[4+2] Cycloadditions between 2-pyrones and benzyne. Application to the synthesis of binaphthyls

Escudero, Sonia; Pérez, Dolores; Guitián, Enrique; Castedo, Luís

doi:10.1016/s0040-4039(97)01176-3

Cited by 24 publications

(6 citation statements)

References 13 publications

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“…A variety of alternative synthetic strategies was accordingly evaluated with a view to scale-up for manufacture. One of these (forming the subject of this contribution) was based on Diels−Alder chemistry to construct the second naphthalene ring, allowing the required 1,3-difunctionality to be established on the carbon atoms destined for one-half of the naphthalene 2-ring system [in bromocoumalate ( 5 )], before assembly of the naphthalene double ring, thereby avoiding the problems of naphthalene ring selectivity. Thus, for example, bromocoumalate ( 5 ) (already bearing the required 1,3-disubstitution pattern in the form of bromo and carboxy substituents on atoms 3 and 5) is reacted with in situ generated benzyne to give, after decarboxylation, 1-bromo-3-naphthalenecarboxylate ester ( 6 ) which is then converted through a series of steps to required cyanoacid ( 1 ) (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

A New Route for Manufacture of 3-Cyano-1-naphthalenecarboxylic Acid

Ashworth

Bowden

Dembofsky

et al. 2002

Org. Process Res. Dev.

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3-Cyano-1-naphthalenecarboxylic acid is an intermediate required for manufacture of tachykinin receptor antagonists. The 1,3-disubstitution pattern on the naphthalene skeleton complicates the synthesis of this cyano acid. Previous literature-based chemistry is unattractive for large-scale manufacture due to stoichiometric use of mercury salts, low yield, and other operational difficulties. An attractive new route has been developed by establishing the 1,3-substitution on the carbon atoms destined for only one-half of the naphthalene 2-ring system, via 3-bromocoumalate, and then building up the rest of the naphthalene ring system by Diels-Alder addition of 3-bromocoumalate to in situ-generated benzyne. The resulting 4-bromo-2-naphthoate was converted to the required cyanoacid by transformation of ester to nitrile followed by carbonylation of the bromo substituent. The new route has been scaled up successfully and offers significant advantages over previous literature chemistry in terms of improved process environmental implications, improved yield, lower cost, and improved robustness and ease of operation at larger scales of operation.

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Section: Introductionmentioning

confidence: 99%

A New Route for Manufacture of 3-Cyano-1-naphthalenecarboxylic Acid

Ashworth

Bowden

Dembofsky

et al. 2002

Org. Process Res. Dev.

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“…The heterocycle 2-chloro-1,4-benzodithiine-S,SЈ-tetraoxide 25 functions as a new synthetic equivalent for benzyne. 172 Reactions between pyrones and benzyne give viable approaches to naphthalenes 173 and to the core ring system of dynemicin A (Scheme 69). 174 Annelated carbazoles can be prepared from 3-vinylindoles and benzyne, 175 but reactions with 3,4-pyridyne failed to generate the desired products.…”

Section: Generalmentioning

confidence: 99%

Cycloadditions in synthesis

Dell¹

1998

J. Chem. Soc., Perkin Trans. 1

114

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“…The carbonyl−alkyne exchange (CAE) reaction − of 2,2-dialkyl-2,3-dihydro-4 H -pyran-4-ones 1 with electron-deficient acetylenes 2 , yielding protected phenols 3 (Scheme ), which has been studied previously in our group, constitutes a novel approach for the regioselective de novo construction of highly functionalized aromatic compounds. Thus, in situ transformation of dihydropyranones 1 into their corresponding silyl enol ethers 4 and [4+2] cycloaddition with acetylenes 2 yieldedvia bicyclic intermediates 5 and electrocyclic extrusion of acetonethe protected phenols 3 in good to excellent yields (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Regioselective Synthesis of Highly Substituted Aromatic Sulfides via Carbonyl−Alkyne Exchange Reaction

1999

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Carbonyl−alkyne exchange reaction of 2,2-dimethyldihydropyran-4-thione-derived dienes with acetylenic ketones leads to highly substituted aromatic sulfides. The reaction proceeds with a high degree of regioselectivity and in good yields. Addition of Et2AlCl considerably increases the scope of usable acetylenic ketones. The starting materials, dihydropyran-4-one and α-alkynyl ketone derivatives, are readily available reactive building blocks. Additional diversity can be introduced through straightforward derivatization reactions at the sulfur atom. The use of solid-supported reagents and trapping agents allows the reaction to be carried out in a parallel format which might render such a concept attractive for the synthesis of compound libraries.

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[4+2] Cycloadditions between 2-pyrones and benzyne. Application to the synthesis of binaphthyls

Cited by 24 publications

References 13 publications

A New Route for Manufacture of 3-Cyano-1-naphthalenecarboxylic Acid

A New Route for Manufacture of 3-Cyano-1-naphthalenecarboxylic Acid

Cycloadditions in synthesis

Regioselective Synthesis of Highly Substituted Aromatic Sulfides via Carbonyl−Alkyne Exchange Reaction

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