Exchange halogen-lithium

Shenlin Huang has implemented method C with 2,4-bis-OBoc-3-bromobenzyaldehyde 27 (Fig. 4.22) and 2-(trimethylsilyl)ethoxy]methyl-lithium 38 at —78 °C in THF.24 Surprisingly, lithium-halogen exchange does not happen and the intermediate benzyl alcohol undergoes reduction with sodium borohydride in the same pot to afford the desired bromophenol 39 in 68% yield. This material... 

Kobayashi and co-workers have described a new synthesis of a range of 1,4-disubstituted isoquinoline derivatives 117 <06S2934>. Initially, a lithium halogen exchange of 118 was performed to form 119, followed by treatment with a variety of nitriles 120 resulting in 1,4-disubstituted isoquinolines 117. 

In the highly competitive arena surrounding the Pfizer compounds CP-263,114 and CP-225,917 (Figure 4.2), Nicolaou and co-workers employed a hydrozirconation—iodination sequence to produce vinyl iodide 4 [17]. Lithium—halogen exchange and subsequent conversion to enone 5 sets the stage for a Lewis acid assisted intramolecular Diels—Alder reaction affording polycyclic 6 as the major diastereomer (Scheme 4.3). 

Two traditional methods have been used to Introduce a carboxyl substituent at C-5 of uracil. 0ns iasolves bromlnatlon at C-5, metalatlon via a lithium-halogen exchange, and finally quenching with carbon dioxide (32) to give the C-5 carboxylic acid. The... 

Two routes to the electrophilic fluorination of pyrrolo[2,3-3]pyridine A -oxide lead to the 4-fluoro derivative. The Balz-Schiemann reaction route, via a diazonium tetrafluoroborate salt, or a lithium/halogen-exchange reaction followed by quenching with an electrophilic fluorine source, generates the 4-fluoro product in moderate yields <20030L5023>. 

Our preference for using benzyl chloride (rather than the bromide) is based on the expectation that side-reactions, such as formation of dibenzyl and the occurrence of lithium-halogen exchange (resulting in PhCH2Li) are less likely (compare ref. 72). 

The scope of the Negishi-coupling is not limited to aryl and vinyl halides and sometimes acyl chlorides might also be converted to ketones by this protocol. The 2,3-dihalopyrrole derivative shown in 6.22. was converted into its 2-lithio derivative by selective lithium-halogen exchange at -78 °C. Addition of zinc chloride effected the formation of the appropriate pyrrolylzinc chloride, which was coupled with a functionalised butyroyl chloride in the presence of tetrakis(triphenylphosphino)palladium and furnished the expected 2-acylpyrrole in 61% yield.27... 

In an analogous case (7.6.) the 9-borabicyclo[3.3.1]nonane (BBN) unit was introduced onto the quinoline core through lithium-halogen exchange and the quenching of the intermediate with 9-BBN-OMe. The quinolylborane coupled with 3-bromopyridine under the earlier mentioned conditions (THF, , TBAB) to give the pyridylquinoline in acceptable yield.8... 

Trifluorovinyllithium was first prepared by Seyferth et al via the reaction of phenyltris(trifluorovinyl)tin and phenyllithium in ether at -40°C [111] and then more conveniently obtained via lithium-halogen exchange reaction of bromotrifluoroethylene with -butyllithium or methyllithium at -78°C [112]. Later Normant reported an inexpensive route to trifluorovinyllithium by reaction of the readily available chlorotrifluoroethylene with sec-butyllithium or terf-butyllithium [113] (Scheme 40). 

Pentafluorophenyllithium can be readily prepared by direct reaction of penta-fluorophenyl halides with lithium amalgam [193,194] or lithium-hydrogen and lithium-halogen exchange reactions of pentafluorophenyl halides with alkyl-lithiums [195-205] (Scheme 70). 

Notably, treatment of 2-(p-bromophenyl)-3,3-dimethyl-1 -methylenecyclopropane with BuLi in TFIF followed by HgCl2 led to mercuration of the aromatic ring (equation 302). This indicates that lithium-halogen exchange at the aromatic ring is preferable to direct lithiation of the three-membered ring372. 

Cyclization of ta-iodoepoxides. Lithium-halogen exchange (/-BuLi) of Lewis acids can affect the regiochemistry.2 Example ... 

Lithium-Halogen Exchange and the Chemistry of 1-Lithio-l -halocyclopropanes 1007... 

Cooke, M. P. Widener, R. K. Lithium—halogen exchange-initiated cydization reactions. 3. Intramolecular conjugate addition reactions of unsaturated acylphosphoranes. J. Org. Chem. 1987, 52,1381-1396. 

Step 4a At least 4 equivalents of w-BuLi are required for the transformation to proceed (2 x -OH deprotonation, 1 x Br elimination, 1 x acetylenic-Br lithium-halogen exchange). 

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