Copper-catalyzed hydroamination of propargyl imidates

Fricke, Patrick J.; Stasko, Jenna L.; Robbins, Dylan T.; photographer, Gardner, Alexander, ,; Stash, Jacqueline; Ferraro, Mark; Fennie, Michael W.

doi:10.1016/j.tetlet.2017.10.043

Cited by 15 publications

(5 citation statements)

References 20 publications

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“…A degassed solution of toluene containing N -phenylmaleimide or ethyl glyoxylate reacted with the corresponding oxazoline [ 5 ] and thiazoline [ 6 ] methylidenes was heated at reflux overnight and resulted in an ene reaction providing twelve new chiral azole compounds. The detailed processes and reactions are presented elsewhere [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…As outlined in Scheme 1 , racemic analytes were prepared via short two and three-step sequences beginning with readily available propargylic derivatives XIII and XIV. In the case of the oxazole derivatives I-V, ene substrates were prepared through reaction of propargyl alcohol (XIII) with the appropriate nitrile derivative in the presence of HCl, affording the corresponding imidate XV in good-to-excellent yield [ 5 ]. Treatment of the imidates with CuI resulted in hydroamination of the alkyne and formation of the methylidene oxazoles XVI [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

“…In the case of the oxazole derivatives I-V, ene substrates were prepared through reaction of propargyl alcohol (XIII) with the appropriate nitrile derivative in the presence of HCl, affording the corresponding imidate XV in good-to-excellent yield [ 5 ]. Treatment of the imidates with CuI resulted in hydroamination of the alkyne and formation of the methylidene oxazoles XVI [ 5 ]. Exposure of XVI to either N -phenylmaleimide or ethyl glyoxylate delivered the corresponding ene adducts I-V in modest to good yields [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

“…Pyridines, oxazoles, and thiazoles are aromatic N -containing heterocycles with a six-membered ring with a single N atom, five-membered rings with both O and N heteroatoms, and S and N heteroatoms, respectively [ 3 , 4 ]. The copper-catalyzed hydroamination of propargyl imidates was recently proposed as an efficient way to obtain alkyl-or aryl-substituted dihydrooxazoles providing interesting intermediates for further elaboration [ 5 ]. Recent investigations from our laboratory have focused on the synthesis and reactivity of “pre-aromatic” heterocycles derived from propargylic systems [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Enantiomeric Separation of New Chiral Azole Compounds

et al. 2021

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Twelve new azole compounds were synthesized through an ene reaction involving methylidene heterocycles and phenylmaleimide, producing four oxazoles, five thiazoles, and one pyridine derivative, and ethyl glyoxylate for an oxazole and a thiazole compound. The twelve azoles have a stereogenic center in their structure. Hence, a method to separate the enantiomeric pairs, must be provided if any further study of chemical and pharmacological importance of these compounds is to be accomplished. Six chiral stationary phases were assayed: four were based on macrocyclic glycopeptide selectors and two on linear carbohydrates, i.e., derivatized maltodextrin and amylose. The enantiomers of the entire set of new chiral azole compounds were separated using three different mobile phase elution modes: normal phase, polar organic, and reversed phase. The most effective chiral stationary phase was the MaltoShell column, which was able to separate ten of the twelve compounds in one elution mode or another. Structural similarities in the newly synthesized oxazoles provided some insights into possible chiral recognition mechanisms.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enantiomeric Separation of New Chiral Azole Compounds

et al. 2021

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“…Overman and co-workers reported a thermal- or DBU-promoted cyclization of propargyl imidates, affording oxazolines (Scheme a). Recently, an analogous transformation was performed via copper iodide catalysis (Scheme b). The formation of six-membered rings was restricted to trichloroacetimidates and occurred via gold or silver catalysis (Scheme c).…”

Section: Introductionmentioning

confidence: 99%

DBU-Catalyzed Alkyne–Imidate Cyclization toward 1-Alkoxypyrazino[1,2-a]indole Synthesis

et al. 2018

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1-(Propargyl)indol-2-carbonitriles react with alcohols to afford 1-alkoxypyrazino[1,2- a]indoles under DBU-catalyzed microwave-assisted conditions. The reaction scope includes a wide range of indoles, primary and secondary alcohols, and a thiol. The initial mechanistic study shows that the domino process presumably proceeds through an alkyne-allene rearrangement, imidate formation, and nucleophilic cyclization reaction sequence.

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Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

et al. 2019

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Described herein is an asymmetric allylic aromatization (AAAr) strategy that employs readily accessible equivalents of benzylic nucleophiles in iridium-catalyzed allylic substitution reactions with the concomitant formation of aromatic rings by aromatization. The optimizedr eaction conditions involving ac atalyst derived from ac ommercially available iridium precursor and the Carreira ligand are compatible with equivalents of benzylic nucleophiles derived from 4-or 5-methyloxazoles,5 -methylthiazoles,4 -o r5methylfurans,2 -o r3 -methylbenzofurans,3 -methylbenzothiophene,3 -methylindole,1 -methylnaphthalene,a nd methylbenzene. This strategy provides straightforwarda ccesses to valuable heterocyclic aromatic compounds,b earing ah omobenzylic stereogenic center,inanenantiopure form and would be difficult to access otherwise.T he versatility of the reaction was showcased by the further elaboration of the products into useful building blocks and adrug analogue.

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Copper-catalyzed hydroamination of propargyl imidates

Cited by 15 publications

References 20 publications

Enantiomeric Separation of New Chiral Azole Compounds

Enantiomeric Separation of New Chiral Azole Compounds

DBU-Catalyzed Alkyne–Imidate Cyclization toward 1-Alkoxypyrazino[1,2-a]indole Synthesis

Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

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