Diastereoselective Photocycloaddition Reaction of Vinyl Ether Tethered to 1,4‐Naphthoquinone

Abstract

The intramolecular asymmetric photocycloaddition between 1,4‐naphthoquinone and vinyl ether with a small (R)‐point‐chiral group on the tether was studied. Under photoirradiation, [2+2] cyclobutane products were exclusively obtained for this intramolecular system. The effect of solvent polarity on the stereoselectivity was significant, with predominant formation of the (2R,S3) over the (2R,R3) isomer in non‐polar solvents being reversed in slightly polar dichloromethane. The detailed temperature‐dependent study revealed the dominant diastereo‐differentiating processes, which were switched between the ground‐state equilibrium, the relative rate of bond formation in the triplet manifold, as well as deactivation processes between the pro‐(S3) and pro‐(R3) precursors, depending on the temperature domain examined. The enthalpic contribution (ΔΔH≠) was always compensated by the entropic factor (ΔΔS≠), implying the importance of solvation on the diastereo‐differentiation steps. The mechanism of photocycloaddition, especially for the face‐selective processes, is thoroughly discussed, which is supported by quantum chemical calculations on the ground‐state circular dichroism (CD) spectral behavior as well as on the diastereomeric transition states in the triplet excited state.

Visible Light-Induced Regio- and Enantiodifferentiating [2 + 2] Photocycloaddition of 1,4-Naphthoquinones Mediated by Oppositely Coordinating 1,3,2-Oxazaborolidine Chiral Lewis Acid

“…This explanation is compatible with our observation in the solvent effect, where the enantioselectivities were highly dependent on the nature of the solvent (note that the opposite enantiomers were favored in dichloromethane), while the regioselectivity was rather insensitive to the solvent employed (Table ). The absolute ΔΔ H ⧧ and ΔΔ S ⧧ values are considerably larger than those observed in the face selectivities in the related photocycloaddition of vinyl ether-tethered naphthoquinones . In this example, the facial selectivity is determined by the presence of point chirality introduced within the molecule.…”

“…As such, electron donor substituents at the 2-position of naphthoquinone (such as in vitamin K) increase the triple-state energy, and the cyclobutane formation is significantly preferred . Accordingly, [2 + 2] photocycloaddition of 2-alkenyl-substituted naphthoquinones have been successfully employed for achieving the tetracyclic skeleton and has been applied in a natural product synthesis such as elecanacin and congeners. , Due to an efficient ISC of naphthoquinone derivatives, cycloaddition occurs through the triplet excited state, and subsequently, the formed 1,4-biradical intermediate undergoes ring closure. Although the regio- and stereocontrol of photocycloaddition of naphthoquinone derivatives have been moderately explored, an enantioselective photocycloaddition of naphthoquinones has not been examined thus far.…”

“…18 Accordingly, [2 + 2] photocycloaddition of 2-alkenyl-substituted naphthoquinones have been successfully employed for achieving the tetracyclic skeleton and has been applied in a natural product synthesis such as elecanacin and congeners. 19,20 Due to an efficient ISC of naphthoquinone derivatives, 21 enantioselective photocycloaddition of naphthoquinones has not been examined thus far. First, the photoreaction of 2-alkenyl naphthoquinones 1a−c, with trimethylene tether, was examined in the absence of Lewis acid.…”

Relevance of the Entropy Factor in Stereoselectivity Control of Asymmetric Photoreactions

“…41 Indeed, in our recent investigation on a diastereoselective photocycloaddition of a vinyl ether tethered to 1,4-naphthoquinone (25), the temperature dependence behavior was not uniform over the temperature range examined, but distinctly different multiple linear correlations were found due to the temperature-caused change in the rate-determining step (Scheme 6). 42 Thus, at higher temperatures, the observed diastereoselectivity for cyclized products 26 was more sensitive to the temperature, the enthalpy factor being compensated by the entropy term, but both factors became oppositely signed and the (S,S,S)-isomer was always favored in the low temperature domain.…”

“…Activation parameters in kJ mol -1 in methylcyclohexane at 298 and 173 K, respectively. 42 In addition to temperature and excitation wavelength as a means for control of the selectivity, entropy-related external factors, such as pressure, solvent polarity, and concentration, have been employed as convenient yet effective tools for manipulating the weak interactions in the ground as well as excited states, allowing dynamic control of the (stereo)selective outcomes. 43 For instance, as the pressure effect is orthogonal to the temperature effect, the selectivity of the reaction was demonstrated to be more precisely and critically controlled by simultaneously varying both these factors in a multidimensional manner.…”