Nucleophilic addition structural effects

Remote steric effects have also been noted to play an unanticipated role in the sense of asymmetric induction. This is apparent from related condensations carried out on aldehydes 106 (26) and 107 (eqs. [76]-[78]) (26,92). Other examples illustrating the influence of remote structural perturbations on the carbonyl addition process have been observed in these laboratories. The addition of the lithio benzoxazole 110 to aldehyde 108 proceeded with good Cram diastereoface selection (95a), whereas the same nucleophilic addition to aldehyde 109 was stereorandom (95b). 

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

In addition to steric effects, other structural effects of R influence the Sn2 reactivity of RX. A double bond /3 to the halogen,6 as in 2-propenyl, phenylmethyl (benzyl), and 2-oxopropyl chlorides enhances the reactivity of the compounds toward nucleophiles. Thus the relative reactivities toward Iein 2-propanone are... 

Interestingly, the crystal structures of 8-methoxy-l-naphtonitrile and 8-nitro-1-naphtonitrile have been determined by X-ray analysis by Procter, Britton, and Dunitz (24). The structure of the methoxy derivative corresponds to 61 where the exocyclic C —0 bond is bent inward (toward the nitrile group), the exocyclic C-CN bond is bent outward (away from the methoxy group). The C-C = N bond angle is 174° instead of 180°. A similar observation has been made with 8-nitro-l-naphtonitrile. Crystals of this compound contain two symmetry independent molecules which differ in structure. Both show a bent C CN bond and a short 0—C = N distance Icf. 62), but the orientation of the nitro group is different with the result that in one molecule the 0i—Cii distance is 2.69 A whereas in the other, it is 2.79 A. This analysis is in complete agreement with the theoretical calculations and the experimental results presented above. Thus, it can be concluded that the nucleophilic addition on triple-bond (and the reverse process) is strongly influenced by stereoelectronic effects which favor the anti mode of addition. 

In a probe for the presence of stereoelectronic effects in nucleophilic addition to 12 sterically unbiased ketones, calculations have identified subtle bond length differences in the C-Nu bond of the diastereomeric alcohol products, where Nu- = H-or Me-.304 The calculated differences are weak (<1%) but consistent the bond is longer in the major product, acting as a fossil record of the TS. Using microscopic reversibility, the easier bond to cleave (the longer one) is the easier to form. The effect bears comparison with the kinetic anomeric effect in sugars, where such bond length differences in calculation are borne out in X-ray crystal structures. 

Our work on nucleophile addition to quinone methides is a direct extension of studies on the formation and reaction of ring-substituted benzyl carboca-tions,89,90,128 146 and has shown strong overlap with the interests of Kresge and coworkers. The main goal of this work has been to characterize the effect of the strongly electron-donating 4-0 substituent on the reactivity of the simple benzyl carbocation, with an emphasis on understanding the effect of this substituent on the complex structure reactivity relationships observed for nucleophile addition to benzylic carbocations. 

Meisenheimer complex formation as separate reactions. Meisenheimer complexes can be considered as the anionic pseudobases derived from neutral aromatic molecules, and in this light it is clear that heterocyclic Meisenheimer complexes are appropriately considered in the current Review. By so doing, it is hoped that attention can be drawn to potentially mutual benefits that may be derived from comparative studies of neutral and anionic pseudobases. Certainly, the spectroscopic techniques applicable to the study of pseudobase and Meisenheimer complex formation are identical. Quantitative studies of substituent effects and structural effects on rates and equilibria for nucleophilic addition should be relevant both to neutral and to anionic e-complex formation. The general rules enunciated by Strauss23,318 and Fendler319 for the prediction of the relative stabilities of Meisenheimer complexes should be directly applicable to analogous pseudobases. Terrier et al.2n have made an important contribution in this area with a detailed comparison of kinetic and thermodynamic parameters for formation of a benzofuroxan Meisenheimer complex and an isoquinoline pseudobase. 

For such systems, it was found [64] that external addition of some weak nucleophiles, such as esters and ethers for vinyl ethers, decelerates the polymerization, narrows the polymer MWDs, and eventually leads to polymers with controlled molecular weights (cf., Figure 17, A, C, and E). In the example shown in Figure 17C, the added nucleophile is tetrahydro-furan. Later studies by Kennedy and associates revealed that a similar methodology is applicable to isobutene [106]. Examples of the externally added nucleophiles are shown in the following sections for respective monomers. Importantly, those nucleophiles that are effective depends on the structure of monomers. 

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