Development of a Vinylated Cyclic Allene: A Fleeting Strained Diene for the Diels-Alder Reaction

Abstract

Fleeting molecules possessing strained multiple bonds are important components in organic synthesis due to their ability to undergo various chemical reactions driven by the release of strain energy. Although the use of strained π-bonds as 2π components, represented by dienophiles in Diels-Alder reactions, has been well studied, "the strained diene (4π component) approach" for molecular construction remains underexplored. Herein, we report the design of a vinyl cyclic allene (1-vinyl-1,2-cyclohexadiene) as a highly reactive strained diene and the development of its Diels-Alder reactions. Experimental and computational studies of vinyl cyclic allenes revealed that this diene system undergoes cycloaddition with dienophiles regio- and stereoselectively under mild reaction conditions. These studies also provide insight into the reactivity and selectivity of the system. The strained diene approach enables the convergent construction of polycyclic molecules through bond disconnections distinct from conventional retrosynthetic analysis, thus offering an efficient strategy for the assembly of functional molecules.

Keywords: Activation strain model; Carbocycles; Diels–Alder reaction; Strained diene; Vinylated cyclic allene.

Figure 1

Diels–Alder reaction of a) cyclic allene, b) acylated cyclic allene, and c) vinylated cyclic allene (this work). Depicted HOMO was computed at HF/6‐31G level of theory.

Figure 2

Diels–Alder reaction of a vinyl cyclic allene generated from a Kobayashi‐type precursor, which affords terpenoids relevant skeletons.

Scheme 1

Preparation of the precursor 15.

Figure 3

Scope and limitations of dienophiles.^{[ 60 ]}

Figure 4

Scope and limitations of the substituted vinyl cyclic allenes.^{[ 60 ]}

Scheme 2

Alternative precursors for the Diels–Alder reaction of vinyl cyclic allene. a) Investigation of the substituent effects. b) Cycloaddition of a deuterium‐labelled vinyl cyclic allene.^{[ 60 ]}

Figure 5

DFT calculations of the vinyl cyclic allene Diels–Alder reactions. a) Transition state (TS) structures and their energy profiles. Energies in kcal mol⁻¹ are for the ωB97XD/6‐311+G(d,p)/SMD(MeCN) level. The distance between atoms is indicated in Å. b) Visualized isosurface of HOMO of vinyl cyclic allene 39.

Figure 6

Activation strain model (left) for the exo1 and endo1 pathway for the Diels–Alder reaction of 39 and methyl acrylate (positions of TS indicated with a dot), and NCIplot isosurface of the calculated TSexo1 and TSendo1 (right). The green surface indicates weak attractive interactions.

Figure 7

DFT calculations of the vinyl cyclic allene Diels–Alder reactions of 42. a) Transition state (TS) structures and their energy profiles. Energies in kcal mol⁻¹ are for the ωB97XD/6‐311+G(d,p)/SMD(MeCN) level. The distance between atoms is indicated in Å. b) Activation strain model (left) for the exo1 and endo1 pathway for the Diels–Alder reaction of 42 and methyl acrylate (positions of TS indicated with a dot), and NCIplot isosurface of the calculated TSexo1 and TSendo1 (right). The green surface indicates weak attractive interactions.