Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams*.

ABSTRACT: An iridium-catalyzed reductive three-component coupling reaction for the synthesis of medicinally relevant α-amino 1,3,4-oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N-isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol %) Vaska's complex (IrCl(CO)(PPh₃ )₂ ) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of α-amino 1,3,4-oxadiazole architectures were accessed from carboxylic acid feedstock coupling partners. Extension to α-amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C-, S-, or N-centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult-to-access, heterocycles. The high chemoselectivity of the catalytic reductive activation step allowed late-stage functionalization of 10 drug molecules, including the synthesis of heterodiazole-fused drug-drug conjugates.

SUBMITTER: Matheau-Raven D

PROVIDER: S-EPMC8457168 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides and Lactams.

Project description:An iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3 + 2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent regio- and diastereoselective, inter- and intramolecular dipolar cycloaddition reactions with variously substituted electron-deficient alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures, which ultimately control the unusual selectivities observed in certain cases.

| S-EPMC8291578 | biostudies-literature

Mild Reductive Functionalization of Amides into <i>N</i>-Sulfonylformamidines.

Project description:The development of a protocol for the reductive functionalization of amides into N-sulfonylformamidines is reported. The one-pot procedure is based on a mild catalytic reduction of tertiary amides into the corresponding enamines by the use of Mo(CO)6 (molybdenum hexacarbonyl) and TMDS (1,1,3,3-tetramethyldisiloxane). The formed enamines were allowed to react with sulfonyl azides to give the target compounds in moderate to good yields.

| S-EPMC5542752 | biostudies-literature

Iridium-catalyzed reductive Ugi-type reactions of tertiary amides.

Project description:Amides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of chemical transformations routinely used in organic synthesis. Accordingly, the development of chemoselective carbon-carbon bond-forming methodologies arising from the functionalization of the amide functionality should find widespread use across academia and industry. We herein present our findings on a series of Ugi-type reactions of tertiary amides enabled by an initial chemoselective iridium-catalyzed partial reduction, followed by reaction with isocyanide and (thio)acetic acid or trimethylsilyl azide, thus providing a multicomponent synthesis of α-amino (thio)amide or α-amino tetrazole derivatives. The reductive Ugi-type reactions are amenable to a broad range of amides and isocyanides, and are applicable to late-stage functionalization of various bioactive molecules and pharmaceutical compounds.

| S-EPMC6053461 | biostudies-literature

Solid-phase synthesis of diverse peptide tertiary amides by reductive amination.

Project description:The synthesis of libraries of conformationally constrained peptide-like oligomers is an important goal in combinatorial chemistry. In this regard an attractive building block is the N-alkylated peptide, also known as a peptide tertiary amide (PTA). PTAs are conformationally constrained because of allylic 1,3 strain interactions. We report here an improved synthesis of these species on solid supports through the use of reductive amination chemistry using amino acid-terminated, bead-displayed oligomers and diverse aldehydes. The utility of this chemistry is demonstrated by the synthesis of a library of 10,000 mixed peptoid-PTA oligomers.

| S-EPMC4447181 | biostudies-literature

Tertiary amine synthesis via reductive coupling of amides with Grignard reagents.

Project description:A new iridium catalyzed reductive coupling reaction of Grignard reagents and tertiary amides affording functionalised tertiary amine products via an efficient and technically-simple one-pot, two-stage experimental protocol, is reported. The reaction - which can be carried out on gram-scale using as little as 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and TMDS as the terminal reductant for the initial reductive activation step - tolerates a broad range of tertiary amides from (hetero)aromatic to aliphatic (branched, unbranched and formyl) and a wide variety of alkyl (linear, branched), vinyl, alkynyl and (hetero)aryl Grignard reagents. The new methodology has been applied directly to bioactive molecule synthesis and the high chemoselectivity of the reductive coupling of amide has been exploited in late stage functionalization of drug molecules. This reductive functionalisation of tertiary amides provides a new and practical solution to tertiary amine synthesis.

| S-EPMC5676097 | biostudies-literature

?-Amino functionalization of cinnamic Weinreb amides in ionic liquid.

Project description:2-Ns-Protected ?-amino Weinreb amides were synthesized by aminochlorination of ?,?-unsaturated Weinreb amides in an ionic liquid, 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([BMIM][NTf2]). Processed without the use of metal catalysts or the need of an inert gas atmosphere, the presented process can be readily performed as a one-pot synthesis at room temperature. Moreover, the preparation has the distinct advantages of the use of 2-NsNCl2 as an inexpensive and stable nitrogen/halogen source and the ionic liquid as a recyclable reaction media. Nine examples were examined, and modest to good isolated chemical yields (40-83%) were obtained.

| S-EPMC5238596 | biostudies-literature

Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization.

Project description:Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species.

| S-EPMC4629799 | biostudies-literature

Bis{μ-2,5-bis-[4-(2-pyridylmethyl-amino)phen-yl]-1,3,4-oxadiazole}bis-[dichlorido-mercury(II)].

Project description:In the title centrosymmetric compound, [Hg(2)Cl(4)(C(26)H(22)N(6)O)(2)], each Hg(II) center adopts a distorted HgN(3)Cl(2) trigonal bipyramidal coordination geometry, formed by two pyridine N atoms, one imine N atom and two chloride anions. Within the organic ligand, the oxadiazole ring is nearly coplanar with the two benzene rings [dihedral angles = 5.9 (4) and 6.5 (4)°] and nearly perpendicular to the two pyridine rings with the same dihedral angle of 77.4 (4)°. The two organic ligands bridge two Hg(II) ions to form the macrocyclic complex. Inter-molecular N-H⋯Cl and N-H⋯N hydrogen bonding helps to stabilize the crystal structure.

| S-EPMC2961020 | biostudies-literature

Towards a general ruthenium-catalyzed hydrogenation of secondary and tertiary amides to amines.

Project description:A broad range of secondary and tertiary amides has been hydrogenated to the corresponding amines under mild conditions using an in situ catalyst generated by combining [Ru(acac)3], 1,1,1-tris(diphenylphosphinomethyl)ethane (Triphos) and Yb(OTf)3. The presence of the metal triflate allows to mitigate reaction conditions compared to previous reports thus improving yields and selectivities in the desired amines. The excellent isolated yields of two scale-up experiments corroborate the feasibility of the reaction protocol. Control experiments indicate that, after the initial reduction of the amide carbonyl group, the reaction proceeds through the reductive amination of the alcohol with the amine arising from collapse of the intermediate hemiaminal.

| S-EPMC6006866 | biostudies-literature

2-Phenyl-5-(p-tol-yl)-1,3,4-oxadiazole.

Project description:The title compound, C(15)H(12)N(2)O, adopts the expected near-planar geometry, the phenyl and tolyl rings being inclined relative to the oxadiazole ring by 3.8 (3) and 8.3 (2)°, respectively. This allows adjacent mol-ecules to pack in a parallel fashion and form stacking along [010] via π-π inter-actions [centroid-centroid distances = 3.629 (2) and 3.723 (2) Å]. Further inter-molecular inter-actions include C-H⋯π inter-actions and weak C-H⋯N hydrogen bonds, giving rise to a crossed herringbone packing motif.

| S-EPMC3152068 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data