Metathesis Approach to the Synthesis of Polyheterocyclic Structures from Oxanorbornenes

Winkler, Jeffrey D.; Asselin, Sylvie M.; Shepard, Stacey; Yuan, Jing

doi:10.1021/ol0484106

Cited by 41 publications

(12 citation statements)

References 9 publications

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Section: S Y N T H E S I S O F C O N S T R a I N E D B -A M I N O E Smentioning

confidence: 98%

“…2 Application of this methodology for synthesis and reactions of amino acids has also seen recent interest, with a notable recent report from Winkler et al who described a series of tandem metathesis reactions on b-amino acids based on the oxanorbornene core. 3 We disclose herein our efforts in this area which demonstrate that metathesis can be a powerful tool for the conversion of readily accessible b-amino acids based on the norbornene skeleton into novel, highly constrained b-bicyclic amino acids.The initial starting point for the synthesis was to be endob-amino ester 1, which was readily prepared, as shown in Scheme 1. 4 Cyclopentadiene and maleic anhydride were reacted to give the expected Diels-Alder adduct, the endo-product was obtained via a single recrystallization.…”

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confidence: 98%

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Application of Olefin Metathesis for the Synthesis of Constrained β-Amino Esters from Norbornenes

Nadany¹,

Mckendrick²

2006

Synlett

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S y n t h e s i s o f C o n s t r a i n e d b -A m i n o E s t e r s f r o m N o r b o r n e n e sAbstract: Synthesis of a number of novel, conformationally rigid b-amino esters has been achieved via a tandem olefin metathesis reaction. The starting materials are readily accessible from the Diels-Alder adduct between cyclopentadiene and maleic anhydride.The ring-opening/ring-closing metathesis reaction of norbornene substrates has attracted much attention in the recent literature, due to the inherent ring strain present in such bridged alkenes. 1 Thus, the reaction has been utilized to excellent effect in a number of complex synthesis of both natural and non-natural products. 2 Application of this methodology for synthesis and reactions of amino acids has also seen recent interest, with a notable recent report from Winkler et al. who described a series of tandem metathesis reactions on b-amino acids based on the oxanorbornene core. 3 We disclose herein our efforts in this area which demonstrate that metathesis can be a powerful tool for the conversion of readily accessible b-amino acids based on the norbornene skeleton into novel, highly constrained b-bicyclic amino acids.The initial starting point for the synthesis was to be endob-amino ester 1, which was readily prepared, as shown in Scheme 1. 4 Cyclopentadiene and maleic anhydride were reacted to give the expected Diels-Alder adduct, the endo-product was obtained via a single recrystallization. Ring-opening of the anhydride was easily achieved following the method reported by Sabitha to give the monoester. 5 Curtius rearrangement of the monoester under standard conditions gave the desired amino ester, which was immediately protected as the corresponding toluenesulfonamide in order to prevent further reaction and to aid purification. 6Alkylation of the nitrogen, with either allyl bromide or propargyl bromide in the presence of potassium carbonate, lead to the corresponding allyl-and propargyl-substituted norbornenes 2 and 3 (Scheme 2).Conversion of these norbonenyl b-amino esters was initially attempted using the first generation Grubbs catalyst, since reports from the groups of Grubbs and Bolm had demonstrated that the reaction was feasible on similar substrates. 7 Norbornenes 2 and 3 were dissolved in dichloromethane and ethene was added, historically believed to reduce ring-opening polymerization of the norbornene. 8 Grubbs I catalyst (10 mol%) was added and the extent of reaction monitored by TLC, even after an Scheme 1 Synthesis of protected b-amino ester 1

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Section: S Y N T H E S I S O F C O N S T R a I N E D B -A M I N O E Smentioning

confidence: 98%

mentioning

confidence: 98%

Application of Olefin Metathesis for the Synthesis of Constrained β-Amino Esters from Norbornenes

Nadany¹,

Mckendrick²

2006

Synlett

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“…66 Even more complex methatesis cascades were used for the preparation of polyheterocyclic structures 86, 87 from the derivatives of the amino acid 33c. 67 …”

Section: Scheme 23mentioning

confidence: 99%

Bicyclic β-amino acids

Grygorenko

2015

Tetrahedron

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“…55 Dialdehyde 7 is converted to amine 8 with NaBH(OAc) 3 and benzylamine, 56 and lactol 9 likewise affords lactam 10 under similar conditions. 57 Indole aldehyde 11 undergoes reductive amination with allylamine (and others) to give tetrahydro-γ-carboline 12.…”

Section: Scheme 4 Products Of Reductive Amination Of Aldehydes Usingmentioning

confidence: 99%

The Synthetic Versatility of Acyloxyborohydrides

Gribble

2006

Org. Process Res. Dev.

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Acyloxyborohydrides are unsurpassed in their versatility as reagents in organic synthesis. In addition to their superior ability in effecting reductive amination of aldehydes and ketones, acyloxyborohydrides can reduce nitrogen heterocycles (indoles, quinolines, isoquinolines), imines, enamines, oximes, amides, nitriles, benzylic alcohols, aryl ketones, aldehydes (but not ketones), acetals, -hydroxy ketones, and other substrates. The ability to control chemoselectivity, regioselectivity, and stereoselectivity by adjusting the carboxylic acid, borohydride reagent, stoichiometry, and temperature has no parallel in the repertoire of the organic chemist.

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Metathesis Approach to the Synthesis of Polyheterocyclic Structures from Oxanorbornenes

Abstract: [reaction: see text] The synthesis of stereochemically defined tri- and penta-heterocyclic ring systems 9 and 28, respectively, via the metathesis reaction of substituted oxanorbornanes derived from 3 is described.

Cited by 41 publications

References 9 publications

Application of Olefin Metathesis for the Synthesis of Constrained β-Amino Esters from Norbornenes

Application of Olefin Metathesis for the Synthesis of Constrained β-Amino Esters from Norbornenes

Bicyclic β-amino acids

The Synthetic Versatility of Acyloxyborohydrides

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