Abstract
In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported.
Highlights
We report the successful implementation of signed based on the close spectral similarity of 14 with 2, and this strategy through conversion of fused b-lactams of general the expected dithiocarbamate group transfer to the intermedistructure 9 in three or four steps to keto-bridged bicyclic lac- ate cyclohexyl radical
The N-benzyl system 1.[5,25a] Treatment of p-methoxyaniline 12, Attention turned to elimination of the dithiocarbareadily prepared through alkylation of p-anisidine with 3-bro- mate group to form a ring-fused a,b-unsaturated b-lactam mocyclohexene, with triphosgene gave an isolable carbamoyl suitable for further oxidation
Carbamoyl radical mediated synthesis of b-lactams: The 4exo-trig carbamoyl radical cyclization has been previously investigated to a limited extent for the synthesis of b-lactams.[41,42,43,44,45]
Summary
Citation for published item: Betou, Marie and Male, Louise and Steed, Jonathan W. and Grainger, Richard S. (2014) 'Carbamoyl radical-mediated synthesis and semipinacol rearrangement of -lactam diols.', Chemistry : a European journal., 20 (21). pp. 6505-6517. The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:. A full bibliographic reference is made to the original source a link is made to the metadata record in DRO the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full DRO policy for further details. Durham University Library, Stockton Road, Durham DH1 3LY, United Kingdom Tel : +44 (0)191 334 3042 | Fax : +44 (0)191 334 2971 https://dro.dur.ac.uk
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