DIENE-DIENOPHILE HYDROGEN-BONDING CONTROL OF DIELS-ALDER REACTIONS WITH DIENES BEARING A REMOTE STEREOGENIC CENTER - AMPLIFICATION OF THE RECEPTOR NATURE OF DIENES BY CONFORMATIONAL TUNING LEADING TO HIGH DIASTEREOFACIAL DISCRIMINATION

The Diels-Alder reactions of 1-(O-methylmandeloxy)butadiene and its analogues, bearing a remote stereogenic center, have been studied to elucidate the stereoselective control elements. Several model dienes (5a-5f) have been designed to enhance the facial selectivity at room temperature. The design concept of these dienes is based on our proposed perpendicular model (Siegel, C.; Thornton, E.R. Tetrahedron Lett. 1988, 29, 5225-5228), which we used to rationalize the diastereofacial preference observed with diene 1. Our approach to increasing the diastereoselectivity was to enhance the population of the preferred diene rotamer in the ground state as well as in the transition structure. From X-ray structures of the cycloadducts and the reversal of facial selectivity with dienes having a free hydroxy group at the chiral center, we conclude that diene-dienophile coordination through hydrogen bonding plays an important role in promoting chirality transfer. We postulate that facial selectivity is controlled by a balance of two competing forces (stereoelectronics vs hydrogen bonding) on the diene conformation in the transition structure. Conformational tuning at the stereogenic center helped in designing a diene (5e), which aims at maximizing the hydrogen-bonding interaction by decreasing the stereoelectronic preference. This diene exhibited high diastereoselectivity with an array of dienophiles at ca. 25-degrees-C, without employing any external catalyst.