Barbier synthesis

It is noteworthy that in 1912 Smith and Kipping678 applied the Barbier synthesis, i.e. the addition of organic halide to a mixture of Mg and SnCU in ether (without preliminary preparation of the Grignard reagent) to obtain organylchlorostannanes in a good yield678,679. 

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),... 

Murray and coworkers have used the Sml2-printramolecular Barbier synthesis to produce 3-protoadamantanol (equation 41). Although the yield in this example was not particularly high, it was the only method among several attempted that proved successful. ... 

On the other hand it may just have been scientific interest or perhaps a spark of inspiration that led Grignard to perform the Barbier synthesis in two... 

Molle and Bauer " have demonstrated that contrary to generally accepted opinion, the Barbier synthesis does not necessarily involve the formation in situ of a Grignard-type, organometallic compound. 

The aqueous Barbier-Grignard-type reaction has also been used in the synthesis of natural products. Chan and Li used the zinc mediated allylation as a key step in a total synthesis of (+)-muscarine (Scheme 8.5).72 The strategy was based on the observation that the diastereoselectivity of the allylation reaction in water can be reversed through the protection of the a-hydroxyl group. 

In 1991, Whitesides etal. reported the first application of aqueous medium Barbier-Grignard reaction to carbohydrate synthesis through the use of tin in an aqueous/organic solvent mixture (Eq. 8.48).106 These adducts were converted to higher carbon aldoses by ozonolysis of the deprotected polyols followed by suitable derivatization. The reaction showed a higher diastereoselectivity when there was a hydroxyl group present at C-2. However, no reaction was observed under the reaction conditions when there was an /V-acctyl group present at the C-2 position. 

Anomeric acetates 104 have been also used as electrophiles toward alkynylindium reagents 105 under Barbier conditions. Good yields and 1,2-cA-stereoselectivities were observed during the reaction (Scheme 36). The alkynylation was applied to the synthesis of an a-(l —>6)-C -disaccharide (110) analogue of methyl isomaltoside.108... 

L. Allain-Barbier, M.-C. Lasne, C. Perrio-Huard, L. Barre, Synthesis of 4-[F-18] fluorophenylalkenes and -arenes via palladium-catalyzed coupling of 4-[F-18]fluor-oiodobenzene with vinyl and aryl tin reagents, Acta Chem. Scand. 52 (1998)... 

Cholic acid may be converted in several steps into the 3,9-epoxy-carboxyIic acid (246) which has the ABC ring system of batrachotoxin. The synthesis of 24-nor-5a-cholic acid from methyl cholate involved the Barbier-Wieland degradation of the side-chain and treatment of the resultant 24-nor-5/3-cholic acid with Raney nickel. A major product of this reaction was the 5a-3-oxo-compound (247) which... 

Scheme 2.2.5.17 Synthesis of disaccharide analogues with variable configuration and tether length from generic dialdehyde precursors by Barbier allylation and tandem a.co-aldolization.

To better compare modern protocols for the Reformatsky reactions, hereinafter discussed in this section, it is interesting to read, as an example, the experimental procedure reported by R. B. Woodward and coworkers in 1956 for the synthesis of the Lysergic acid precursor 3 (equation 2)14. The procedure adopted was a Barbier-like protocol, involving the addition of Zn and of methyl bromoacetate (la) in three portions to a solution of 2 in hot benzene. 

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