A simple synthesis of tropones and related compounds

Barbier, Michel; Barton, D. H. R.; Devys, Michel; Topgi, Ravindra Satish

doi:10.1016/s0040-4020(01)87681-x

Cited by 24 publications

(9 citation statements)

References 31 publications

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“…To test the regioselectivity of the newly developed method, the synthesis of 2,7‐dimethyl‐tropone 6 was first undertaken according to a method reported by Barbier et al (Scheme ) for similar transformations. In the first step, dichlorocarbene is generated in situ and undergoes a directed addition to 2,6‐dimethylphenol 7 at the ortho position to the OH group to form product 8 .…”

Section: Resultsmentioning

confidence: 99%

“…6‐(Dichloromethyl)‐2,6‐dimethylcyclohexa‐2,4‐dien‐1‐one (8): Modified literature procedure . To a solution of 2,6‐dimethylphenol 7 (20.0 g, 164 mmol) in CHCl 3 (44.0 mL, 549 mmol) was added a 25 % aqueous solution of cetyltrimethylammonium chloride (0.541 mL, 0.423 mmol), and the reaction mixture was heated to 50 °C in an ambient atmosphere.…”

Section: Methodsmentioning

confidence: 99%

“…2,7‐Dimethylcyclohepta‐2,4,6‐trien‐1‐one (6): Method using substrate 8 ; modified literature procedure . To a solution of 8 (3.00 g, 14.6 mmol) in dry C 6 H 6 (294 mL) under N 2 atmosphere was added AIBN (0.241 g, 1.47 mmol) in one portion followed by tributyltin hydride (9.89 mL, 36.7 mmol) through slow addition.…”

Section: Methodsmentioning

confidence: 99%

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Dialkylated Dihydroazulene and Vinylheptafulvene Derivatives – Synthesis and Switching Properties

et al. 2017

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Functionalization of molecular photoswitches at specific positions offers a way of tuning their switching properties. The work presented here describes the development of a new protocol towards the synthesis and functionalization of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo‐/thermoswitch. The key step is a facile condensation reaction using a functionalized tropone derivative, and the new synthetic method was employed in the regioselective preparation of a novel dimethyl‐substituted DHA photoswitch. This compound presents the first accessible derivative with alkyl groups on the seven‐membered ring of the system ― at positions C5 and C7. From experimental and theoretical kinetics studies on the thermal VHF‐to‐DHA electrocyclic reaction, the influence of the electron‐donating methyl groups was elucidated. In addition, we subjected a small selection of 4,8a‐dialkylated compounds to a computational study to elucidate how steric interactions can alter the relative DHA–VHF stabilities. The synthetic methodology offers access to novel DHA scaffolds and substitution patterns, which in turn can lead to systems that can help to address broader questions concerning the potential applicability of the DHA/VHF system in the context of solar‐thermal energy‐storage systems or other photochromic applications.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Dialkylated Dihydroazulene and Vinylheptafulvene Derivatives – Synthesis and Switching Properties

et al. 2017

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“…22 In addition, radical-based approaches have been successful in synthesizing tropolones from ortho-dearomatized catechols (5) through a selective radical ring expansion mechanism ( Figure 1B). [25][26] This approach required pre-functionalization of the arene to ensure that radical initiation occurred at the methyl halide ipso to the site of dearomatization, leading to the desired rearrangement ( Figure 1B). [25][26] While these methods have been successful in enabling ring expansion, they require arduous synthetic efforts to achieve the desired substitution pattern of the tropolone natural product, preventing facile access to the target compound.…”

Section: Introductionmentioning

confidence: 99%

Radical Tropolone Biosynthesis

Doyon¹,

Skinner²,

Yang³

et al. 2020

Preprint

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<div> <div> <div> <p>Non-heme iron (NHI) enzymes perform a variety of oxidative rearrangements to advance simple building blocks toward complex molecular scaffolds within secondary metabolite pathways. Many of these transformations occur with selectivity that is unprecedented in small molecule catalysis, spurring an interest in the enzymatic processes which lead to a particular rearrangement. In-depth investigations of NHI mechanisms examine the source of this selectivity and can offer inspiration for the development of novel synthetic transformations. However, the mechanistic details of many NHI-catalyzed rearrangements remain underexplored, hindering full characterization of the chemistry accessible to this functionally diverse class of enzymes. For NHI-catalyzed rearrangements which have been investigated, mechanistic proposals often describe one-electron processes, followed by single electron oxidation from the substrate to the iron(III)-hydroxyl active site species. Here, we examine the ring expansion mechanism employed in fungal tropolone biosynthesis. TropC, an α-ketoglutarate- dependent NHI dioxygenase, catalyzes a ring expansion in the biosynthesis of tropolone natural product stipitatic acid through an under-studied mechanism. Investigation of both polar and radical mechanistic proposals suggests tropolones are constructed through a radical ring expansion. This biosynthetic route to tropolones is supported by X-ray crystal structure data combined with molecular dynamics simulations, alanine-scanning of active site residues, assessed reactivity of putative biosynthetic intermediates, and quantum mechanical (QM) calculations. These studies support a radical ring expansion in fungal tropolone biosynthesis. </p> </div> </div> </div>

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“…An inspection of the published work revealed that 4-aminotropones had only been synthesised in a stepwise manner from 4-aminotropolone sulphate [33] and 4-hydroxytropone. [34] The formation of N-Boc-4-aminotropone 10 was assumed to proceed from an initial a-sulfinyl carbanion I, resulting upon basic treatment of the p-quinamine 3, which evolved to a norcaradiene-like intermediate II, [35,36] by an intramolecular 1,4-addition on the cyclohexadienone moiety. A subsequent elimination of the p-toluene sulfenate anion from this intermediate occurred with simultaneous ring expansion leading to 10 (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4‐Aminotropones from [(Sulfinyl or Sulfonyl)methyl]‐Substituted p‐Quinamines

Carreño¹,

Ortega-Guerra²,

Ribagorda³

et al. 2007

Chemistry A European J

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An efficient synthesis of 4-aminotropones has been achieved in excellent yields by simple treatment of 4-amino-4-[(p-tolylsulfinyl)methyl]-2,5-cyclohexadienones (p-quinamines) with NaH. The method allowed regiocontrolled access to 3-methyl, 5-methyl- and 3,5-dimethyl-substituted derivatives starting from p-quinamines with adequate substituents at the cyclohexadienone moiety and/or at the carbon linked to the sulfur function. The p-quinamines in turn were easily accessible from N-Boc p-anisidines (Boc=tert-butoxycarbonyl) by electrochemical oxidation in MeOH to quinone imine monoketals, followed by addition of a alpha-lithium sulfinyl carbanion to the imino group, and ketal hydrolysis. Oxidation of the sulfoxide gave the sulfonyl-substituted p-quinamines that, upon basic treatment, behave similarly. The p-quinamine 55 and bis-p-quinamine 56, resulting in the addition of the anion derived from dimethyl sulfone to the p-quinonimine ketal 14, also gave the 4-aminotropone. The mechanism involves the initial formation of a alpha-sulfonyl carbanion, which intramolecularly attacks the cyclohexadienone giving a norcaradiene-like enolate intermediate, the evolution of which through a ring-expansion process, pushes off a methyl sulfinate anion or SO2. This efficient process fulfils the criteria of atom economy. The introduction of a proline substituent in the nitrogen of the starting p-quinamine allowed the synthesis of an enantiopure 4-aminotropone, the asymmetric Diels-Alder reactions of which with maleimide occurred in a highly endo and pi-facial diastereoselective manner.

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A simple synthesis of tropones and related compounds

Cited by 24 publications

References 31 publications

Dialkylated Dihydroazulene and Vinylheptafulvene Derivatives – Synthesis and Switching Properties

Dialkylated Dihydroazulene and Vinylheptafulvene Derivatives – Synthesis and Switching Properties

Radical Tropolone Biosynthesis

Synthesis of 4‐Aminotropones from [(Sulfinyl or Sulfonyl)methyl]‐Substituted p‐Quinamines

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