American Chemical Society
jo802077t_si_001.cif (17.28 kB)

Synthesis of Fused Cyclic Systems Containing Medium-Sized Rings through Tandem ROM-RCM of Norbornene Derivatives Embedded in a Carbohydrate Template

Download (17.28 kB)
posted on 2009-03-06, 00:00 authored by Chanchal K. Malik, Ram Naresh Yadav, Michael G. B. Drew, Subrata Ghosh
A general approach for the synthesis of fused cyclic systems containing medium-sized rings (7−9) has been developed. The key steps involve a diastereoface-selective Diels−Alder reaction of the dienophiles 4ad attached to a furanosugar with cyclopentadiene and ring opening (ROM)-ring closing metathesis (RCM) of the resulting norbornene derivatives 10ad and 11ad. Diels−Alder reaction of the dienophiles 4ad with cyclopentadiene in the absence of a catalyst produced 10ad as the major product arising through addition of the diene to the unhindered Si-face. The most interesting and new aspect of the Diels−Alder reaction of these dienophiles is the accessibility of the Re-face that was blocked by the alkenyl chains under Lewis acid catalysis producing the diastereoisomers 11ad exclusively. The reversal of facial selectivity from an uncatalyzed reaction to a catalyzed one is unprecedented. The observed stereochemical dichotomy is attributed to rotation of the enone moiety along the σ bond linking the sugar moiety during formation of the chelate 13. This makes the Re-face of the enone moiety in 4ad unhindered. Diels−Alder reaction of the carbocyclic analogue 15 under Lewis acid catalysis produced a 1:1 mixture of the adducts 16 and 17 confirming the participation of sugar ring oxygen in chelate formation. Finally ROM-RCM of 10ad and 11ad with Grubbs’ catalyst afforded the cis-syn-cis and cis-anti-cis bicyclo-annulated sugars 21ad and 23ad, respectively, containing 7−9 membered rings.