The first example of samarium diiodide-promoted intramolecular ketone–ester coupling of ketones tethering acyloxyalkyl side chains producing 2-hydroxy cyclic hemiacetals

Total Synthesis and Biological Activity of (±)‐Rocaglamide and Its 2,3‐Di‐epi Analogue

“…Quite surprisingly, intramolecular reductive coupling of 6c- and keto-cyano reductive couplings have been disclosed before, [5,6] this is the first report concerning the intramolecular reductive coupling of α-cyano-δ-oxocarboxylates. This result also implied that intramolecular keto-ester coupling was much easier than keto-cyano coupling.…”

Synthetic methods : Part (i) Free-radical reactions

“…With samarium(II) iodide, a ketyl radical 17 is formed from a ketone 16 and this undergoes cyclisation on to a formate ester to furnish hemi-acetal 18 (Scheme 5). 6 Alternatively, a titanium(III) reagent can convert an epoxide 19 into a a-hydroxy radical that, again, cyclises onto a formate ester to give 20 (Scheme 6). 4 Intriguingly, in both methodologies, successful cyclisations are limited to substrates in which the ether-type oxygen is situated between the radical precursor and radical acceptor.…”

Reaction mechanisms : Part (i) Radical and radical ion reactions

“…88 Hasegawa reported the intramolecular addition of samarium ketyl radicals to ester carbonyls as illustrated in Scheme 26. 89 Finally, Wright used radical cation cyclizations onto furans and thiophenes for the synthesis of annulated heterocycles. 90 For radical cations, incorporation of a pendant nucleophile can lead to cyclization via a polar process, as is illustrated by recent results reported by Crich 91 and Roth (Scheme 27).…”