Introducing a New Class of <i>N-</i>Phosphoryl Ynamides via Cu(I)-Catalyzed Amidations of Alkynyl Bromides

DeKorver, Kyle A.; Walton, Mary C.; North, Troy D.; Hsung, Richard P.

doi:10.1021/ol201947b

Cited by 53 publications

(32 citation statements)

References 41 publications

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“…[64] In contrast, phosphoramidate-derived ynamides 14, recently introduced by Hsung and co-workers as attractivea lternatives to the N-sulfonyl patterns,proved effective. [65] Oxazoles 18 were formed in high yield even with more functionalised aminides 6k and 6l. Despite such systems not having been previously employed in gold catalysis, the reactiono fN-alkynylinScheme 5.…”

Section: The Ynamidementioning

confidence: 97%

Efficient and Flexible Synthesis of Highly Functionalised 4‐Aminooxazoles by a Gold‐Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition

2016

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Oxazolesa re important motifs within bioactive and functional materials.C omplex, fully substituteda nd functionalised 4-aminooxazoles are accessed by an efficienti ntermolecular reactionb etween an ynamide and an N-acylpyridinium N-aminide in the presence of ag old catalyst. Thef ormal [3+ +2] dipolar cycloaddition employs an ucleophilic nitrenoid approach to access the 1,3-N,O-dipole character in ac ontrollable fashion.T he selectivity for ac ycloaddition pathwayp rovides as tark contrast against the indiscriminate reactivity of electrophilic acyl nitrenes.P rotocolsf or the formation of acylfunctionalised aminides are reported from accessible precursors including carboxylic estersa nd acids.T he function of these aminides in the oxazole-forming reaction has been exploreda nd it is shown that substantial elaboration is accommodated despite proximity to the reactivec entre.A saresult functional oxazole-based motifs,s uch as chiral oxazoles with biologically pertinent substitution patterns,a re readily accessible.T he use of ynamide types that are unexplored or little used in gold catalysis has been evaluated. Unusual all-heteroatom substitution patterns around the oxazole are shown to be accessible using thio-ynamides.T he studys hows that ac lose stoichiometry of reactantsi ss uitable alongsider elatively low loadings of the bench-stable precatalysts in practicallys traightforward multi-mmol scale reactions.T he efficiency and flexibility of this regioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.

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Section: The Ynamidementioning

confidence: 97%

Efficient and Flexible Synthesis of Highly Functionalised 4‐Aminooxazoles by a Gold‐Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition

2016

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“…DeKorver and Hsung 69 described a moderately stereoselective Staudinger-type ketenimine-imine [2 + 2] cycloaddition using N -phosphoryl ynamide 313 giving azetidin-2-imine 315 bearing a quaternary carbon center (Scheme 60). The ketenimine intermediate 314 was generated in situ via an aza- Claisen reaction.…”

Section: Rearrangementsmentioning

confidence: 99%

Ynamides in Ring Forming Transformations

et al. 2013

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Conspectus The ynamide functional group activates carbon-carbon triple bonds through an attached nitrogen atom that bears an electron-withdrawing group. As a result, the alkyne has both electrophilic and nucleophilic properties. Through the selection of the electron-withdrawing group attached to nitrogen chemists can modulate the electronic properties and reactivity of ynamides, making these groups versatile synthetic building blocks. The reactions of ynamides also lead directly to nitrogen-containing products, which provides access to important structural motifs found in natural products and molecules of medicinal interest. Therefore, researchers have invested increasing time and research in the chemistry of ynamides in recent years. This Account surveys and assesses new organic transformations involving ynamides developed in our laboratory and in others around the world. We showcase the synthetic power of ynamides for rapid assembly of complex molecular structures. Among the recent reports of ynamide transformations, ring-forming reactions provide a powerful tool for generating molecular complexity quickly. In addition to their synthetic utility, such reactions are mechanistically interesting. Therefore, we focus primarily on the cyclization chemistry of ynamides. This Account highlights ynamide reactions that are useful in the rapid synthesis of cyclic and polycyclic structural manifolds. We discuss the mechanisms active in the ring formations and describe representative examples that demonstrate the scope of these reactions and provide mechanistic insights. In this discussion we feature examples of ynamide reactions involving radical cyclizations, ring-closing metathesis, transition metal and non-transition metal mediated cyclizations, cycloaddition reactions, and rearrangements. The transformations presented rapidly introduce structural complexity and include nitrogen within, or in close proximity to, a newly formed ring (or rings). Thus, ynamides have emerged as powerful synthons for nitrogen-containing heterocycles and nitrogen-substituted rings, and we hope this Account will promote continued interest in the chemistry of ynamides.

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“…1–3 In our own effort during the past several years, we have been heavily interested in using Pd-catalyzed and thermal aza -Claisen 4,5 rearrangements as a means of activating N -allyl ynamides towards (1) nucleophilic additions of amines 6 and alcohols, 7 (2) inter- 8 and intramolecular 9 [2 + 2] cycloaddition reactions, (3) skeletal rearrangements yielding nitriles, 6c and (4) carbocyclizations 10 and cationic polyene cascades.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Cyclopentenimines from N-Allyl Ynamides via a Tandem Aza-Claisen Rearrangement–Carbocyclization Sequence

et al. 2013

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We describe here details of our investigations into Pd-catalyzed and thermal aza-Claisen–carbocyclizations of N-allyl ynamides to prepare a variety of α,β-unsaturated cyclopentenimines. The nature of the ynamide electron withdrawing group and β-substituent plays critical roles in the success of this tandem cascade. With N-sulfonyl ynamides, the use of palladium catalysis is required, as facile 1,3-sulfonyl shifts dominate under thermal conditions. However, since no analogous 1,3-phosphoryl shift is operational, N-phosphoryl ynamides could be used to prepare similar cyclopentenimines under thermal conditions through zwitter ionic intermediates that undergo N-promoted H-shifts. Alternatively, by employing ynamides bearing tethered carbon nucleophiles, the zwitter ionic intermediates could be intercepted giving rise rapidly to more complex fused bi- and tricyclic scaffolds.

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Introducing a New Class of N-Phosphoryl Ynamides via Cu(I)-Catalyzed Amidations of Alkynyl Bromides

Cited by 53 publications

References 41 publications

Efficient and Flexible Synthesis of Highly Functionalised 4‐Aminooxazoles by a Gold‐Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition

Efficient and Flexible Synthesis of Highly Functionalised 4‐Aminooxazoles by a Gold‐Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition

Ynamides in Ring Forming Transformations

Synthesis of Cyclopentenimines from N-Allyl Ynamides via a Tandem Aza-Claisen Rearrangement–Carbocyclization Sequence

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