Efficient Synthetic Approaches to the Common Scaffold of Indole Alkaloids

Beniazza, Rédouane; Dunet, Julie; Robert, Frédéric; Schenk, Kurt; Landais, Yannick

doi:10.1021/ol701493k

Cited by 34 publications

(11 citation statements)

References 37 publications

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“…6 was previously prepared from 3a 10 using Wacker type conditions (Pd(OAc) 2 , pyridine, O 2 in xylene at 80°C). The formation of 6 may proceed through heterocyclization prior to -hydride elimination as shown in Figure 2 (Path B).…”

Section: Figurementioning

confidence: 99%

“…4 Our continuous interest for this class of compounds 1,5,6 has led recently to the development of a methodology focused on a palladium-catalyzed aza-Wacker process [7][8][9] using 1-arylcyclohexa-2,5-dienes as precursors. 10 The pendant ethylamino moiety on the quaternary center was thus shown to add onto the dienyl system, affording the corresponding 5-membered ring along with a new conjugated diene, which could be functionalized further. For instance, starting from an ortho-substituted arylcyclohexa-2,5-diene such as 1, this strategy offered a straightforward entry toward the tetracyclic core 2 of aspidosperma alkaloids (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

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Unexpected ring contraction of 1-aryl-cyclohexa-2,5-dienes under palladium catalysis

Lebeuf¹,

Robert²,

Landais

2013

Arkivoc

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Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unexpected ring contraction of 1-aryl-cyclohexa-2,5-dienes under palladium catalysis

Lebeuf¹,

Robert²,

Landais

2013

Arkivoc

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“…This cascade reaction is a useful method to provide a key structure, the azabicyclo[4.3.0]nonane system, found in various alkaloids [28] (Scheme 16) . The same group described two different approaches to the tetracyclic core of the aspidosperma alkaloids by a double oxidative amination and double conjugate addition process [29]. Treating the cyclohexadiene 48 with Pd(OAc) 2 and O 2 in DMSO provided the tetracyclic compound 49 as a single isomer in 75% yield.…”

Section: Miscellaneous Reactionsmentioning

confidence: 99%

Diastereoselective Desymmetrization of Symmetric Dienes and its Synthetic Application

Nakahara

Fujioka

2010

Symmetry

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Abstract:The desymmetrization of symmetric compounds is a useful approach to obtain chiral building blocks. Readily available precursors with a prochiral unit could be converted into complex molecules with multiple stereogenic centers in a single step. In this review, recent advances in the desymmetrization of symmetric dienes in the diastereotopic group differentiating reaction and its synthetic application are presented.

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“…Few years ago, our group has also developed a Pd(II)-catalyzed double oxidative amination of cyclohexadienes with the trapping of the final allyl-palladium by an acetate forming a highly functionalized cyclohexene as a single diastereoisomer (Scheme 1). 8 Scheme 1. Pd(II)-catalyzed double oxidative amination cascade.…”

Section: Introductionmentioning

confidence: 99%

Palladium-mediated domino oxidative amination of cyclohexadienes as an entry to indole alkaloids

et al. 2019

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Scheme 2. Pd(II)-catalyzed oxidative amination. We then attempted a cyclization starting from an aromatic sulfonamide 5, available in two steps from 2-aminobiphenyl through a Birch reductive alkylation 10 (after the protection of the aniline). Oxygen concentration was found to be a critical factor, indicating that Pd 0 reoxidation is the turnover limiting step of the process. 11 Inefficient reoxidation of Pd 0 into Pd II leads to aggregation of Pd 0 and precipitation of Pd metal, a process which could be prevented by addition of charcoal. 12 The presence of stoichiometric NaOAc as a base also enhanced the yield of these reactions (Scheme 3). 13 It should also be noticed that Zhu et al. have developed recently an elegant palladium oxidative amination on cyclohexadienes using chiral ligands, allowing the extension of our strategy to an enantioselective version. 14 Scheme 3. Oxidative amination of aromatic sulfonamide. At this stage, a sequential double addition confirmed the formation of the acetate insertion product as a unique diastereoisomer, identical to that obtained through the one pot process (Scheme 1 and 4). However, when the reaction was run with an acrylamide (e.g. 8), instead of an acetate, only the tetracyclic product 9 was formed with no trace of the desired pentacyclic system, resulting from an insertion (and elimination) of the intermediate palladium species into the double bond in a Heck-type fashion. Scheme 4. Sequential double oxidative amination. The double bond of the acrylamide being quite far away from the palladium center in the putative allyl-Pd intermediate, an amide 10 with a longer arm was then synthesized (Scheme 5). Unfortunately, if the desired tricyclic product 11, an advanced intermediate in the synthesis of iboxyphylline, an aspidosperma alkaloid, 15 was effectively formed, yields were always low and the reaction difficult to reproduce. The faster oxidation of the terminal double bond of 10 (through a Wacker type process) or a competing 6-exo carbopalladation followed by an oxidation of the exocyclic double bond might explain the low yield of 11, the only compound stable to overoxidation. Scheme 5. Double oxidative amination and insertion. In the search for a nucleophile that would stand the harsh oxidative conditions, different acyl groups bearing electron-rich aromatics, a malonate, a tosylamine... were then introduced on the primary amine (Scheme 6). Amides 12-16 were thus isolated in good overall yield (in 2 steps from 6), except amide 17 formed after sulfone elimination. Scheme 6. Acid coupling When the palladium oxidative amination was performed on the six amides above, only two cyclized products were observed. Starting from 17, low amount of tetracyclic acetate 18 was isolated. However, when the reaction was carried out on tosylamine 16, pentacyclic 19 could be observed, albeit in very low yield (Scheme 7). Scheme 7. Oxidative amination on substrates 16 and 17. From these failures, it appeared that sulfonamides, stable under the harsh oxidative conditions, would constitute s...

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Efficient Synthetic Approaches to the Common Scaffold of Indole Alkaloids

Cited by 34 publications

References 37 publications

Unexpected ring contraction of 1-aryl-cyclohexa-2,5-dienes under palladium catalysis

Unexpected ring contraction of 1-aryl-cyclohexa-2,5-dienes under palladium catalysis

Diastereoselective Desymmetrization of Symmetric Dienes and its Synthetic Application

Palladium-mediated domino oxidative amination of cyclohexadienes as an entry to indole alkaloids

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