Aza Cope rearrangements in the cyclopropenyl- and allyl-substituted .DELTA.2-oxazolinone systems

Padwa, Albert; Akiba, Mitsuo; Cohen, L. A.; MacDonald, J. Gavin

doi:10.1021/jo00153a015

Cited by 35 publications

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“…2‐Allyl‐3‐oxazolin‐5‐one derivatives 3 might undergo carbon dioxide extrusion upon thermolysis to yield a nitrile ylide intermediate, which after an internal reorganization and oxidation might furnish trisubstituted pyridines (Scheme ).…”

Section: Methodsmentioning

confidence: 99%

Rhodium‐Catalyzed Regioselective Domino Azlactone–Alkyne Coupling/Aza‐Cope Rearrangement: Facile Access to 2‐Allyl‐3‐oxazolin‐5‐ones and Trisubstituted Pyridines

2017

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Rhodium-catalyzed regioselective addition of azlactones to internal alkynes combined with aza-Cope rearrangement provides efficient atom economic access to 2-allyl-3-oxazolin-5-one derivatives.E xtension to at riple domino process,i nw hich the abovep rocess is combined with in situ azlactone formation starting from amino acids renders this process even more attractive.S ubsequent thermolysis of the 2-allyl-3-oxazolines enabled the de novo synthesis of trisubstituted pyridines.

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Section: Methodsmentioning

confidence: 99%

Rhodium‐Catalyzed Regioselective Domino Azlactone–Alkyne Coupling/Aza‐Cope Rearrangement: Facile Access to 2‐Allyl‐3‐oxazolin‐5‐ones and Trisubstituted Pyridines

2017

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“…The spectral data do not support the formation of a hemiaminal intermediate such as 38 . On addition of Et 3 N and Ac 2 O, imine 35 is acetylated to give 39 , which subsequently isomerizes to the product enamide 2 27…”

Section: Methodsmentioning

confidence: 99%

Direct Titanium‐Mediated Conversion of Ketones into Enamides with Ammonia and Acetic Anhydride

et al. 2012

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“…On addition of Et 3 N and Ac 2 O, imine 35 is acetylated to give 39, which subsequently isomerizes to the product enamide 2. [27] In summary, we have developed a practical, safe and economical one-step synthesis of enamides from ketones using Ti(OiPr) 4 , ammonia, and acetic anhydride. The reaction occurs under mild conditions and shows excellent functional-group tolerance.…”

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confidence: 99%

Direct Titanium‐Mediated Conversion of Ketones into Enamides with Ammonia and Acetic Anhydride

et al. 2012

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N-Acyl enamides are useful compounds in organic synthesis. In the realm of catalytic asymmetric hydrogenation, they are among the most exhaustively studied class of substrates, and provide access to valuable chiral amine building blocks. [1] These substrates have also demonstrated broad utility in catalytic asymmetric CÀC bond forming processes such as aza-ene, [2] Michael, [3] Friedel-Crafts, [4] cycloaddition, [5] and arylation [6] reactions. Despite the extensive applications of Nacyl enamides, their preparation remains challenging. The direct condensation of acetamide with ketones, while attractive in its simplicity, proceeds either in low yields or not at all for the majority of ketone substrates.[7] The Pd-catalyzed cross-coupling of vinyl electrophiles with amides [8] and the Heck reaction of N-vinylacetamide with aryl halides [9] often require additional steps for preparation of coupling precursors and employ a costly transition metal catalyst.[10] The addition of alkyl magnesium or alkyl lithium reagents to nitriles followed by trapping with Ac 2 O or AcCl has limited functional-group tolerance [11] and requires low reaction temperatures.[12] By far the most commonly employed procedure is the two-step conversion of ketones through ketoximes (Scheme 1). [13] This reaction was first described in 1975 by Barton and coworkers. After a first step of oxime formation, the ketoxime was then treated with Ac 2 O and either pyridine at reflux, Cr(OAc) 2 , or Ti(OAc) 3 for reductive acylation.[13] Subsequently, numerous alternative reducing agents were developed.[14] The most commonly employed reductant is Fe powder, which was first demonstrated by Barton and Zard in 1985 [14a] and subsequently developed by Burk and Zhang in 1998. [14b,c] From a large scale perspective, the use of highenergy hydroxylamine, generating a high-energy oxime intermediate, and reducing the oxime at high temperatures present safety concerns. In addition, the workup of the Fe process is often tedious, requiring filtration of large amounts of inorganic salts. While several alternatives to Fe metal have emerged recently, these still rely on the same overall two-step process through a ketoxime.[14d-g] Our own requirements for large-scale synthesis of N-acetyl enamides for asymmetric hydrogenation prompted us to develop a more direct and process-friendly alternative in which hydroxylamine is replaced with ammonia. Herein we describe a direct, redoxfree synthesis of enamides from ketones, ammonia, and Ac 2 O mediated by Ti(OiPr) 4 . In addition, we introduce the use of edte (N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine) to effect water solubilization of the Ti and allow a simple extractive workup.Our strategy for enamide synthesis was based on condensation of a ketone with ammonia to give an N-unsubstituted imine or enamine, followed by N-acetylation on addition of Ac 2 O. The imine formation presented a challenge due to the volatility of ammonia, which excluded the common method for imine formation by azeotropic distillation for remo...

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Aza Cope rearrangements in the cyclopropenyl- and allyl-substituted .DELTA.2-oxazolinone systems

Cited by 35 publications

References 0 publications

Rhodium‐Catalyzed Regioselective Domino Azlactone–Alkyne Coupling/Aza‐Cope Rearrangement: Facile Access to 2‐Allyl‐3‐oxazolin‐5‐ones and Trisubstituted Pyridines

Rhodium‐Catalyzed Regioselective Domino Azlactone–Alkyne Coupling/Aza‐Cope Rearrangement: Facile Access to 2‐Allyl‐3‐oxazolin‐5‐ones and Trisubstituted Pyridines

Direct Titanium‐Mediated Conversion of Ketones into Enamides with Ammonia and Acetic Anhydride

Direct Titanium‐Mediated Conversion of Ketones into Enamides with Ammonia and Acetic Anhydride

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