Aldehydes pinacolic coupling reactions

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. 

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... 

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. 

Titanium(iv) iodide" " or a combination of a titanium(iv) salt and an iodide source promotes pinacol coupling reactions of aromatic aldehydes. The combination of the reagents is considered to generate titanium(m) species along with U. 

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). 

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. ... 

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)). ... 

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. 

As expected with a reagent that is csq)able of generating ketyls, intermolecular pinacolic coupling reactions can also be carried out with considerable efficiency using Smh. Treatment of aldehydes or... 

Periplanone C. McMurry has reported an enantioselective synthesis of (-)-periplanone C, a sesquiteipene that serves as a sex pheromone for cockroaches, through a route involving a pinacol cyclization of a 1,10-keto aldehyde (Eq. 3.7) [24]. MM2 calculations based on a model for predicting the stereoselection of titanium-mediated pinacol coupling reactions were in qualitative, but not quantitative, agreement with the experimental results. 

Palominol. Corey has reported the application of an intramolecular titanium-mediated pinacol coupling reaction to the synthesis of a 15-membered ring, en route to palominol, a marine diterpenoid that displays cytotoxicity toward the human colon cell line (Eq. 3.10) [28]. Slow addition of the keto aldehyde (32 h) to the titanium reagent furnished the cyclized product in 53% yield as a mixture of diastereomers (2.1 1). 

Shikonin. Torii has accomplished an efficient intermolecular pinacol coupling reaction, en route to the total synthesis of shikonin, a compound with antiinflammatory, antibacterial, and antitumor activity (Eq. 3.11) [29], Because the aromatic aldehyde possessed a substituent capable of chelating to vanadium, Torii anticipated, based on precedent, that selective cross-coupling would be possible. The pinacol reaction proceeded in 73% yield and with good diastereoselectivity (5.5 1). 

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). 

From a synthetic standpoint the intermolecular pinacolic coupling reaction is limited because only homocoupling reactions are generally practical. Cross-coupling reactions mediated by SmF are restricted to specialized, matched partners [35]. Thus a-dicarbonyl compounds can be heterocoupled with aldehydes, providing facile entry to 2,3-dihydroxy ketones. Although selectivities vary, in some cases the diastereoselectivity of the process can be quite high (Eq. 25). 

Pinacol coupling reactions also involve radical-radical recombinations thus, enan-tiocontrol in these reactions remains a daunting problem. Initially it was found that addition of TMEDA as an additive increased the solubility of TiCl2, thus increasing the conversion of the aldehyde to diol product [19]. It was hypothesized that addition of an optically active amine would not only help to solubilize the Lewis acid, but also offer enantiocontrol in the coupling. When chiral diamines such as 41 were added, modest levels of enantioselectivity were achieved (Eq. 14). 

---