Synthesis of Novel Chiral Diamino Alcohols and Their Application in Copper-Catalyzed Asymmetric Allylic Oxidation of Cycloolefins

Abstract

Optically active amino alcohols are one of the important classes of compounds because of their presence in the natural products. They have also found applications as chiral ligands and auxiliaries for a variety of asymmetric reactions. Furthermore, diamino alcohols and their hydroxyldiamide precursors, in particular, are core units in many medicinal compounds such as HIV protease inhibitors A80987 (3), A77003 (4) and lacosamide (5) (Scheme 1). Due to the importance and high efficiency of chiral hydroxyldiamide, chiral amino alcohols and their methoxy analogy, our attention was focused on the development of a simple and efficient method to produce a small library of enantiomerically pure diamino alcohols 1 and their hydroxyldiamide precursors 2 from readily available starting materials. Although the asymmetric synthesis of vicinal amino alcohols has been extensively studied, however, there have been a few reports of asymmetric synthesis to diamino alcohols, which may become precursors of new kinds of amino alcohol compounds. The chiral hydroxyldiamides 2, which appear structurally similar to molecules 3-5, can be expected to provide more opportunities for the development of biologically active compounds. Moreover, the chiral diamino alcohols, 1, can be used in the asymmetrical reactions as a catalyst to increase reaction rate and as a chiral auxiliary or chiral ligand to induce the chirality in the synthesis of chiral products. Enantioselective allylic oxidation of olefins using copper chiral complexes have been the subject of great interest during the last decade. This reaction provides an access to chiral allylic alcohols, which are the key intermediates in natural products synthesis. Since the use of chiral amino alcohol ligands has been less studied on asymmetric Kharasch reaction, our increasing interest was concentered on the demonstration of catalytic and asymmetric effects of the chiral tridentate diamino alcohols 1 in the asymmetric copper-catalyzed allylic oxidation of cycloolefins. To the best of our knowledge, all the reported allylic oxidations suffer from at least one disadvantage in terms of long reaction times, unsatisfactory yields, or low enantioselectivities. Apparently, yields and ees achieved in this work are superior for the allylic oxidation of cycloolefins in comparison with other works that used chiral amino alcohols as ligands.