David C. Harrowven

Radical cyclisation reactions with indoles

Several radical cyclisation reactions involving indoles are described. Most notably, we have shown that radical additions to C3 of an indole are frequently facile. A dichotomy in the course of radical cyclisation reactions to C2 of the indole has also been exposed wherein 6-endo-trig cyclisations are propagated by the loss of a hydrogen atom from C2 while 5-exo-trig cyclisations are propagated by hydrogen atom abstraction at C3 from tributyltin hydride. Cyclisations involving the addition of indolyl radical intermediates to arenes have also been demonstrated.

KF-Silica as a stationary phase for the chromatographic removal of tin residues from organic compounds

Through the simple expedient of using a mixture of KF and silica as the stationary phase in column chromatography, levels of organotin impurities from tributyltin hydride mediated reductions have been reduced from stoichiometric levels to approximately 30 ppm.

Intramolecular radical additions to quinolines

The paper is concerned with intramolecular radical additions to quinolines. Radical additions to C-2, C-3 and C-4 of a quinoline have all been shown to proceed under neutral conditions. In each case formation of heteroaromatic products, rather than dihydroquinolines, was observed (implicating the so called oxidative tin hydride pathway).

[5]Helicenes by tandem radical cyclisation

A new and rapid approach to [5]helicenes is described. A central feature is the use of a sequential, non-reducing radical cyclisation reaction of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives, viz. 3→1, mediated by tributyltin hydride.

‘Cascade’ radical reactions in synthesis: Condensed thiophenes from ketenethioacetals.

A novel radical centred tandem cyclisation - tandem fragmentation sequence is described for the direct convertion of ketenethioacetals e.g. 1, 6, 9, 12 and 16 into condensed thiophenes e.g. 2, 7, 10, 13 and 17.

Radical cyclisations to arenes for the synthesis of phenanthrenes

6-exo/endo-Trig intramolecular additions of aryl radicals to electron-rich, unsubstituted and electron-deficient arenes have all been shown to proceed efficiently to give the corresponding phenanthrenes in high yield.

Cascade cobalt group transfer - radical trapping - tandem radical cyclisation reactions in synthesis

Abstract Cobalt mediated tandem radical cyclisations, viz ( 1 ), → ( 3 ), ) 5 ) → ( 7 ), ( 10 ) → ( 13 ), can be carried out in sequence with isolation of intermediate organocobalt reagents, i.e ( 2 ), ( 6 ), ( 11 ), or alternatively in a ‘one-pot’ operation. In the presence of reactive radical trapping agents (e.g. 3 O 2 , TEMPO) the intermediate organocobalt reagents undergo functional group exchange, [e.g. ( 11 ) → ( 15 ) and ( 14 ) respectively], whereas in the presence of less reactive styrene, a cascade of cobalt group transfer-radical trapping-tandem radical cyclisation - dehydrocobaltation reactions result allowing, for example, the five step ‘one-pot’ synthesis of ( 12 ) from ( 10 ) in 20% overall yield.

A new cascade radical reaction for the synthesis of biaryls and triaryls from benzyl iodoaryl ethers

The paper describes a new method of synthesizing biaryls and triaryls through an intramolecular ipso-substitution reaction initiated by the addition of an aryl radical to a benzyl ether. A tandem variant of the reaction has also been demonstrated. A short synthesis of isoaucuparin 27, a natural product found in the sapwood tissue of Sorbus aucuparia, is also described.

Zirconium tetrachloride as a mediator for ambient temperature ortho-fries rearrangements

Abstract Zirconium tetrachloride has been found to be an excellent mediator of the Fries reaction. Rearrangements occur at ambient temperature and are highly selective; giving the acetophenone derived from acetyl migration to the sterically least encumbered adjacent carbon.

The synthesis of a natural product family: from debromoisolaurinterol to the aplysins

Total syntheses of (+/-)-aplysin 1, (+/-)-debromoaplysin 2, (+/-)-isoaplysin 3, (+/-)-aplysinol 4, (+/-)-debromoaplysinol 5, (+/-)-aplysinal 6, (+/-)-isolaurinterol 7 and (+/-)-debromoisolaurinterol 8 are described. Key features are a diastereoselective, sulfur mediated radical cyclisation of diene 12 to give 35; a new radical to polar crossover sequence mediated by Bu3Sn that transforms diene 12 into (+/-)-debromoisolaurinterol 8; and a series of biomimetic cyclisation and oxidation reactions.