Pinacol coupling mixed

If the primary chemical process is still abstraction of a hydrogen atom to produce the benzophenone ketyl radical, one would expect to observe some mixed pinacol product arising from coupling of the benzophenone ketyl and acetone ketyl radicals,... 

An interesting deoxygenation of ketones takes place on treatment with low valence state titanium. Reagents prepared by treatment of titanium trichloride in tetrahydrofuran with lithium aluminum hydride [205], with potassium [206], with magnesium [207], or in dimethoxyethane with lithium [206] or zinc-copper couple [206,209] convert ketones to alkenes formed by coupling of the ketone carbon skeleton at the carbonyl carbon. Diisopropyl ketone thus gave tetraisopropylethylene (yield 37%) [206], and cyclic and aromatic ketones afforded much better yields of symmetrical or mixed coupled products [206,207,209]. The formation of the alkene may be preceded by pinacol coupling. In some cases a pinacol was actually isolated and reduced by low valence state titanium to the alkene [206] (p. 118). 

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). 

Low-valent niobium and tantalum are also effective for homocoupling of aldehydes leading to 1,2-diols. " Not only commercially available NbClglDME) but also a combination of NbCls and zinc can be used for the pinacol coupling. Reactions in a mixed solvent of 1,4-dioxane and toluene (1 4) give better diastereoselectivity than those in DME or THE (Equation (52)). ... 

Iron-catalyzed Suzuki-Miyaura coupling reactions were also reported by Nakamura and colleagues (entry 27) [67]. Alkyl halides 1 and mixed pinacol aryl(butyl)borates, generated in situ from arylboronates and butyllithium, were used as the reagents and 10 mol% of the iron complexes 16a or 16b as the catalysts. The addition of 20 mol% of MgBr2 was essential for the success of the reaction. Products 3 were isolated in 65-99% yield. The methodology tolerates ester and nitrile functions. The reaction starts probably by initial boron-iron transmetalation to generate a diaryliron(II) complex. 

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... 

The photoreduction of benzophenone in methanol and ethanol gives benzopinacol and a cross-coupled product.Moreover, Weiner reported that photoreduction of benzophenone in 2-propanol yields a pinacol-type compound and the mixed pinacol (QH5)2C(OH)C(OH)(CH3)2-5 These reactions occur by the free ketyl radicals. 

Photoinitiators are generally aryl alkyl ketones or diaryl ketones (Table 2.19). For aryl alkyl ketones two free radicals are produced by homolytic scission of a C-C bond (Eq. (2.96)). Diaryl ketones are usually mixed with a tertiary amine the mechanism of production of free radicals involves H abstraction from the tertiary amine by the excited state PI, via a charge-transfer stabilized exciplex (Eq. (2.97)). The a-amino alkyl radical formed is very reactive and is in fact the true initiator because the cetyl radical disappears rapidly through a coupling reaction (formation of pinacol). 

The reduction mechanism of carbonyl compounds and its dependence on pH has been outlined in section 8.2. Pinacol formation occurs either by dimerization of the hydroxymethyl radical 101 (Eq. (185) ) or by mixed coupling of 101 with the ketyl 102. Dimerization of 102 seems less probable due to electrostatic repulsion of the two negative charges. Besides coupling, 101 or 102 may be further reduced to the alcohol 103. With active cathodes (e.g., Hg, Sn) 101 forms organo-... 

Path 1) is assumed for the mixed coupling of ketones to pinacols, for which examples are given in Table 16. 

Enones may react either as ketones (cf. Chapter 10) or as activated alkenes thus giving pinacols, y6,y6 -coupling, or mixed coupling products. Another feature of enone reduction is that the radical anions, A, in the presence of proton donors are protonated at oxygen in a fast process, and the resulting enol radical, B , is more difficult to reduce than the neutral substrate (Sec. II.A. 1). Radical anions derived from other activated double bonds tend to protonate at carbon in the presence of proton donors, and the resulting radical is more easily reduced than the neutral substrate (Schemes 1 and 3). 

The CHDs formed by intramolecular addition often eliminate water to give another of,)6-unsaturated ketone. For mesityl oxide (4-methyl-3-pentene-2-one), 22b, the influence of the reaction conditions on the product distribution was examined in detail [96]. Mixtures of four dimeric species were observed, resulting from initial 4,4 -coupling (24b-d), or from mixed 2,4 -coupling, 24a. Pinacol formation (2,2 -coupling) was not observed [Eq. (6)]. 

Mono-enol ethers of -diketones (26) are formally alkoxy substituted enones, and by reductive coupling followed by hydrolysis they yield conjugated bis-enones [Eq. (8)]. This is the more stable product, independent of whether the initial coupling product is a pinacol, a bis-ketone, or mixed coupling product. Reduction of the substrates (26a-b) in ethanol/water (1 1) (Me4NCl) gave the corresponding bis-enones in 20-40% yield [101]. 

A mixture of pinacol and cyclized mixed coupling products, 39a and 41a were formed upon reduction of 3-methylcrotonaldehyde (37a) at pH 5 (Table 9) [112]. Under these conditions, the intermediates undergoing coupling are expected to be the neutral radicals obtained by protonation at oxygen. The effect of increasing size of R in 37 on the dimeric products [113] is shown in Table 9. In all cases, 39 resulting from the mixed 1,3 -coupling was the major isomer [113]. 

Reichwein, J. F., Pagenkopf, B. L. New Mixed Phosphonate Esters by Transesterification of Pinacol Phosphonates and Their Use in Aldehyde and Ketone Coupling Reactions with Nonstabilized Phosphonates. J. Org. Chem. 2003, 68,1459-1463. 

The reductive coupling of a,p-unsaturated carbonyl compounds can lead to three types of dimerization products pinacols (1,2-coupling), 1,6-diones (1,4-coupling), and y-hydroxycarbonyl compounds (mixed coupling). These couplings are further complicated by the ability of the initially formed dimerization products to undergo further reactions and complex product mixtures can sometimes result. ... 

Mixed coupling of ketones and a,P-unsaturated ketones can be profoundly affected by the pH of the solution. Thus the Wieland-Miesher ketone (80) undergoes intramolecular coupling to give the cyclopropanol (81) under basic conditions whilst in neutral media 1,2-hydrodimerization occurs leading to the pinacol (82 equation 107). ... 

Other unsymmetrical diols, prepared (inefficiently) by the coupling of mixtures of ketones, have been studied. The preferred cation argument is also found to be applicable to mixed medium-ring analogs, i.e. the kinetically favored pinacol rearrangement product is that predicted by consideration of the relative stabilities of the two possible, initially formed, carbocations. ° Earlier work with these compounds may have given misleading results due to product instability. To illustrate, Mundy observed that (24) is converted to (25) as the temperature is increased. 

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