Intramolecular radical cyclisations to pyridines

Harrowven, David C.; Sutton, Benjamin J.; Coulton, Steven

doi:10.1016/s0040-4039(01)01937-2

Cited by 33 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aromatic homolytic substitution on pyridine and related heteroarenes has been reviewed recently by Harrowven and Sutton. Harrowven and co-workers have investigated cyclisation onto pyridines [80][81][82][83] and quinolines 84 in detail. A good example is shown in Scheme 22 for the synthesis of the alkaloid toddaquinoline 32 (R 5 H), used in Asian folk remedies.…”

Section: Cyclisation Onto Heteroarenesmentioning

confidence: 99%

Synthesis using aromatic homolytic substitution—recent advances

2007

View full text Add to dashboard Cite

This critical review aims at presenting recent developments in intramolecular aromatic homolytic substitution which has become one of the common methodologies in modern synthesis. The application of Bu3SnH-mediated cyclisations have proved especially useful. The critical review illustrates the mechanistic considerations required for planning synthetic applications and a wide range of synthetic protocols and natural product syntheses are shown. The latest evidence for the mechanisms involved in aromatic homolytic substitution are presented. (152 references).

show abstract

Section: Cyclisation Onto Heteroarenesmentioning

confidence: 99%

Synthesis using aromatic homolytic substitution—recent advances

2007

View full text Add to dashboard Cite

show abstract

“…)methyl]seleno benzoic acid Sephenyl ester 47. The same procedure as for the seleno-ester 43 was used to convert 2-[(4-oxo-4H-quinazolin-3-yl)methyl]benzoic methyl acid 46 to 2-[(4-oxo-4H-quinazolin-3-yl)methyl]seleno benzoic acid Se-phenyl ester 47 as colourless crystals (0.31 g, 0.71 mmol, 68%), mp 314-316 The reaction between 2-[(4-oxo-4H-quinazolin-3-yl)methyl]seleno benzoic acid Se-phenyl ester 47 (0.044 g, 0.1 mmol) and hexamethylditin (0.099 g, 0.3 mmol) was carried out in benzene (20 cm 3 ) and was refluxed and irradiated with a UV lamp for 3 h. The benzene was removed under vacuum and the crude product was purified by column chromatography using silica gel as absorbent and light petroleum-EtOAc (4 : 1) as eluent yielding 11-hydroxy-11H-isoquinolino[3,2-b]quinazolin-6,13-dione 50 as colourless needles (0.011 g, 0.04 mmol, 39%), mp 176-177 (43), 249 (40), 221 (26), 135 (38), 119 (36), 105 (100), 91 (45), 84 (60), 77 (68) and 51 (69). The structure was confirmed by X-ray crystallography.…”

Section: -[(4-oxo-4h-quinazolin-3-ylmentioning

confidence: 99%

“…Examples of these cyclisations include: a. alkyl radicals onto pyrroles, 8,9 imidazoles, 8 pyrazoles, 10 indoles, 9,11, 12 1,2,3-triazoles, 13 pyridinium salts, 14 and quinolones; 15 b. acyl radicals onto pyrroles, 16 quinolines, 17 pyridines 18 and arenes; 19 c. aryl radicals onto indoles, 20,21 pyrroles, 9 pyridones, 22 and 5-amino-and 5-hydroxyuracils, 23 2-quinolones, 24 quinolines 25 and pyridines. 26 All of the above cyclisations are 'oxidative' i.e. the intermediate p-radicals are not reduced by triorganometal hydrides [e.g.…”

mentioning

confidence: 99%

Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

et al. 2007

View full text Add to dashboard Cite

Alkyl, aryl, heteroaryl and acyl radicals have been cyclised onto the 2-position of 3H-quinazolin-4-one. The side chains containing the radical precursors were attached to the nitrogen atom in the 3-position. The cyclisations take place by aromatic homolytic substitution hence retain the aromaticity of the 3H-quinazolin-4-one ring. The highest yields were obtained using hexamethylditin to facilitate cyclisation rather than reduction without cyclisation. The alkaloids deoxyvasicinone 2, mackinazolinone 3, tryptanthrin 4, luotonin A 5 and rutaecarpine 8 were synthesised by radical cyclisation onto 3H-quinazolin-4-one.The 3H-quinazolin-4-one ring system is important to the biological activity of both naturally occurring alkaloids, biosynthesised from anthranilic acid, and pharmaceuticals. The alkaloids include vasicinone 1 and deoxyvasicinone 2, 1 mackinazolinone 3, 2 tryptanthrin 4, 3 luotonins A 5, B 6 and E 7 4 and rutaecarpine 8. 5 3H-Quinazolin-4-one alkaloids have been recently reviewed. 6 All the 3H-quinazolin-4-one natural products have interesting biological activity and have therefore been extensively investigated for useful pharmaceutical activity. The 3H-quinazolin-4-one ring is regarded as a 'privileged structure' in combinatorial synthesis. 7 These are structures which represent molecules that are capable of binding at multiple sites with high affinity and facilitate more rapid discovery of useful medicinally active compounds. 7Our study involved the development of protocols involving radical cyclisation for the synthesis of polycyclic 3H-quinazolin-3-ones (Scheme 1). The protocols have also been used for the synthesis of novel polycyclic quinazolinones including the natural Department of Chemistry, Loughborough University, Loughborough, Leics, UK LE11 3TU. E-mail: g.w.weaver@lboro.ac.uk; Fax: 44(0) 1509 223925; Tel: 44(0) All of the above cyclisations are 'oxidative' i.e. the intermediate p-radicals are not reduced by triorganometal hydrides [e.g. tributyltin hydyride (Bu 3 SnH)] as normally observed for these reagents. The cyclisations proceed by aromatic homolytic substitution with abstraction of hydrogen in a rearomatisation process. Aromatic homolytic substitution has been recently reviewed 27 and the mechanism of Bu 3 SnH mediated 'oxidative' cyclisation elaborated. 28 The pyrimidin-4-one ring of the quinazolin-4-ones has some aromaticity and therefore aromatic homolytic substitution could be predicted, and was observed in our studies, as shown in Scheme 1 (9 to 11 via the p-radical 10). However, the lower aromaticity could favour reductive cyclisation in which the intermediate p-radical 10 is intercepted by reagents such as Bu 3 SnH. Our prediction that radical cyclisation onto the quinazolin-4-one ring would be 'oxidative' was supported by the 'oxidative' radical cyclisation onto related ring systems, e.g. pyrimidine-2,4-diones, 23,24This journal is

show abstract

“…The Bu 3 SnH oxidative mediated radical cyclization onto pyrroles [81], pyridines [82], quinolones [83], uracil [84,85], pyridinediones [85], pyridones [85], dihydroindoles [85], and indoles [86] is a common protocol to benzoheterocycles, for instance, different intramolecular variants to achieve benzocarbazoles have been reported including aryl cyclization onto indole derivatives, or vice versa, indolyl radical cyclization onto an arene as radical acceptor (eq. 31) [86].…”

Section: ) This Protocol Provides a Good Access To Enantio Enrichementioning

confidence: 99%