Total Synthesis of (±)-Methyl Atis-16-en-19-oate via Homoallyl−Homoallyl Radical Rearrangement

Toyota, Masahiro; Wada, Toshihiro; Fukumoto, Keiichiro; Ihara, Masataka

doi:10.1021/ja9739042

Cited by 119 publications

(56 citation statements)

References 28 publications

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“…Although trimethylsilyl (TMS) and triethylsilyl (TES) were also tried, tert-butyldimethylsilyl (TBS) enol ethers proved the most reproducible and stable for purification of the enol silane prior to the cycloalkenylation reaction. In addition, there is evidence from the Toyota lab that TBS enol silanes work best in palladium-catalyzed cycloalkenylation reactions 53 . The use of a bulkier base (iPr 2 NEt), kinetic conditions (LiHMDS at −78°C) or a bromomagnesium diisopropylamide 54 failed to improve the yield or the ratio of desired to undesired enol silane.…”

Section: Resultsmentioning

confidence: 99%

The enantioselective construction of tetracyclic diterpene skeletons with Friedel–Crafts alkylation and palladium-catalyzed cycloalkenylation reactions

et al. 2015

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Due to the profound extent to which natural products inspire medicinal chemists in drug discovery, there is demand for innovative syntheses of these often complex materials. This article describes the synthesis of tricarbocyclic natural product architectures through an extension of the enantioselective Birch-Cope sequence with intramolecular Friedel-Crafts alkylation reactions. Additionally, palladium-catalyzed enol silane cycloalkenylation of the tricarbocyclic structures afforded the challenging bicyclo[3.2.1]octane C/D ring system found in the gibberellins and the ent-kauranes, two natural products with diverse medicinal value. In the case of the ent-kaurane derivative, an unprecedented alkene rearrangement converted four alkene isomers to one final product.

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Section: Resultsmentioning

confidence: 99%

The enantioselective construction of tetracyclic diterpene skeletons with Friedel–Crafts alkylation and palladium-catalyzed cycloalkenylation reactions

et al. 2015

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“…Treatment with catalytic Pd(OAc) 2 and PPh 3 provided allylation product (±)- 72 . Subsequent Luche reduction and rearrangement under acidic conditions provided enone 73 , esterification of the primary alcohol and silylation gave silyl dienol ether 74 , and aerobic oxidative cyclization under Toyota’s conditions [32] afforded [3.2.1] bicycle 75 . Addition of silyl ketene acetal 76 provided conjugate adduct 77 , subsequent tosylhydrazone formation and skeletal rearrangement led to [2.2.2] bicycle 78 , and Weinreb amide formation and treatment with methyllithium gave hemiacetal 79 as an inconsequential mixture of diastereomers.…”

Section: Catalytic Asymmetric Synthesis Of Natural Productsmentioning

confidence: 99%

The Construction of All‐Carbon Quaternary Stereocenters by Use of Pd‐Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis

2013

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All-carbon quaternary stereocenters have posed significant challenges in the synthesis of complex natural products. These important structural motifs have inspired the development of broadly applicable palladium-catalyzed asymmetric allylic alkylation reactions of unstabilized non-biased enolates for the synthesis of enantioenriched α-quaternary products. This microreview outlines key considerations in the application of palladium-catalyzed asymmetric allylic alkylation reactions and presents recent total syntheses of complex natural products that have employed these powerful transformations for the direct, catalytic, enantioselective construction of all-carbon quaternary stereocenters.

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“…The desired compound 131 was obtained in a large quantity. 88,89) The AB ring of kaurene was constructed by the intramolecular Diels-Alder reaction of 132. The presence of the ester function on the diene is important for the stereoselective production of the desired compound 133.…”

Section: Cascade Reaction Under Transition Metal-catalyzed Conditionsmentioning

confidence: 99%

“…No formation of kaurene derivative was observed (Chart 28). 88,89) Methyl atisirenoate (135) was converted into serofendic acids (136) in 5 steps. Recently, serofendic acids (136) have alternatively been synthesized without use of the toxic tin hydride.…”

Section: Cascade Reaction Under Transition Metal-catalyzed Conditionsmentioning

confidence: 99%

Syntheses of Biologically Active Natural Products and Leading Compounds for New Pharmaceuticals Employing Effective Construction of a Polycyclic Skeleton

Ihara

2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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IntroductionWhen various functional groups exist on a polycyclic skeleton, the three-dimensional relationships of the functional groups are restricted and a specific biological activity would be expected due to the rigid conformation (Chart 1). Therefore the development of an efficient method for the construction of polycyclic ring systems is highly desirable, particularly in the field of medicinal chemistry. Cascade reactions 2-7) forming a number of bonds in one operation are useful for the creation of polycyclic compounds. Many stereogenic centers can be created at the same time. A reduction in the number of reaction steps save reagents and energy and reduce waste. Therefore cascade reactions are important from the economic and green chemistry points of view. In this context, we have been studying cascade reactions under various reaction conditions, such as pericyclic, polar, radical, and transition metal-catalyzed reaction conditions. Cascade Reaction under Polar Conditions 2.1. Double Michael ReactionThe bicyclo[2.2.2]octane skeleton is a framework of several natural products. We encountered difficulty in the stereoselective synthesis of the corresponding polycyclic systems using the intramolecular Diels-Alder reaction.8) The problem was solved by employing the intramolecular double Michael reaction, as shown in Chart 2. The treatment of cyclohexenones 1 and 3 with an a,b-unsaturated ester side chain at the 6 or 5 position with LiN(TMS) 2 provided the polycyclic bridged compounds 2 and 4 in highly stereoselective manners, respectively. 9,10) The objective products were produced via ideal transition states, fixed by the coordination with lithium ion.As a typical example of the application of this methodology, the synthesis of (Ϯ)-culumorin (13) 11) is shown in Chart Cascade reactions are useful methods for the construction of polycyclic skeletons, which are important cores for biological activities. A variety of cascade reactions carried out under multiple reaction conditions, such as pericyclic, polar, radical, and transition metal-catalyzed reaction conditions, have been investigated. Culmorin, pentalenene, pentalenic acid, deoxypentalenic acid, longiborneol, cedrandiol, 8,14-cedranoxide, atisirene, atisine, and estrane-type steroids were synthesized via the intramolecular double Michael reaction. Aza double Michael reaction was applied to the syntheses of tylophorine, epilupinine, tacamonine, and paroxetine. Furthermore, sequential Michael and aldol reactions were performed in both intramolecular and intermolecular manners, leading to the formation of polycyclic compounds fused to a four-membered ring. Synthesis of paesslerin A utilizing a multicomponent cascade reaction revealed an error in the proposed structure. Unique cascade reactions carried out under radical and transition metal-catalyzed reaction conditions were also investigated. With the combination of several cascade reactions, serofendic acids and methyl 7b b-hydroxykaurenoate, both of which have neuroprotective activity, were synthesized in a...

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Total Synthesis of (±)-Methyl Atis-16-en-19-oate via Homoallyl−Homoallyl Radical Rearrangement

Cited by 119 publications

References 28 publications

The enantioselective construction of tetracyclic diterpene skeletons with Friedel–Crafts alkylation and palladium-catalyzed cycloalkenylation reactions

The enantioselective construction of tetracyclic diterpene skeletons with Friedel–Crafts alkylation and palladium-catalyzed cycloalkenylation reactions

The Construction of All‐Carbon Quaternary Stereocenters by Use of Pd‐Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis

Syntheses of Biologically Active Natural Products and Leading Compounds for New Pharmaceuticals Employing Effective Construction of a Polycyclic Skeleton

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