Urea-amine bifunctional catalyst reaction

Very recently. Barber et al. reported a tandem reaction combining bifunctional urea and Au(I) salt for the asymmetric synthesis of valuable tetrahydropyridine derivatives [80]. This reaction consisted of a urea-promoted nitro-Mannich reaction of an alkyne-tethered secondary nitroalkane to N-Boc-protected imines and an Au(I) complex-catalyzed intramolecular hydroamination and isomerization (Scheme 9.75). Notably, since the inherent Lewis basic tertiary amine-tethered urea would deactivate the Au catalyst, the reaction system was acidified by additional DPP before addition of an Au catalyst to ensure the success of the overall process. 

On the other hand, Chen et al. have reported an asymmetric three-component reaction of aldehydes, diethyl a-aminomalonate and nitroalkenes. The Michael adducts were obtained in excellent yields and enantioselectivities of up to 98% ee by using a chiral bifunctional urea-tertiary amine as the organo-catalyst (Scheme 1.64). 

Despite the prevalence of amine/metal or Brpnsted acid/metal binary catalysis, bifunctional (thio)urea/metal binary catalysis finds only limited applications in in cascade or tandem reactions and is much less well developed. This may be due partially to deactivation of the Lewis acidic metal catalysts by coordinative (thio)urea catalysts. The examples reported often adopted the strategy of sequential additions of catalysts and substrates to solve the problans mentioned above. 

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