Since the formal characterization of diversity-oriented synthesis (DOS), identification of effective examples of DOS remains an important endeavor for synthetic and pharmaceutical chemists requiring new strategies to generate broader skeletal diversity. Over the last decade, the formal homo-Nazarov cyclization has been an increasingly popular strategy for the concise assembly of functionalized six-membered rings due to the advent of catalytic methods to promote the transformation under milder reaction conditions. Moreover, using the formal homo-Nazarov cyclization as a mechanistic template, reactions can be strategically devised as an effort towards diversity-oriented synthesis. The resulting “homo-Nazarov-inspired” reactions are then demonstrated as a means to access broad structural diversity. This review discusses the development of these catalytic approaches and the successful implementation of the formal homo-Nazarov reaction as a viable template for diversity-oriented synthesis.

An Al(OTf)₃-catalyzed intramolecular cascade ring-opening benzannulation of 2,3-dihydrofuran O,O- and N,O-acetals is described. The cascade sequence involves the dihydrofuran ring-opening by acetal hydrolysis, an intramolecular Prins-type cyclization, and aromatization to generate an array of benzo-fused (hetero)aromatic systems in up to 95 % yield. This method represents the first example of dihydrofuran acetal usage in benzannulation reactions. The approach provides excellent regiocontrol based on the choice of alkenes used to form the requisite dihydrofuran acetals.

A catalytic formal [5+2] cycloaddition approach to the diastereoselective synthesis of azepino[1,2-a]indoles is reported. The reaction presumably proceeds through a Lewis acid catalyzed formal [2+2] cycloaddition of an alkene with an N-indolyl alkylidene β-amide ester to form a donor–acceptor cyclobutane intermediate, which subsequently undergoes an intramolecular ring-opening cyclization. Azepine products are formed in up to 92 % yield with high degrees of diastereoselectivity (up to 34:1 d.r.).

A catalytic formal [5+2] cycloaddition approach to the diastereoselective synthesis of azepino[1,2-a]indoles is reported. The reaction presumably proceeds through a Lewis acid catalyzed formal [2+2] cycloaddition of an alkene with an N-indolyl alkylidene β-amide ester to form a donor–acceptor cyclobutane intermediate, which subsequently undergoes an intramolecular ring-opening cyclization. Azepine products are formed in up to 92 % yield with high degrees of diastereoselectivity (up to 34:1 d.r.).