Pyrimidine annelated heterocycles - synthesis and cycloaddition of the first pyrimido[1,4]diazepine N-oxides

Heaney, Frances; Burke, Cathriona; Cunningham, Desmond; McArdle, Patrick

doi:10.1039/b007163n

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…The resonance signals for 6a (CDCl 3 , room temperature) were sharp suggesting either that the tricyclic framework adopts a single preferred conformation or that equilibration between conformational isomers is very rapid at room temperature. This observation is in line with our earlier finding that the isoxazolobenzodiazepinones 7 11 and the isoxazolopyrimidodiazepinone 8 12 have sharp pmr spectral signals, on the other hand Romeo's related tricycles, e.g. 9 (R = Et, Me) exist as a mixture of slowly interconverting diastereomers 13,14 .…”

Section: Resultssupporting

confidence: 81%

“…We have previously observed that the analogous isoxazolobenzodiazepinones 21 have sharp pmr and 13 C nmr spectral signals at room temperature 7,11 whilst similar adducts, e.g. 22 from Aversa's laboratory 14 and the isoxazolopyrimidodiazepine 23 which we have recently reported 12 , display signal duplication and signal broadening respectively at room temperature. Upon perusal of the pmr spectral characteristics (room temperature) of the aforementioned molecules it is apparent that the conformational freedom of the 5,7,6-tricyclic framework is not easily predictable.…”

Section: Figurementioning

confidence: 99%

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Isoxazolo[2,3-d][1,4]benzoxazepine rings from 1,3-dipolar cycloaddition of [1,4]benzoxazepine N-oxides with acetylenic and olefinic dipolarophiles

Heaney¹,

O'Mahony²,

McArdle³

et al. 2003

Arkivoc

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1,3-Dipolar cycloaddition of [1,4]benzoxazepine N-oxides to triple and double bonded dipolarophiles affords di-and tetrahydro-isoxazolobenzoxazepines in the first reported synthesis of this tricyclic ring system. It is observed that in addition to the acetylenic dipolarophiles the diastereofacial selectivity varied both with the nature of the C-nitrone substituent as well as on the degree of substitution of the dipolarophile. Addition to alkene substrates occurred regiospecifically furnishing "5-substituted" isoxazolidine rings. For each olefinic dipolarophile the major cycloadduct arose via an endo-addition of the dipolarophile to the β-face of the dipole. Some of the new tricycles displayed sharp signals in their pmr spectra whilst signal duplication/broadening was evident for others indicating the adducts exist in solution as pairs of conformational isomers which reach coalescence at or close to room temperature. Preliminary investigations show the isoxazolidine ring of the tricycles can be cleaved under reductive and oxidative conditions affording novel benzoxazepines. The structure of the cycloadduct 6a formed between the C-phenyl nitrone 5a and dimethyl acetylenedicarboxylate and has been solved by single crystal xray analysis.

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Section: Resultssupporting

confidence: 81%

Section: Figurementioning

confidence: 99%

Isoxazolo[2,3-d][1,4]benzoxazepine rings from 1,3-dipolar cycloaddition of [1,4]benzoxazepine N-oxides with acetylenic and olefinic dipolarophiles

Heaney¹,

O'Mahony²,

McArdle³

et al. 2003

Arkivoc

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“…The rearrangement likely proceeds by a mechanism parallel to that previously suggested for the oxa analogue 15d. 21 The pyrroloketopiperazine skeleton is found infrequently in the chemical literature, however it does occur naturally in the alkaloid peramine 17. 22 The marine metabolites longamide 18a, and hanishin, 18b, also have a 3,4-dihydropyrrolopiperazinone framework.…”

Section: Introductionmentioning

confidence: 99%

α-Keto amides as precursors to heterocycles—generation and cycloaddition reactions of piperazin-5-one nitrones

et al. 2003

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α-Keto amides 10a,b, formed from reaction of pyruvic or benzoylformic acid with allyl amine are found to present as single rotameric forms whilst their tertiary amido analogues 10c,d present as two rotamers in solution at rt. The hydroxyimino derivatives 8 share the conformational characteristics of their parents. The geometrical make-up of the new α-amidooximes is seen to depend on the structure of the starting acid and on the degree of substitution of the amido group. The oxime 8a derived from pyruvic acid and allyl amine is formed solely as the (E )-isomer whilst its tertiary amido analogue 8c is formed as both (E )-and (Z )-isomers. Oximes derived from benzoylformic acid have the opposite selectivity with both geometrical isomers forming from the secondary amide 8b and only the (Z )-isomer from the tertiary amide 8d. With the exception of 8b all oximes were configurationally stable with (Z )-isomers reacting to form isoxazolopyrrolidinones 11-compounds with a relatively rare bicyclic nucleus and (E )-isomers cyclising to piperazin-5-one nitrones 1-ketopiperazine N-oxides have to date only appeared once in the literature. New nitrones were trapped with phenyl vinyl sulfone, dimethyl acetylenedicarboxylate and methyl propiolate yielding isoxazolidine and isoxazoline fused piperazinones 13,15,21 and 22. Cycloadducts from dimethyl acetylenedicarboxylate and 8a,b are thermally labile and their rearrangement provides a novel route to pyrrolopiperazinones 16. The structure of a representative isoxazolopyrrolidinone, 11c, and a 2,3-dihydroisoxazoline fused piperazinone, 21b, are unambiguously solved following x-ray structural analysis.

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“…The facility of S N Ar displacement for halopyrimidines follows a predictable order, as shown here. Nucleophilic aromatic substitution reactions have also been commonly applied to the transformation of pyrimidines into introduce a wide variety of new hetero and carbon ring substituents, as illustrated in Scheme 19.150 [168].…”

Section: With Replacement Of Good Leaving Groupsmentioning

confidence: 99%

Six‐Membered Heterocycles: 1,2‐, 1,3‐, and 1,4‐Diazines and Related Systems

Cabal

2011

Modern Heterocyclic Chemistry

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Pyrimidine annelated heterocycles - synthesis and cycloaddition of the first pyrimido[1,4]diazepine N-oxides

Cited by 14 publications

References 28 publications

Isoxazolo[2,3-d][1,4]benzoxazepine rings from 1,3-dipolar cycloaddition of [1,4]benzoxazepine N-oxides with acetylenic and olefinic dipolarophiles

Isoxazolo[2,3-d][1,4]benzoxazepine rings from 1,3-dipolar cycloaddition of [1,4]benzoxazepine N-oxides with acetylenic and olefinic dipolarophiles

α-Keto amides as precursors to heterocycles—generation and cycloaddition reactions of piperazin-5-one nitrones

Six‐Membered Heterocycles: 1,2‐, 1,3‐, and 1,4‐Diazines and Related Systems

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