Total Synthesis of Limaol

Hess, Stephan N.; Mo, Xiaobin; Wirtz, Cornelia; Fürstner, Alois

doi:10.1021/jacs.0c12948

Cited by 24 publications

(40 citation statements)

References 59 publications

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“…The first catalyst would partially reduce the heterocyclic core yielding a 2,3dihydrobenzofuran, rendering this compound as a chiral intermediate, while the second catalyst would perform a full hydrogenation of the remaining six-membered all-carbon ring. We envisioned that the second catalyst would be able to utilize the installed stereocenter to guide a downstream diastereoselective reduction, [9] for example, on a solid surface under a Horiuti-Polanyi mechanism. [10] To catalyze the first step we chose the established Ru((R,R)-SINpEt) 2 catalyst 3, [11] which features two N,N'bis(naphthylethyl)imidazolidinium-2-ylidene (NHC) ligands and was previously shown to catalyze the partial hydrogenation of benzofurans with high enantiomeric excess under mild conditions (TOF 1092 h À1 ).…”

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confidence: 99%

Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis

Moock

Wagener

et al. 2021

Angew Chem Int Ed

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We report an enantio-and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation of up to six new defined stereocenters and produces architecturally complex octahydrobenzofurans, prevalent in many bioactive molecules. A unique match of a chiral homogeneous ruthenium-N-heterocyclic carbene complex and an in situ activated rhodium catalyst from a complex precursor act in sequence to enable the presented process.

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mentioning

confidence: 99%

Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis

Moock

Wagener

et al. 2021

Angew Chem Int Ed

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“…Although 10 was obtained as a C7-diastereomeric mixture, the two diastereomers converged into geometrically pure 8 by a subsequent π-allyl Stille coupling reaction. When 10 and vinyl tributylstannane 9 were treated with LiCl, CuCl, and catalytic Pd(PPh 3 ) 4 in DMSO and 1,4-dioxane at 90 °C, the requisite trisubstituted E -olefin formed to afford 8 as a single isomer in 58% yield. , The remarkable regio- and stereoselectivity was likely controlled by the steric environment of the π-allylpalladium intermediate, generated from 10 under the reaction conditions . Intermediate A has a more unfavorable steric interaction than equilibrating B due to the proximity of the C-ring and the bulky C20-OTIPS group.…”

Section: Results and Discussionmentioning

confidence: 99%

Unified Total Syntheses of Rhamnofolane, Tigliane, and Daphnane Diterpenoids

et al. 2021

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Rhamnofolane, tigliane, and daphnane diterpenoids are structurally complex natural products with multiple oxygen functionalities, making them synthetically challenging. While these diterpenoids share a 5/7/6-trans-fused ring system (ABC-ring), the three-carbon substitutions at the C13- and C14-positions on the C-ring and appending oxygen functional groups differ among them, accounting for the disparate biological activities of these natural products. Here, we developed a new, unified strategy for expeditious total syntheses of five representative members of these three families, crotophorbolone (1), langduin A (2), prostratin (3), resiniferatoxin (4), and tinyatoxin (5). Retrosynthetically, 1–5 were simplified into their common ABC-ring 6 by detaching the three-carbon units and the oxygen-appended groups. Intermediate 6 with six stereocenters was assembled from four achiral fragments in 12 steps by integrating three powerful transformations, as follows: (i) asymmetric Diels–Alder reaction to induce formation of the C-ring; (ii) π-allyl Stille coupling reaction to set the trisubstituted E-olefin of the B-ring; and (iii) Eu(fod)3-promoted 7-endo cyclization of the B-ring via the generation of a bridgehead radical. Then 6 was diversified into 1–5 by selective installation of the different functional groups. Attachment of the C14-β-isopropenyl and isopropyl groups led to 1 and 2, respectively, while oxidative acetoxylation and C13,14-β-dimethylcyclopropane formation gave rise to 3. Finally, formation of an α-oriented caged orthoester by C13-stereochemical inversion and esterification with two different homovanillic acids delivered 4 and 5 with a C13-β-isopropenyl group. This unified synthetic route to 1–5 required only 16–20 total steps, demonstrating the exceptional efficiency of the present strategy.

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“…[35] (Scheme 19). [36] Compound 39 was C-glycosylated with allyltrimethylsilane for the synthesis of the core fragment, and the resulting primary product was elaborated into aldehyde using standard protecting group and oxidation state management. Sonogashira coupling yielded compound 40.…”

Section: Spirocyclization Via Other Modes Of Reactionmentioning

confidence: 99%

“…Fürstner group demonstrated the synthesis of limaol via 3,3′‐dibromo‐BINOL‐catalyzed asymmetric propargylation, gold‐catalyzed spirocyclization, and substrate‐controlled allylation (Scheme 19). [36] Compound 39 was C‐glycosylated with allyltrimethylsilane for the synthesis of the core fragment, and the resulting primary product was elaborated into aldehyde using standard protecting group and oxidation state management. Sonogashira coupling yielded compound 40 .…”

Section: Intramolecular Gold‐catalyzed Synthesis Of Spirocyclesmentioning

confidence: 99%

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Gold‐Catalyzed Synthesis of Spirocycles: Recent Advances

2022

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Different types of gold‐catalysts with additives yielded high enantioselective and stereoselective spiro carbocyclic and spiro heterocyclic scaffolds. Gold‐catalyzed spirocyclization proceeds through key intermediates like gold‐alkyne and gold‐allene complex which give direct access to spiro products via cyclization, dearomatization, hydroamination, hydroalkoxylation, cascade reaction, etc. This review article aims to provide an overview of gold‐catalyzed reactions for the formation of spirocycles from various substrates, mentioning methodologies, applications, and mechanistic insights.

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Total Synthesis of Limaol

Cited by 24 publications

References 59 publications

Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis

Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis

Unified Total Syntheses of Rhamnofolane, Tigliane, and Daphnane Diterpenoids

Gold‐Catalyzed Synthesis of Spirocycles: Recent Advances

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