Pinacol homocoupling

Zirconium. Schwartz has reported that (Cp2ZrCl)2 is an effective reagent for the pinacol homocoupling of 2,3-di-O-isopropylidene-D-glyceraldehyde (Eq. 3.27) [44]. The diastereoselection is temperature dependent - whereas equal amounts of the two syn isomers are produced if the reaction is run at room temperature, a 7 1 mixture of isomers is generated at -78°C->0°C. At either temperature, neither of the anti isomers is observed. 

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 monoprotected pinacol can be obtained in 81% yield by intramolecular coupling of 2,2 -biaryldicarbaldehyde mono-dibenzyloxy acetal, using samarium(ii) iodide in THF in the presence of BF3-OEt2 (Equation (47)). As in the case of homocoupling of 2,2 -biaryldicarbaldehyde, the /ra r-isomer is produced selectively. Addition of the Lewis acid is important to obtain high yields, otherwise the yield drops to 37%. ... 

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)). ... 

Sm(OTF)3 reduced with ethylmagnesium bromide at —78°C promotes the reductive homocoupling of aldehydes and ketones to give pinacols. 

The last two side reactions are fairly easy to control. The reductive dehalogenation appears to be caused by the concomitant oxidation of a primary alcohol (either from the boronic ester or from an alcohol cosolvent). Consequently, it can be minimized simply by utilizing boronic esters from tertiary alcohols (such as pinacol) and by avoiding the use of alcohol cosolvents. Since oxidative homocoupling is facilitated by ambient oxygen, the impact of this side reaction... 

In the absence of the aldehyde, homocoupled pinacol and a ctxnpound resulting from a double carbon-ylation are isolated in low yields. Both products are consistent with initial formation of a samarium acyl anion. 

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). 

The aminoalditol 23 was prepared by a pinacol-like homocoupling of an appropriately protected L-serine-derived aldehyde and promoted by a vanadium-zinc complex [V2Cl3(THF)6)]2[Zn2Cl6]. (See Section 2.2 for the further transformation of compound 23). 

McMurry pinacol couplings can proceed with stereochemical induction from nearby stereogenic carbons. For example, diastereomer 21 was the major heterocoupled stereoisomer observed when aldehyde 19 and ketone 20 were treated under McMurry conditions. A diastereomer of 21 was also produced in 22% yield along with the product of homocoupling of... 

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