Formal [2 + 2 + 2] Cycloaddition Strategy Based on an Intramolecular Propargylic Ene Reaction/Diels−Alder Cycloaddition Cascade

Abstract

A formal, metal-free, [2 + 2 + 2] cycloaddition strategy is described based on a cascade of two pericyclic processes. The first step involves an intramolecular propargylic ene reaction of a 1,6-diyne to generate a vinylallene, which then reacts in an inter-or intramolecular Diels-Alder reaction with an alkenyl or alkynyl dienophile. Reactions involving unsymmetrical alkenyl and alkynyl dienophiles proceed with good to excellent regioselectivity, and the diastereoselectivity in the Diels-Alder step is also high, with endo cycloadducts produced as the exclusive products of the reaction. In the case of alkynyl dienophiles, [4 + 2] cycloaddition initially generates an isotoluene-type intermediate that isomerizes to the isolated aromatic product upon exposure to a catalytic amount of DBU at room temperature. The mechanism of several earlier fully intramolecular related transformations have been shown to involve an analogous process rather than the diradical-mediated pathways proposed previously.

Domino Reaction Sequence for the Synthesis of [2.2.2]Diazabicycloalkenes and Base-Promoted Cycloreversion to 2-Pyridone Alkaloids

“…1 Pyridines are one of the most prevalent aromatic heterocycles found in bioactive molecules and functional materials. 2 Cascade pericyclic processes 3 such as merged cycloaddition/ cycloreversion strategies, 4 particularly those employing 1,2,3- and 1,2,4-triazines, 5 are a valuable synthetic complement to traditional and more contemporary 6 condensation methods. 7 In comparison, merged cycloaddition/cycloreversion approaches for the direct synthesis of 2-pyridones are not common; 8 however, Hoornaert and co-workers validated the possibility of this approach using cycloaddition of chlorinated pyrazinone intermediates.…”

Rhodium‐Catalyzed Cascade Reactions of Dienynes Leading to Substituted Dihydronaphthalenes and Naphthalenes

“…The absolute configuration of naphthalene (+)-7 d was determined to be (S) by the anomalous dispersion method (Figure 1). [18] This transformation represents another synthetic utility of the present cascade reaction product. The desired alcohol (+)-7 a was indeed obtained with almost the same level of chirality transfer as that obtained with the cationic rhodium(I)/(R)-xylbinap complex (68 % ee, Scheme 4).…”

“…With cycloalkanone-derived substrates 1 i and 1 j, the carbonyl ene reaction did not even succeed at 80 8C. [18,19] In order to confirm whether the cationic rhodium(I) complex catalyzes the carbonyl ene reaction step, the isolated aldehyde (+)-5 a (78 % ee), prepared from 1 a by using the cationic rhodium(I)/(R)-xyl-binap catalyst, was treated with the cationic rhodium(I)/rac-binap complex (10 mol %) at 80 8C. The absolute configuration of naphthalene (+)-7 d was determined to be (S) by the anomalous dispersion method (Figure 1).…”

“…Indeed, the reaction of dienyne 1 k in the presence of the cationic rhodium(I)/rac-binap catalyst at 80 8C gave vinyl-substituted 1,4-dihydronaphthalene 9 k, instead of 1,2-dihydronaphthalene, in good yield as a mixture of diastereomers (Table 3, entry 1). [18] The reactions of both arylacetylene-and alkylacetylene-derived dienynes 1 l-n furnished vinyl-substituted 1,4-dihydronaphthalenes 9 l-n in good yields (Table 3, entries 2-4). [18] The reactions of both arylacetylene-and alkylacetylene-derived dienynes 1 l-n furnished vinyl-substituted 1,4-dihydronaphthalenes 9 l-n in good yields (Table 3, entries 2-4).…”

A New Approach for the Synthesis of Highly Substituted Aromatic Rings: The Alkyne‐Mediated Approach

“…[1] Danheiser and co-workerss howed that intermolecular cascade reactions could efficiently yield bicycles and tricycles (depending on the nature of the dienophile). [11] The diyne species (3)u ndergoes an intramolecular propargylic ene reactiont o form an intermediate allene followed by the concomitantintermolecular Diels-Alder reaction in the presence of ad ienophile to yield the polycyclic product (Scheme 2). Parsons and coworkers have also demonstrated that an intra/intermolecular reactioncan take place.…”