Palladium-Catalyzed Cross-Coupling of Terminal Alkynes with 4-Trifloyloxazole:  Studies toward the Construction of the C26−C31 Subunit of Phorboxazole A

Schaus, Jennifer V.; Panek, James S.

doi:10.1021/ol991306h

Cited by 60 publications

(18 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the supply of material from natural sources is severely limited, a significant effort toward the preparation of phorboxazoles has been launched within the international organic synthesis community. The unprecedented structural features have provided the impetus for several exploratory studies (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Recent total syntheses of phorboxazole A (23-27) and phorboxazole B (28,29) have been reported.…”

Section: Resultsmentioning

confidence: 99%

“…Generation of aldehyde 19 led to the second asymmetric allylation with stannane 7 and the (S,S)-1,2-diamino-1,2-diphenylethane bissulfonamide controller (20) to produce polyol derivative 21 in 96% yield [92:8 diastereomeric ratio (dr)]. In this case, cyclization by inversion at C9 directly yielded the desired 2,6-trans-pyran 23 after PMB deprotection.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A

Williams

Kir'yanov

Emde

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A highly convergent total synthesis of the potent anticancer agent (؉)-phorboxazole A (1) is accomplished. Four components (3-6) are assembled with considerations for control of absolute and relative stereochemistry. Iterative asymmetric allylation methodology addresses key stereochemical features in the preparation of the 2,6-cisand 2,6-trans-tetrahydropyranyl rings of the C3-C19 component (3). The stereocontrolled asymmetric allylation process is also used for development of the C28 -C41 fragment (4). Novel Barbier coupling reactions of ␣-iodomethyl oxazoles and related thiazoles are described with samarium iodide. The convergent assembly of components 4 and 5 features formation of the fully substituted C22-C26 pyran by intramolecular capture of an allyl cation intermediate with high facial selectivity, and further efforts lead to E-C19͞C20 olefination. The synthesis culminates with use of a modified Julia olefination for attachment of the C42-C46 segment and subsequent late-stage macrocyclization by installation of the (Z)-C2͞C3 ␣,␤-unsaturated lactone. P horboxazoles A (1) and B (2) are natural product diastereoisomers from extracts of the rare Indian Ocean sponge Phorbas sp., which is found near Muiron Island off the coast of Western Australia (1). These unique macrolides exhibit an unusual array of structural features, including a 21-membered macrocyclic lactone that accommodates four adjoining smaller rings along its perimeter. This feature includes a 2,4-disubstituted oxazole, the pentasubstituted tetrahydropyran containing the C22-C26 segment, and the 2,6-cis-and 2,6-trans-disubstituted pyranyl rings installed along the C5 to C15 backbone. A highly unsaturated side chain (C27-C46) comprises nearly one-half of the total carbon atoms of the molecular architecture. This portion of the structure displays a conjugated oxazole and the tetrahydropyranyl ketal terminating with an Ealkenyl bromide. The relative stereochemistry within the macrolide of 1 and 2 was assigned by extensive 2D NMR spectroscopy (1, 2), and the absolute configuration of the macrocycle and the C33-C38 stereochemistry was reported subsequently (3). Finally, the elusive C43 stereochemistry was determined by degradation studies completing the structural elucidation of these novel natural products (4, 5).Phorboxazoles display unprecedented cytostatic activity against all 60 cell lines of the National Cancer Institute human cancer test panel with a mean GI 50 of 1.58 nM. Thus, these compounds rank among the most potent cytostatic agents discovered to date. . Although a mechanism to account for the biological action of these agents is currently uncharted, phorboxazole A does not inhibit microtubulin polymerization or affect microtubule stabilization. Moreover, phorboxazole A has been shown to arrest the cell cycle of Burkitt lymphoma CA46 cultures in S phase (4). Thus, the extraordinary anticancer activity of these metabolites suggests unique opportunities and insights for the discovery of new chemotherapeutic agents. Materials and MethodsA des...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A

Williams

Kir'yanov

Emde

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…A melhor opção de base para as fosfinamidas terciárias é tBuLi, por seu maior impedimento estérico e elevada reatividade a -90°C. 42 A conversão conseguida nas reações de metalação-adição eletrofílica sobre os substratos 7 e 9 está compreendida entre 73 e 84% para eletrófilos como PhCHO, Me 3 SnCl e MeI. No caso das fosfinamidas 9 e 10 se empregou uma quantidade mais ampla de eletrófilos com o propósito de alcançar uma maior diastereosseletividade.…”

Section: Figura 1 Fosfinamidas Utilizadas Para O Estudo Da Desprotonunclassified

General Principles ofortho-Lithiation in Arylphosphinamides

Bastos¹,

Popovici²,

Souza³

et al. 2014

Revista Virtual De Química

View full text Add to dashboard Cite

General Principles of ortho-Lithiation in ArylphosphinamidesAbstract: The development of alternatives to render the ortho-lithiation reaction of arylphosphinamides a diastereoselective and enantioselective process turned this class well explored among the organophosphorus compounds. The use of organolithium bases is the most suitable method for ortho functionalization in aromatic systems. In general, the reaction proceeds in two stages. Firstly, the removal of the ortho hydrogen promoted by the organolithium base takes place, followed by electrophilic neutralization leading to the formation of 1,2-disubstituted product. The improvement of the potential of the organolithium bases is often achieved by using chelating agents, such as N,N,N',N'-tetramethylethylenediamine (TMEDA) and (-)sparteine. Despite being subject of many theoretical and experimental studies, the mechanism of ortho-metallation remains controversial. Therefore, this paper will discuss the main mechanisms involved in the orthometallation of arylphosphinamides as well as the processes of synthesis of this class of organophosphorus compounds.Keywords: ortho-lithiation; mechanism; phosphinamide. ResumoO desenvolvimento de alternativas para que a reação de orto-litiação de arilfosfinamidas transcorresse de modo diastereosseletivo e enantiosseletivo tornou esta classe bem explorada entre os organofosforados. A utilização de bases organolíticas é o método mais adequado de funcionalização na posição orto de sistemas aromáticos. De forma geral a reação acontece em duas etapas. Na primeira ocorre a abstração do próton orto pela base organolítica, seguindo-se à neutralização eletrofílica, que implica na formação do produto 1,2-dissubstituído. O melhoramento do potencial das bases organolíticas muitas das vezes é alcançado utilizando agentes quelantes, tais como

show abstract

“…[101] 3294 Scheme 45. Carboalumination of an alkyne followed by Pd-catalyzed coupling with the triflate gave the alkenyloxazole 133 with the desired E-stereochemistry (Scheme 45).…”

Section: Carboaluminationmentioning

confidence: 99%

“…Alternatively, a Stille method was investigated, which finally afforded the desired compound. [101] 3294 Scheme 45.…”

Section: Carboaluminationmentioning

confidence: 99%

Cross‐Coupling Reactions on Azoles with Two and More Heteroatoms

et al. 2006

View full text Add to dashboard Cite

Recent progress in the field of transition‐metal‐catalyzed cross‐coupling reactions on various azole systems is summarized. Most important C–C‐ and C–X‐bond formation methodologies (Negishi, Suzuki–Miyaura, Stille, Kumada–Corriu–Tamao, Hiyama, Sonogashira, Heck, C–H activation) are reviewed and discussed for the imidazole, oxazole, thiazole, pyrazole, isoxazole, and isothiazole system, as well as for azoles with more than two heteroatoms. This review covers the literature that appeared in the past ten years up to the end of 2005 with corresponding azoles used either as metal organyl or halide (including triflates and some other less frequently applied leaving groups); literature describing azole structures only as ligands was not included.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

show abstract

Palladium-Catalyzed Cross-Coupling of Terminal Alkynes with 4-Trifloyloxazole: Studies toward the Construction of the C26−C31 Subunit of Phorboxazole A

Cited by 60 publications

References 9 publications

Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A

Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A

General Principles ofortho-Lithiation in Arylphosphinamides

Cross‐Coupling Reactions on Azoles with Two and More Heteroatoms

Contact Info

Product

Resources

About