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...

Allenamides: A Powerful and Versatile Building Block in Organic Synthesis

“…Pérex-Castells 120 reported the first intermolecular Pauson-Khand reaction of allenamides 452 promoted with Co(CO) 8 (Scheme 119). These reactions were both regio- and stereoselective with several alkynes 453 to give functionalized cyclopentenones 454 bearing an exo -cyclic E -enamide.…”

The Intermolecular Pauson–Khand Reaction

“…Pérez‐Castells and co‐workers recently observed high regio‐ and stereoselectivity in the reactions of allene amides 44 with alkynes in the NMO‐promoted version of the reaction (Scheme ) 66. Allenes have also been used by Witulski and Gößmann,15g who treated 2‐methylbuta‐2,3‐diene with an alkynyl amide in an aminoxide‐promoted intermolecular Pauson–Khand reaction, and Hailes and co‐workers who used undeca‐5,6‐diene in a key intermolecular Pauson–Khand reaction in the synthesis of novel compounds with olfactory properties 67…”

“… Alleneamides in the intermolecular NMO‐promoted Pauson–Khand reaction (Pérez‐Castells and co‐workers66). PG=protecting group; Ts= p ‐toluenesulfonyl.…”

Intermolecular and Intramolecular Pauson–Khand Reactions of Functionalized Allenes

“…In a preliminary communication of this work, we observed high regio-and stereoselectivities in the reactions between allenamides and alkynes. [11] There we used NMO for promotion and reached yields varying from moderate to good (45-85 %). Here we present our complete work on allenes substituted with different heteroatoms and different types of alkynes.…”