Pinacol coupling aromatic ketones

In the absence of activation, the carbonyl group (aliphatic ketones and aldehydes) is too weak an electrophore to exhibit a specific reduction in aqueous media. Moreover, aldehydes may lead to hydrates, the reduction of which is even more difficult. On the contrary, activation by a double bond(s) or an aromatic ring in the a position allows one to reduce carbonyl groups. Thus, in acidic media one observes a one-electron step (reduction of the protonated form of carbonyl) that affords the formation of dimers a mixture of pinacols with aromatic ketones or coupling in s-diketones with c/./l-elbylenic ketones. 

Unlike Mn/AcOH, Rieke manganese efficiently couples aromatic ketones, furnishing good to excellent d,l selectivity (Eq. 3.17). As with Mn/AcOH, dialkyl ketones are not suitable substrates for Rieke Mn-mediated pinacol coupling. 

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. 

Pinacol coupling. Yb(0) metal can effect pinacol reduction of aromatic, but not aliphatic ketones.1 However, it can effect cross-coupling of benzophenone with aliphatic ketones, often in high yield (equation I). 

The electroreductive coupling of the hindered aromatic ketones (367) has been achieved in a DMF-BU4NBr-(Hg) system by the aid of CrCh or MnCl2 as the electrocatalyst (Scheme 134) [484, 485]. The reductive coupling proceeds at a less negative potential [ 1/2 —1.44 —1.53 V (SCE)] than the reduction of the ketone (—1.63 —2.01 V). In some cases, Mn electrocatalysts favor the reduction to the carbinol (369), whereas a Cr catalyst promotes the formation of the pinacol (368). 

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). 

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

I, 5-dithioniabicyclo[3.3.0]octane bis(trifluoromethanesulfonate) 7 in acetonitrile at 50°C. The salt promotes pinacol coupling of aromatic ketones even at —40 °C. In addition, the diastereoselectivity dl meso) of the coupling reaction of acetophenone in acetonitrile at —40°G is 94 6. "... 

Nil2 or Fe(acac)3 in a catalytic amount also accelerates the pinacol coupling in pivalonitrile. The system can be applied to the coupling reactions of aromatic and aliphatic ketones (Equation (33)). ... 

In most cases, carbon-carbon bond formation occurs at the least substituted terminus of the allylic unit. A wide range of aldehydes and ketones can be utilized in the reaction, and one cyclization process has been reported (equation 16). Aromatic and a,3-unsaturated substrates cannot be used owing to cran-petitive pinacolic coupling reactions promoted by Sml2. 

Alkenyl halides and aromatic halides are unreactive with ketones in the presence of Sml2 in THF. Pinacolic coupling products can be detected in 10-20% yield under these conditions. In THF/HMPA, io-dobenzene reacts in the presence of a ketone to generate a phenyl radical, which abstracts a hydrogen from THF. Samarium diiodide induced coupling of the THF radical to the ketone (or ketyl) provides the major observed product (equation 21). ... 

Indium. Kim has developed an indium-mediated pinacol coupling of aromatic aldehydes that proceeds in water or in water/t-BuOH (Eq. 3.14) [33]. Sonication greatly enhances the rate of the reaction. The diastereoselectivity of the pinacol coupling is variable, with d,l meso ratios ranging from 6 1 to 1 2. Aliphatic aldehydes, as well as ketones, are inert to these conditions. 

Manganese. Li and Chan [34] and Rieke [35] have independently reported that manganese reagents can accomplish the pinacol coupling of aromatic carbonyl compounds. In the Li/Chan study, reaction of an array of aromatic aldehydes proceeded in good to excellent yield in the presence of Mn/Ac0H/H20, albeit with poor diastereoselectivity (Eq. 3.15). Under these conditions, aliphatic aldehydes are reduced to the corresponding alcohol, and ketones (aromatic or aliphatic) do not react. 

Niobium. Szymoniak has developed a niobium-based method for the pinacol coupling of aliphatic aldehydes, aromatic aldehydes, and aromatic ketones (Eq. 3.18) [37]. In the presence of NbCl3, intermolecular couplings proceed with consistently high diastereoselectivity. In many cases, the diol forms an acetal with the remaining aldehyde, and this is isolated at the end of the reaction. The stereoselection of... 

Chromium. In 1998, Boland reported a chromium(n)-catalyzed pinacol coupling reaction of aromatic aldehydes and ketones (Eq. 3.28) [46-48J aliphatic aldehydes are inert to these conditions. The turnover step relies upon a combination of manganese and Me3SiCl to regenerate CrX2 from an intermediate chromi-um(III) species (Fig. 3-3). 

Vanadium. Hirao has established that pinacol couplings of aliphatic aldehydes and aromatic ketones can be accomplished by CP2VCI2 (cat.)/Me3SiCl/Zn with modest to good stereoselectivity (Eqs. 3.43 and 3.44) [64]. Higher diastereoselec-tivity is obtained if a more bulky silyl chloride (PhMeaSiCl) is employed, and a mechanism analogous to that illustrated in Fig. 3-3 is believed to be operative. No catalysis is observed in the absence of Me3SiCl. 

The use of HMPA can modify the course of a reaction. It is well known that aromatic aldehydes or aromatic ketones readily couple to pinacols 21 on treatment with Sml2 in THF, but addition of 2.8 equiv of HMPA leads to the formation of product 22 that results from connecting a para carbon with the carbonyl of another molecule (Scheme 22). 

In 1983 we recognized that aprotic THF solutions of Sml2 gave pinacol formation from aldehydes or ketones the reaction being quite fast with aldehydes or aromatic ketones [117]. However, aromatic carbonyl compounds were coupled in THF by the samarium/I2/MeOH system, Sml2 being formed in situ [118]. 

We report here a very rapid procedure for the pinacolization of aromatic carbonyl compounds using tellurium powder and potassium hydroxide. We have observed that aromatic aldehydes and ketones undergo rapid coupling in the presence of tellurium powder and potassium hydroxide at ambient temperature in methanol [eqn. (1)]. The molar ratio of substrate tellurium powder potassium hydroxide varies with the carbonyl compound. 

In aqueous media, the coupling of the radical anion can be avoided. In water, it was found that reduction of aromatic ketones by amines proceeded rapidly to form a secondary alcohol rather than a pinacol (Scheme 29). ... 

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