A stereocontrolled intramolecular cycloaddition – sigmatropic rearrangement approach to a tricyclo[7.4.0<sup>1,6</sup>.0<sup>1,10</sup>]tridecane precursor for (±) gascardic acid

The Krapcho reaction involves esters with α‐electron‐withdrawing substituents such as malonates, β‐keto esters, and α‐cyano esters, which undergo dealkoxycarbonylation on being heated in polar aprotic solvents (such as DMSO, DMF, or HMPT) in the presence of water, or in polar aprotic solvents with water in the presence of added salts (such as NaCN, NaCl, LiCl, LiI, or MgCl 2 ). This procedure avoids the use of strongly aqueous acidic and alkaline conditions and tolerates many functional and protecting groups. The chapter presents the mechanistic aspects of this procedure, which include reaction parameters such as solvents, salts, other additives, and the use of microwave irradiation. The diastereoselectivity of protonation of the enolate intermediate leading to the dealkoxycarbonylated products is discussed. Trapping of the intermediate enolate by electrophiles other than a proton is illustrated. Potential side reactions and same‐pot subsequent reactions of substrates are discussed along with functional‐group compatibility for halogens and nitrogen, oxygen, sulfur, selenium, and carbon functional groups. Several examples of applications of this methodology for the synthesis of natural products along with experimental conditions and procedures are presented. Closely related methods are discussed in the Comparison with Other Methods section. The tables, which consist of 371 pages, are grouped according to substrate structure. Selective entries for other methods (excluding classical aqueous acidic or basic methods) are included in the tabular survey for comparative purposes.

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ChemInform Abstract: A Stereocontrolled Intramolecular Cycloaddition ‐ Sigmatropic Rearrangement Approach to a Tricyclo(7.4.01,6.01,10)tridecane Precursor for (.+‐.) Gascardic Acid.

Bérubé

Fallis

1991

ChemInform

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Can. J. Chem. 69,77 (199 1). A general intramolecular Diels-Alder anionic oxy-Cope strategy for the synthesis of tricyclic skeletons and its application to the preparation of the gascardic acid precursor 21 is described. In situ generation of the appropriate cyclopentadiene 9 by isomerization (Et3N) afforded the [4+2] adduct directly or with EtA1Cl2 as catalyst. The requisite potassium salt of the 1,5 diene 16 rearranged with concomitant epimerization at 67OC to the fused ring ketone 18. Selective allylic oxidation and reduction provided 21. GERVAIS B~RUBB et ALEX G. FALLIS. Can. J. Chem. 69, 77 (1991). On dtcrit une strategic gtnerale, basee sur des reactions de Diels-Alder intramolCculaire et d'oxy-Cope anionique, pour effectuer la synthkse des squelettes tricycliques ainsi que son application B la preparation du precurseur 21 de l'acide gascardique. Utilisant une isomerisation (Et3 N), on a realis6 une generation in situ du cyclopentadikne approprie 9 qui a fourni I'adduit [4+2] soit directement ou sous I'influence du EtA1Cl2 comme catalyseur. A 67"C, le sel de sodium approprie 16 du 1,5-dikne se transpose avec une 6pimCrisation concomitante qui conduit B la cCtone cyclique condensCe 18. Son oxydation allylique selective I I et une kduction subsequente conduisent au produit 21.

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A stereocontrolled intramolecular cycloaddition – sigmatropic rearrangement approach to a tricyclo[7.4.0^1,6.0^1,10]tridecane precursor for (±) gascardic acid

Cited by 15 publications

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Methyl Dilithioacetoacetate

Methyl Dilithioacetoacetate

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

ChemInform Abstract: A Stereocontrolled Intramolecular Cycloaddition ‐ Sigmatropic Rearrangement Approach to a Tricyclo(7.4.01,6.01,10)tridecane Precursor for (.+‐.) Gascardic Acid.

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A stereocontrolled intramolecular cycloaddition – sigmatropic rearrangement approach to a tricyclo[7.4.01,6.01,10]tridecane precursor for (±) gascardic acid

Cited by 15 publications

References 6 publications

Methyl Dilithioacetoacetate

Methyl Dilithioacetoacetate

The Krapcho Dealkoxycarbonylation Reaction of Esters with α‐Electron‐Withdrawing Substituents

ChemInform Abstract: A Stereocontrolled Intramolecular Cycloaddition ‐ Sigmatropic Rearrangement Approach to a Tricyclo(7.4.01,6.01,10)tridecane Precursor for (.+‐.) Gascardic Acid.

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A stereocontrolled intramolecular cycloaddition – sigmatropic rearrangement approach to a tricyclo[7.4.0^1,6.0^1,10]tridecane precursor for (±) gascardic acid