Synthesis of γ,γ‐Disubstituted Butenolides through a Doubly Vinylogous Organocatalytic Cycloaddition

Abstract

A novel organocatalytic approach to γ,γ-disubstituted butenolides is described. It is based on a fully site-selective functionalization of 5-alkylidenefuran-2(5H)-ones via trienamine-mediated [4+2]-cycloaddition with α,β,γ,δ-diunsaturated aldehydes. The developed methodology proceeds with excellent stereocontrol and constitutes a unique example of trienamine chemistry with vinylogous dienophiles. Importantly, the reaction has very broad scope and allows for the introduction of substituents also in the α- or the β-position of the butenolide ring. Usefulness of the products obtained has been confirmed in the intramolecular Stetter reaction leading to polycyclic product.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…Henceforth, an impressive, flourishing number of reports appeared by these and other research groups, which focused on the ε,β-regioselective [4 + 2] cycloaddition between polyenals and a wide array of diverse dienophiles ranging from nitroalkenes, alkylidene heterocycles, to azadienes, enones, etc. For an immediate glance at this varied reaction panorama, a table is given (Table ), collectively depicting these contributions. − …”

An Enantioselective Aminocatalytic Cascade Reaction Affording Bioactive Hexahydroazulene Scaffolds

“…The authors have cited additional references within the Supporting Information. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]…”

Site-Selective and Enantioselective α,β,γ-Functionalization of 5-Alkylidenefuran-2(5H)-ones: A Route to Polycyclic γ-Lactones

“…As a consequence, much effort has been devoted toward the development of methods for their preparation, in particular in a stereoselective fashion (Scheme ). − One strategy involves the use of furan-2­(5 H )-ones as a template for further structural modifications. These highly useful building blocks undergo Michael-type addition with selected nucleophiles, thus introducing new substituents in the β-position .…”

“…In contrast, site-selective α- or γ-functionalization of the γ-butenolide architecture is possible via the corresponding dienolate formation or related systems . Recently, we have developed an alternative approach for the synthesis of γ,γ-disubstituted-γ-butenolides . It involves the usage of 5-alkylidenefuran-2­(5 H )-ones as a new type of building block.…”

“…Such a recognition profile determines both site selectivity and enantioselectivity of the cascade. The fact that the Michael reaction occurs at the less-hindered electrophilic position of the molecule is also of importance with the observed site selectivity being in contrast to our previous results concerning the reactivity of 1 , where the nucleophilic attack that occurs at the exocyclic double bond has been preferred . Intramolecular aldol reaction takes place in the second stage of a cascade, leading to the introduction of the oxygen-centered nucleophile into the molecule.…”