Barbier conditions

Perfluorovinyl organotin compounds can be prepared from perfluorovinyl Grignard reagents and organotin halides [76] (equation 11) Yields are slightly improved under Barbier conditions [76]... 

Under Barbier conditions, trifluoromethyl bromide reacts with electrophiles, such as aldehydes, Orkelo esters, activated esters, and anhydrides in the presence of pyridine to give trifluoromethylated compounds [35, 45 46] (equations 34 37)... 

Barbier conditions have been used to carry out a silicon-induced addition of perfluoroalkyl iodides to DMF to give stable hemiaminal intermediates, which give the perfluonnated aldehydes upon heating with sulfuric acid [47 (equation 38)... 

Diastereoselective allylation under aqueous Barbier conditions of a-amino aldehydes with the chiral building block (Ss)-3-chloro-2-(p-tolylsulfinyl)-l-propene to give enantiomerically pure sulfinyl amino alcohols in good yields and with high diastereoselectivity was reported (Eq. 8.34).73... 

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... 

Grignard reagents usually give poorer yields than do the alkali metal reagents, but some reactions give good yields under Barbier conditions with ultrasonic assistance (Equation (56)).7... 

For the purpose of carrying out carbonyl addition reactions, allylstannanes can be prepared in situ from metallic tin and an allyl halide (Barbier conditions),259 for example, Equation (93).260... 

The naphthalene-catalyzed (8%) lithiation of phenyl sulfones 80 under Barbier conditions in THF at temperatures ranging between —78 and 20 °C led, after hydrolysis, to the formation of the corresponding products 20 (Scheme 33). ... 

Anomeric 2-pyridylsulfones, such as 48, were introduced by Skrydstrup and Beau [18] and have a LUMO energy level low enough that reductive samariation is possible in THF alone (no HMPA needed). Under Barbier conditions, good yields of C-glycosides 50-53 are available with aldehydes and ketones (Scheme 13) [ 19]. The low selectivity associated with 50-53 is again a consequence... 

An example of a 4-lithio species that has been prepared is the 2-methylthio derivative 325 that has been prepared from the iodo compound 324 by both conventional halogen-metal exchange reaction with butyllithium <2001TL311, 2001TL8697, 2005JOC6204> and under Barbier conditions with sonication <2000T3709>. 

The solvated vinylzinc reagent does not add to benzaldehyde however, under Barbier conditions, the reaction of Zn°, Z-CF3CF=CFT in DMF stereospecifically gives the L -allyl alcohol consistent with trapping of the carbanion intermediate (Scheme 2). 

Despite the lower reactivity of solvated perfluoroalkylzinc reagents, perfluoroalkyl iodides undergo synthetically useful zinc-mediated reactions under Barbier conditions which often employ ultrasound and co-catalysts. Under these conditions, the zinc reagents are not well characterized and radical intermediates and SET mechanisms are proposed in some cases. Representative examples are presented below and include the ultrasound-promoted, zinc-mediated perfluoroalkylation of various substrates as reported by Ishikawa and coworkers (Scheme 10)123 126. Yields of carbinols could be improved by use of Ti(II) co-catalyst. Ultrasound promoted the coupling of perfluoroalkyl iodides with vinyl and allyl halides in the presence of Pd co-catalysts. 

In some cases, such as with the allylic bromosulfone 17, the best reaction conditions to add to imines are obtained under Barbier conditions, reaction in this manner gives the unsaturated aminosulfone 18. Treatment with catalytic potassium hydride, results in a 5-endo-trig cyclization to form the pyrrolidine 19 in 65% yield (Scheme 1.8).25,26... 

Reaction of halodifluoroacetates with carbonyl compounds in the presence of zinc gives a,a-difluoro-(3-hydroxyesters (Equation 4.9).21-23 The intermediate zinc reagent is typically trapped in situ with aldehydes (Barbier conditions). 

A similar reaction presumably underlies one of the most remarkable transformations yet achieved by reductive lithiation with catalytic DBB the transformation of a nitrile into an organolithium with cleavage of a C-C bond.99 The electrophile needs to be present in the reaction mixture (Barbier conditions), but silylation or reaction with a carbonyl compound competes successfully with deprotonation of the nitrile starting material ... 

The reaction of heteroaryl halides with Rieke Mg, performed in the presence of electrophiles (Barbier conditions), affords sometimes better results than the usual stepwise method (Scheme 4). ... 

A number of methods were developed for the electrophilic amination of Grignard reagents306,30 3 to prepare primary amines. One of the recent examples uses l,3-dioxolan-2-one O-sulfonyloxime.307 The reaction gives imine, which affords primary amine after hydrolysis (Scheme 106). By using acetone 0-(mesitylsulfonyl)-oxime the amination can be performed under Barbier conditions from aryl bromide and magnesium.308... 

Trifluoromethylaldimine reacts with various allylic bromides, under Barbier conditions in the presence of indium in DMF, to provide the corresponding homoallylamines (Equation (57)).255 a-Methylene-y-butyro-lactams are prepared by the indium-mediated reaction of 2-(bromomethyl)acrylic acid with aldimines (Equation (58)).256... 

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