Coupling pinacol

Pinacol coupling reactions also involve radical-radical recombinations thus, enan-tiocontrol in these reactions remains a daunting problem. Initially it was found that addition of TMEDA as an additive increased the solubility of TiCl2, thus increasing the conversion of the aldehyde to diol product [19]. It was hypothesized that addition of an optically active amine would not only help to solubilize the Lewis acid, but also offer enantiocontrol in the coupling. When chiral diamines such as 41 were added, modest levels of enantioselectivity were achieved (Eq. 14). 

The pinacol coupling reaction is a powerful method for forming from two carbonyl groups a doubly functionalized carbon-carbon bond (Eq. 3.1). The discovery of this venerable process dates from a report by Fittig in the middle of the nineteenth century [IJ. Because the pinacol coupling reaction has already been the subject of a number of reviews [2], this chapter will focus on studies published during the past decade, specifically  

This is known as pinacol coupling. The use of Zn-Cu couple to couple unsaturated aldehydes to pinacols was recorded as early as 1892. Subsequently chromium and vanadium and some ammonical-TiCl3 based reducing agents were used. 

The coupling of carbonyl compounds to give 1,2-diols, known as the pinacol coupling, has been carried out in aqueous media. Clerici and Porta extensively studied the aqueous pinacol coupling reactions mediated by Ti(III). Schwartz reported a stereoselective pinacol coupling with a cyclopentadienetitanium complex. Pinacol-type couplings were also developed by using a Zn-Cu couple, Mn, ° 

A cross-coupling reaction of aldehydes with a-diketones proceeded in the presence of water to give the corresponding adducts in moderate to good yield. It is possible to use the substrates such as phenyl-glyoxal monohydrate, aqueous methylglyoxal, formalin, and aqueous a-chloroacetaldehyde for this reaction.  

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The use of reducing metals nowadays is mainly restricted to acyloin and pinacol coupling reactions (see p. 53f.) and Birch reductions of arenes (A.A. Akhrcm, 1972 see p. 103f.) and activated C—C multiple bonds (see p. 103f.). 

A variety of such ternary catalytic systems has been developed for diastereoselective carbon-carbon bond formations (Table). A Cp-substituted vanadium catalyst is superior to the unsubstituted one,3 whereas a reduced species generated from VOCl3 and a co-reductant is an excellent catalyst for the reductive coupling of aromatic aldehydes.4 A trinuclear complex derived from Cp2TiCl2 and MgBr2 is similarly effective for /-selective pinacol coupling.5 The observed /-selectivity may be explained by minimization of steric effects through anti-orientation of the bulky substituents in the intermediate. 

Table, Cat. CpjVCh/MesSiCl/Zn-Induced Pinacol Coupling of Aliphatic Aldehydes1...

Scheme 5 Catalytic pinacol coupling reaction using [(t-BuO)3pe]K 26 [7]...

Another reagent that has found use in pinacolic coupling is prepared from VC13 and zinc dust.264 This reagent is selective for aldehydes that can form chelated intermediates, such as (3-formylamides, a-amidoaldehydes, a-phosphinoylaldehydes,265 and 8-ketoaldehydes.266 The vanadium reagent can be used for both homodimerization and heterodimerization. In the latter case, the reactive aldehyde is added to an excess of the second aldehyde. Under these conditions, the ketyl intermediate formed from the chelated aldehyde reacts with the second aldehyde. 

Mn. Manganese is also effective for mediating aqueous carbonyl ally-lations and pinacol-coupling reactions. Manganese offers a higher reactivity and complete chemoselectivity toward allylation of aromatic aldehydes.178... 

Catalytic turn-over [59,60] in McMurry couplings [61], Nozaki-Hiyama reactions [62,63], and pinacol couplings [64,65] has been reported by Fiirst-ner and by Hirao by in situ silylation of titanium, chromium and vanadium oxo species with McaSiCl. In the epoxide-opening reactions, protonation can be employed for mediating catalytic turn-over instead of silylation because the intermediate radicals are stable toward protic conditions. The amount of Cp2TiCl needed for achieving isolated yields similar to the stoichiometric process can be reduced to 1-10 mol% by using 2,4,6-collidine hydrochloride or 2,6-lutidine hydrochloride as the acid and Zn or Mn dust as the reduc-tant (Scheme 9) [66,67]. 

Catalytic Reductive Coupling of Carbonyl Compounds -The Pinacol Coupling Reaction and Beyond... 

Abstract Recent advances in the metal-catalyzed one-electron reduction reactions are described in this chapter. One-electron reduction induced by redox of early transition metals including titanium, vanadium, and lanthanide metals provides a variety of synthetic methods for carbon-carbon bond formation via radical species, as observed in the pinacol coupling, dehalogenation, and related radical-like reactions. The reversible catalytic cycle is achieved by a multi-component catalytic system in combination with a co-reductant and additives, which serve for the recycling, activation, and liberation of the real catalyst and the facilitation of the reaction steps. In the catalytic reductive transformations, the high stereoselectivity is attained by the design of the multi-component catalytic system. This article focuses mostly on the pinacol coupling reaction. 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

The ternary system consisting of a metallic catalyst, a chlorosilane, and a stoichiometric co-reductant has been reported by us for the first time to achieve the catalytic pinacol coupling. The homo coupling of aliphatic aldehydes is catalyzed by CpV(CO)4, Cp2VCl2, or Cp2V in the presence of a chlorosilane and Zn in DME to give the 1,3-dioxolanes 1 via the coupling and acetalization (Scheme 3) [18,19]. 

Based on these observations [18,19,23], a variety of modified catalytic systems have been reported for the diastereoselective reductive carbon-carbon bond formation (Scheme 8). A complex 5 derived from Cp2TiCl2 and MgBr2 is proposed to be an efficient catalyst for the DL-diastereoselective pinacol coupling of aromatic aldehydes [24], Addition of a solution of benzalde-... 

The above-mentioned results indicate the additive effect of protons. Actually, a catalytic process is formed by protonation of the metal-oxygen bond instead of silylation. 2,6-Lutidine hydrochloride or 2,4,6-collidine hydrochloride serves as a proton source in the Cp2TiCl2-catalyzed pinacol coupling of aromatic aldehydes in the presence of Mn as the stoichiometric reduc-tant [30]. Considering the pKa values, pyridinium hydrochlorides are likely to be an appropriate proton source. Protonation of the titanium-bound oxygen atom permits regeneration of the active catalyst. High diastereoselectivity is attained by this fast protonation. Furthermore, pyridine derivatives can be recovered simply by acid-base extraction or distillation. 

Low-valent lanthanides represented by Sm(II) compounds induce one-electron reduction. Recycling of the Sm(II) species is first performed by electrochemical reduction of the Sm(III) species [32], In one-component cell electrolysis, the use of sacrificial anodes of Mg or A1 allows the samarium-catalyzed pinacol coupling. Samarium alkoxides are involved in the transmet-allation reaction of Sm(III)/Mg(II), liberating the Sm(III) species followed by further electrochemical reduction to re-enter the catalytic cycle. The Mg(II) ion is formed in situ by anodic oxidation. SmCl3 can be used in DMF or NMP as a catalyst precursor without the preparation of air- and water-sensitive Sm(II) derivatives such as Sml2 or Cp2Sm. 

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