,m in intramolecular additions2 or using iminium salts.3 In 1981, Danishefsky and co-workers reported the first general cycloadditions involving simple, unac- tivated imines using zinc chloride in THF with 1-methoxy-3-(trimethylsilyloxy)-1,3-butadiene (1, .4 Though the reactions were carried out at room temperature, long reactfon times (1.5 to 2 days) and a large excess of the diene (3.0 to 4.6 equiv) were required. Recently Ojima reported that this reaction is facilitated by using titanium tetrachloride as a catalyst.5 We herein report our studies in this area and the unexpected observation of a chelation-controlled process in the reaction of an a,E-dihydroxy imine protected as a ketal. The highly reactive 1,3-dimethoxy-1-(trimethylsilyloxy)butadiene (Brassard’s dienej6 (2) and the unactivated benzylidenemethylamine (2, R=Ph, R’=Me) were chosen for study. Initially it was found that zinc chloride or the mild Lewis acid Eu(hfc)32a,b did not induce reaction, even after prolonged periods of several days. Magnesium bromide provided the desired lactam in moderate yield at room temperature in a matter of hours, prompting us to further expand our study. A survey of common Lewis acids indicated that the stronger Lewis acids, titanium tetrachloride, boron trifluoride etherate and boron tribromide, provided even more rapid addi- tion with less polymerization of the diene and consequently higher yields. These results were in marked contrast to the those obtained in the additions of aldehydes in which the stronger Lewis acids induced greater decomposition of the diene and lower yields of lactonas.*a Finally, the use of highly reactive diethylaluminum chloride was found to cause addition to occur at such a rate that low temperatures were required. 4653