Total Syntheses of (−)-Mesembrane and (−)-Mesembrine <i>via</i> Palladium-Catalyzed Enantioselective Allylic Substitution and Zirconium-Promoted Cyclization

Mori, Miwako; Kuroda, Shinji; Zhang, Chang-Shan; Sato, Yoshihiro

doi:10.1021/jo9701187

Cited by 87 publications

(24 citation statements)

References 32 publications

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“…[13] These natural products attracted considerable attention over the years because of their diverse structures and potent bioactivities. The asymmetric aza-Wacker reaction developed in this study is indeed tailor-made for these alkaloids as illustrated by the realization of divergent synthesis of (À)-mesembrane (3) [24] and (+ +)-crinane (4), [25] In summary,w er eported ac atalytic enantioselective desymmetrizing aza-Wacker reaction. [23] Since both enantiomers of some members of these families of natural products exist in nature,the development of catalytic enantioselective approach is particularly appealing.…”

Section: Zuschriftenmentioning

confidence: 72%

Palladium‐Catalyzed Enantioselective Desymmetrizing Aza‐Wacker Reaction: Development and Application to the Total Synthesis of (−)‐Mesembrane and (+)‐Crinane

2018

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Reported is an unprecedented catalytic enantioselective desymmetrizing aza-Wacker reaction. In the presence of ac atalytic amount of an ewly developed Pd(CPA) 2 (MeCN) 2 catalyst (CPA = chiral phosphoric acid), ap yroxl igand, and molecular oxygen, cyclization of properly functionalized prochiral 3,3-disubstituted cyclohexa-1,4-dienes afforded enantioenriched cis-3a-substituted tetrahydroindoles in good yields with excellent enantioselectivities.Acooperative effect between the phosphoric acid and the pyroxl igand ensured efficient transformation. This reaction was tailor-made for Amaryllidaceae and Sceletium alkaloids as illustrated by its application in the development of the concise and divergent total synthesis of (À)-mesembrane and (+ +)-crinane. Scheme 1. Enantioselective aza-Wacker reaction. Ts = 4-toluenesulfonyl.

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Section: Zuschriftenmentioning

confidence: 72%

Palladium‐Catalyzed Enantioselective Desymmetrizing Aza‐Wacker Reaction: Development and Application to the Total Synthesis of (−)‐Mesembrane and (+)‐Crinane

2018

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“…On the other hand, allylic oxidation of 18 followed by deformylation of 19 was carried out to give 20, which was led to (Ϯ)-mesembrine. 15) Thus we succeeded in the total syntheses of (Ϯ)-mesembrane and (Ϯ)-mesembrine using zirconium-mediated cyclization.…”

Section: Total Syntheses Of (؊)-Mesembrane and (؊)-Mesembrine Using Zmentioning

confidence: 97%

Development of a Novel Synthetic Method for Ring Construction Using Organometallic Complexes and Its Application to the Total Syntheses of Natural Products

Mori

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Organometallic complexes are useful tools in synthetic organic chemistry. In particular, they play an important role in carbon-carbon bond formation. A metalacycle, i.e., a ring compound containing a transition metal, is a useful intermediate in synthetic organic chemistry. Oxidative cyclization of unsaturated hydrocarbons, such as alkene, alkyne, carbonyl compounds, or nitrile, using a low-valent transition metal is a useful reaction for synthesis of metalacycles. It is known that a metalacycle formed from a late transition metal and unsaturated hydrocarbons is not stable and is easily converted into the reductive elimination product or b-hydrogen elimination product (Eq. 1). Since the low-valent metal complex is regenerated in this reaction, the reaction proceeds with a catalytic amount of the transition metal. On the other hand, the metalacycle formed from an early transition metal and unsaturated hydrocarbons is fairly stable and can be converted into various compounds with functional groups by treatment with various agents (Eq. 2). Therefore a stoichiometric amount of the metal complex is required in this reaction.(1) (2) Negishi et al.2) and Nugent and Calabrese 3) reported the syntheses of zirconacycles 2 from diene, enyne, and diyne 1 using zirconocene (Cp 2 Zr). Hydrolysis of zirconacycle afforded the cyclized compound 3 (Chart 1).Negishi et al. also found a synthetic method of dibutylzirconocene (Cp 2 ZrBu 2 ) from zirconocenedichloride (Cp 2 ZrCl 2 ) and butyl lithium, and dibutylzirconocene is easily converted into zirconocene coordinated by a butene ligand in situ at room temperature 4) (Eq. 3).This was a great discovery in zirconium chemistry because it is difficult to isolate zirconocene with no ligand. We were interested in those results and attempted to form carbon-carbon bonds between the unsaturated hydrocarbons, such as enyne and diene, using zirconocene. Synthesis of Heterocycles Using Zirconium-Mediated Cyclization and Total Synthesis of (؊)-DendrobineThe zirconacycles 2 were easily synthesized in situ from Cp 2 ZrCl 2 and diene, enyne, or diyne 1. To a THF solution of Cp 2 ZrCl 2 and unsaturated hydrocarbon 1 was added BuLi at Ϫ78°C under argon gas, and the solution was stirred at room Organometallic complexes are useful tools in synthetic organic chemistry. We investigated a novel synthetic method for ring construction using organometallic complexes and synthesized natural products and biologically active substances using these methods. Metalacycles formed from an early transition metal and diene, enyne, and diyne are stable under the reaction conditions and they are easily converted into compounds with functional groups by the addition of various agents. We have developed a novel synthetic method of heterocycles from enyne and diene using Cp 2 ZrBu 2 . The total syntheses of (؊)-dendrobine, (؎)-mecembrane, and (؎)-mecembrine were achieved using this procedure. To synthesize these natural products as a chiral form, a novel palladium-catalyzed asymmetric allylic amination was developed, an...

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“…Despite its usefulness, the success of this type of reaction is limited. [46][47][48][49][50] Although no reaction occurred when 2-phenylcyclohexenyl acetate was used as the substrate, allylic amination of 2-phenylcyclohexenyl carbonate 48 with benzylamine proceeded smoothly in acetonitrile, affording the corresponding product 49a in 93% yield and 93% ee (Chart 15). Chart …”

Section: Chart 11 Enantioselective Construction Of Quaternary Centermentioning

confidence: 99%

Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

Hamada

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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2,6-Dimethyl-9-Aryl-9-phosphabicyclo[3.3.1]nonanes (9-PBN and 9-NapBN) and the chiral diaminophosphine oxides (DIAPHOXs) derived from aspartic acid have been introduced as useful ligands and preligands, respectively, for transition metal-catalyzed asymmetric synthesis. anti-Selective asymmetric hydrogenation of α-amino-β-ketoesters using Ru-, Rh-, Ir-, and Ni-catalysts through dynamic kinetic resolution have been developed for the first time, producing efficiently important anti β-hydroxy-α-amino acids. The total synthesis of several biologically active natural products was achieved by use of the transition metal-catalyzed reaction using DIAPHOX, anti-selective asymmetric hydrogenation, and reactions developed by us. Synthesis of tangutorine, an antitumor indole alkaloid, has been enantioselectively achieved for the first time. Enantioselective synthesis of a martinelline chiral core was accomplished using the asymmetric tandem Michael-Aldol reaction as a key step developed by us. This synthesis represents the formal total synthesis of martinelline and martinellic acid. Papuamide B was synthesized through the elucidation of unknown stereostructures by using the anti-selective asymmetric hydrogenation and reactions developed by us.

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Total Syntheses of (−)-Mesembrane and (−)-Mesembrine via Palladium-Catalyzed Enantioselective Allylic Substitution and Zirconium-Promoted Cyclization

Cited by 87 publications

References 32 publications

Palladium‐Catalyzed Enantioselective Desymmetrizing Aza‐Wacker Reaction: Development and Application to the Total Synthesis of (−)‐Mesembrane and (+)‐Crinane

Palladium‐Catalyzed Enantioselective Desymmetrizing Aza‐Wacker Reaction: Development and Application to the Total Synthesis of (−)‐Mesembrane and (+)‐Crinane

Development of a Novel Synthetic Method for Ring Construction Using Organometallic Complexes and Its Application to the Total Syntheses of Natural Products

Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

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