Development of Asymmetric Reactions by use of Chiral Bronsted Acid

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Development of novel efficient catalysts continue to be a challenging topics in synthetic organic chemistry. We have synthesized a cyclic phosphoric acid derivatives, starting from (R)-BINOL. The phosphoric acid exhibited excellent catalytic activity in the nucleophilic addition reaction toward imines.1) Mannich-type reaction of silyl enolate to imines.Chiral Bronsted acid catalyzed Mannich-type reaction proceeded smoothly in the presence of 10 mol% of a cyclic phosphate derived from 3,3'-bis(4-nitrophenyl)-substituted binaphthol. β-Amino esters were obtained in high to excellent yields and with excellent enantioselectivities. The substituents on binaphthol played a crucial role in enantioselectivity and reactivity. Imines derived from o-HOC_6H_4NH_2 gave the highest enantioselectivity. Presence of o-hydroxy group is essential for the chiral induction. Based on the results, we would like to propose 9-membered transition state, wherein phosphoryloxygen forms hydrogen bond with OH moiety.2) Hydrophosphonylation reactionHydrophosphonylation of diisopropyl phosphite to imine also took place highly enantioselectively to give α-amino phosphonate in high yields with good to high enantioselectivities. In this case, use of a chiral phosphate bearing 3,5-(CF_3)_2C_6H_3 group on 3,3'-position of binaphthyl ring is essential for attaining high enantio selectivity.3) Cycloaddition reactionAza Diels-Alder reaction of Danishefsky's diene with imine also proceeded smoothly by means of the chiral Bronsted acid catalyst. In this case, 2,4,6-triisopropylphenyl group substituted one gave the best results.Contrary to conventional metal-based chiral catalysts, present Bronsted acid is free from metal and is stable in air. Present catalysts adds a new entry into chiral organocatalysts.