New Regio‐ and Stereoselective Intermolecular Pauson—Khand Reactions of Allenamides.

Abstract

Abstract-Intermolecular Pauson-Khand reactions are still quite limited in scope and yields. There are also few reports using allenes as the olefinic part in this version. We report herein new regio and stereoselective reactions of allenamides with several alkynes. These reactions give functionalized cyclopentenones bearing an exocyclic enamide, which can be useful synthetic intermediates. Ó 2004 Elsevier Ltd. All rights reserved.Allenamines and allenamides are an emerging group of substrates that are becoming useful in organic synthesis. 1 Although there are still very few literature examples using allenamines, this electron enriched allenes have found use in some reactions with electrophiles and in certain cyclizations. The parent allenamides are more stable and thus are increasing their use in synthetic methodologies. 2 On the other hand, the Pauson-Khand reaction (PKR) is a powerful tool in the synthesis of cyclopentenones, a structural feature present in a large variety of natural products. 3 The intermolecular version of this reaction is still quite limited, as unstrained olefins scarcely react. 4 Some vinylethers/esters 5 and vinyl sulfoxides 6 are also useful in the intermolecular PKR. The use of traceless tethers 7 or directing groups like pyridisilyl 8 are strategies that circumvent partially this problem, also avoiding the formation of regioisomeric mixtures. In the majority of cases, the intermolecular PKR is regioselective from the alkyne being the bulkier substituent situated adjacent to the carbonyl in the final product. It has been demonstrated recently that both steric and electronic effects may be responsible for this regioselectivity. 9 Unsymmetrical olefins usually give mixtures of regioisomers (Scheme 1).There are a wide variety of catalytic protocols available to effect this reaction, some of them under mild conditions. Nevertheless the catalytic PKR is not a completely solved problem specially in the intermolecular processes where there are still few results. 3bAllenes are one of the most promising substrates for the PKR introduced in the past years. Several groups have used the intramolecular allenic PKR for the synthesis of medium sized rings. However there is only one precedent in the use of simple allenes in an intermolecular PKR due to Cazes and co-workers. 10 There is also a precedent of an intramolecular PKR with an allenamide equivalent. 11 We herein report new intermolecular PKR of allenamides. These reactions show many possibilities in selectivity, and as we will see have resulted to be very regio and stereoselective.To explore this chemistry we carried out the synthesis of a series of allenamides bearing aromatic rings. This synthesis was effected using a classical strategy depicted Tetrahedron Letters in Scheme 2. Starting from tosylanilides and acetanilides 1, propargylation under sonication using solid KOH as the base gave the corresponding propargylamides 2 in good yields. These compounds were converted totally into the corresponding allenamides 3 by treatment with t BuOK. In...

A Facile and Mild Synthesis of Enamides using a Gold-Catalyzed Nucleophilic Addition to Allenamides

“…Allenamides represent a fascinating and versatile functional group whose chemical utility has been exploited by a number of groups. 13 The chemistry in which allenamides have participated include radical cyclizations, 14 tandem epoxidation/cycloadditions, 15 Pauson-Khand cyclizations, 16 [4 + 2] 17 and [4 + 3] 18 cycloadditions, acid-catalyzed cyclizations/rearrangements, 19 palladium-mediated transformations, 20 cyclopropanations, 21 base-catalyzed CO 2 capture, 22 and finally, gold-mediated transformations. 23 The use of gold salts for the activation of allenamides is an attractive concept as it would negate the use of acidic conditions for allenamide activation 24 and would therefore be more functional group tolerant.…”