Intramolecular Pd‐Catalyzed Formal <i>anti</i>‐Carboalkoxylation of Alkynes: Access to Tetrasubstituted Enol Ethers

Schitter, Theresa; Jones, Peter G.; Werz, Daniel B.

doi:10.1002/chem.201803721

Cited by 25 publications

(14 citation statements)

References 77 publications

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“…There are several precedents in the literature of related Pd-catalyzed cascade reactions involving the syn carbopalladation of alkynes and subsequent isomerization prior to the final C–Pd bond functionalization. 14 , 22 , 25 , 63 − 67 Generally, the isomerization of the alkenyl-Pd intermediates is driven by steric factors. Nevertheless, α-alkyl-substituted alkynyl substrates, such as 1a , require the use of bulky phosphine ligands (Q-Phos, X-Phos, or P t Bu 3 among others) to increase the steric hindrance around the Pd center and therefore promote the isomerization.…”

Section: Results and Discussionmentioning

confidence: 99%

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

et al. 2022

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We report a Pd-catalyzed route to heterocycles bearing a tetrasubstituted alkene fragment. Our approach merges the intramolecular carbopalladation of tethered alkynes with an alkylation step produced by the C–C cleavage of cyclobutanol derivatives. An alkenyl-Pd(II) intermediate has been isolated and characterized by X-ray diffraction studies. Interestingly, the nature of the tethering alkynyl chain influences the E / Z stereochemistry of the alkenyl fragment in the functionalized heterocycles.

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Section: Results and Discussionmentioning

confidence: 99%

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

et al. 2022

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“…[11] Isomerization of the vinylapalladium intermediate formed by intramolecular insertion of the triple bond into the Ar-PdBr bond permitted the second annulation process, which occurred through the formation of a palladacycle followed by reductive elimination (Scheme 8). [11] Scheme 8. Synthesis of tricyclic enol ethers starting from aryl bromides bearing a triple bond and an hydroxyl in suitable positions.…”

Section: Oxidative Addition Of Ar-x To Pd(0) Followed By Carbocyclizamentioning

confidence: 99%

“…Another example concerns the synthesis of tricyclic enol ethers starting from the corresponding aryl bromides bearing a triple bond and an hydroxyl in suitable positions (Scheme ) . Isomerization of the vinylapalladium intermediate formed by intramolecular insertion of the triple bond into the Ar–PdBr bond permitted the second annulation process, which occurred through the formation of a palladacycle followed by reductive elimination (Scheme ) …”

Section: Pd(0)‐catalyzed Processesmentioning

confidence: 99%

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Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances

et al. 2019

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In this minireview, we discuss some recently reported methods for the synthesis of polycyclic heterocycles by palladium‐catalyzed double cyclization processes. Paradigmatic examples taken by the most recent literature (from 2014 to the beginning of 2019) are presented. Only transformations in which palladium is involved in at least one cyclization stage are taken into consideration. The first part deals will Pd(0)‐catalyzed processes. Double cyclizations initiated by the oxidative addition of an Ar–X bond or other functional groups are treated first, followed by processes beginning with carbopalladation by Pd(0) attack to unsaturated bonds. The second part concerns Pd(II)‐catalyzed reactions, and begins with double cyclizations initiated by intramolecular nucleophilic attack to unsaturated bonds coordinated to Pd(II), followed by processes initiated by aromatic palladation.

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“…Thereby, ketals of type 44 were formed (Scheme 18). 20 By shortening the length of the tether connecting the alkyne and the hydroxy group to two carbon atoms, a broad variety of highly substituted furans 48 was accessed (Scheme 19). 21 The previously reported Pd-catalyzed domino process was extended by an elimination leading to aromatization.…”

Section: Termination With Heteronucleophilesmentioning

confidence: 99%

Cascades Involving anti-Carbopalladation Steps: From Our Initial Hypothesis to Natural Product Synthesis

Schitter¹,

Reding²,

Werz

2019

Synlett

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Our endeavors in the design, realization and application of a formal anti-carbopalladation of alkynes are summarized. Whereas numerous examples of syn-carbopalladation steps embedded in cascade reactions are known, there have been almost no examples of the corresponding anti-carbopalladation steps. From a personal perspective, this account provides insights on the original considerations and hypotheses, and their validation or invalidation by experimental and computational means. This account also aims at clarifying how different ideas have been developed and how novel reaction sequences paving the way to a plethora of different scaffolds have been designed. The reader will recognize the importance of the interplay between elucidating reaction mechanisms and developing novel methodologies. As a result, useful methods to create homo- and heterotetrasubstituted double bonds have been developed. The broad versatility of these methods has been demonstrated by a novel total synthesis of the indole alkaloid (+)-lysergol.1 Introduction2 Initial Studies3 Various Termination Steps4 Termination with Heteronucleophiles5 Natural Product Synthesis6 anti-Carbopalladations Realized by the Lautens Lab7 Conclusion and Outlook

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Intramolecular Pd‐Catalyzed Formal anti‐Carboalkoxylation of Alkynes: Access to Tetrasubstituted Enol Ethers

Cited by 25 publications

References 77 publications

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances

Cascades Involving anti-Carbopalladation Steps: From Our Initial Hypothesis to Natural Product Synthesis

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