Singlet O₂ Feat

STEREOCHEMISTRY

Simple, nonchiral molecule resolves racemates with surprising selectivity

What if resolving a racemic mixture did not require elaborate chiral auxiliaries or expensive transition-metal complexes? What if the task required only a reaction with a very simple, very small molecule?

That possibility is here, courtesy of singlet oxygen, a reactive species formed by the action of light on molecular oxygen.

Chemistry professors Nicholas J. Turro at Columbia University and Waldemar Adam at the University of Puerto Rico, Río Piedras, and their colleagues have demonstrated the principle with the chiral compound methyldesoxybenzoin hitched to an oxazolidinone to form an enecarbamate.

They find that under specific conditions, particularly of temperature, singlet oxygen adds to the enecarbamate's double bond to form one of two possible dioxetane diastereoisomers. This intermediate dissociates, releasing the corresponding enantiomer of methyldesoxybenzoin in 97% enantiomeric excess. At a different temperature, the other diastereoisomer is formed, from which the other enantiomer is released, also in 97% enantiomeric excess [J. Am. Chem. Soc., 126, 10498 (2004)].

The paper "reveals truly remarkable effects" of experimental parameters on the stereoselectivity, comments Miguel A. Garcia-Garibay, a chemistry professor at the University of California, Los Angeles. "Changes in solvent and variations in temperature result in unusually large changes in the enantiomeric excess of the product. "

That singlet oxygen--a small, simple, and nonchiral molecule--can display such selectivity is "unprecedented," Turro says. Singlet oxygen is too small to exert a steric effect, but it has special characteristics that could explain the observed behavior.

Singlet oxygen forms weak complexes, which equilibrate prior to the addition of oxygen across the double bond. "These reversible complexes nicely account for the large variations in ena ntiomeric excess observed and suggest the potential of an underutilized strategy in stereoselective synthesis," Garcia-Garibay says.

Moreover, singlet oxygen deactivates through vibrational coupling with its environment. For example, in water, it is short lived, but in deuterated water it can survive for up to 50 times longer. Reaction conditions could render pathways leading to one side of the double bond deactivating. Singlet oxygens along these paths would simply dissipate their energy, whereas singlet oxygens along the pathways leading to the opposite side could reach the double bond and react before they could be deactivated. This hypothesis can be tested by deuteration of selected groups in the substrate, Turro says.