Microenvironmental control of enantiodifferentiating photocyclization of 5‐hydroxy‐1,1‐diphenylpentene through selective solvation

Abstract

For mechanistic elucidation of the photosensitized cyclization of 5-hydroxy-1,1-diphenylpentene (1), its methyl ether (4) was synthesized as an unreactive "dummy" substrate and used as a quencher of the sensitizer fluorescence to reveal the intervention of an exciplex intermediate that was unable to detect when reactive substrate 1 was used as a quencher/reactant In the enantiodifferentiating photocyclization of 1 to 2-(diphenylmethyl)tetrahydrofuran (2) sensitized by a chiral saccharide ester of 1,4-naphthalenedicarboxylate (3), the enantiomeric excess (ee) of chiral product 2 obtained in methylcyclohexane (MCH) at 25 °C was significantly enhanced from 20% to 35% upon 10-fold dilution of the sample solution by MCH, for which the reduced solvent polarity, discouraging dissociation of the intervening radical ionic exciplex, is likely to be responsible. Further attempts to microenvironmentally control the photochirogenic reaction and enhance the product's ee through selective solvation of polar cosolvent to the diastereomeric exciplex pair in nonpolar solvent were not successful probably due to the inherently high local polarity around the exciplex of saccharide-appended 3 with alcoholic substrate 1.

Entrainer Effects on Enantiodifferentiating Photocyclization of 5-Hydroxy-1,1-diphenylpentene in Near-Critical and Supercritical Carbon Dioxide

“…Somewhat surprisingly, all of the entrainers (toluene, ether, and acetonitrile) added to nc- and scCO 2 significantly enhanced the enantioselectivity to give the highest ee values among those obtained in pure solvent and CO 2 media. When compared with the low ee's (1–5%) obtained in pure acetonitrile (Table , runs 5 and 6), the much higher ee’s (32–44%) achieved by adding acetonitrile as an entrainer to nc- and scCO 2 are spectacular (Table , runs 59–67). This ee enhancement over the entire range of CO 2 pressure also contrasts with the unsuccessful attempts to improve the product ee of the same photocyclization, through preferential solvation of acetonitrile (or other polar solvents) added to nonpolar methylcyclohexane, unveiling the unique nature and advantage of entrainer clustering in nc- and scCO 2 media.…”

“…When compared with the low ee's (1–5%) obtained in pure acetonitrile (Table , runs 5 and 6), the much higher ee’s (32–44%) achieved by adding acetonitrile as an entrainer to nc- and scCO 2 are spectacular (Table , runs 59–67). This ee enhancement over the entire range of CO 2 pressure also contrasts with the unsuccessful attempts to improve the product ee of the same photocyclization, through preferential solvation of acetonitrile (or other polar solvents) added to nonpolar methylcyclohexane, unveiling the unique nature and advantage of entrainer clustering in nc- and scCO 2 media. Another important feature is the very global and consistent ee enhancement by the entrainers of varying polarities, which is hardly anticipated from the conventional solvation phenomena, but beneficially allows us to use a wide variety of solvents, including environmentally more benign ones, for the ee enhancement through entrainer clustering.…”

“…The sign of ee does not mean the sign of optical rotation or absolute configuration but is tentatively assigned according to the elution order. The first eluted enantiomer is given a positive sign. d Data from ref . e [ 1 ] = 20 mM; [ 2 ] = 3 mM. …”

“…To circumvent this dilemma, we prepared 5-hydroxy-1,1-diphenyl-1-pentenol (1) as a "self-containing" substrate with a built-in alcohol molecule and gained improved ee's for the anti-Markovnikov cyclization product (3) obtained upon sensitization with bis(1,2;4,5-di-O-isopropylidene-α-fructopyranosyl), i.e., diacetone-fructosyl (DAF), 1,4-naphthalenedicarboxylate (2) in organic solvents (Scheme 1). 12 In a recent communication, 13 we have demonstrated that diethyl ether, added as an entrainer, enhances the product ee in this enantiodifferentiating photocyclization performed in nc-and scCO 2 . This observation is of particular interest, suggesting the positive role of entrainer clustering in manipulating the exciplex structure and, hence, the product ee upon photochirogenesis in nc-and scCO 2 .…”

“…This is because the existence of methanol (up to 0.5 M), added as an essential reagent, inevitably deteriorates the diastereodifferentiating sensitizer–substrate interactions by facilitating the dissociation or solvent separation of the radical-ionic exciplex intermediate. To circumvent this dilemma, we prepared 5-hydroxy-1,1-diphenyl-1-pentenol ( 1 ) as a “self-containing” substrate with a built-in alcohol molecule and gained improved ee’s for the anti-Markovnikov cyclization product ( 3 ) obtained upon sensitization with bis(1,2;4,5-di- O -isopropylidene-α-fructopyranosyl), i.e., diacetone-fructosyl (DAF), 1,4-naphthalenedicarboxylate ( 2 ) in organic solvents (Scheme ) . In a recent communication, we have demonstrated that diethyl ether, added as an entrainer, enhances the product ee in this enantiodifferentiating photocyclization performed in nc- and scCO 2 .…”