4- lithio-5-bromo

Synthetic procedures are available for the preparation of fluoro, chloro, bromo and iodo compounds from the corresponding lithio derivatives. Perchloryl fluoride (FCIO3), N-chlorosuccinimide, bromine and iodine are examples of reagents which can be used to introduce fluorine, chlorine, bromine and iodine, respectively. 

Benzo[h]selenophene, 3-bromo-2-lithio-synthesis, 4, 956 Benzo[h]selenophene, 3-chloro-synthesis, 4, 116... 

Selenophene, bis(TV-chlorothioimino)-molecular structure, 4, 939 Selenophene, 2-bromo-mercuration, 4, 946 Selenophene, 3-bromo-lithiation, 4, 949 synthesis, 4, 955 Selenophene, 3-bromo-2-lithio-synthesis, 4, 955 Selenophene, bromonitro-debromination, 4, 78 synthesis, 4, 955 Selenophene, 2-chloromethyl-solvolysis, 4, 952 Selenophene, 3-cyano-synthesis, 4, 955 Selenophene, deutero-deuterium exchange, 4, 949 Selenophene, 2,5-diacyl-3,4-dihydroxy-synthesis, 4, 964... 

Bromo-2,3-diphenylquinoxaline (51, R = Br) gave 6-lithio-2,3-diphenylqui-noxaline (51, R = Li) (BuLi >80%) and thence 6-iodo-2,3-diphenylquinoxa-... 

A novel approach to 3-substituted indolines and indoles via the anionic cyclization of 2-bromo-lV,lV-diallyanilines has been developed simultaneously by Bailey <96JOC2596> and Liebeskind <96JOC2594>. Thus, treatment of 2-bromo-lV,lV-diallylanilines 78 with 2 equivalents of BuLi at -78 °C leads to the formation of the intermediate 79 which may be trapped with an electrophile to afford 3-substituted indolines 80. Aside from ease of preparation, an additional benefit of the intramolecular carbolithiation of <7-lithio-W,Al-diallyl-anilines is the production of Al-allyl-protected indolines, which are easily deprotected using... 

The presence of Me3Sn and Me3Ge radicals was ascertained by reactions of the lithio reagents with cyclopropylcarbinyl bromide and 6-bromo-l-heptene, whereupon products of free radical reactions were produced along with those from direct displacement. 

So far, many syntheses of p, or m-silylphenol derivatives were reported(56-60). p-Trimethylsilyloxy trimethylsilyl benzene was synthesized from trimethylsilyl chloride and p-trimethylsilyloxychloro(or bromo)benzene in the presence of Mg, or Na(56,57,59,60). A similar compound was also synthesized from triphenylchlorosilane and p-lithio phenoxy lithium(58). m-Trimethylsilyloxytrimethylsilylbenzene was prepared from m-trimethylsilyloxy bromobenzene and trimethylsilylchloride(59). 

The formation of l-lithio-.io so. si.ssi 2.iithio-, and 3-lithiodibenzothiophene has been achieved by translithiation of the appropriate bromodibenzothiophene (Section VI, C, 3) with butyllithium. Higher yields of derivatives are obtained from 2-lithiodibenzothiophene by conducting the reactions at 0° rather than at room temperature. The comparatively low yield of compounds derived from 3-lithiodibenzothiophene at 0° may indicate that even lower reaction temperatures are required for this particular isomer, reduced yields probably being due to ortho-translithiation to the thermally stable 4-lithiodibenzothiophene (cf. the instability of 3-lithio-benzo[6]thiophene at 0° ). Both 2-lithio- and 3-lithio-4-methyldibenzo-thiophene have been prepared from the respective bromo compound, and a similar synthesis of 1 -lithio-4-methoxydibenzothiophene has been described. ... 

In the latter reaction, remarkable examples of diastereoselectivity have been reported. Thus, the treatment of 7,7-dibromonorcarane 22 with n-butyllithium leads to exo-7-bromo-ewdo-7-lithiobicyclo[4.1.0]heptane23 exclusively, as shown by carboxylation (Scheme 8). It turns out that a slight excess of dibromonorcarane 22 relative to butyllithium is prerequisite to that high degree of stereoselectivity. The result is explained as follows the exo-bromine atom in 22 is exchanged first in a kinetically controlled reaction so that the ewrfo-bromo-exo-lithio-isomer 24 is formed. In a second step, an equilibration occurs by means of another bromine-lithium exchange, which takes place between 24 and the dibromonorcarane 22 (still present because used in excess). Thus, the thermodynamically... 

Sequential nucleophilic and electrophilic reactivity of a bromo lithio carbenoid is a feature of the transformation that permits a ring enlargement of cyclic ketones (Scheme 15)367,368 -pijug nucleophilic addition of dibromo lithio methane, which has been generated by deprotonation of dibromomethane, to cyclododecanone 119 leads to the... 

It turned out that the requirements of such a chiral d reagent are fulfilled by the l-bromo-l-lithio-l-aUcenes S- and /f-41, which are available from the corresponding enantiomer of lactate . When added to aldehydes or imines, significant diastereose-lectivity will be displayed only by the fi-diastereomer 41. Thus, the selective exchange of the bromine atom in the Z-position of the dibromoaUcene 40, outlined in Scheme 9, is prerequisite to the efficiency of this concept. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

A stereochemical behavior similar to that of the 1-bromo-l-lithio aUcene 164 with regard to chiral aldehydes is shown by the hthiated methoxyallene 183. When added to iV,iV-dibenzylated a-aminoaldehydes 188, it reacts with non-chelate control so that awh -carbinols 189 are obtained predominantly. Diastereomeric ratios of 189 190 range from 80 20 to 95 5. As outlined above, the hydroxyalkylated allenes 189/190 can be converted into furanones 191/192 upon treatment with potassium f-butoxide and subsequent acid hydrolysis" . When, on the other hand, the adducts of 183 to the aldehydes 193 are submitted to an ozonolysis, A-protected a-hydroxy-/3-amino esters 194/195 result (Scheme 25)"" . 

Korneev and Kaufmann successfully lithiated 2-bromo-l,l-diphenylethylene (46) by bromide-lithium exchange to form 2-lithio-l,l-diphenylethylene (47). A second lithia-tion could be effected in four hours at room temperature by deprotonation of the aromatic ring with w-butyllithium in the presence of TMEDA (Scheme 17). Like in the synthesis of compound 23, the first lithiation activates the ortho-hydrogen atom of the Z-phenyl substituent to give 1,4-dilithium compound 48. In total, three equivalents of the alkyl-lithium base are required the third equivalent is consumed in the trapping reaction of w-bromobutane with generation of octane. 

The 3-lithio species has also been generated from the analogous 3-bromo compound [85JOC5900 90H(30)627] and has now been successfully used in the synthesis of a number of natural products (83JOC2690 85JOC5900). 

Less success has been obtained with removable N-substituents, however, the trityl and THP derivatives of 4-bromopyrazole both giving low yields of products derived from reaction of the lithio derivatives with carbonyl compounds [62CB222 82ACS(B)101]. Magnesium metal has also been used to produce l-methyl-4-(trimethylsilyl)pyrazole by an in situ Grignard reaction on the analogous 4-bromo compound in HMPT (84JOC4687). 

Low temperatures are necessary with orr/io-halolithiopyridines in order to prevent pyridyne formation, and an added complication with some bromopyridines is that rearrangement of the initial lithio derivative can occur via an intermolecular transmetalation process (Scheme 108)(79T1625 85T3433). This result has been used synthetically to give 2-bromo-3-substituted derivatives from 2,6-dibromopyridine [90JOM-... 

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