Methyl group elimination reactions

In the E2 reaction just shown, methoxide reacts as a base rather than as a nucleophile. Most strong nucleophiles are also strong bases, and elimination commonly results when a strong base/nucleophile is used with a poor SN2 substrate such as a 3° or hindered 2° alkyl halide. Instead of attacking the back side of the hindered electrophilic carbon, methoxide abstracts a proton from one of the methyl groups. This reaction takes place in one step, with bromide leaving as the base abstracts a proton. 

Treatment of the sulfone 35 with three equivalents of butyllithium gave an intermediate selectively dimetalated at C-2 and the adjacent methyl group. Subsequent reactions of this species with aromatic or heteroaromatic esters, such as methyl thiophene-2-carboxylate, and final acid induced elimination of water, gave a series of thieno[ 3,2 -6] thiophene 1,1-dioxide systems, for example 36 <07S1827>. On the other hand, 3-methylthiophene undergoes selective deprotonation at C-5 upon treatment with lithium 2,2,6,6-tetramethylpiperidide (LiTMP), giving access to a 2,4-disubstituted thiophene derivatives <07JOC 1031>. 

Ureidomethylphosphonium salts, which contain a hydrogen substituent on N-1, follow a p-elimination pathway similar to the one indicated in equation (IS) giving the tertiary phosphine, but if the N-1 position is blocked by a methyl group the reaction follows the 5np pathway giving the tertiary phosphine oxide (Scheme 41),229... 

In the presence of bulky X ligands, a facile methyl halide elimination reaction is observed (Eq. 2) [3]. In this elimination the siliconium ion complex 2, with its two N—>Si dative bonds, is converted into a neutral pentacoordinate complex 3, with only one remaining dative bond (Fig. 1, Table 1). The reaction is probably driven by partial release of steric interaction, caused by the removal of one of the A-methyl groups. This is indicated by a decrease in elimination rate in the presence of less bulky ligands, cyclohexyl and isobutyl, and the failure to observe elimination when X = methyl. The reactivity order of the halide ions follows their nucleophilicities F > Br > CF, while the less nucleophilic ttiflate ion does not react at all. 

The ability to promote j8 elimination and the electron donor capacity of the jS-metalloid substituents can be exploited in a very useful way in synthetic chemistry. Vinylstannanes and vinylsilanes react readily with electrophiles. The resulting intermediates then undergo elimination of the stannyl or silyl substituent, so that the net effect is replacement of the stannyl or silyl group by the electrophile. The silyl and stannyl substituents are crucial to these reactions in two ways. In the electrophilic addition step, they promote addition and strongly control the regiochemistry. A silyl or stannyl substituent strongly stabilizes carbocation character at the j3-carbon atom and thus directs the electrophile to the a-carbon. Molecular orbital calculations indicate a stabilization of 38 kcal/mol, which is about the same as the value calculated for an a-methyl group. The reaction is then completed by the elimination step, in which the carbon-silicon or carbon-tin bond is broken. 

A similar strategy has been investigated by Barco et al. in their approach to the synthesis of piperidin-4-one derivatives 461 (Scheme 69). Starting from Merrifield-SH resin, Barco et al. prepared 4-benzylsulfonyl-l-triphenyl-phosphoranylidene-2-butanone 457 via addition of butanone/AcOH, oxidation of the sulfide to sulfone and selective bromination of the terminal methyl group. After reaction with aldehydes 458 to a. S-unsaturated ketones 459 a cyclization-elimination process occurs via addition of N-nucleophiles like benzylamine 460. 

Another protecting group of amines is 1-isopropylallyloxycarbonyl, which can be deprotected by decarboxylation and a /3-elimination reaction of the (tt-l-isopropylallyl)palladium intermediate under neutral conditions, generating CO2 and 4-methyl-1,3-pentadiene. The method can be applied to the amino acid 674 and peptides without racemization[437]. 

The least sterically hindered p hydrogen is removed by the base m Hofmann elim matron reactions Methyl groups are deprotonated m preference to methylene groups and methylene groups are deprotonated m preference to methmes The regioselectivity of Hofmann elimination is opposite to that predicted by the Zaitsev rule (Section 5 10) Elimination reactions of alkyltrimethylammonmm hydroxides are said to obey the Hofmann rule, they yield the less substituted alkene... 

Compound 13a can been obtained via two different routes firstly in the reaction of 11 with dimethyl aluminum chloride where LiCl is eliminated and secondly by the reaction of di(pyridyl) phosphane 12 (Py2PH) with trimethyl aluminum where methane is formed, (Scheme 5). The X-ray structure determination of [Me2AlPy2P] 13a, (Fig. 3) elucidates the aluminum atom to be coordinated by the two nitrogen atoms of the pyridyl rings in addition to the two remaining methyl groups leaving the aluminum four... 

In this reaction, methyl groups are cleaved in preference to other saturated alkyl groups. A similar reaction takes place between a Mannich base (see 16-15) and a secondary amine, where the mechanism is elimination-addition (see p. 430). See also 19-5. 

Silane reduces the palladium acetate in 119 to the palladium hydride 120, which undergoes reductive elimination to provide the organic product and the catalytic Pd(II) species. This mechanistic hypothesis was supported by the use of EtsSiD as the reductant product was formed with D incorporation at only the methyl group [70]. This reaction is best performed with a Pd(0) precatalyst in the presence of acetic acid and 10 eq. of silane, which suppresses the competitive cycloisomerization reaction [70]. 

The electrochemical oxidation is often more sensitive to the reaction conditions than to the substituents. Platinum electrodes are recommended for methoxylation and the equivalent acetoxylation procedures.290 In acetonitrile buffered by hydrogen carbonate ion, 3,4-diethylfuran affords the 2,5-dihydroxy-2,5-dihydro derivative (84%) and Jones oxidation readily leads to diethylmaleic anhydride in what is claimed to be the best general method for such conversions.291 In unbuffered methanol and under current density control, the oxidation of 2-methylfuran appears to eliminate the methyl group since the product is the acetal-ester 111 also obtained from methyl 2-furoate.292 If sodium acetate buffer is used, however, the methyl group is retained but oxidized in part to the aldehyde diacetate 112 in a... 

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