Coupling reactions benzyllic halides

The coupling of benzyl halides with stannanes has been occasionally used in synthesis.One illustrative example is the total syntheses of piericidin A1 (119) and B1 (120).i2o in these syntheses a heterobenzylic Stille cross-coupling reaction of 116 with alkenylstannane 117 proceeded in the presence of a Pd(0) complex bearing bulky PrBuj as the ligand to give key intermediate 118 (Scheme 5.4.23). 

A four-component coupling between benzyl halides and alkynyl stannanes has been developed for the preparation of functionalized enynes. Activated olefins participate in a regioselec-tive Pd(dba)2-catalyzed three-component coupling with allylic acetates and BusSnH. Allylic amines have been prepared via reaction of vinyl halides, alkenes, and amines in the presence of Pd(dba)2 and BU4NCI. Organogermanes and silanes have been constructed via multicomponent carbogermanylation and carbosilylation sequences. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

The homo-coupling reaction of benzylic halides by metallic nickel proceeded at room temperature. 1,2-Diarylethanes having a variety of functional groups could be easily prepared by this method in good to high yields. 

The cross-coupling reactions of benzylic halides and acyl halides produced the expected ketones in good to high yields(39,47). The present method can supplement the corresponding Grignard reaction, which does not work well since benzylmagnesium halides undergo dimerization readily. 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Alkenylfurans can be prepared by coupling of bromofurans with styrene (Eq. 14).91 This type of process (Eq. 14) is a logical extension of analogous reactions of aryl,92 vinyl92,93 and benzylic halides,92 and has been successfully applied to a variety of heterocyclic halides.91... 

The possibility that substitution results from halogen-atom transfer to the nucleophile, thus generating an alkyl radical that could then couple with its reduced or oxidized form, has been mentioned earlier in the reaction of iron(i) and iron(o) porphyrins with aliphatic halides. This mechanism has been extensively investigated in two cases, namely the oxidative addition of various aliphatic and benzylic halides to cobalt(n) and chromiumfn) complexes. 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

The added advantage of the C (1 )-stannylated glycals is their abUity to participate in palladium-catalyzed coupling reactions with organic halides, a process independently reported by Beau [75] and Friesen [81]. Vinyl stannane 237 can be benzylated, allylated or acylated provided that appropriate catalysts are used [75,77] and representative examples are given in Scheme 59. The C-arylation of... 

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