Pinacol aromatic aldehydes

Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

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. 

Samarium diiodide is another powerful one-electron reducing agent that can effect carbon-carbon bond formation under appropriate conditions.257 Aromatic aldehydes and aliphatic aldehydes and ketones undergo pinacol-type coupling with Sml2 or SmBr2. 

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... 

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. 

Titanium-mediated pinacol coupling reactions have been reviewed until 2000.80 81 Since then, various intermole-cular pinacol couplings have been reported with aldehydes, - ketones, a-ketoesters, and imines, as well as asymmetric versions thereof.101-104 Scheme 29 shows one example of an asymmetric pinacol coupling of aromatic aldehydes, promoted and catalyzed by the new chiral titanium complex (A)-75, that has been developed by Riant and co-workers.101 Yields for pinacol products 76 are generally high. Under catalytic conditions, ee is moderate (up to 63%), while stoichiometric conditions allow to obtain up to 91% ee. 

A pinacol-type silylative dimerization of various aromatic aldehydes promoted by a cationic thiolate-bridged diruthenium complex has been reported by Flidai and co-workers (Equation (28)).344 l,2-Diaryl-l,2-disiloxyethanes 153 were isolated as the major products along with the corresponding arylmethyl silyl ethers as minor products. 

Aromatic aldehydes undergo a pinacol reaction when treated with hexamethyl-disilane and tetra-n-butylammonium fluoride [55] using procedure 3.1.14.D. 

Reduction of aromatic aldehydes to pinacols using sodium amalgam is quite rare. Equally rare is conversion of aromatic aldehydes to alkenes formed by deoxygenation and coupling and accomplished by treatment of the aldehyde with a reagent obtained by reduction of titanium trichloride with lithium in dimethoxyethane. Benzaldehyde thus afforded /ra/is-stilbene in 97% yield [206, 209]. 

Good yields of pinacols from aromatic aldehydes and ketones are obtained by adding catechol to the TiCl3-Mg reagent prior to the coupling.164... 

Titanium(iv) iodide" " or a combination of a titanium(iv) salt and an iodide source promotes pinacol coupling reactions of aromatic aldehydes. The combination of the reagents is considered to generate titanium(m) species along with U. 

Pinacol coupling reactions of aromatic aldehydes with commercially available TiCU /> a mixed solvent of THE and dichloromethane show high 47-selectivities." Also, high 47-selectivities are observed with TiCU-BuUTe in DME and TiCU-Bu"Li in Et20 at -50 °C. (see Table 1). 

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

Several studies have been made of the effect of added metal ions on the pinacol/alcohol ratio. Addition of antimony(m) chloride in catalytic amounts changes the product of the electrochemical reduction of acetophenone in acidic alcohol at a lead electrode from the pinacol in the absence of added metal salt to the secondary alcohol in its presence53. Antimony metal was suspected to be an intermediate in the reduction. Conversely, addition of Sm(in) chloride to DMF solutions of aromatic aldehydes and ketones54 and manganese(II) chloride to DMF solutions of hindered aromatic ketones55 results in selective formation of pinacols in excellent yields. When considering these results one should keep in mind the fact that aromatic ketones tend to form pinacols in DMF even in the absence of added metal ions1,29,45. 

The pinacol-type coupling of aliphatic aldehydes, in the presence of niobium(IH) salts, occurs, with a high anti diastereoselectivity (equation 131)512. In the case of aromatic aldehydes and ketones the alkene product is sometimes formed513. In both cases the cyclic acetals may also be formed. 

Pinacols (61) derived from a variety of aromatic aldehydes have been employed in enantio- and diastereo-selective allylations of aliphatic aldehydes.174 Their allyl-boronate derivatives react under Lewis acid conditions (SnCU) with a variety of aldehyde types, in good yield and ee. Even better results are obtained by addition of (61) as a I irons led acid (auto)catalyst, via coordination/activation of the tin catalyst. 

A (salan)Mo(VI) oxo complex proved to be an efficient precatalyst for the pinacol coupling of aromatic aldehydes [236]. After reduction to the catalytically active (salan)Mo(IV) complex using stoichiometric amounts of Zn and TMSC1, pinacols were obtained with moderate to good /j,/,-selectivities and ee values. 

The samarium(ll)-mediated Barbier reaction has been used as an alternative to the deprotonation chemistry to generate 2-alkyl-metallated oxazoles (Scheme 43). This reaction is very useful for the coupling of 2-iodomethyl oxazoles and aliphatic aldehydes. However, reactions with aromatic aldehydes gave mainly pinacol coupling products <20050L4099>. 

Cerium isopropoxide catalyzes the highly diastereoselective pinacol coupling of aliphatic and aromatic aldehydes (eq. (15)) [139]. 

The relative ease of pinacolization is primarily determined by the reduction potential of the carbonyl group involved. Many reductants are therefore selective for aromatic and other electronically activate systems. Moreover, as a result of this ready reduction, pinacolization of such carbonyls can be effected by either anionic or radical routes. For example, treatment of aromatic aldehydes or ketones with Mg/TMSCl in HMPA promotes pinacolization via formation of an a-silyloxy carbanion - and nucleophilic attack on a second carbonyl group (equation 2). Furthermore, with benzaldehyde the reaction is stereodirecting with a preference for /it-coupling. Whilst an alternate coupling metht using the milder... 

The reduction of dialkyl acetals of aromatic aldehydes or ketones with a titanium(II) reagent gives pinacol ethers or the corresponding alkene in high yield (46-100% equation 116). Acetals derived from aliphatic aldehydes or ketones are reduced to the corresponding ethers. 

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