Preparation of Optically Active Calophyllum Coumarins

Formylation of 5,7-dihydroxy -( -propyl)-coumarin (1) provided on 8-formy-lated product (26). Treatment of the compound 26 with 3-chloro-3-methyl-l-butyne to introduce regioselectively the chromene 27 because the phenolic hydroxyl group at the C position was less accessible for formylated substitution because of a presumed hydrogen-bonding interaction. To construct the enantiomerically pure rra i-2,3-dimethyl chroman-4-ol system, Deshpande et al. ° used organoborone 

Using ( )-Quinine Catalyzed Intramolecular oxo-Michael Addition  

Ishikawa et al. reported that ( )-quinine-catalyzed asymmetric intramolecular oxo-Michael addition (IMA) of 7-hydroxy-8-tigloylcoumarin gave cis-2,3-dimethyl-4-chromanone systems with high enantioselectivity and moderate diaster-eoselectivity, especially when chlorobenzene was used as a solvent. Therefore, total synthesis of (+)-calanolide A (1) was achieved by application of the (—)-quinine-catalyzed asymmetric IMA. However, the synthetic route starting from 1,3,5- trimethoxybenzene was too long (13 steps with 3.5% overall yield) to practice. Finally, the authors improved and shortened the original synthetic route by application of Mgl2-assisted demethylation. 

3 Total Synthesis of (+)-Calanolide A (1) Using (-)-Quinine Catalyzed IMA  

The total synthesis of (+)-calanolide A (1) was carried out by application of the synthetic method for (+)-inophyllum B (3) using the same strategy. 

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