Halogen-lithium exchange, selective

SELECTIVE HALOGEN-LITHIUM EXCHANGE REACTIONS OF 2- 2 -HAL0PHENYL)ETHYL HALIDES ... 

Selective halogen-lithium exchange in some secondary and tertiary (bromophenyl)alkyl 481... 

Selective halogen-lithium exchange in bromo- 487 phenylalkyl halides./. Org. Chem. 1976, 41, 1184-1186. 

For halothiazoles the conditions for selective deprotonations at the thiazole nucleus are quite variable depending on both the kind and position of the halogen atom (see Section 3.06.7.9.2). Thus, butyllithium deprotonates selectively 2-chlorothiazole at C-5 <90JCS(Pi)329> and 4-bromothiazole at the C-2 <92JCS(P1)215>. The same reaction cannot be carried out with 2-bromothiazole due to the halogen-lithium exchange much faster than with 2-chlorothiazole. Deprotonation at C-5 in 2-bromothiazole must be done with LDA <88CJC1617>. In a similar way 2,4-dihalothiazoles yield the... 

A synthesis of the natnral product meridianin D demonstrates selectivity in halogen-lithium exchange and substrate selectivity, using a halogenated boronic acid. The presence of the A-tosyl probably controls the halogen exchange selectivity. ... 

Dianions 126, alkenyllithium compounds of type VIII, have been obtained by halogen-lithium exchange from the corresponding chlorinated or brominated precursors 125 using lithium naphthalenide it was necessary to carry out a previous deprotonation with PhLi. The reaction of 126 with electrophiles gave regio-selective functionalized allyl amines 127 (Scheme 2.17) [106]. 

Successful lithiation of aryl halides—carbocyclic or heterocyclic—with alkyUithiums is, however, the exception rather than the rule. The instability of ortholithiated carbocyclic aryl halides towards benzyne formation is always a limiting feature of their use, and aryl bromides and iodides undergo halogen-metal exchange in preference to deprotonation. Lithium amide bases avoid the second of these problems, but work well only with aryl halides benefitting from some additional acidifying feature. Chlorobenzene and bromobenzene can be lithiated with moderate yield and selectivity by LDA or LiTMP at -75 or -100 °C . 

This type of carbenoid can also be generated from alkyl dichloromethyl ethers by halogen-metal exchange employing methyllithium in the presence of lithium iodide5. Interestingly, in certain cases, this method provides cyclopropanes with remarkably high cis or endo selectivity (for procedures, see Vol. E 19b, pp 1631 -1639). 

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