Abstract
The hypervalent iodine reagent PIFA promotes the intramolecular electrophilic cyclization of easily accessible N-aryl and N-methylalkynylamides leading to the formation of the pyrrolidinone skeleton in a very efficient way. This strategy has found application in the preparation of a key intermediate in the total synthesis of (±)-clausenamide alkaloid.
Highlights
When properly substituted amides are treated with the hypervalent iodine reagent PIFA,1 [bis(trifluoroacetoxy)iodo]benzene, an acylnitrenium ion (B and E) is formed provided that an electron-releasing group is attached to the nitrogen to stabilize such deficient species.[2]
(±)-Clausenamide is the main component of aqueous extract of the leaves of Clausena lansium, a plant extensively employed in chinese folk medicine.[8]
At this moment we were considering that the presence of an aryl group (i.e. PMP) in substrate 1a was essential for the stabilization of the acylnitrenium intermediate of type B presumably formed after treatment with PIFA.[16]
Summary
When properly substituted amides are treated with the hypervalent iodine reagent PIFA,1 [bis(trifluoroacetoxy)iodo]benzene, an acylnitrenium ion (B and E) is formed provided that an electron-releasing group is attached to the nitrogen to stabilize such deficient species (see Scheme 1).[2]. Our first attempt (see Scheme 2) started with the cyclization of the preformed[14] alkynylamide 1a, which on treatment with PIFA in trifluoroethanol[15] at 0 oC afforded the desired pyrrolidinone 2a in 62% yield. At this moment we were considering that the presence of an aryl group (i.e. PMP) in substrate 1a was essential for the stabilization of the acylnitrenium intermediate of type B presumably formed after treatment with PIFA.[16] But to the view of the difficulties associated with the N-methylation step, and trying to simplify the synthesis, we designed a second attempt starting from the N-methylalkynylamide 1b.
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