Asymmetric reaction by means of movel high activation of aza-aromatics

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Development of methodology for stereoselective introduction of useful carbon substituents into nitrogen heterocycles is of great importance for synthesis of various physiologically and pharmacologically active nitrogen heterocyclic cmopounds. One of the methodology comprises addition reactions of various carbon nucleophiles to activated aza-aromatics and has been extensively investigated. All of them reported so far, however, have exploited diastereoselctive additions of achiral organometallic reagents to aza-aromatics bearing a chiral auxiliary in an activating group or on the aromatic ring. There has been no highly enantioselective addition reaction of a chiral organometallic reagent to achiral aza-aromatics.We have found that highly activated N-acylated aza-aromatic ions can be generated when aza-aromatics such as us isoquinoline and qinoline are treated with phenyl chloroformate and silver triflate and that N-acylated aza-aromatic ions thus produced can readily react with allylsilanes and alkynylsilanes.On the basis of the above results, we have found in the present study that the addition reactions of a chiral allylsiane to highly activated N-acylated aza-aromatic ions proceed in a highly enantioselective manner. To the best of our knowledge, this is the first example of a highly enantioselective addition reaction of a chiral organometallic reagent to an aza-aromatic.A variety of functional groups, such as ester, bromo, formyl, cyano, and nitro, on isoquinoline and quinoline are tolerated in the present asymmetric addition reactions with more than 90% enantioselectivity, showing the high chemoselectivty. The absolute configurations of the products are confirmed and it is supported that the reactions proceed via anti-periplanar anti-SE' mechanism.