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The oxime ethers 2a-e have been cyclised with Bu,SnH to the alkoxyamino-3-methylidenechromanes 3a-e. Seven-membered ring formation was observed when the oxime ethers 7a. b were converted into the dibenzo[b,e]oxepines 8a. b under similar conditions. 1 -Methoxyaminoindanes 12a. b were produced from the cyclisation of the substrates I l a , b and the cis-fused cyclic products 15a, b and 18 were obtained from compounds 14a. b and 17, respectively.The construction of carbocyclic rings using intramolecular radical cyclisation has become a common strategy in organic synthesis. The first example of the intramolecular trapping of a radical by an oxime ether was reported by Corey and Pyne in 1983.2 The particular advantage of using an oxime ether seems to ! i F in the extra stability of the alkoxy aminyl radicalPaper 410289 1 K

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Heterocyclic architectures offer powerful creative possibilities to a range of chemistry end-users. This is particularly true of heterocycles containing a high proportion of sp-carbon atoms, which confer precise spatial definition upon chemical probes, drug substances, chiral monomers and the like. Nonetheless, simple catalytic routes to new heterocyclic cores are infrequently reported, and methods making use of biomass-accessible starting materials are also rare. Here, we demonstrate a new method allowing rapid entry to spirocyclic bis-heterocycles, in which inexpensive iron(III) catalysts mediate a highly stereoselective C-C bond-forming cyclization cascade reaction using (2-halo)aryl ethers and amines constructed using feedstock chemicals readily available from plant sources. Fe(acac) mediates the deiodinative cyclization of (2-halo)aryloxy furfuranyl ethers, followed by capture of the intermediate metal species by Grignard reagents, to deliver spirocycles containing two asymmetric centres. The reactions offer potential entry to key structural motifs present in bioactive natural products.

Introduction: Apaziquone (also known as EO9 and Qapzola TM ) is a prodrug that is activated to DNA damaging species by oxidoreductases (particularly NQO1) and has the ability to kill aerobic and/or hypoxic cancer cells. Areas covered: Whilst its poor pharmacokinetic properties contributed to its failure in phase II clinical trials when administered intravenously, these properties were ideal for loco-regional therapies. Apaziquone demonstrated good anti-cancer activity against non-muscle invasive bladder cancer (NMIBC) when administered intravesically to marker lesions and was well tolerated with no systemic side effects. However, phase III clinical trials did not reach statistical significance for the primary endpoint of 2-year recurrence in apaziquone over placebo although improvements were observed. Post-hoc analysis of the combined study data did indicate a significant benefit for patients treated with apaziquone, especially when the instillation of apaziquone was given 30 min or more after surgery. A further phase III study is ongoing to test the hypotheses generated in the unsuccessful phase III studies conducted to date. Expert opinion: Because of its specific pharmacological properties, Apaziquone is excellently suited for local therapy such as NMIBC. Future studies should include proper biomarkers. ARTICLE HISTORY

l-Proline is grafted onto silica (MCM-41) in a single step and shows high activity and enantioselectivity in an aldol reaction.