Among the most powerful methodologies for constructing five-membered heterocycles are the [3 + 2] (32CA) or 1,3-dipolar (13DC) cycloaddition reactions. In this reaction, a 1,3-dipole, which has 4π electrons, interacts with a dipolarophile that possesses 2π electrons, resulting in the generation of a five-membered heterocyclic compound [1]. The significance of 32CA reactions in organic synthesis [2], medicinal chemistry [3], materials science [4], and biological chemistry [5] makes them pivotal reactions in organic chemistry. 1,3-Dipoles are categorized into two types: allylic dipoles with a bent geometry and propargylic dipoles that possess a linear structure [6]. Examples of allylic dipoles include ylide compounds like carbonyl and thiocarbonyl, and nitrones, while the propargylic types include species such as nitrile imines, nitrile oxides, and azides. The reactivity and selectivity of 32CA reactions can be enhanced by employing a suitable Lewis acid. Upon coordination with the Lewis acid, the electrophile becomes more electron-deficient, an effect that synergistically enhances both reactivity and selectivity [7,8]. Employing allenes in 32CA reactions represents a highly and powerful methodology in organic synthesis, which provides direct access to five-membered ring system bearing an exocyclic double bond. In this type of cycloaddition, the allene reacts with suitable dipolarophiles, leading to the formation of heterocycles with diverse functional groups. The unique geometry and electron-rich character of allenes facilitate their reactivity, often resulting in high yields and selectivity. These reactions have garnered significant interest due to their utility in the synthesis of pharmaceuticals, materials, and natural products. Recent studies also highlight the use of Lewis acids to enhance the reactivity and selectivity of these transformations [[9], [10], [11], [12]].

The incorporation of fluorine atom or fluorinated groups into organic framework significantly modulates their biological activity [[13], [14], [15]]. The selectivity, metabolic stability and lipophilicity of the compound change when a small, electronegative and electron-withdrawing atom or group such as fluorine atom or fluorine-containing groups are inserted to the molecule [16]. The utility of 1,1-difluoroallenes in organic chemistry is demonstrated by their application in various cycloadditions such as Diels-Alder reaction with 1,3-diene and 32CA reaction with various 1,3-dipoles to furnish the corresponding cycloadducts [[17], [18], [19], [20], [21]]. They also participate in the nucleophilic, electrophilic cyclization and addition reactions [[22], [23], [24]].

Fluorine atom can stabilize α-carbocation via mesomeric effect [13,25]. Thus, the reactivity and selectivity of carbocation-mediated reactions can be affected by insertion of fluorine atom in α-position. In this regard and for the first time, Fuchibe et al. reported α,β-selective cycloaddition reaction of 1,1-difluoroallenes catalyzed by Au+ ion with imine oxides and nitrile oxides [18]. They noted that in the absence of catalyst β,γ-double bond undergoes cycloaddition reaction with nitrile oxide in which the oxygen atom interacts with γ-carbon. On the other hand, in Au-catalyzed cycloaddition of 1,1-difluoroallenes and nitrile oxide, the α-carbon atom interacts with the oxygen atom (Scheme 1).

We theoretically investigate the catalyzed and uncatalyzed cycloaddition of a 1,1-difluoroallene (1-(5,5-difluoropenta-3,4-dienyl) benzene FPB) and phenyl nitrile oxide (NO) to elucidate selectivities, reactivities, and molecular mechanism, particularly the catalyst's role in shifting the pathway from β,γ-to α,β-position, thereby expanding upon prior theoretical works [[26], [27], [28], [29]]. Thus, the primary aims of this work are (1) to determine whether the experimental outcomes are supported by computational studies, (2) molecular mechanistic study, and (3) elucidation of the effect of the catalyst on reactivities and selectivities.

In addition, while the experimental study utilized Au+ as the catalyst, this investigation uses Cu+ in computations. This choice was initially made by the considerably lower computational cost and time afforded by the Cu+ system, which shares a closed-shell d10 electronic configuration with the Au + ion. However, this approach also has a broader scientific aim and that is to investigate the potential application of an earth-abundant and cost-effective metal such as copper ion as an effective catalytic instead of an expensive catalyst such as gold in this organic transformation. A key question addressed herein is whether Cu+ facilitates the formation of the same product (CA-3) under reaction conditions.