Cieplak model

This reviews contends that, throughout the known examples of facial selections, from classical to recently discovered ones, a key role is played by the unsymmetri-zation of the orbital phase environments of n reaction centers arising from first-order perturbation, that is, the unsymmetrization of the orbital phase environment of the relevant n orbitals. This asymmetry of the n orbitals, if it occurs along the trajectory of addition, is proposed to be generally involved in facial selection in sterically unbiased systems. Experimentally, carbonyl and related olefin compounds, which bear a similar structural motif, exhibit the same facial preference in most cases, particularly in the cases of adamantanes. This feature seems to be compatible with the Cieplak model. However, this is not always the case for other types of molecules, or in reactions such as Diels-Alder cycloaddition. In contrast, unsymmetrization of orbital phase environment, including SOI in Diels-Alder reactions, is a general concept as a contributor to facial selectivity. Other interpretations of facial selectivities have also been reviewed [174-180]. 

Natural bond orbital analysis of early and late TSs has been carried out to explore the factors involved in tt-selectivity of nucleophilic addition to carbonyls.209 Cieplak s o —r o hyperconjugation hypothesis (where o is the incipient bond) is not supported by the results for early TSs, and evidence in favour of Felkin-Anh s o er hypothesis is weak. Late TSs are devoid of o 7r(t=() interactions here, the Cieplak model may be applicable. 

Fig. (9). Stereoelectoronic effect. (A) Funk model (B) Cieplak model)...

Cieplak ° countered the Anh explanation with an alternative orbital model. He noted that reductions of cyclohexanones and other additions at carbonyls occasionally resulted in the major product coming from the Eelkin-Anh minor TS. Arguing that since the incipient bond was electron deflcient—a partial bond lacks the full two-electron occupation—it is donation of density from the Oc2-l into the Oc-nuc oi ital that will stabilize the TS (Scheme 6.3). Support for the Cieplak model was provided by experimental results for nucleophilic addition to... 

Frenking also examined the reaction of LiH with 3-fluorocyclohexanone, for which four TSs were located. Fluorine can occupy either the equatorial (32) or the axial (33) position and then attack can come from the axial or equatorial faces. The Cieplak model does not distinguish between 32 and 33, predicting axial attack for both. While axial attack is preferred in 32, equatorial attack is favored by 2.3 kcal mol over axial attack in 33. Frenking suggests that this difference is reflected in the orbital coefficients of the LUMO of 32 and 33. A simpler explanation, one that will be further explored next, is that electrostatic interactions between the hydride and the axial fluorine destabilize 33ax relative to 33eq. 

Figure 6-9. Cieplak model for axial and equatorial attack a clear preference for axial addition is indicated [32J.

Le Noble has pointed out a similarity between Cieplak transition state stabilization and Win-stein s proposal of (T assistance in the formation of carbocations [8a, 51]. In the Cieplak model, neighbouring cr-electrons delocalise into the electrons delocalise into a vacant p orbital. 

D. Kaneno and S. Tomoda, Origin of facial diastereoselection in 2-adamantyl cations. Theoretical evidence against the Felkin-Anh and the Cieplak models, Tetrahedron Lett., 45 (2004) 4559 1562. 

The reduction of 4-ferf-butylcyclohexanone by LiAlH4 in THF at 0 °C affords a mixture of the tram- and ris-alcohols in 88.5 11.5 ratio (Table 1) [9]. The predominant attack takes place obviously from the axial direction as predicted above by the Cieplak model. This selectivity is expected to diminish when the ring carries an equatorial methyl group on C3 because it will (a) not introduce an element of steric interaction during the course of the nucleophilic addition, and (b) raise... 

Following the Cieplak model, the ease of axial approach of a given nucleophile must therefore decrease in the same order. However, from the experimental results... 

Like the N- m e t h y I - 2 - ad a m a n ta n o ne species above, 5-aza-2-adamantanone N-oxide exhibits axial selectivity by a margin of 96 4 on reduction with NaBH4 in isopropanol. Cieplak model predicts axial selectivity for the overall electron-attracting character of the N+-0 bond. The Anh-Felkin model fails as it is opposite of the Cieplak model in concept and allows attack of a nucleophile anti to the more electron-deficient bond on the a carbon. The computed 3D structures of 5-aza-2-adamantanone N-oxide and its protonated derivative are shown in Fig. 12. 

The Cieplak model fails as it predicts axial attack for the electron-attracting nature of the boron atom. For the same reason, however, the Anh-Felkin model succeeds in predicting the equatorial selection. Houk s TS model also succeeds in predicting the equatorial preference. Since D2 is 4° larger than D1 in 5-bora-2-adamantanone, less destabilizing interactions in the TS for equatorial attack over those in the TS for axial attack are expected. The computed 3D structures of 5-bora-2-adamantanonc and its above derivatives are shown in Fig. 13. 

The Cieplak model emphasizes an alternative interaction, between the ct orbital of the C-X bond and the antibonding orbital to the nucleophile.In this case, a better donor X should be the most stabilizing. Li and le Noble pointed out that both of these hyperconjugative interactions will be present in the transition structures There is also general agreement that addition of reactive nucleophiles have early transition states, which would suggest that substituent effects might best be examined in the reactant. 

Both the Felkin-Ahn and Cieplak models are also applied to alkyl substituents. 

These effects are attributed to differences in the a-donor character of the C-C bonds resulting from the substituent (Cieplak model). Electron-attracting groups diminish the donor capacity and promote syn addition. An alternative explanation invokes a direct electrostatic effect arising from the C-X bond dipole. ... 

The diastereofacial selectivity is inconsistent with a Cieplak model, since the crotyl group would have to approach from the side syn to the CT methyl. The low C2, C3 synjanti selectivity could be due to competitive rearrangement via a boat transition state, although it is not obvious why the boat transition state should be of similar energy in this case. 

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