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Tandem Cyclization And Fluorination

Approach eases synthesis of complex fluorinated steroidal compounds for pharmaceutical or agricultural applications

by Jyllian Kemsley
January 14, 2013 | A version of this story appeared in Volume 91, Issue 2

Cascade reaction cyclizes and then fluorinates polyenes in the presence of a platinum catalyst, a base, and XeF2.
A scheme depicting a tandem cyclization and flourination using platinum and xenon diflouride.
Cascade reaction cyclizes and then fluorinates polyenes in the presence of a platinum catalyst, a base, and XeF2.

Widely sought but difficult-to-make fluorinated compounds are now more accessible, through a combination method that cyclizes and fluorinates polyenes. The method should ease the synthesis of fluorinated steroids, report Nikki A. Cochrane, Ha H. Nguyen, and Michel R. Gagné of the University of North Carolina, Chapel Hill (J. Am. Chem. Soc., DOI: 10.1021/ja3116795). The bioactivity of fluorinated compounds makes them highly desired for pharmaceutical and agricultural chemical applications. The UNC researchers took advantage of known platinum(II)-catalyzed C–C bond-forming cascades and turned what was previously a β-hydrogen elimination step into a fluorination step through the addition of XeF2. They combined various alcohol- and phenol-terminated dienes and trienes with a diphosphine-platinum(II) catalyst and a base to initiate the cascade, producing a platinum-bound polycyclic intermediate. The researchers believe F+ attacks the intermediate to produce a fluorinated platinum(IV) species that subsequently undergoes a stereoretentive reductive elimination to the product. Although some substrates “behaved peculiarly” in response to different bases, Cochrane and colleagues write, yields generally ranged from 56 to 69% with enantiomeric excesses as high as 87%.


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