Reinvestigation of Mucohalic Acids, Versatile and Useful Building Blocks for Highly Functionalized α,β-Unsaturated γ-Butyrolactones

Ji, Zhang; Blazecka, Peter G.; Belmont, Daniel; Davidson, James G.

doi:10.1021/ol027122b

Cited by 54 publications

(37 citation statements)

References 30 publications

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“…However, under our PTC conditions (25 °C), α,β-unsaturated β-aryl-α- bromo-γ-butyrolactone 49 was prepared from dibromobutenolide 47 and arylboronic acid 48 in 91% yield (Scheme 10). 21 The regioisomer was not observed. The methodology described herein has been successfully applied to the synthesis of rofecoxib (51) (Scheme 10), providing the title compound in four steps and 79% overall yield from mucobromic acid (2).…”

Section: Scheme 8 Attempted Reductive Amination Of Mucohalic Acids Wimentioning

confidence: 97%

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Recent Progress in the Chemistry of Mucohalic Acids: Versatile Building Blocks in Organic Synthesis

Zhang

Sarma

Curran

2013

Synlett

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This account documents our recent progress in exposing some of the potential of mucohalic acids in synthetic applications. Understanding their stability and reactivity in different reaction media allows the development of mild and regioselective methods to access various substituted butenolides, butenolactams, and 4,5-dihalopyridazin-3(2H)-ones and to create other novel, multifunctionalized building blocks.

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Section: Scheme 8 Attempted Reductive Amination Of Mucohalic Acids Wimentioning

confidence: 97%

“…21 When benzyl acetal 170 was used in the coupling, protected butenolide 171 was isolated in 90% yield. This study highlighted the instability of the dihalobutenolide portion when applying classical basic conditions and established the beneficial use of CsF under phase-transfer conditions.…”

Section: Other Applicationsmentioning

confidence: 99%

Recent Progress in the Chemistry of Mucohalic Acids: Versatile Building Blocks in Organic Synthesis

Zhang

Sarma

Curran

2013

Synlett

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“…Neste trabalho, a furanona 2 foi diarilada com 2,4 equivalentes do ácido fenil-borônico (38) em um sistema bifásico na presença de 29 A aplicação desta metodologia na síntese do Vioxx (59b) partindo-se de 2 e realizada somente em três etapas demonstra o potencial sintético desta furanona em reações de acoplamento cruzado mediado por paládio (Esquema 32).…”

Section: Reações Da 34-dibromofuran-2(5h)-ona -Acoplamento Cruzado Munclassified

Aplicações sintéticas do ácido mucobrômico e da 3,4-dibromofuran-2(5H)-ona

Cunha¹,

Oliveira²

2011

Quím. Nova

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Recebido em 23/11/10; aceito em 1/4/11; publicado na web em 10/6/11 SYNTHETIC APPLICATIONS OF MUCOBROMIC ACID AND 3,4-DIBROMOFURAN-2(5H)-ONE. This review describes the use of two biomass-derivate butenolides as intermediates in organic synthesis, mucobromic acid and its reduced derivative 3,4-dibromofuran-2(5H)-one. The ambiphilic and ambident character of such butenolides make them versatile starting materials in the synthesis of natural and/or bioactive compounds. Thus, the reactions of mucobromic acid with C-nucleophiles and heteronucleophiles are described, as well as the nucleophilic addition to carbonyl reactions of 3,4-dibromofuran-2(5H)-one. Besides, both compounds are active in diverse metal cross-coupling reactions, manly with palladium in Suzuki and Sonogashira reactions.Keywords: mucobromic acid; 3,4-dibromofuran-2(5H)-one; butenolides. INTRODUÇÃOA ciência Síntese Orgânica passa por um momento de revitalização que inclui, entre outros aspectos, a preocupação com a eficiência da metodologia sintética e sua aplicação numa síntese total, quer seja um produto natural ou uma substância valorada por suas propriedades biológicas ou físico-químicas.1-3 A incorporação de materiais de partida obtidos de fontes renováveis, a preocupação com o menor consumo de energia, o emprego de métodos e técnicas para acelerar e/ou promover reações antigas e novas passaram a ser metas do planejamento sintético.4,5 Estas modificações podem ser relacionadas com incrementos no design experimental. Desta forma, Carlson propôs o conceito da reação ideal, que deve ser realizada em água, o material de partida de fácil acesso, barato, não tóxico e o produto facilmente isolado em rendimento quantitativo. 6 Complementarmente, Wender preconizou que a economia de etapas é o fator de maior influência na viabilidade de uma síntese, pois determina tempo, custo, geração de resíduos e escala do processo.7 Portanto, novas reações devem ser desenvolvidas para que os princípios da Química Verde sejam atendidos.8 Estas condições de idealidade para uma síntese norteiam os desafios a serem perseguidos pela comunidade sintética no século atual.Uma das formas de se obter, em poucas etapas, um aumento significativo de complexidade estrutural consiste em empregar molé-culas polifuncionalizadas ambifílicas e polidentadas de fácil acesso, que possam, assim, atuar como eletrófilos e/ou nucleófilos. Dentre as que apresentam todas estas características, merecem destaque as furanonas halogenadas como o ácido mucobrômico (1) e o seu derivado reduzido, a 3,4-dibromofuran-2(5H)-ona (2) (Figura 1).

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“…In recent years, MXA have also attracted much attention in organic synthesis owing to their high functionalization and availability, and they have been used in the synthesis of heterocycles such as gamma‐substituted gamma‐butenolides and gamma‐lactams, and other furanone derivatives 23–35…”

Section: Introductionmentioning

confidence: 99%

Genotoxic halofuranones in water: isomerization and acidity of mucohalic acids

Gómez‐Bombarelli

González‐Pérez

Pérez‐Prior

et al. 2011

J of Physical Organic Chem

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Among the genotoxic halofuranones formed by chlorination in water are mucochloric acid (MCA, 3,4‐dichloro‐5‐hydroxyfuran‐2(5H)‐one) and mucobromic acid (MBA, 3,4‐dibromo‐5‐hydroxyfuran‐2(5H)‐one). These acids are direct genotoxins and potential carcinogens, with the capacity to alkylate the DNA bases. In recent years, they have also attracted attention in the synthesis of furanone derivatives. Mucohalic acids (MXA) exist in solution as an equilibrium between three species; a cyclic lactone‐lactol , an open‐chain aldehyde‐acid , and the dissociated form of the latter . The distribution of the three species in the equilibrium has synthetic, toxicological, and environmental implications owing to their different functionalization. The case of the neutral open‐chain form is of special interest, since it is expected to be highly reactive. We have experimentally determined the apparent dissociation constant of the cyclic species . Their values suggest that at neutral pH MXA are mostly present as the dissociated carboxylate‐aldehyde. The dissociation constant of the open‐chain neutral species and the cyclization equilibrium constant were determined in water and organic solvents, using density functional theory and ab initio methods. The results suggest that the undissociated aldehyde is a minor species at any given pH. The structure of MXA in solution and the influence of the level of theory on the calculated geometry are discussed. Copyright © 2011 John Wiley & Sons, Ltd.

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Reinvestigation of Mucohalic Acids, Versatile and Useful Building Blocks for Highly Functionalized α,β-Unsaturated γ-Butyrolactones

Cited by 54 publications

References 30 publications

Recent Progress in the Chemistry of Mucohalic Acids: Versatile Building Blocks in Organic Synthesis

Recent Progress in the Chemistry of Mucohalic Acids: Versatile Building Blocks in Organic Synthesis

Aplicações sintéticas do ácido mucobrômico e da 3,4-dibromofuran-2(5H)-ona

Genotoxic halofuranones in water: isomerization and acidity of mucohalic acids

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