Tertiary Phosphine Promoted Tandem Cyclization Reaction Yielding Lactone Derivatives

In recent years, nucleophilic phosphine catalytic reaction has become a powerful approach for the preparation of a variety of functionalized unsaturated carbocyclic and heterocyclic compounds. The formaldehyde-derived MBH carbonates (y-nonsubstituted) usually favor y-attack due to steric encumbrance from the adjacent phosphonium group in the a-attack. Therefore, the formaldehyde-derived MBH carbonates are among the most studied MBH carbonates with various coupling partners and also highly reactive for the development of a tandem process. Meanwhile, trifluoromethyl-containing analogues of bioactive molecules frequently exhibit unique physical, chemical and physiological properties, which enable a range of potential application in chemical biology and pharmaceutical discovery. We disclose two novel tandem reactions between formaldehyde-derived MBH carbonates and aryl trifluoromethyl ketones.(l)The fused bicyclic y-butyrolactone are characteristic skeletal core in some bio-interesting natural products, their synthesis frequently required unavailable starting materials and multistep manipulation. We have developed a novel chemoselective phosphine-mediated tandem reaction between nonsubstituted MBH carbonates and aryl trifluoromethyl ketones, which provides a facile access to bistrifluoromethylated fused bicyclic y-butyrolactone with three contiguously adjacent stereogenic centers under mild reaction conditions. By a simple reaction operation, the reaction would provide two arrays of lactones with moderate to good yields and high chemoselectivty and stereoselectivity. The new chemistry affords a step-economical approach to CF3-substituted scaffolds with structural complexity from readily available starting materials.(2) We have developed a phosphine-promoted reaction between nonsubstituted MBH ester (tert-butyl (2-methylene-3-oxobutyl) carbonate)and trifluoromethyl ketone under mild conditions. With brief investigation on aryl ketone scope, we have synthesized a series of trifluoromethylated 2,3-dihydrofuran derivatives.