Barbier condensation

In diethyl ether, the yields of the zinc-mediated Barbier condensation are medium or poor,1 and THF should be preferred for most of the synthetic uses. Sonication is frequently used, e.g. in the reaction of methallyl bromide and salicylaldehyde which provide the expected alcohol27 The condensation of 4-bromo-2-sulfolene with a series of aldehydes and ketones was effected with the zinc-silver couple and ultrasound.28 The reaction occurs without transposition, which is not the case in the presence of magnesium. In refluxing... 

It is well known that iminium salts show a reactivity comparable to that of carbonyl compounds towards organometallics. Consequently, we tried a similar Barbier condensation with the Eschenmoser s salt, but without success (Fig 11). 

Fig. 11. Failure of the Barbier condensation with the Eschenmoser s salt...

Owing to a limited yield obtained in the preparation of benzyltrifluoromethylsulfide another route to triflic acid was prefered the direct Barbier condensation with sulfur dioxide (Fig. 14) (ref. 21). 

The condensation between xanthen-9-one and an organometallic derived from tropylium bromide is not feasible due to the antiaromatic character of the anion. The problem was solved by an "umpolung" Barbier condensation (Eq. 7).82 The LiDBB radical anion, from lithium and DBB, releases its electron in a two-step reaction to reduce the carbonyl group to the dianion, making the process catalytic in DBB. Without sonication, the process is too slow to be useful. 

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) °. ... 

Baeyer-Villiger reaction, 9, 3 43, 3 Bamford-Stevens reaction, 23, 3 Barbier Reaction, 58, 2 Bart reaction, 2, 10 Barton fragmentation reaction, 48, 2 Bechamp reaction, 2, 10 Beckmann rearrangement, 11, 1 35, 1 Benzils, reduction of, 4, 5 Benzoin condensation, 4, 5 Benzoquinones ... 

Barbier reaction Samarium(II) iodide, 270 Benzoannelation Chromium carbene complexes, 82 Dicarbonylcyclopentadienylcobalt, 96 Ethyl (Z)-3-bromoacryIate, 130 Grignard reagents, 138 Methyl acrylate, 183 Methyllithium, 188 Ruthenium(III) chloride, 268 Benzoin condensation Benzyltriethylammonium chloride, 239 3-EthyIbenzothiazolium bromide, 130 Benzoylation (see also Acylation) Cadmium, 60 Dibutyltin oxide, 95 Birch reduction Birch reduction, 32... 

Barbier synthesis of 1-phenylethanol [54] Dry benzene (12 ml) (HAZARD), dry THF (3 ml) and magnesium (high purity, preferably sublimed) are placed in a dry reaction vessel fitted with a reflux condenser and a dropping funnel and furnished with an atmosphere of argon. The Barbier mixture , consisting of freshly distilled benzaldehyde (5.3 g),... 

The nature and amount of the amine used for acid deprotonation determines the reaction yield. In most cases, dienediolates of unsaturated carboxylic acids can be generated, without Barbier s reduction or Michael adduct formation, by deprotonation of the corresponding acid with butyllithium in the presence of a catalytic amount of amine198. This renders dienediolates compatible with a large number of functional groups, as happens with nitriles where self-condensation is minimized under these conditions. Unfortunately, this cannot be considered a general rule and it is convenient to optimize the amine and its amount for each acid and nitrile. 

Hydroxy esters and a,(3-unsaturated esters may also be prepared either via a single-step Barbier-type condensation of a r-Bu-bromoester with carbonyl compounds in the presence of Mg metal or via a two-step condensation with Li-enolates, as depicted below. 

A similar mechanism is thought to be involved in the formation of a-trilluoromethyl ketone 7 instead of expected amine 6 during the reaction of iminium salt 5 with CF3Br under Barbier conditions (equation 4) . It was proposed that pyridine probably transforms iminium ion 5 into the enamine (l-pyrrolidino)-l-cyclohexene by elimination of HQ, which then undergoes a radical chain reaction with CF Br as shown in Scheme 1 to give 7. This is supported by the observation that no condensation products are observed when iminium salts lacking removable a-hydrogens are used. 

We remarked that the first step of the radical-anion chain mechanism (Fig. 4) can be considered as a reduction of the halide by the nucleophile. Consequently, we tried to use well known reductants such as zinc. However, no reaction occurred when the halide is placed in the presence of zinc in various solvents. By analogy with the thiophenoxide condensation, we attempted the transformation in DMF under slight pressure. Consumption of the reagents was only observed when electrophilic substrates, such as carbonyl compounds, are present since the beginning of the reaction. These Barbier like condensations started more easily in pyridine than in DMF (ref. 19). Moderate yields were obtained with aldehydes as substrates (Fig. 6). 

Organolithiums. Barbier-type condensation occurs when an alkyl nitrile and a carbonyl compound are treated with LDTBB. Trialkyl phosphates are converted to alkyllithiums in the same way. ... 

Allylation of aldehydes. In this Barbier-type condensation different catalysts are also added to promote the activity of tin(II) chloride. These include Nal," CuX, and Mg."... 

Ketones. Sonochemical Barbier reaction allows direct access to ketones from the condensation of lithium carboxylates and organohalides in the presence of Li. An interesting approach to 2-furanyl ketones involves in situ deprotonation of furan with nascent t-BuLi (generated with the assistance of ultrasound) and subsequent reaction with RCOOLi. 

Barbier conditions have been developed to inprove the olefination yields, but they are not always compatible with highly functionalized carbonyl derivatives. Among the various heterocyclic sulfones studied in this reaction, the most inportant variant was introduced by Kocienski et al., who used bulky tetrazolylsulfones with low propensity toward selfcondensation 1-phenyl-lJf-tetrazol-5-yl sulfone 43 (PT-sulfone, Scheme 19 171 and 1-tert-butyl-lJJ-tetrazol-5-yl sulfones (TBT-sulfone). Their stability under basic conditions allows sulfone premetallation, thereby broadening the scope of conpatible carbonyl derivatives for the condensation. 

The sonochemical Barbier reaction was used advantageously in condensations... 

Reintroduction of Zinc. Perhaps one of the most striking developments in modern Barbier chemistry is the increasingly successful reintroduction of zinc as the metal for this category of condensation reactions. In fact, zinc had never... 

Stereochemical Studies 1987. In a stereochemical study of ultrasound-supported Li-Barbier reactions of S( + ) 2-halooctane and cyclohexanone, Luche and coworkers obtained an optically active alcohol in each of the reactions performed [91]. Its enantiomeric excess and absolute configuration strongly suggested the existence of two reactive intermediates following different pathways to form the condensation alcohol. The following scheme was given to account for the results ... 

Moretti L, De Stefano L, Rendina I (2007) Quantitative analysis of capillary condensation in fiuctal-like porous silieon nanostructures. J Appl Phys 101 024309 Nyehyporuk T, Lysenko V, Barbier D (2005) Fractal nature of porous silicon nanocrystallites. APS J Phys Rev B 71 115 02... 

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. 

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