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).

The fate of intermediate π radicals is crucial in Bu3SnH‐mediated cyclization by homolytic aromatic substitution, for example, of bromo compound 1 via radical 2 to give oxindole 3 (AIBN=azobisisobutyronitrile). The results indicate that the mechanism requires the abstraction of a hydrogen radical from the intermediate π radical by the radical initiator or a product of initiator breakdown, and also that arene solvents are not always the best solvents for radical reactions.

Abstract. Deuterium‐labelled ABA‐aldehyde was fed to various tomato genotypes. Normal and notabilis mutant plants incorporated substantial amounts of the label into ABA. In contrast, two ABA‐deficient mutants, flacca and sitiens, reduced ABA‐aldehyde to a mixture of cis‐ and trans‐ABA alcohol rather than oxidizing it to ABA. It was concluded that ABA‐aldehyde is the immediate precursor of ABA in higher plants. It appears that the flacca and sitiens lesions both act to block the last step of the ABA biosynthetic pathway. The mutant gene loci are likely to be involved in coding for different sub‐units of the same dehydrogenase enzyme.

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

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