Bromine—lithium exchange yield

The power of Muchowski s method is seen by the fact that these bromopyrroles can be subjected to bromine-lithium exchange to afford the versatile 3-lithio species that can be quenched with a variety of electrophiles in good to excellent yields [18-21]. This is illustrated by a synthesis of verrucarin E (11) [19]. 

Mono- or bis-bromine-lithium exchange on dibromopyrrole 77 affords stannylpyrroles 78 or 79, respectively, and N-BOC-2-trimethylstannylpyrrole is obtained in 75% yield from N-BOC pyrrole by lithiation with LTMP and quenching with Me3SnCl [15]. 

Bromodesilylation T-methoxy-l-indanones. Cyclization contrary to the normal para-selectivity of anisole derivatives can be effected by temporary use of an ort/jo-trimethylsilyl group introduced by directed orf/io-metallation (11,75). Thus the anisole derivative 1 undergoes bromodesilylation and hydrolysis to provide 2. This product undergoes cyclization to 3 in good yield on conversion to the lithio salt followed by bromine-lithium exchange (8,65-66). 

Recently, two more stereoselective cases of bromine-lithium exchange reactions have been observed. Both the glyceraldehyde-derived bromoalkene 45 and lactaldehyde-derived 47 yield the -configurated lithium carbenoids 46 and 48, respectively, when treated with... 

When the bromoalkenes 146, which are obtained in 88 to over 98% de, are submitted to another bromine-lithium exchange, the dilithium compound 148 is generated. This reaction takes place under complete retention of the configuration, as proven by the protonation that yields the Z-alkenes 149 . A debromination protocol that is based on a free... 

The 3-thienyl substituted silane 30 was trilithiated by Nakayama and coworkers, when reacted with a three-fold excess of n-butyllithium (Scheme 11). Target molecule 31 can also be obtained by bromine-lithium exchange, but with a reduced yield. 

The 4-sodio and 4-potassio derivatives are known but are less convenient to obtain than the 4-lithio derivative, which is readily available by metallation of dibenzofuran with butyllithium. Metallation can also be achieved with cross-linked poly(p-lithiosytrene) but offers no advantage in yield. The 4,6-dimetallo derivatives of dibenzofuran can be made by treatment of dibenzofuran with butyllithium or butylsodium. Lithiodiben-zofurans and dilithiodibenzofurans are also available by bromine-lithium exchange with butyllithium. " ... 

Indole synthesis. Fuhrer and Gschwend3 have converted N-pivaloylaniline into the dilithio derivative a by reaction with 2 equivalents of n-bulyllithium and have reported that orr/io-substituted derivatives are obtained in good yield by reaction of I Wilh an electrophile. The same species can be prepared somewhat more efficiently from iin o-bromo-N-pivaloylaniline (1) by bromine lithium exchange and N-deprotonation with methyllithium and r-butyllithium (equation I). This dilithium riegcnl can be used for synthesis of indoles.4 Thus it reacts with a bisclcctrophile... 

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-... 

Several chromans have been synthesized using the Parham cycloalkylation technique (76JOC1184). l-Bromo-3-(2-bromophenoxy)propane, prepared from phenol and 1,3-dibromopropane, is treated with n-butyllithium at — 100 °C. Halogen-lithium exchange yields the aryllithium (278) which cyclizes either at — 100°C or in some instances only at an acceptable rate at higher temperatures. This method offers the advantage of regio-specificity since cyclization is controlled by the location of the o-bromine atom (Scheme 72). 

The thiepines 180 were prepared via a bromine/lithium exchange for /7/%-lithiation of 179 (Equation 26). Lithiation was achieved using /-BuLi (2equiv for each bromine) and sulfur diimidazole was used as the sulfur electrophile. Thiepines 180a-d were obtained in 12-38% yield. 

Thieno[3,4-Z ]thiophene (25) has been obtained (>50% yield) from 3,4-dibromothiophene (332) by a sequence involving Pd(II)-Cu(l) catalysed cross-coupling with trimethylsilylethyne giving (333), bromine-lithium exchange, thiolation with elemental sulfur (334) and ring-closure in aqueous medium (Scheme 27) (90SC2275). 

The mixed 1,2-bimetallic Zn/Si reagent 108 is a versatile species, which reacts with aldehydes in high diastereo-selectivity (Scheme 40).314 It is prepared by a bromine/lithium exchange reaction, followed by a transmetallation with ZnCl2- The reaction with acetaldehyde leads initially to the alkenylzinc species 109, which reacts with MesSiCl providing the alkenylsilane 110 in 41% yield and with a diastereoselectivity >9 1. 

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