Domino aldol-cyclisation reaction

On the other hand, another cooperative catalysis approach was developed by Oh and Kim with a highly diastereo- and enantioselective domino aldol-cyclisation reaction occurring between aldehydes and methyl a-isocyanoacetate. The process employed a combination of a chiral cobalt complex derived from brucine amino diol and an achiral thiourea. The reaction was applicable to a range of aliphatic, aromatic and heteroaromatic aldehydes, providing the corresponding chiral oxazolines in good yields and diastereoselectivities of up to >90% de combined with good to excellent enantioselectivities of up to 98% ee, as shown in Scheme 7.12. 

In 2010, Shibata and co-workers developed an enantioselective enamine-trifluoropyruvate domino aldol-cyclisation reaction to yield chiral pyrroli-dones. Several commercially available derivatives of cinchona alkaloids were screened in combination with Ti(Oi-Pr)4. Hydroquinine diether ((DHQD)2AQN) was found to be the best ligand and afforded the products in high yields and enantioselectivities of up to 92% ee, as shown in Scheme 7.19. Using this system, five cyclic enamines with different protecting groups were screened with remarkable results. The enantiomers of the products were also accessible by applying the pseudoenantiomeric cinchona alkaloid. 

Scheme 7.19 Domino aldol-cyclisation reaction catalysed by chiral cinchona catatysis and titanium catalysis.

Scheme 4.9 Domino aldol-type/cyclisation reaction of aldehydes with isothiocyanatooxindoles.

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