Excellent stereocontrol in intramolecular Buchner cyclisations and subsequent cycloadditions; stereospecific construction of polycyclic systems

Abstract

Highly diastereoselective rhodium@) acetate-catalysed intramolecular addition of a-diazo ketones to aromatic rings to form the azulenones 3 has been achieved; the norcaradiene form of 3 undergoes efficient stereospecific cycloaddition with phenyltriazolinedione, in either a stepwise or a tandem process, leading to the pentacyclic systems 4 as a single diastereomer in each case.

A study of the norcaradiene–cycloheptatriene equilibrium in a series of azulenones by NMR spectroscopy; the impact of substitution on the position of equilibrium

“…In practice, the major diastereomer of azulenones substituted at C-2 is the cis-azulenone (C-2 relative to C-8a) while the trans-azulenone (C-3 relative to C-8a) is the major product of the C-3 substituted azulenones due to a conformational preference in the transition states for the aromatic addition. 45,47 In many instances, and particularly with sterically demanding groups at position C-3, the azulenones are formed as single diastereomers. The overall diastereoselectivity is sensitive to the nature of the rhodium catalyst.…”

Catalyst and substituent effects on the rhodium(II)-catalysed intramolecular Buchner reaction

“…4 Research from our team has previously demonstrated excellent diastereocontrol in Rh 2 (OAc) 4 -catalysed aromatic addition reactions of substrates bearing a stereogenic centre on the chain linking the diazoketone and aromatic moieties. 12,13 Herein, we report the influence of variation of catalysts and the linking chain substituents (R) on the efficiencies, regio-and stereoselectivities of the aromatic addition process. Construction of the bicyclo [5.3.0]decane systems in which the stereochemistry at the quaternary bridgehead centre is entirely controlled by internal asymmetric induction from the stereogenic centre in the side chain has considerable synthetic potential.…”

Exploiting Continuous Processing for Challenging Diazo Transfer and Telescoped Copper-Catalyzed Asymmetric Transformations

“…Initial studies focused on debenzoylative diazo transfer to β-diketone 19 (prepared via the corresponding acyl benzotriazole 67 ) conducted in batch, prior to investigation in flow. Thus, 2,5-dimethyl-1,5-diphenylhexan-1,3-dione (19) was transformed to α-diazoketone 11, employing DBU as base and p-nitrobenzenesulfonyl azide (p-NBSA) as diazo-transfer reagent in dichloromethane at 0 °C (Scheme 4), in an adaption of Taber's original route. 65 Purification of αdiazoketone 11 proved challenging due to coelution with the sulfonyl benzamide byproduct resulting in 37% yield, which was later improved through alteration of the sulfonyl azide (vide infra).…”

“…The desired α-diazoketone 11 was afforded in 93% yield after chromatography. 19 F NMR spectra were recorded for the isolated product to ensure that no residual triflyl azide or other fluorinated byproducts, without observable signals in the 1 H NMR spectrum, were present. There is one report in the literature of the byproduct trifluoromethylsulfonyl benzamide (δ F −76.97); 78 this compound was not observed or isolated during this work and was presumably retained on the silica gel.…”