Transition state/structure cyclohexanone with

For more conformationally-constrained chiral substrates, however, diastereoselectivity can be expected to be good to excellent. Lithium enolates derived from sterically unencumbered cyclohexanones undergo preferential axial acylation as illustrated by the reductive acylation of (R)-(-)-carvone 4 to afford a 3 1 mixture of esters 5 and 6. whereas equatorial acylation is favored in compounds that possess an alkyl substituent in a 1,3-syn-axial relationship to the reacting center, as in the conversion of tricyclic enone 7 to ester 8 (epimeric with the product from the more traditional sequence of acylation followed by alkylation). (In substrates of this kind it is assumed that the transition state structure is based on a twist-boat conformation which permits the reagent to approach along an axial-like trajectory on the less encumbered, lower face of the substrate.) ... 

The diamond lattice model (Figure 7) was developed using six-membered ring ketone substrates. The determination of forbidden and undesirable positions was achieved by analysis of the relative rates of reduction of a series of cyclohexanones and decalones of known absolute configuration. The geometry indicated at the C-0 centre was considered to resemble the structure of the alcohol rather than that of the ketone in the transition state. It was assumed that all substrate molecules bound with oxygen in the... 

The axial and equatorial transition structures for reduction of cyclohexanone [6] with AIH3 (3-2IG ) (Fig. 6-15) show incipient Hnu-C bond distances of 1.891 and 1.889 A. These are somewhat shorter than for LiH reduction (2.057 and 2.028 A) [28, 51], indicative of a later transition state for AIH3. 

The equatorial transition state shows a Cf-C/j bond extension to 1.560 A (0.84%) compared with the calculated bond length of cyclohexanone (1.547 A), with no extension of the C -Hax bond. Similarly, the C -Cc=o bond length shortened in both axial (1.509 A, 0.4%) and equatorial structures (1.499 A, 1.1%) compared to the corresponding calculated bond length in cyclohexanone (1.515 A). 

With less hindered hydride donors, particularly sodium borohydride and lithium aluminum hydride, cyclohexanones give predominantly the equatorial alcohol. There has been less agreement about the factors that lead to this result. The equatorial alcohols are, of course, the more stable of the two isomers. The stereochemistry of hydride reduction is determined by kinetic control, but it was argued that the relative stability of the equatorial alcohol might be reflected in the transition state and be the dominant factor when no major steric problems intervened. The term product development control was introduced to indicate this explanation of the reaction stereochemistry. A number of objections were raised to this idea, primarily on the basis of the Hammond principle. The common hydride reductions are exothermic reactions with low activation energies. The transition state should resemble starting ketone and reflect little of the structural features that are present in the product, so that it is difficult to see why product stability should determine the product composition. 

With the axial-aryl chair conformation clearly established for all cases of alkaloids in the mesembrine subgroup previously studied, it was surprising to find that the hydrochloride of (—)-mesembrine exists in the solid state with the cyclohexanone ring in a twist-boat conformation, as indicated in 17 (24). A study of the CD of mesembrine hydrochloride in H2O was undertaken in an attempt to seek a possible correlation between the conformation of the hydrochloride in the solid state revealed by the X-ray structure analysis and the solution conformation. Unfortunately, the CD spectrum of mesranbrine hydrochloride in H2O shows the absence of an n ni transition associated... 

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