Impact of Excited-State Antiaromaticity Relief in a Fundamental Benzene Photoreaction Leading to Substituted Bicyclo[3.1.0]hexenes

Abstract

Benzene exhibits a rich photochemistry which can provide access to complex molecular scaffolds that are difficult to access with reactions in the electronic ground state. While benzene is aromatic in its ground state, it is antiaromatic in its lowest ππ* excited states. Herein, we clarify to what extent relief of excited-state antiaromaticity (ESAA) triggers a fundamental benzene photoreaction: the photoinitiated nucleophilic addition of solvent to benzene in acidic media leading to substituted bicyclo[3.1.0]hex-2-enes. The reaction scope was probed experimentally, and it was found that silyl-substituted benzenes provide the most rapid access to bicyclo[3.1.0]hexene derivatives, formed as single isomers with three stereogenic centers in yields up to 75% in one step. Two major mechanism hypotheses, both involving ESAA relief, were explored through quantum chemical calculations and experiments. The first mechanism involves protonation of excited-state benzene and subsequent rearrangement to bicyclo[3.1.0]hexenium cation, trapped by a nucleophile, while the second involves photorearrangement of benzene to benzvalene followed by protonation and nucleophilic addition. Our studies reveal that the second mechanism is operative. We also clarify that similar ESAA relief leads to puckering of S₁-state silabenzene and pyridinium ion, where the photorearrangement of the latter is of established synthetic utility. Finally, we identified causes for the limitations of the reaction, information that should be valuable in explorations of similar photoreactions. Taken together, we reveal how the ESAA in benzene and 6π-electron heterocycles trigger photochemical distortions that provide access to complex three-dimensional molecular scaffolds from simple reactants.

Scheme 1. Photochemical Rearrangement and Addition of Nucleophilic Solvent to Benzene under Acidic Conditions Leading to Bicyclo[3.1.0]hexenyl Derivatives

Scheme 2. The Two Mechanisms Explored, A and B, for the Photorearrangement of Benzene in Nucleophilic Media (here MeOH) Leading to 4-Methoxy-bicyclo[3.1.0]hex-2-ene (1)

Note that benzene in the T₁ state can act as a triplet sensitizer of benzvalene 4, which ring-opens to the S₀ state of benzene.

Figure 1

Previously reported (i) substrates, (ii) nucleophiles for photoinduced rearrangement and addition to simple arenes, and (iii) observed products.

Scheme 3. Rearrangement Mechanisms of Bicyclo[3.1.0]hexenes: (a) Acid-Catalyzed Epimerization, (b) Acid-Catalyzed Racemization, (c) Sensitized Vinylcyclopropane Rearrangement, and (d) Sensitized Rearrangement through [2.1.1]Hexenyl Derivative 6(37)

Scheme 4. Main Photoaddition Products of the Tested Model Substrates

Reaction conditions: 70 mM substrate, Rayonet reactor, FEP tube reactor, irradiation time 30 min, (a) 1 mM AcOH (aq.), (b) AcOH (conc.), (c) 1.25 mM dichloroacetic acid in MeOH. Isolated reaction yields of the major isomerization product are shown.

Scheme 5. Synthesis of Diastereomeric Esters 7

Scheme 6. Formation of the S₁-State Homoaromatic Structure through Relaxation of the Excited Benzenium Cation

Figure 2

Reaction coordinate for benzenium cation (2) leading to bicyclo[3.1.0]hexenium cation (3) in the S₀ and T₁ states calculated at the (U)B3LYP/6-311+G(d,p) level.

Figure 3

Fluorescence spectra of TMS-benzene (c = 1.0 mM, λ_exc = 254 nm) in anhydrous MeOH, degassed (solid line, purged with argon) and non-degassed (dashed line) in the absence and presence of anhydrous HCl (c = 0–1250 mM). The absorption spectra are shown in the inset.

Figure 4

(A) Potential energy surface of benzene in the S₁ state from S₁ planar minimum (D_6h symmetry) until the S₁/S₀ conical intersection. The experimentally determined activation energy (∼8.6 kcal/mol) given in ref (69) is indicated by a line. (B) The NICS(1)_zz at the various structures along the IRC. Geometries were calculated at the SA4-CASSCF(6,6)/ANO-RCC-VTZP level, energies were obtained at the MS4-CASPT2(6,6)/ANO-RCC-VTZP level, and NICS(1)_zz values were determined at the CASSCF(6,6)/6-31++G(d,p) level. The plane defined by the C1, C2, C4, and C5 atoms was used to define the central position of the ghost atom located 1 Å below the plane (displayed as a green dot in the inset) for NICS. For computational details and NICS values in the opposite direction, see Figure S47.

Figure 5

Potential energy surfaces at the CASPT2//CASSCF and CASSCF levels from the S₁ minimum to the S₁/S₀ conical intersection for (A) silabenzene and (B) the pyridinium cation. Respective NICS(1)_zz for (C) silabenzene and (D) the pyridinium cation. For further computational details, see Supporting Information, section 7.2.

Scheme 7. Photochemistry of Pyridinium Salts and Acid-Promoted Ring Opening of the Bicyclic Product

See refs (87) and (88).

Scheme 8. Isotopic Labeling Experiments of Photoaddition of Water to Benzene

Figure 6

Back-reaction from benzvalene to benzene initiated by formation of T₁-state benzvalene through triplet energy transfer from T₁-state benzene (inset), and the T₁ and S₀ potential energy curves for its rearrangement to T₁ benzene, calculated at the (U)B3LYP/6-311+G(d,p) level (electronic energies include ZPE corrections; vertically excited energies given in parentheses are purely electronic energies). Energies given in red are relative to S₀-state benzene, and energies given in blue are relative to S₀-state benzvalene.