Reduction pinacols

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... 

A variety of natural products have been synthesized via application of reductive pinacolic couplings. An early example is the cyclization of the keto aldehyde (51) to the alkene (52 equation 89) a precursor to the terpene, cuparene (18).A modified McMurry procedure provides a novel route to steroids such as estrone methyl ether, via chemoselective cyclization of the keto aldehyde (53 equation 90). The... 

The mixed coupling of aliphatic compounds is also well established. Through the use of an excess (usually 10-fold) of one of the reactants cross-coupling of aliphatic carbonyls is highly effective. This protocol was first developed by (Torey and then applied to reductive pinacolic couplings by McMurry. Li et al. applied this method to the synthesis of the alkaloid isoharringtonine (83 equation... 

A three-step methodology, starting from a propargylic dialdehyde, takes advantage of the Pedersen reductive pinacol reaction. This method is... 

Reductive pinacol-type rearrangement of chiral a-mesyloxy ketones was executed by in situ reduction with DIBAH followed by addition of Et3Al or EuAlCl. The resulting aldehyde is reduced as formed to an optically pure 2-aryl- or 2-alkenylpropanoI [63]. 

Pinacol reduction. Pinacol reduction is generally carried out with amalgamated magnesium or aluminum in benzene. Schreibmann1 reports that higher yields are obtained with amalgamated aluminum in either methylene chloride or THF, in which the aluminum pinacolates are very soluble. They are thus easily separated from excess metal before hydrolysis to the pinacol. 

Stereospecific pinacol reductions. Pinacol reduction of (1) and (3) in the presence of trimethylchlorosilane (4, 183) gives only one of the three possible... 

In conjuction with Triethylaluminum, DIBAL has been used to mediate a reductive pinacol rearrangement. with enantiocontrol,... 

The reduction of ketones with Sm(II) reductants to ketyls constitutes the first step in a number of important reactions including reductions, pinacol couplings and ketyl-olefin couplings. In spite of this, little was known about the nature of the intermediates in these reactions. To study these systems in detail, Hou et al. exposed Sm(Cp )2(THF)2 in THE to an equimolar amount of fiuorenone in an attempt to isolate the ketyl intermediate (Hou et al., 1998). Evaporation of the solvent provided a crystalline product that was dissolved in toluene, which after concentration of the solvent produced (Cp )2Sm(biphenyl-2,2 -diyl ketyl)(THF) in an overall 87% yield (eq. (128)). 

Acetone when treated in ethanol with sodium undergoes reduction mainly to isopropanol. By modifying the conditions, however, acetone may be induced to undergo a bimolecular reduction to pinacol. 

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

Pinacol-pinacolone rearrangement Prileschajew epoxidation reaction Reformataky reaction Reimer-Tiemanii reaction Rosenmund reduction Sandmeyer reaction Schiemaim reaction Schmidt reaction or rearrangement Schotten-Baumann reaction Skraup reaction Sommelet reaction. ... 

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.). 

Huffman found that treatment of cholan-12-one (65b) with lithium and ammonia for 2 hours followed by addition of propanol gives 40 % of a pinacol together with 48.5 % of 12-ols in which the ratio of 12j5 12a is 19 1. This predominance of the 12 -ol was interpreted in terms of slow formation of a dianion of type (62) followed by its equilibration to the thermodynamically most stable configuration, i.e. one which affords the 12j5-ol upon protonation. An alternative explanation is that reduction in the presence of methanol involves protonation of a ketyl such as (61) by methanol, whereas in the absence of methanol reduction proceeds via the dianion (62) which is protonated on... 

Solvent plays a key role in the course of reductions by active metals Changing the solvent of the reaction of hexafluoroacetone with magnesium from tetrahydro turan to dimethylformamide induces bimolecular reduction to the pinacol [5] (equation 2)... 

Electrochemical reduction of carbon-fliionne bonds occurs at high pH when a carbonyl group is adjacent Polaiographic reduction of a a,a-tnfluoroacetophe-none without loss of fluonne predominates in acidic media to give the alcohol and the corresponding pinacol, whereas reduction of the unprotonated ketone results in hydrogenolysis of the tnfluoromethyl group to form acetophenone as product Il] (equation 8)... 

Reductive dunenzation to form fluorinated benzopinacols proceeds m the partly fluormated case either with zinc or by photolysis but is not observed with perfluorobenzophenone [651 (equation 53). Trifluoroacetophenone is reduced electrochemically in dimethylformamide to a stable radical anion, which, m the presence ot lithium ion, rapidly dunerizes to pinacol in higher yield than that available by photoreduction [66] (equation 54)... 

A general study of the reduction of acetone to pinacol. Calvert, India Rubber Rev. 26, No. 9, 48 (1926). 

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. 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

Furthermore, it is now clear that organometallic compounds may be unstable intermediates in other electrode processes. Thus, the reduction of acetone at a series different metals in aqueous sulphuric acid has been studied (Sekine etal., 1965), and the products of controlled-potential electrolyses are shown in Table 3. The reduction of isopropanol or pinacol... 

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. 

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