Conformationally rigid acyclic 2,2,6,6-tetramethyl-3,5-heptanediol (TMHDiol) derivative as a new class of chiral auxiliaries

Article abstract of DOI:10.1021/ja00075a032

As a new chiral auxiliary, a 2,2,6,6-tetramethyl-3,5-heptanediol (TMHDiol) derivative has been developed. This chiral auxiliary is an acyclic, but strongly conformationally biased, molecule. Conjugate addition of lithium TV-benzyl-W-(trimethylsilyl)amide (LSA) to the enoates having a TMHD auxiliary proceeded with high diasteroselectivities to give β-amino esters in high yields, although the use of conventional auxiliaries such as 8-phenylmenthyl and oxazolidone resulted in low diastereoselectivity. Organocopper conjugate addition to TMHD crotonate, heptanoate, and cinnamate produced high diastereoselectivities, and Diels-Alder reaction of TMHD acrylate with cyclopentadiene in the presence of TiCl₄ afforded an endo adduct exclusively with high diasteroselectivity. The addition of LSA proceeded via an s-cis conformation of enoates, but the organocopper addition in the presence of BFOEt₃· and the Diels-Alder reaction in the presence of TiCl₄ proceeded through an s-trans form.