2-Lithiomethyl

Lithiomethyl)quinoxahne (87) with bis(trimethylsilyl) peroxide (88) gave 2-ethylquinoxaline (89) (lithiation by LiNPr, THF then synthonj, —78°C, N2, 2 h 40%) several homologs likewise. ... 

Lithiomethyl-3-phenylquinoxaline (114) and o-chlorobenzonitrile gave 2-(f>-amino-o-chlorostyryl)-3-phenylquinoxaline (115) (no details 28%).973... 

A similar type of transmetalation was also seen with l,2-dimethyl-5-trimethylstannylimidazole, which gave the 5-lithio derivative at -100°C, but rearranged to the 2-lithiomethyl derivative at higher temperatures [83JCS(P1)271]. However, transmetalation does not occur with Grignard reagents and 5-substituted imidazoles can be successfully prepared via this route (Scheme 49) (81 Mil 82OPP409). 

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

As shown in Schemes 13.30 and 13.32, LDA is commonly used as the stoichiometric base, and in the presence of DBU. Recent systematic screening of a variety of lithium amide bases confirmed the superior performance of LDA [64]. It was, however, also found that in the presence of DBU, w-BuLi can be used with similar efficiency [64]. Ahlberg et al. have found it is beneficial to replace the commonly used LDA by 2-(lithiomethyl)-l-methylimidazole (64, Scheme 13.33) [66], Under these conditions, 20 mol% of O Brien s base 60 (Schemes 13.28 and 13.33) afford 93% ee in the isomerization of cyclohexene oxide [66]. Similarly, 2-lithio-l-... 

Thiazole and benzothiazole exchange the C-2 hydrogen for lithium or magnesium when treated with an ethereal solution of phenyl- or butyl-lithium at -60 °C or ethylmagnesium bromide at 0 °C then at 25 °C (Scheme 31). When the 2-position of thiazole is occupied by a methyl group, the reaction of butyl-lithium at low temperature (-100 °C) affords three independent lithio salts (54, 55 and 56 Scheme 32) in the approximate ratio 52 3 45. As the temperature is increased, the 2-lithiomethyl derivative (54), which is less stable than the 5-lithio isomer (56), decomposes up to +5 °C at which point it has almost entirely disappeared. 

Addition of the l-benzyl-2-lithiomethyl-4,5-dihydroimidazole 705 to aldehydes or ketones, and the subsequent retro-ene reaction to revert back to the starting material, was discussed in (Scheme 171). The reaction of 705 with nitriles results in the formation of )3-amino ot,)3-unsaturated imidazoline 706 after in situ isomerization <1999T2695>. 

Meyers aldehyde synthesis. Synthesis of aldehydes R-CH2CHO from alkylhalides R-X and 2-lithiomethyl-tetrahydro-3-oxazine. 

Conversion of 2-Methylpyridine, 2,4-Dimethylpyridine, 2,6-Dimethylpyridine, and 2,4,6-Trimethylpyridine into the 2-Lithiomethyl Derivatives... 

Evans and co-workers developed a regioselective lithiation protocol of 2-methyl-4-substituted oxazoles 945 during their synthesis of phorboxazoles. In particular, the authors required a general method to generate regioselectively a 2-(lithiomethyl)oxazole and to functionalize the intermediate without competitive lithiation and reaction at C(5). Among the bases investigated, lithium diethylamide was particularly effective and selective for the required transformation (Scheme 1.253, p. 206). 

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