Furan cocatalysts

Substituted TMM complexes also cycloadd to aldehydes in the presence of a tin cocatalyst such as MesSnOAc and MesSnOTs [31]. Reaction of 2-heptenal with methyl precursor (6) gave a mixture of methylenetetrahydrofurans (68) and (69). This regioselectivity is reversed with 10-undecenal and methyl precursor (5), where adduct (70) now predominates over (71). As in the carbocyclic system, the phenylthio group also functions as a regiocontrol element in reaction with cyclohexyl aldehyde. The initially formed adduct (72) eliminates the element of thio-phenol on attempted allyl rearrangement, and the overall process becomes a cycloaddition approach to furans (Scheme 2.21) [20]. 

Tetrahydro-4-methylene-2-[( )-2-phenylethcnyl]furan (39) (tributyltin acetate as cocatalyst) l> ... 

In 2014 Phiko, Papai et al. tested a series of (25,55)-2,5-disubstituted pyrrolidines as catalysts for enantioselective Mukaiyama-Michael reactions between 2-silylo qr-furans and a,p-unsaturated aldehydes and found that 33, used in the presence of 4-nitro-benzoic acid as the cocatalyst, was the best catalyst in terms of selectivity (Scheme 11.31). Since 33 is not so sterically hindered, the authors also performed a detailed high-level DPT computational study to rationalise the stereochemical outcome, which was found to be controlled not by steric effects, but by the sum of a number of attractive noncovalent interactions involving the catalyst aromatic rings and the furan system. 

Furans represent an important class of electron-rich heterocycles which are useful intermediates in synthetic chemistry and are broadly found as structural motifs of many natural products and pharmaceutically important substances [333]. Since furans are generally less nucleophilic than indoles and pyrroles, their catalytic enantioselective Friedel-Crafts-type conjugate addition has been much less developed so far. Very recently Harada et al. have developed a catalytic system able to achieve good enantioselectivities in the Friedel-Crafts alkylation of electron-rich furans with acychc a,p-unsaturated ketones [334]. As depicted in Scheme 2.117, a//o-threonine-derived oxazaborolidinone 190 (10 mol%) in the presence of V,V-dimethyl benzylamine (10 mol%) as cocatalyst in ether at -40°C, is an efficient catalytic system for the reaction affording the corresponding functionalized furans with good yields and enantioselectivities. 

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