Barbier-type coupling

Aryl radical cyclization.10 Sml2 in HMPA/THF at 25° can effect cyclization of l-allyloxy-2-iodobenzene to a Sm(III) intermediate (a) that can be trapped by electrophiles, including aldehydes or ketones. The report suggests that a similar mechanism operates in the Barbier-type coupling generation of an alkyl radical followed by formation of RSml2, which adds to a carbonyl compound to form an adduct that is hydrolyzed to an alcohol. 

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... 

Indium trichloride promotes catalytically the addition of alkynylstannanes to aldehydes (Table 25).42 Metallic indium also mediates the same Barbier-type coupling between alkynyl halides and aldehydes or ketones to give secondary or tertiary propargyl alcohols (Table 26). Secondary alcohols can be oxidized in situ according an Oppenauer process.395 Thus, alkynyl ketones have been prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They are also obtained via an indium-mediated alkynylation of the relevant acyl chlorides (Table 27).396... 

Utilization of THF-HMPA as solvent for the reaction provides another useful technique for facilitating the Sml2-mediated Barbier-type coupling reaction. Even in the absence of a catalyst, both Bu"Br and Bu Br are cleanly coupled with 2-octanone within 1 min at room temperature in this solvent system, providing greater than 90% yields of the desired tertiary alcohols. 

In addition to serving as a useful replacement for lithium or magnesium in Barbier-type coupling reactions, SmI also provides advantages over zinc as a reductant in Reformatsky-type coupling reactions (equation 54).The latter only performs well when an activated form of zinc is utilized, and thus the homogeneous conditions afforded by SmI provide the advantage of enhanced reactivity under milder conditions. 

The Barbier-type coupling of Bu SnCl with allylic halides is a... 

Annulation of five- and six-membered rings proceeds with excellent diastereoselectivity via an intramolecular Barbier-type process (eq 16). The Barbier-type coupling scheme provides a reliable and convenient alternative to other such methods for preparing fused bicyclic systems. 

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