Pinacol diketone coupling

The 1,5- and 1,6-dialdehydes 22 and 24 undergo the annulative pinacol coupling to give the cyclic vzc-diols 23 and 25, respectively (Scheme 13) [29]. The vanadium-catalyzed intramolecular coupling reaction of 1,5-diketone 26 also proceeds with excellent selectivity (Scheme 14) although the intermolecular coupling of ketones such as acetophenone results in low diastereoselectivity under these conditions [21]. 

The acyloin condensation is closely related to the radical anion coupling forming pinacolate anions two ester radical anions couple to form a dianion, which readily loses two alkoxide ions. The resulting diketone then is reduced by sodium, first to a semidione radical anion, then to the dianion. Finally, aqueous work-up produces the acyloin. Acyloins are convenient precursors for the generation of semidione radical anions. ... 

Although yields and diastereoselectivities are moderate, a cross-pinacol coupling reaction between a 1,2-diketone and an aldehyde is accomplished with Sml2 in the presence of HMPA. ... 

Reductive dimerization of a,p-unsaturated ketones is effected by either Cr" or V" chloride to give 1,6-diketones, but aliphatic a, -unsaturated aldehydes are dimerized to the allylic glycals. Interestingly, nonconjugated aldehydes are stable towards these reagents. Similar pinacolic couplings of aldehydes and ketones with Ti" reagents were developed by Corey. ... 

A variation of the pinacol coupling treats acyl nitriles with indium metal and ultrasound to give a 1,2-diketone. Another variation couples acetals to give 1,2-diols. ... 

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]. 

Intramolecular pinacolic coupling reactions have also proven successful with Stnl2. Yields with simple diketones are relatively low. i> However, excellent yields and diastereoselectivities are achieved in intramolecular pinacolic coupling reactions of P-keto ester and P-ketoamide substrates (equation 72). A variety of substitution patterns can be tolerated in these reactions to generate five-membered carbo-cycles. Six-membered rings can also be generated by this process, but substantially lower yields and diastereoselectivities are observed (equation 73). Yields obtained for p-ketoamide substrates are also lower than those observed in the P-keto ester series. 

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. 

Mukaiyama has described a total synthesis of taxol wherein pinacol cyclization of a diketone was employed to construct the A ring in good yield (Eq. 3.13) [31J. In this work, partially reduced alcohols and rearranged compounds were the major side products of the titanium-mediated coupling process. 

In fact, diketones in a medium sized ring give several transannular reactions such as pinacol coupling [equation (i)] or aldolization [equation The later reaction also occurs during hydrogenation of aliphatic monoketones under favorable conditions (Pd-on-carbon, zeolite, 200°C, 4 X 10 kPa) to produce methyl isobutyl ketone from acetone (in 96%) -... 

In his recent s5mthesis of 19-hydroxytaxoid 18, an intermediate in the synthesis of the anti-cancer agent 19-hydroxytaxol, Mukaiyama performed an intermolecular McMurry pinacol coupling on diketone 17. Note that the reaction temperature was sufficiently low to allow isolation of the diol intermediate. 

---