Approaches to the synthesis of (+)- and (−)-epibatidine †

Barros, M. Teresa; Maycock, Christopher D.; Ventura, M. Rita

doi:10.1039/b002980g

Cited by 51 publications

(33 citation statements)

References 27 publications

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“…[24,30,31] To establish the best conditions for cross coupling, we tested 2-iodocyclohex-2-enone (14) [32] in its reaction with boronate 10. No reaction was observed with 5 mol-% Pd(PPh 3 ) 4 and potassium carbonate, [27] barium hydroxide, [25] or potassium phosphate as base, but utili- zation of cesium carbonate (3 equiv.)…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Altenuene and Isoaltenuene

2006

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Total synthesis of altenuene and isoaltenuene, toxins produced by various alternaria fungi, were achieved for the first time in ten steps, starting with quinic acid and commercially available acetal‐protected phloroglucinic acid, with the longest linear sequence consisting of seven steps. The key reactions are palladium‐catalyzed Suzuki‐type couplings between an arene boronate and iodinated cyclohexenes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Section: Introductionmentioning

confidence: 99%

Total Synthesis of Altenuene and Isoaltenuene

2006

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“…Numerous syntheses of epibatidine have since been published, most of which are racemic 22. One commonly employed strategy to introduce the pyridyl group involves an organometallic coupling with a 2‐halosustituted cyclohexanone,23, 24 a reaction that cannot be rendered asymmetric (since the starting material is already chiral). As depicted in our retrosynthesis (Scheme ), the direct coupling of a 4‐substituted cyclohexanone with a pyridyl iodonium salt not only shortens the synthetic pathway but also renders the synthesis asymmetric.…”

Section: Methodsmentioning

confidence: 99%

Enantioselective α‐Arylation of Cyclohexanones with Diaryl Iodonium Salts: Application to the Synthesis of (−)‐Epibatidine

Aggarwal¹,

Olofsson

2005

Angew Chem Int Ed

145

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The enantioselective introduction of electrophiles a to carbonyl groups is a central topic in asymmetric synthesis. Although asymmetric a-alkylations have been well developed, high enantioselectivity in a-arylation of ketones has only been achieved in a very limited number of cases. These involve arylation of trisubstituted enolates using binap-Pd complexes which gives non-epimerizable, tetrasubstituted ketones. [1,2] However, this strategy cannot be used in the desymmetrization/arylation of cyclic ketones, since even if the enolate was generated enantioselectively, the ketone product would racemize the starting enolate (through proton transfer) at the high temperatures required for arylation.An alternative strategy involves a-arylation of b-ketoesters with aryl lead reagents (Scheme 1).[3] This strategy can be rendered asymmetric through 1) desymmetrization/bketoester formation, [4] 2) arylation, [3] and 3) decarboxylation and subsequent equilibration.However, a direct asymmetric arylation of cyclohexanones would clearly be superior. If this could be achieved, we envisaged that this strategy could be applied to a short asymmetric synthesis of the alkaloid (À)-epibatidine (1) (Scheme 2). Herein, we describe our success in achieving these goals.As possible electrophilic sources of aryl reagents, we considered diaryl iodonium(iii) salts since scattered reports existed of couplings with silyl enol ethers, [5] ketones, [6] and malonates, [7] albeit with varying yields. The scope and limitations of these couplings had not been investigated, and no successful asymmetric reactions have been reported. [8]

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“…Enantiopure 53 was thus prepared from cyclohexenone 55, which in turn is available in 7 steps from quinic acid. 46 Narasaka's earlier synthesis of rac-50 had started with (±)−55, but except for the optical purity of 55, the two routes are identical. 4 and NaIO 4 in the presence of PhB(OH) 2 ] to reveal dialdehyde 65.…”

Section: The Narasaka Synthesis Of Sordarinmentioning

confidence: 97%