Development of Palladium-Catalyzed Cycloalkenylation and its Application to Natural Product Synthesis

Toyota, Masahiro; Ihara, Masataka

doi:10.1055/s-2002-32946

Cited by 65 publications

(44 citation statements)

References 27 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10a, 10d, 12d , and 14b , where greater regiocontrol could be expected in the palladium-catalyzed cycloalkenylation. Consistent with literature reports on similar compounds 36–38 , cyclohexenones 10a and 10d afforded a 75 and 66% yield of the cycloalkenylation product upon conversion to an enol silane and exposure to the standard cyclization conditions (10 mol% Pd(OAc) 2 , O 2 , DMSO, 45°C). However, both cycloalkenylation products failed to undergo the Friedel-Crafts alkylation.…”

Section: Resultssupporting

confidence: 89%

“…In the process, the strategy would create ring D and the bicyclo[3.2.1]octane at a later stage, after rings A-C have been generated. To the best of our knowledge, this approach has not previously been used with the palladium-catalyzed cycloalkenylation 35–38 . The Friedel-Crafts alkylation would rely on precedent 39–43 and would be the second example of an intramolecular carbon nucleophile conjugate addition to the enone system of the Birch-Cope sequence product; along with the Rauhut-Currier reaction that we have recently communicated 44, 45 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Use of TBS rather than a TMS protecting group hinders the formation of the dehydrosilylation by‐product that arises from from β‐hydride elimination (Scheme ). The authors speculate37f that the bulky TBS group may hinder the formation of the oxo‐π‐allyl intermediate, thus causing a change in mechanism to backside attack of the silyl enol ether on the coordinated alkene. This methodology has been applied to the total synthesis of several biologically active terpenoid natural products (Figure 1).…”

Section: Oxidation Of Alkenesmentioning

confidence: 99%

CE‐ESI‐MS coupled with dynamic pH junction online concentration for analysis of peptides in human urine samples

Xia

Lin

et al. 2010

Electrophoresis

View full text Add to dashboard Cite

In this article, an approach has been developed for the analysis of some small peptides with similar pI values by CE-ESI-MS based on the online concentration strategy of dynamic pH junction. The factors affected on the separation, detection and online enrichment, such as BGE, injection pressure, sheath flow liquid and separation voltage have been investigated in detail. Under the optimum conditions, i.e. using 0.5 mol/L formic acid (pH 2.15) as the BGE, preparing the sample in 50 mM ammonium acetate solution (pH 7.5), 50 mbar of injection pressure for 300 s, using 7.5 mM of acetic acid in methanol-water (80% v/v) solution as the sheath flow liquid and 20 kV as the separation voltage, four peptides with similar pI values, such as L-Ala-L-Ala (pI = 5.57), L-Leu-D-Leu (pI = 5.52), Gly-D-Phe (pI = 5.52) and Gly-Gly-L-Leu (pI = 5.52) achieved baseline separation within 18.3 min with detection limits in the range of 0.2-2.0 nmol/L. RSDs of peak migration time and peak area were in the range of 1.45-3.57 and 4.93-6.32%, respectively. This method has been applied to the analysis of the four peptides in the spiked urine sample with satisfactory results.

show abstract

“…Recently, we have performed the reaction using a catalytic amount of palladium when the reaction is carried out in DMSO under an oxygen atmosphere (Chart 26). 82,83) With this method, gibberellins 124-126 84) and aphidicolin (127) 85) were effectively synthesized. Finally, syntheses of serofendic acids (136) using the above methodologies are discussed.…”

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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Development of Palladium-Catalyzed Cycloalkenylation and its Application to Natural Product Synthesis

Cited by 65 publications

References 27 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

CE‐ESI‐MS coupled with dynamic pH junction online concentration for analysis of peptides in human urine samples

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

Contact Info

Product

Resources

About