Barbier-type conditions

The application of the naphthalene-catalyzed (10%) lithiation to benzylic ureas 69 under Barbier-type conditions in THF at —78 or — 30°C led to the formation of the expected products 35, after hydrolysis (Scheme 28) °. 

A special case of functionalized aryllithium reagents appears when the corresponding aryl group bears a ketal moiety at the benzylic position due to the lability of the benzyUc carbon-oxygen bonds. However, working under Barbier-type conditions and using naphthalene (10%) as the electron carrier catalyst, the reaction of chlorinated materials 242 afforded, after hydrolysis with water, the corresponding polyfunctionalized products 243 (Scheme 81). ... 

Barbier-type conditions can be used to convert 2- and 3-halopyridines to the pyridyllithium in situ in the presence of electrophiles. Sonication of the bromo- or iodopyridine with lithium powder containing 0.5% sodium in the presence of aldehydes or diphenyldisulfide as electrophile in THF at room temperature gives the pyridyl alcohol or sulfide in moderate to good yield <2000T3709>. 

When (Z)-6-chloro-l-phenylhex-l-ene 200 was lithiated under DTBB catalysis, the cyclized product 202 was always obtained either at —78 or at —30 °C. After the first chlorine-lithium exchange a carbolithiation took place to yield the intermediate 201, which by reaction with electrophiles, E, and final hydrolysis gave products 202 (Scheme 60). At —78 °C the reaction under Barbier-type conditions did not work. Also in this case, the corresponding reduced product (202 with E = H) was the main by-product detected. 

At the start of this work, the dual nucleophilic-electrophilic character of the a-sulfonyl carbanion 213 created some problems since this anion could react not only with the carbonyl derivative (aldehyde or ketone) but also with itself, generating via this competitive pathway some homocoupling by-products. However, a wise selection of the sulfone electrophilic substituent and the use of Barbier-type conditions considerably increased the chemoselectivity of the addition reaction and directed the addition onto the carbonyl function. Benzothiazole derivatives (hereafter denoted BT) were the first substrates to be utilized in this process. After some fine tuning, they proved to be suitable candidates, affording the desired alkenes with a reasonable efficiency (Table 3.11). 

In 1998, Kociensky et al. proposed a variation of this method that obviated the use of Barbier-type conditions and made this sequence more compatible with complex aldehydic substrates [137]. They also extended the range of sulfone heterocycles to l-isoquinohnoyl, l-methyl-2-imidazoyl, 4-methyl-2-imidazoyl, 4-methyl-l,2,4-triazol-3-yl, and l-phenyl-lH-tetrazol-5-yl (hereafter denoted PT), with the latter system being the most promising. Among the various trends that they observed from 96 comparative experiments, it was deduced that the -alkyl PT-sulfones gave better yields than their BT-substituted counterparts (suggesting that PT sulfones are less prone to self-condensation). Moreover, careful combination of the solvent and the counter ion proved to have a profound effect on the yield and the stereochemical outcome of the elimination. 

A series of aryltriethoxysilanes 14 were synthesized from the reaction of aryl bromides 13 with magnesium powder, 1,2-dibromoethane and tetraethylorthosilicate in tetrahydrofuran via sonochemical Barbier-type conditions. DeShong previously reported the preparation of aryltrialkoxysilanes via treatment of aryl Grignard or lithium reagents with... 

The synthesis of terminal alkenes from carbonyl compounds is a very important reaction in organic synthesis. Najera and co-workers found out that BTFP methyl sulfone is a good reagent to perform methylation reactions of carbonyl compounds through the Julia-Kocienski protocol. The reaction proved to be much more efficient when Barbier-type conditions were used. Example, alkene 90 was obtained in 45% yield by reacting sulfone 88 with diketone 89 in the presence of P4- -Bu in THF. For example, the sulfone 92, prepared from 84 by two-steps reaction in 81% yield, was converted to alkene 94 in 95% yield and 96 in 71% yield respectively. 

The use of substoichiometric amounts of an arene (naphthalene or biphenyl) was first studied in the reaction of bromobenzene and benzaldehyde with sodium, under Barbier-type reaction conditions The possibility of using a substoichiometric amount of DTBB... 

Barbier-type reaction conditions ) in THF at —30°C (—78°C for phenylacetonitrile) yielding, after hydrolysis, the expected compounds 20 (Scheme 8) . ... 

Thus, chloro enamines 113, either under Barbier-type reaction conditions (—40 °C) or in a two-step process (hthiation at —90 °C and Sg reaction at —90 to —40 °C), were lithiated with DTBB (5%) and finally hydrolyzed, after condensation with different electrophiles, giving the expected functionalized enamines 114 (Scheme 44) °. ... 

Functionalized propargyUc organolithium compounds are probably involved in the transformation of chlorinated ethers or amines 211 into polyfunctionalized products 212, which were achieved through a DTBB-catalyzed lithiation under Barbier-type reaction conditions (Scheme 73). The reaction failed for the corresponding thioethers (Y =... 

Barbier-type reaction conditions) to yield, after hydrolysis with phosphate buffer and final esterification with methanol under PTSA catalysis, the corresponding functionalized methyl esters 229 (Scheme 77) . 

In the case of chlorobenzyl chlorides 504, the same process had to be performed under Barbier-type reaction conditions. These dichlorinated materials 504 were lithiated with DTBB in a catalytic amount (4%) in the presence of different electrophiles to give, after final hydrolysis with water, the corresponding difunctionalized products 505 (Scheme 141) ". ... 

Benzamides 565 without any substituent at the para position reacted with lithium and a catalytic amount of naphthalene under Barbier-type reaction conditions (in the presence of a carbonyl compound) in THF at —78 °C to give, after hydrolysis, the corresponding dearomatized products 566 (Scheme 151). When 567 was used as starting material with a 4-ferf-butyl group in p-position, and using 3-pentanone as electrophile and under the same reaction conditions, the fraw -product 568 was the only one isolated . 

Indium-promoted organometallic reactions are greatly accelerated in water, especially when the coreactant carbonyl compound also has good water solubility. Otherwise, aqueous tetrahydrofuran can be used. To date, indium is the most effective metal for promoting Barbier-type reactions under aqueous conditions. As illustrated here, this is of particular value where formaldehyde is concerned, since the need to generate monomeric formaldehyde by thermal cracking is avoided. 

Indium mediated Barbier-type cross coupling between carbonyl compounds and allyl halides proceed efficiently under solvent-free conditions. No apparent competing pinacol-coupling or homo-coupling of the allyl halide was observed. The reactions were found to be mediated also by zinc, tin, bismut and copper [45]. 

Reformatsky reactions have a bad reputation as being difficult to entrain. To the authors experience, however, the reactive donors such as alkyl bromo-acetates do not pose particular problems even under rather conventional conditions. Commercial zinc dust activated by pre-treatment with either iodine of preferentially with cuprous chloride (i.e. Zn(Cu)) readily inserts into these halocarbonyl compound with formation of the corresponding zinc enolates. Protocols 1 and 2 describe prototype examples for Reformatsky reaction in the conventional two-step or Barbier-type set-up, respectively. 

Indium-mediated Barbier-type coupling between carbonyl compounds and allyl halides has been revealed to proceed effectively in diverse reaction media. Even under solvent-free conditions, allylation works well, although no reaction is observed with benzyl bromide and a-halo carbonyl compounds.59 Various aldehydes react with allyl bromide mediated by indium in liquid carbon dioxide to give homoallylic alcohols (Scheme 1). In contrast to the corresponding neat allylation, the liquid C02-mediated reaction can allylate solid aldehydes successfully.60 Indium-mediated allylations of carbonyl compounds with allyl bromide proceed in room temperature ionic liquids. In [bmim][BF4] and [bmim][PF6] (bmin l-butyl-3-methylimidazolium), the desired homoallylic alcohols are formed with good levels of conversion.61 Homoallyllic alcohols are also prepared by the reaction of resin-bound aldehydes (Equation (l)).62... 

E = H) resulting from a lithium—hydrogen exchange in intermediate 198. This hydrogen abstraction from the reaction medium, probably from THF at the a-position, has already been observed in other cases for very reactive organolithium intermediates. The use of Barbier-type reaction conditions did not improve the obtained results124. 

Much milder reaction conditions in the Barbier-type reaction can be employed by utilizing iron(III) salts as catalysts. For example, when 2 mol % FeCb is added to Smh, the Barbier reaction between a primary organic iodide and a ketone is complete within 3 h at room temperature (equation 19). The iron(III) is probably reduced by Smh to a low-valent species which serves as an efficient electron transfer catalyst, thus lowering the activation energy for the coupling process vide infra). 

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