Effect of stereoelectronics

The effect of stereoelectronic interactions on three- and four-bond proton-proton couplings in hydrocarbons has been studied by Sproviero and Burton. ... 

Redirecting reactions via conformational control In the final example of this chapter, we will show how understanding of enzyme stereoelectronics allows one to redirect reactivity of known substrate into a new direction. When the stractural constraints of enzyme active sites are removed, a new set of stereoelectronic constraints can be imposed on the same substrate to enforce a different reactivity. For example, the effect of stereoelectronic factors on the relative order of steps in the deprotonation/decarboxylation sequence were recently analyzed for an enzyme-catalyzed vs. Cu-catalyzed reactions of the similar substrates (Figure 11.66). The first process is involved in the biosynthesis of polyketides and fatty acids where enzymatic activation of... 

The more stable the LUMO, the stronger is the interaction with the HOMO of the approaching nucleophile. The observed (Cram s rule) stereoselectivity is then a combination of stereoelectronic effects ftiat establish a preference for a perpendicular substituent and a steric effect that establishes a preference for the nucleophile to approach from the direction occupied by the smallest substituent. 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

In contrast to ordinary chiral aldehydes (having no ability to be chelated), the reaction of 9-allyl-9-borabicyclo[3.3.1]nonane(allyl-9-BBN) with the corresponding chiral imines 4 produces the isomer syn-6 either exclusively or predominantly (Cram selectivity Table 8)5,6. The very high 1,2-asymmetric induction is explained by a six-membered. chair-like transition state, in which the inline R group occupies an axial position due to the stereoelectronic effect of imines (R CH = NR). 

The diastereoselectivity observed can be explained by a synclinal transition state, probably influenced by chelation and/or stereoelectronic effects of the developing cation38. The minor product is formed via an antiperiplanar transition state. All compounds obtained are useful precursors for several spirocyclic natural products, such as terpenes like lubimine or acoradi-ene. 

A further example of the importance of this type of stereoelectronic effect is seen in the reactions of /-butoxy radicals with spiro[2,n]alkanes (22) where it is found that hydrogens from the position a- to the cyclopropyl ring arc specifically abstracted. This can be attributed to the favorable overlap of the breaking C-H bond with the cyclopropyl cr bonds.120131 No such specificity is seen with bicyclo[n, 1,0]alkanes (23) where geometric constraints prevent overlap. 

This chapter describes the chemical behavior of a-sulfinyl and a-sulfonyl carbanions. The stereoelectronic effects of these sulfur-containing groups have been the subject of much controversy for more than a decade which has now gradually settled down. Meanwhile, the special features of the chemical behavior of these groups have been utilized for syntheses of thousands of useful organic substances. This chapter deals with the... 

Sulphuranes - see also Dialkoxysulphuranes, Oxysulphuranes as intermediates 406 Sulphur bonding 484-493 Sulphur-containing groups, stereoelectronic effects of 584-594 Sulphur dioxide addition to 215-217 extrusion of 137, 140, 141, 158, 163, 397-402, 801, 805, 962, 1098 Sulphur monoxide, extrusion of 397-402 Sulphur trioxide, reactions of 217, 218 Sultenes, as intermediates 743 Sultines 679, 943 as photolytic products 881, 882... 

The efficiency of cyclization can also be affected by stereoelectronic factors. For example, there is a significant difference in the efficiency of the cyclization of the Z- and F-isomers of 3. Only the Z-isomer presents an optimal alignment for electronic stabilization.14 These effects of the terminating substituent point to considerable concerted character for the cyclizations. 

Carbocations, as we learned in Chapter 4 of Part A, can readily rearrange to more stable isomers. To be useful in synthesis, such reactions must be controlled and predictable. This goal can be achieved on the basis of substituent effects and stereoelectronic factors. Among the most important rearrangements in synthesis are those directed by oxygen substituents, which can provide predictable outcomes on the basis of electronic and stereoelectronic factors. 

This stereoelectronic effect also explains the contrasting regioselectivity of cis- and fra x-2-fluoro-4-f-butylcyclohexanone.235 As a result of a balance between its polar effect and hyperconjugation, the net effect of a fluoro substituent in acyclic systems is small. However, in 2-fluorocyclohexanones an unfavorable dipole-dipole interaction comes into play for the cis isomer and preferential migration of the fluoro-substituted carbon is observed. 

A further test of the stereoelectronic theory of reactivity of phosphate esters has been attempted using measurements of the rates of displacement of 4-nitrophenate from the esters (23) and (24), their phosphorus epimers, and also (25), in aqueous methanol the introduction of the 4a-Me group into the system would, it was hoped, reduce the the flexibility of the bicyclic structures and so possibly eliminate the participation of twist-boat conformations. The presence of the 4a-Me group has no effect of the rate of displacement of the axial ArO group... 

Deeth RJ (2001) The ligand field molecular mechanics model and the stereoelectronic effects of d and s electrons. Coord Chem Rev 212 11... 

A further example of the importance of stereoelectronic effects results from the behavior of cis- and m w-2-ii-propyl-4-f-butylcyclohexanone,<9B)... 

The selectivity in the Heck reaction of allylic alcohol 111 is interesting, and the factors that lead to the observed preference for (3-hydride elimination toward nitrogen in this system are unclear, although a combination of steric effects and stereoelectronic factors (i.e., alignment of C-H and C-Pd bonds, nN a c H interactions) is likely involved. Examination of related examples from the literature (Scheme 4.20) reveals no clear trend. Rawal and Michoud examined substrate 115, which lacks the influence of both the amine and hydroxyl substituents and also seems to favor (3-hydride elimination within the six-membered ring over formation of the exocyclic olefin under standard Heck conditions [18a]. However, under... 

The strong stereoelectronic effect of vicinal nN donors is also evident in the product guanidinium cation,... 

White, J. M., Stereoelectronic Effects of the Group 4 Metal Substituents in Organic Chemistry, 22, 137. 

Meyers et al. also studied the stereoelectronic and steric effects of the 7r-lacial... 

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