Aldehydes pinacols

Some additives accelerate the pinacol coupling reactions. Addition of Me3SiCl to Sml2 also accelerates the pinacol coupling reactions of aliphatic ketones and aldehydes. Pinacol coupling reactions are also promoted with samarium metal and a Lewis acid such as Et2AlCl or MesSiCl. Coordination of such a Lewis acid to a carbonyl oxygen facilitates the one-electron reduction by samarium. 

Keywords ketone, aldehyde, pinacol coupling reaction, Zn, ZnCl2, a-glycol... 

Rocaglamide. Taylor has employed an intramolecular keto-aldehyde pinacol coupling reaction in a synthesis of rocaglamide, an anti-leukemia natural product (Eq. 3.4) [20]. Other reducing agents were either completely ineffective (e.g., Zn/ TMSCl and Zn/TiCU) or significantly less efficient (e.g., Mg/Hg/TiCU and LiAlHVCpTiCls) than Smli. 

Sodium me/aperiodate (NalO ) in cold aqueous solution readily oxidises 1,2-diols with splitting of the molecule and the consequent formation of aldehydes or ketones thus ethylene glycol gives formaldehyde and pinacol gives acetone. In the case of a 1,2,3-triol, the central carbon atom of the triol... 

The pinacol hydrate may be used (i) for conversion to pina-colone (see below), and (ii) to illustrate the oxidation of 1,2-diols to aldehydes or ketones by periodic acid (p. 145),... 

The pinacol rearrangement reaction is of limited synthetic importance although it can be a useful alternative to the standard methods for synthesis of aldehydes and ketones." Especially in the synthesis of ketones with special substitution pattern—e.g. a spiro ketone like 5—the pinacol rearrangement demonstrates its synthetic potential ... 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

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. 

Diols (pinacols) can be synthesized by reduction of aldehydes and ketones with active metals such as sodium, magnesium, or aluminum. Aromatic ketones give better yields than aliphatic ones. The use of a Mg—Mgl2 mixture has been called the Gomberg-Bachmann pinacol synthesis. As with a number of other reactions involving sodium, there is a direct electron transfer here, converting the ketone or aldehyde to a ketyl, which dimerizes. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

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. 

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... 

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. 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

The electroreduction of aldehydes and ketones often involves the formation of dimeric hydroxy derivatives—pinacols ... 

The Prins cyclization can also be coupled with a ring-contraction pinacol rearrangement, as illustrated in Scheme 1.6. This allows a smooth conversion of alkyl-idene-cyclohexane acetal 1-16 to single bond-joined cyclohexane cyclopentane aldehyde 1-17 [le]. 

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