Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 4‐Substituted Coumarins Catalyzed by a Chiral Lewis Acid

Abstract Eight coumarins, which carry a terminal alkene tethered by a CH 2 XCH 2 group to their 4‐position (X=CH 2 , CMe 2 , O, S, NBoc, NZ, NTs, NBn), were synthesized in overall yields of 51–80 %. Starting materials for the syntheses were either commercially available 4‐hydroxycoumarin or 4‐formylcoumarin. The intramolecular [2+2] photocycloaddition of these coumarins gave diastereoselectively products with a tetracyclic 3,3a,4,4a‐tetrahydro‐1 H ‐cyclopenta[2,3]cyclobuta[1,2‐c]chromen‐5(2 H )‐one skeleton. Direct irradiation at λ =300 nm in dichloromethane ( c =10 m M ) led to product formation in good yields for most substrates, presumably via a singlet excited state intermediate. Due to the low coumarin absorption at λ >350 nm the photocycloaddition was slow upon irradiation at λ =366 nm. Addition of a chiral oxazaborolidine‐based Lewis acid (50 mol %) increased the reaction rate at λ =366 nm and induced a significant enantioselectivity in the [2+2] photocycloaddition. Six out of eight coumarin substrates (X=CH 2 , CMe 2 , O, NBoc, NZ, NTs) gave the respective products in yields of 72–96 % and with 74–90 % enantiomeric excess ( ee ) upon irradiation in dichloromethane ( c =20 m M ) at −75 °C. The Lewis acid presumably acts by coordination to the coumarin carbonyl oxygen atom, which leads to a bathochromic shift (redshift) of the UV absorption and which increases the singlet state lifetime. A second electrostatic interaction of the hydrogen atom at C3 with the oxygen atom of the oxazaborolidine is likely.