Torsional and Steric Effects Control the Stereoselectivities of Alkylations of Pyrrolidinone Enolates

Torsional control of stereoselectivities in electrophilic additions and cycloadditions to alkenes

“…40 The two alkylation transition states located by HF calculations are shown in Figure 18; these are similar to those reported by Blake. 39a The α-attack was favored over β-attack by 1.7 kcal/mol.…”

“…The Houk group synthesized the corresponding cyclopentanone, and established that the same α-stereoselectivity occurred upon alkylation of the enolate. 40 …”

Theoretical Evidence for Pyramidalized Bicyclic Serine Enolates in Highly Diastereoselective Alkylations

“…This phenomenon is seen to a greater extent among other carbanionic species, [13] but very little theoretical evidence for pyramidalized enolates has been reported to date. [14] Moreover, to the best of our knowledge, all reported calculations concerning the stereoselective alkylation of enolates refer to cyclic or bicyclic lactams (diazepine-2-ones, [15] pyrrolidinones, [16] oxazolopiperidones [17] ) or lactones, [18] in which the enolate moiety is endocyclic; in our case the enolate is exocyclic.…”

Novel peptidomimetic structures: enantioselective synthesis of conformationally constrained lysine, ornithine and alanine analogues from pyroglutamic acid

“…Molecular modeling of the N-acetyl analogue 11 of compound 10 25 demonstrated that two well defined conformations existed, differing by 2.3 kcal mol 21 in energy, with the two substituents either pseudodiequatorial or diaxial, and the latter being the more stable; since a 2.7 kcal mol 21 energy difference corresponds to a 99+1 ratio of species at equilibrium, 34 the This journal is © The Royal Society of Chemistry 1999 minor diequatorial conformer would not be expected to be observable at room temperature by NMR analysis, and 1 H NMR VT analysis provided no evidence for the diequatorial conformer even at 223 K. The stability of the diaxial conformer could be attributed to the presence of A-strain 35 between the two substituents and the planar amide system; the importance of torsional strain in five-and six-membered ring heterocycles for the control of stereochemistry has been investigated in detail, 36 although its importance in lactams has only recently been appreciated. 37 Thus, the diaxial conformer minimises the interations of the relatively bulky C(2) and C(4) substituents with the planar amide function (which would occur in the diequatorial conformer 12a) by placing C(2)-H and C(4)-H in an eclipsing conformation with the lactam system 12b (Fig. 2).…”