The reaction of singlet oxygen with enecarbamates: a mechanistic playground for investigating chemoselectivity, stereoselectivity, and vibratioselectivity of photooxidations.

Photochirogenesis, the control of chirality in photoreactions, is one of the most challenging problems in stereocontrolled photochemistry, in which the stereodifferentiation has to be imprinted within the short lifetime of the electronically excited state. Singlet oxygen (1O2), an electronically excited molecule that is known to be sensitive to vibrational deactivation, has been selected as a model case for testing stereoselective control by vibrational deactivation. The stereoselectivity in the reaction of 1O2 with E/Z enecarbamates 1, equipped with the oxazolidinone chiral auxiliary, has been examined for the mode selectivity ([2 + 2]-cycloaddition versus ene-reaction) and the stereoselectivity in the oxidative cleavage of the alkenyl functionality to the methyldesoxybenzoin (MDB) product. Through the appropriate choice of substituents in the enecarbamate, the mode selectivity (ene versus [2 + 2]), which depends on the alkene geometry (E or Z), the steric bulk of the oxazolidinone substituent at the C-4 position, and the C-3' configuration on the side chain, may be manipulated. Phenethyl substitution gives exclusively the [2 + 2]-cycloaddition product, irrespective of the alkene geometry. The stereoselection in the resulting methyldesoxybenzoin (MDB) product is examined in a variety of solvents as a function of temperature by using chiral GC analysis. The extent (% ee) as well as the sense (R versus S) of the stereoselectivity in the MDB formation for the E isomer depends significantly on solvent and temperature, whereas the corresponding Z isomers are not affected by such variations. The complex temperature and solvent effects are scrutinized in terms of the differential activation parameters (DeltaDeltaS++, DeltaDeltaH++) for the photooxygenation of E/Z-enecarbamates in various solvents at different temperatures. The enthalpy-entropy compensations provide a mechanistic understanding of the temperature dependence of the ee values for the MDB product and the difference in the behavior between the Z and E enecarbamates. The E enecarbamates show a relatively high contribution from the entropy term and an appreciable contribution from the enthalpy term; both terms possess the same sign. In contrast, the corresponding relative insensitivity of Z enecarbamates to temperature and solvent variation is convincingly explained by the near-zero DeltaDelta S++ and DeltaDelta H++. Such effects, associated with temperature- and solvent-dependent conformational factors, are most likely dictated by the stereogenic center at the C-3' phenethyl substituent. The high stereocontrol during the photooxygenation of the chiral enecarbamates is shown to be independent of the steric demand of the oxazolidinone substituent at the C-4 position. In view of the reduced stereocontrol on deuteration of the oxazolidinone substituent at the C-4 position, we propose that the unusual stereoselective vibrational quenching of the attacking singlet oxygen (excited-state reactivity), a novel mechanistic concept, works in concert with the usual steric impositions (ground-state reactivity) exercised by the substituents to afford the high stereoselectivity observed in the dioxetane product during the [2 + 2] cycloaddition. Such synergistic interplay is held responsible for the highly stereoselective photooxidative cleavage of the chiral enecarbamates. The efficacy of stereocontrol in this photooxidation is demonstrated by kinetically resolving the epimers of the enecarbamate cleavage product (MDB) in essentially perfect stereoselectivity, a new methodology that we coin "photo-Pasteur-type kinetic resolution".