Investigating the pi-facial discrimination phenomenon in the conjugate addition of amines to chiral crotonates: A convenient basis for the rational design of chiral auxiliaries

This paper is concerned with the nature of the chiral inducer in the high pressure-induced conjugate addition of amines to auxiliary-tethered crotonates. Almost complete stereocontrol was obtained in the addition of diphenylmethanamine to crotonates derived from the ''arylmenthol'' auxiliaries 18a, 18c, and 4 bearing an o-methoxyphenyl, p-phenoxyphenyl, or beta-naphthyl substituent, respectively. This high efficiency has been attributed to the predominance of stacked conformations in such crotonates, a hypothesis supported by the H-1 NMR spectra, calculated energy of conformational optima of the corresponding crotonates, and X-ray crystal structure of 5a. The arene and enoate appendages are roughly coplanar, separated by 3.4-4 Angstrom. In contrast, only moderate selectivities could be achieved using various trans-2-arylcyclohexanols (27, 28, 2c, 29) as auxiliaries. In these cases the efficiency appears to be seriously compromised by the ''widening V'' arrangement exhibited by the two pi-systems, as shown in the X-ray crystal structures of crotonates 5 h and 5 k. The sense of stereochemical induction of this conjugate addition has been determined by condensing diphenylmethanamine with enantiopure crotonate (+)-5a. The adduct 9a was converted to amino alcohol (S)-11, of known configuration. This correlation is consistent with the preferential attack of the amine to the less sterically hindered enoate pi-face of(+)-5a, in its s-trans conformation. Finally, the stereochemistry of the proton transfer was determined by adding N,N-dideuteriodiphenylmethanamine to crotonate (+/-)-5a. The stereochemical outcome of this addition is consistent with the anti-addition of the incoming nitrogen nucleophile and the deuterium atom.