Parabolic Relationship between the Basicity of the Nucleophile and π-Face Selection in Addition of the Substituted Acetylide Ions to Cyclohexanone and Cyclohexanethione

Abstract

Energy changes, structural variation, and electron density shifts during nucleophilic addition to cyclohexanone and cyclohexanethione were examined by means of the ab initio calculations at the HF/6-31G level. The atomic charge on the carbonyl C was found to become more positive upon approach of the nucleophile; the density deformation maps suggest that the charge polarization occurs to a large extent in the pi bond. Since this effect is not compensated for by charge transfer until in the late stage of addition, the reaction site is considerably electron deficient (more so than the carbonyl C in the substrate) for most of the reaction path, and its interactions with the ligands are dominated by hyperconjugation with the vicinal C-H and C-C bonds. Relative stabilities of the axial and equatorial transition-state structures were examined in the series HN=C, ON&tbd1;C(-), N&tbd1;C(-), FC&tbd1;C(-), HC&tbd1;C(-), SBeC&tbd1;C(2-), O(3)SC&tbd1;C(2-), H(3)AlC&tbd1;C(2-), SC&tbd1;C(2-), H(3)BC&tbd1;C(2-), and C&tbd1;C(2-) and found to depend on polarization of the electrophiles, C=O vs C=S, and basicity of the nucleophiles. The latter dependence is parabolic: the axial preference reaches a maximum for the moderately basic anions, and it is diminished or even reversed for the most and least basic nucleophiles, i.e., in the case of reactions proceeding through the very early or very late transition states. Thus, the stereoelectronic effect is largest in the region of the reaction coordinate where the electron deficiency at the reaction site reaches a maximum. These findings corroborate the premises of the hypothesis of hyperconjugative assistance to bond formation and are consistent with major trends in the experimental data if the stereochemistry of alkylation of 4-tert-butylcyclohexanone is correlated with Pauling electronegativity of metals in the case of methylmetals, methylmetal ate complexes, allylmetals and arylmetals, and with the pK(a) of conjugated acids in the case of sulfur-, carbonyl-, and nitrile-stabilized carbanions.

Electronic Control of Facial Selection in Additions to Sterically Unbiased Ketones and Olefins

“…Systematic investigations of the dependence of diastereoselectivities on reagents and solvents are clearly warranted. In particular, electrostatic effects can be effectively monitored by using a greater range of nucleophiles. , The double hyperconjugation model and through-space participation of the C2−C3 bond in the norbornyl systems need closer analysis.…”

Inductive and Resonance Effects of Substituents on π-Face Selection

“…Given the rigid planar geometry of the ketone, the forming bond cannot remain in the transition state antiperiplanar with respect to the vicinal bonds and eventually has to eclipse those bonds. Therefore, the only hyperconjugative interaction that might be maximized in a relatively advanced transition state is the syn -periplanar stabilization of the incipient bond . The cyclopropane C−C bond, a high-energy and diffuse σ-bond, can be a good resonance donor provided that the location of the transition state along the reaction path secures effective overlap, both in terms of the geometry of the transition state and extension of the σ* ⧧ orbital.…”

“…The reader will find some of those other theories discussed elsewhere in the current issue. Critical appraisals of underpinnings of the concepts such as π-orbital desymmetrization, torsional strain, electrostatic interactions, and approach angle-dependent variation in the transition-structure steric strain have been presented earlier. ,− Finally, the scope of the review is limited to π-face selection processes where the stereogenic center and the incipient center are separated by just one bond. Thus, the classic examples of π-face selection such as the atrolactic synthesis or alkylation of metalated Meyers' oxazolines, where the stereogenic and incipient centers are separated by two intervening trigonal centers, are not included in the present discussion.…”

Using Perturbation and Frontier Molecular Orbital Theory To Predict Diastereofacial Selectivity

“…Of the various authors who have considered hyperconjugative interactions, only Cieplak requires that the C−H be stronger than the C−C interactions. His most recent publication on the subject still maintains this position . The Felkin/Anh/Eisenstein and Klein formulations both require the C−C interaction to be the stronger.…”

“…His most recent publication on the subject still maintains this position. 74 The Felkin/Anh/Eisenstein and Klein formulations both require the C-C interaction to be the stronger. Cieplak needed to reverse the order so that his procedure would correctly predict the (known) diastereofacial selectivity of the reduction of cyclohexanone.…”