TANDEM INTER[4- 17 - THE SPIRO MODE - EFFICIENT AND HIGHLY SELECTIVE SYNTHESIS OF AZAPROPELLANES(2]CYCLOADDITIONS INTRA[3+2]CYCLOADDITIONS )

A new variant of the tandem inter [4 + 2]/intra [3 + 2] nitroalkene cy cloaddition has been developed. Intermolecular [4 + 2] cycloaddition o f a 2-nitroalkene (bearing an unsaturated ester moiety, the dipolaroph ile) with a vinyl ether produces a cyclic nitronate substituted at C(3 ) wherein the only stereogenic center is the anomeric carbon C(6). Sin ce the dipolarophile is attached to a tether extending from the C(3) o f the nitronate (a-carbon of the nitroalkene), the intramolecular [3 2] cycloaddition affords a spiro tricyclic nitroso acetal. The cycloa ddition proceeds smoothly for three- and four-atom tethers to afford f ive- and six-membered rings. Both E- and Z-unsaturated esters serve we ll as dipolarophiles, but the E-isomers react more selectively. Hydrog enolysis of the nitroso acetals affords the spiro tricyclic alpha-hydr oxy lactams in good yield. Remarkably high levels of asymmetric induct ion are observed with the use of a chiral vinyl ether derived from (1R ,2S)-2-phenylcyclohexanol. The origin of asymmetric induction is a com bination of the established face selectivity of the enol ether and the preference for a distal fold of the tether away from the: substituent on the anomeric carbon. The scope and limitations of this transformat ion and an analysis of the origin of stereoselectivity are provided.