Metal-halogen exchange synthesis

N. Sotomayor, E. Lete, Aryl and Heteroaryllithium Compounds by Metal-Halogen Exchange. Synthesis of Carbocyclic and Heterocyclic Systems, Curr. Org. Chem. 2003, 7, 275-300. 

The metal-halogen exchange reaction is useful in the synthesis of numerous perfluoroalkylmagnesium halides, some of which are shown in Table 2... 

Although the metal-halogen exchange reaction is the preferred method of synthesis, the conventional Grignard synthesis through the reaction of a per-fluoroorgano halide and magnesium occasionally is still used [49, 50]... 

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

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... 

Cyclization of derivatives of bicyclo[1.1.0]butane (10) represents a second important method for the synthesis of [1.1. l]propellanes35,45 (path d). Metal-halogen exchange at the... 

SCHEME 10. Synthesis of oligostannanes via metal-halogen exchange... 

SEM ethers.1 The synthesis of orelline (4), a 2,2-bipyridine derivative, from the SEM ether (1) of 2-bromo-3-hydroxypyridine involves metal-halogen exchange... 

Yields range from 60—80%. None of these reactions gives any evidence of the metal-halogen exchange which was observed in the synthesis of the compound 4 listed in Table 2. 

Recently, a metal-halogen exchange method was described for the synthesis of isatins by lithiation of o/7/ o-bromophenylureas, carbonylation and subsequent intramolecular cyclisation to give the desired products in 71-79% yield51 (Scheme 14). 

Among transition metal complexes, the ubiquitous dicarbonylcyclopentadienyliron (Fp) complexes are the first, and perhaps the best, representatives to demonstrate the utility of metal-halogen exchange reactions in metallacyclopropane synthesis. Thus, reaction of the readily available sodium dicarbonylcyclopentadienyliron [Cp(CO)2Fe]Na (FpNa) with the parent cyclopropyl bromide " and derivatives " gave in moderate yields the corresponding cyclopropane-Fp complexes (equation 3). 

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