Bromination a-methyl

The optical rotatory dispersion curves of steroidal ketones permit a distinction to be made between the conformations, and assignment of configuration is possible without resorting to chemical methods (see, e.g. ref. 36) which are often tedious. The axial halo ketone rule and, in the more general form, the octant rule summarize this principle and have revealed examples inconsistent with the theory of invariable axial attack in ketone bromination. 2-Methyl-3-ketones have been subjected to a particularly detailed analysis. There are a considerable number of examples where the products isolated from kinetically controlled brominations have the equatorial orientation. These results have been interpreted in terms of direct equatorial attack rather than initial formation of the axial boat form. 

A number of alkyl and dialkyl (mainly methyl) benzofuroxans are known. The 4-methyl compound resisted attempts to brominate the methyl group and to oxidize it to the carboxylic acid. ... 

Although the biosynthetic cascade hypothesis predicts the co-occurrence of endiandric acids D (4) and A (1) in nature, the former compound was not isolated until after its total synthesis was completed in the laboratory (see Scheme 6). Our journey to endiandric acid D (4) commences with the desilylation of key intermediate 22 to give alcohol 31 in 95% yield. The endo side chain is then converted to a methyl ester by hydrolysis of the nitrile to the corresponding acid with basic hydrogen peroxide, followed by esterification with diazomethane to afford intermediate 32 in 92% overall yield. The exo side chain is then constructed by sequential bromination, cyanide displacement, ester hydrolysis (33), reduction, and olefination (4) in a straight-... 

Pyrazolo[l,2-a]pyrazoles give 3-bromo products unless the 3-position is blocked by a methyl when bromomethyl products arise (80JA4983 81JOC1666, 87JOCI673). When all of the pyrazole ring positions are filled by phenyl groups, chlorination and bromination occur in thepara-positions (74BCJ946) (see also B, 1,2). 

The most extensive study of the effect of conditions upon the kinetics of bromination was made by Robertson et al.23l 279, who measured the rates of bromination of alkylbenzenes, acetanilide, aceto-p-toluidide, mesitylene, anisole and p-tolyl methyl ether in acetic acid at 24 °C. They found that at relatively high concentrations of bromine (A//40-M/100) the reaction is second-order in bromine, i.e. the rate equation is... 

Recognize molecular symmetry planes and axes. Even approximate, or local symmetry elements may be useful. One should not step back just because, formally, the molecule has no symmetry elements. A methyl and an ethyl substituent, or chlorine and bromine substituent, can be equated. Substituents that disrupt the molecular symmetry but have trivial electronic requirements may be deleted. 

Sn2 and SN2 Reactions with Halides and Sulfonates. Corey and Posner discovered that lithium dimethylcuprate can replace iodine or bromine by methyl in a wide variety of compounds, including aryl, alkenyl, and alkyl derivatives. This halogen displacement reaction is more general and gives higher yields than displacements with... 

Fig. 7 Comparison of the X-dependence of the a-methyl effect in bromination and hydration of X-substituted styrenes (data from Ruasse et al, 1978).

Fig. 12 Selectivity-reactivity relationships in arylolefin bromination. Line A correlates the data for styrenes, stilbenes and their a-methyl derivatives, and line B those of 1,1-diarylethylenes and a-methoxystyrenes (Tables 15 and 17).

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

The reaction of bromine with the optically active (i )-a-methyl-vinyl p-total sulfoxide 322 also yields a mixture of diastereomeric sulfoxides 323 their ratio, estimated by the NMR method, was 71.5 28.5. 

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