A diastereoselective tandem metalloenamine alkylation/aza-annulation of β-tetralones expedites the synthesis of benzoquinolinones

Solid-Phase Synthesis of 1,2,3,4-Tetrahydro-2-pyridones via Aza-Annulation of Enamines

“…In this approach, a carbon−carbon and a carbon−nitrogen bond are efficiently formed in a two-step, one-pot procedure. Several research groups have studied the aza-annulation reaction and successfully utilized it in the preparation of various nitrogen heterocycles. , Generally, the reaction of imines with α,β-unsaturated acid chlorides provided the annulation products in low yields due to the formation of an uncyclized enamide derived from an initial N-acylation, a potential competing reaction 4a. Recently, Stille et al have successfully investigated the reaction of imines with α,β-unsaturated acids in the presence of various acid-activating reagents to increase the yields of the annulation products by suppressing the uncyclized enamide formation 6g.…”

“…Several research groups have studied the aza-annulation reaction and successfully utilized it in the preparation of various nitrogen heterocycles. , Generally, the reaction of imines with α,β-unsaturated acid chlorides provided the annulation products in low yields due to the formation of an uncyclized enamide derived from an initial N-acylation, a potential competing reaction 4a. Recently, Stille et al have successfully investigated the reaction of imines with α,β-unsaturated acids in the presence of various acid-activating reagents to increase the yields of the annulation products by suppressing the uncyclized enamide formation 6g. In the case of enamines, the annulation reaction proceeded smoothly with α,β-unsaturated acid chlorides and led to the isolation of the annulation products in moderate to good yields. 4b,6c,j The aza-annulation strategy has also been extended to the preparation of five-membered lactams and 2-pyridones by reacting enamines with maleic anhydride and α,β-acetylenic esters, respectively.…”

“…Recently, Stille et al have successfully investigated the reaction of imines with α,β-unsaturated acids in the presence of various acid-activating reagents to increase the yields of the annulation products by suppressing the uncyclized enamide formation 6g. In the case of enamines, the annulation reaction proceeded smoothly with α,β-unsaturated acid chlorides and led to the isolation of the annulation products in moderate to good yields. 4b,6c,j The aza-annulation strategy has also been extended to the preparation of five-membered lactams and 2-pyridones by reacting enamines with maleic anhydride and α,β-acetylenic esters, respectively.

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