Tetracyclic compounds, intramolecular cascade

Alcaide et al. have used their methanesulfonate route to fused /3-lactams in a cascade sequence of reactions, including an intramolecular Diels-Alder reaction to obtain tetracyclic compounds (Scheme 17) <2003JOC3106>. 

Intermediate samarium enolates derived from ketones 1522 or 1525 could stereoselectively be trapped with allyl halides, leading to tricycles 1524 and 1526. The intramolecular alkylation by the chloroalkyl terminus of compound 1527 led to tetracyclic compound 1528 with satisfactory efficiency. These cascade reactions selectively generate three continuous stereogenic centers, including a quaternary carbon atom at the 3-position of the dihydroindole moiety, a structural motif of many indole alkaloids. 

Cascade reactions of substituted 1,2,4-triazines are of great interest as simple ways to a dramatic increase in molecular complexity, from planar 1,2,4-triazine unit into a polycyclic system. Indeed, in this multistep process, the diallylamine and cyclopentanone react first in situ to give the corresponding enamine, which undergoes an inverse electron demand cycloaddition reaction with 1,2,4-triazine to give an intermediate dihydropyridine compound. A spontaneous intramolecular Diels-Alder reaction between the allyl moiety and the dihydropyridine gives the tetracyclic compound (Scheme 99) <2004JA12260>. 

One final example that underscores the power of intramolecular domino reactions to achieve the stereoselective synthesis of complex nitrogen heterocycles comes from the work of Barluenga and Gonzalez, who studied the preparation of tetrahydro-quinolines by intramolecular arylation of olefins induced by the in-house developed IPy2BF4 iodonium reagent. When applied to amine 102, this method afforded the tetracyclic compound 103 by the creation of three rings and five stereocenters in an elegant, fully diastereoselective cationic cyclization cascade (Scheme 3.32) [79]. 

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