Benzylic substituent effects

Most benzylic solvolyses generating relatively stable carbocations belong to a category to which the Brown constants are effectively applicable. Extensive data on a,a-dialkylbenzyl solvolyses are available from Brown s original studies, and a wide set of benzylic substituent effects were included in Johnson s (1978) compilation of Brown correlations. Although all these... 

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

The method is very useful for the synthesis of physiologically interesting a-mcthylamino acids, e.g., methyl dopa from the 3,4-dimethoxybenzyl derivative. The excellent stereoselection achieved in the process, however, is caused by the preferential crystallization of one pure diastereomerfrom the equilibrium mixture formed in the reversible Strecker reaction. Thus, the pure diastcrcomers with benzyl substituents, dissolved in chloroform or acetonitrile, give equilibrium mixtures of both diastereomers in a ratio of about 7 347. This effect has also been found for other s-methylamino nitriles of quite different structure49. If the amino nitrile (R1 = Bn) is synthesized in acetonitrile solution, the diastereomers do not crystallize while immediate hydrolysis indicates a ratio of the diastereomeric amino nitriles (S)I(R) of 86 1447. 

A good correlation with ordinary Hammett a values was based on 16 well-behaved substituents, and p-SOMe conformed well to this. Various other substituents showed deviations which were attributed to enhanced + R effects. These included p-SPh and this was explained in terms of 7t(pd) bonding, which was thus taken to play no part in the effect of p-SOMe on the methyl hyperfine splitting. More recently several 4-substituted benzyl radicals of the type RSO C6H4CH2 (n — 0,1 or 2 R = Me, Ph, Tol, COMe or OMe) have been examined by ESR spectroscopy249. The ability to delocalize spin density onto the substituent decreases in general as n increases and the effect of R depends on the oxidation state of sulfur. These authors have devised a new scale of substituent effects (sigma dot... 

Vergely, I. Boggetto, N. Okochi, V. Golpayegani, S. Reboud-Ravaux, M. Kobaiter, R. Joyeau, R. Wakselman, M. Inhibition of human leucocyte elastase by functionalized V-aryl azetidin-2-ones substituent effects at C-3 and benzylic positions. Eur. J. Med. Chem. 1995, 30, 199-208. 

A violent explosion occurred at the start of bulb-tube distillation of a 2 g sample of the crude aldehyde (b.p. 9774 mbar) at 75°C/0.13 mbar [1], It seems likely that the crude product could have formed peroxide during the 2 day s storage (in a closed but not hermetically sealed vessel) between preparation and distillation. The structure is such that the proton on C-2, which effectively has 2 benzyl substituents and an adjacent carbonyl function, seems rather susceptible to autoxidation [2], See other aldehydes, peroxidisable compounds... 

Finally, it is worth noting that the substituent effects are different on the two types of Menshutkin reactions as well. For the benzyl substrates, changing to a better nucleophile, i.e. changing the substituent on the nucleophile from the meta-nitro to a para-methoxy substituent, leads to a later, more product-like transition state with more inverse secondary incoming nucleophile deuterium kinetic isotope effects. Flowever, the same change in nucleophile in the reactions with the methyl and ethyl substrates leads to an earlier transition state and less inverse secondary incoming nucleophile deuterium kinetic isotope effects. 

With label in the benzyl alcohol, the secondary KIE (H/T) is 1.34-1.38 while the equilibrium isotope effect is 1.33-1.34. Substituent effects, by contrast, indicate a transition state that resembles the reactant state, not the product state. 

Benzylic radicals offer themselves to a similar analysis. Some barriers to rotation have been determined (Conradi et ai, 1979). The barrier to rotation of 9.8 + 0.8 kcal mol for the a-cyano-a-methoxybenzyl radical [21] (Korth et al., 1985) could not be interpreted rigorously in terms of a captodative effect because estimates had to be made for the effect of a single captor or donor substituent on the rotational barrier. Within these limitations the barrier does not reflect more than an additive substituent effect. 

TABLE 1. Substituent effect for abstraction of benzylic hydrogen by radicals... 

If this is the case, substituent effects in the distal ring of a 4-biphenylyl-nitrenium ion should resemble those of a benzylic carbenium ion. Ren and McClelland showed that substituent effects on log for a series of distally substituted 4-biphenylylnitrenium ions (75n, 75p-v) were carbenium-ion-like. A plot of log kg vs. cr was not highly scattered but was non-linear and similar to those previously described for diarylmethyl and triarylmethyl... 

In this section we generated an -value of by taking the family of identity exchange reactions of benzyl derivatives (109) (Pross, 1983). That particular -value is sufficiently anomalous to deter any possible application to questions of transition state structure. Yet there are cases that are, in principle, quite similar to the identity exchange reaction in which a-values are utilized as a measure of transition state structure. In such cases we believe the conclusions may not be valid. A typical example (Bell and Sorenson, 1976) is the addition of hydroxide ion to substituted benzaldehydes (110). For this system the sensitivity of rates and equilibria to substituent effects was similar. 

For the effect of benzylic substituents examined with the methoxychlor analogs, Eq. 59 was formulated. 

Arylaziridinium salts exhibit an unusual behavior in aqueous buffer solution in that the half-wave potentials become more negative on introduction of electron-attracting groups this is contrary to expectation. The abnormal substituent effect for aziridinium salts can be interpreted as involving development of a partial positive charge at the benzylic carbon before electron transfer.182... 

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