Reactions reductive coupling

The coupling of ketones to give pinacols is an old reaction that can be promoted with a variety of reducing agents. The reaction takes place via reduction of the carbonyl to a radical anion followed by radical coupling to give pinacol dianion, which is subsequently protonated by the medium or upon quenching. The reaction has frequently been carried out under aqueous conditions. 

Clerici and Porta have extensively investigated the reaction promoted by aqueous TiCb in acidic media [80]. Under these conditions, electron-withdrawing substituted aliphatic, aromatic and heteroaromatic carbonyl compounds give 1,2 diols by a homo-coupling reaction  

The latter reaction is particularly important the addition of an alkyl radical to carbonyl carbon does not give carbon-carbon bond formation because the intermediate alkoxy radical undergoes fast P-bond cleavage. Under aqueous titanium trichloride conditions, the intermediate alkoxy radical is very quickly reduced by Ti(lll), making the addition step irreversible and allowing the formation of a carbon-carbon bond. 

The TiCl3-H20-promoted cross-coupling reaction has been extended to the addition of a carbonyl compound to a,P-unsaturated aldehydes [80c]. The addition occurs selectively to the carbon atom of the carbonyl group, and highly functionalized allylic pinacols are obtained with good yields. 

The couple Zn-Cu also promotes the pinacol reductive cross-coupling between saturated and a,p-unsaturated carbonyl compoimds in aqueous heterogeneous media. The reaction between a,P-unsaturated cycloalkenones and acetone is accelerated by US irradiation and is significantly influenced by the Zn/Cu and Zn/substrate ratios [81]. 

Reductive coupling is a direct method for C-C bond construction between two organic electrophiles. The challenge is the difficulty in achieving selectivity for the crosscoupled product over dimerisation products. Electrochemical methods or stoichiometric reductants such as Zn(0) and Mn(0) are required to perform the transformation in addition to a catalyst. Nickel has been demonstrated to form effective catalysts and organic halides are widely used as coupling partners. 

A nickel-catalysed reductive conjugate addition to enones was recently reported. This method leads to coupling of an a,p-unsaturated ketone or aldehyde with an organic halide in the presence of triallg lchlorosilane and a 

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Reductive coupling reaction of fluonnated vinyl iodides or bromides has been used as a route to fluorinated dienes [246, 247, 248, 249, 250. Generally, the vinyl iodide is heated with copper metal in DMSO or DMF no 1 ntermediate perfluorovmy I-copper reagent is detected. Typical examples are shown m equations 163-165 [246, 247, 249. The X-ray crystal structure of perfluorotetracyclobutacyclooctatetraene, prepared via coupling of tetrafluoro-l,2-diiodocyclobutene with copper, is planar... 

Revis and Hilty, in 1987, first reported the direct reductive coupling reaction of methyl methacrylate (1.0 mol %) and excess acetone at 25 °C catalyzed by of RhCl3H20 (0.09 mol %) and mediated by MeaSiH (1.3 mol%) to give... 

This review will explore reductive coupling reactions using early (Group 3, 4, and lanthanides) and late (Groups 9 and 10) transition metals. The reac-... 

Metal complexes of lanthanides beyond lanthanocenes were used to catalyze the reductive coupling reaction of dienes. La[N(TMS)2h was found to effect the cyclization of 1,5-hexadiene in the presence of PhSiH3 (Eq. 13) [50]. Cyclized products 88 and 89 were isolated in a combined yield of 95% (88 89 = 4 1). It was suggested that the silacycloheptane 89 resulted from competitive alkene hydrosilylation followed by intramolecular hydrosilylation. 

The palladium-catalyzed reductive coupling reactions were used in the synthesis of several natural products, including laurene [75], ceratopicanol [80], and dihydrostreptazolin 141 [81]. The cyclization leading to dihydrostrepta-zolin shown in Eq. 26 highlights the diastereoselectivity and functional group compatibility seen with this catalytic system. 

In addition to the reductive coupling reaction of ketones, certain alcohols can also be reductively coupled using active uranium. Benzhydrol is coupled by active uranium to give TPA as the only coupled product. No TPE is seen. Under similar conditions, no coupling of benzyl alcohol is seen. The chemistry of the active uranium is under continued investigation. 

Low-valent nickel complexes of bpy are also efficient electrocatalysts in the reductive coupling reaction of aromatic halides.207 Detailed investigations are in agreement with a reaction mechanism involving the oxidative addition (Equation (40)) of the organic halide to a zero valent complex.208-210 Starting from [Nin(bpy)2(X)2]0 with excess bpy, or from [Nin(bpy)3]2 +, results in the [Ni°(bpy)2]° complex (Equations (37) and (38)). However, the reactive complex is the... 

Yatabe has developed a slightly modified process for preparing 12 (23). Thus, the reductive coupling reaction of l,4-bis(chlorodimethylsi-lyl)benzene with sodium in toluene in the presence of lQ-crown-6 pro-... 

The cyclophane 35 was obtained by a reductive coupling reaction of l,3,5-tris(chlorodimethylsilyl)benzene with molten sodium metal in refluxing toluene in the presence of 18-crown-6. The GCMS spectrum of the reaction mixture showed the presence of a very small amount of the cyclophane 35 with its parent ion (M+ = 498). After careful isolation, pure samples of 35 were obtained as white solids. This provides the most direct route to 35, but the yield is very low (0.22%) (39) (Scheme 9). 

Carbon dioxide instead of aldehydes can be involved in Ni(0)-promoted reductive coupling reactions (Equations (76) and (77) Scheme 90).434,434a 434c A stoichiometric amount of Ni(COD)2/DBU reacts with C02 and dienes, alkynes, or allenes to afford a metallacycle intermediate. This metallacycle reacts with organozinc compounds or aldehydes in one-pot to give carboxylic acid derivatives. As shown in Scheme 90, double carboxylation occurs in the presence of dimethylzinc, where the stereochemical outcome is opposite to that of the reaction with diphenylzinc. 

Reductive Coupling Reaction via Hydroboration of Allenylidene Intermediates... 

Scheme 7.32 Reductive coupling reactions of propargylic alcohols.

Scheme 7.33 Proposed reaction pathway for reductive coupling reactions.

Reductive Coupling Reactions Promoted by Low-valent Early Transition Metals and Lanthanoids ... 

Due to space limitations, vinylogous reactions of pinacol coupling and reductive coupling using nitriles are not described. Also, reductive coupling reactions between compounds having carbon-carbon multiple bonds and carbonyl compounds are not covered. 

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