Halogen-Metal Exchange Relations

Dechlorination, debromination, demethylthiolation, and demethylsulfonylation of triazole 1-oxides 448 are all formally related to halogen-metal exchange and can also be regarded as reduction processes favored by the formation of a stabilized anion. 

In addition to deprotonation with strong bases, halogen-metal exchange, or trans-metalation, a-heteroatom-substituted carbanions can also be prepared by 1,5-hydro-gen transfer to vinyl radicals, followed by reduction [204, 205] (Scheme 5.21) or by a related intramolecular 1,4-proton transfer [206]. 

Dehalogenation Reactions. Since Uthium naphthalenide is a particularly effective initiator for halogen-metal exchange, it has found widespread use for the conversion of dihaUdes to unsaturated species. Thus, 1,2-dichlorodisilanes have been converted to silenes (eq 8) and diphosphiranes to phosphacumulenes. In a related field, silicon cages have been constracted from trichloro-disilanes. 

Halogen-metal interconversion between bromothiophenes and n -butyllithium occurs almost instantaneously and in very high yield. The reaction with 3-bromothiophene is usually carried out at -70 °C to avoid any (rans-lithiation. When bromine-lithium exchange takes place, steric crowding in the molecule decreases. As a consequence the percentage of 2-lithio derivative in relation to the 5-lithio isomer formed from 3-alkyl-2,5-... 

A related series of reactions derives from dibromocarbene adducts of olefins as in Eq. 28 32,33). Metal-halogen exchange at very low temperature produces the... 

With the aim of developing new analogues of the cyclic AMP phosphodiesterase inhibitor lixazinone (554), the synthesis of agents 553 and 555-557 was undertaken (Scheme 167) (88JMC2136). Thus, all possible 1,2-related N-r-Boc aldehydes 551 were prepared by directed metalation on isomers 549, with the exception of that which required the use of a metal-halogen exchange reaction on the bromo precursor 550 (attempts to metalate 4-TMS-3-N-f-Boc pyridine proved inefficient). As exemplified for one particular isomer, conversion of 551 into 552 by reductive amination... 

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