skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Copper( i )-catalyzed tandem synthesis of 4,5-functionalized oxazoles from isocyanoacetate and aldehydes
Oxazoles are among the most important heterocyclic scaffolds in the fields of natural products and medicinal chemistry. Herein is developed a tandem reaction for the synthesis of a diverse array of 4,5-difunctionalized oxazoles utilizing easily-accessible ethyl 2-isocyanoacetate and aldehydes (26 examples, 31–83% yields). This cascade reaction is facilitated by catalytic CuBr and molecular oxygen as the oxidant. The process involves a catalytic cycloaddition oxidative dehydroaromatization mechanism. The broad aldehyde substrate scope, mild reaction conditions, and atom economy make this protocol an attractive alternative to access functionalized oxazoles.  more » « less
Award ID(s):
2154593
PAR ID:
10431725
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
New Journal of Chemistry
Volume:
46
Issue:
35
ISSN:
1144-0546
Page Range / eLocation ID:
16840 to 16843
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; (, Organic Letters)
    ABSTRACT: Studies have described a highly convergent plan toward the synthesis of leiodolide A (1), a potent cytotoxic sponge metabolite. The enantiocontrolled preparation of aldehyde 6 is achieved with the application of several advances of methodology for the synthesis of substituted 1,3-oxazoles. Efforts have examined the halogen dance reaction, the selectivity of Stille cross coupling reactions of 4-bromo-1,3-oxazoles, and nucleophilic displacement of the 2-phenylsulfonyl substitu-ent with organolithium reagents as preparatively useful reactions. These techniques have facilitated the efficient synthesis of 6 from the starting bromide 12, alkenylstannane 16 and the primary nonracemic alcohol 25. 
    more » « less
  2. ; (, Journal of Computational Chemistry)
    ABSTRACT Diacylglycerol O‐acyltransferase 1 (DGAT1) is an integral membrane protein that uses acyl‐coenzyme A (acyl‐CoA) and diacylglycerol (DAG) to catalyze the formation of triacylglycerides (TAGs). The acyl transfer reaction occurs between the activated carboxylate group of the fatty acid and the free hydroxyl group on the glycerol backbone of DAG. However, how the two substrates enter DGAT1's catalytic reaction chamber and interact with DGAT1 remains elusive. This study aims to explore the structural basis of DGAT1's substrate recognition by investigating each substrate's pathway to the reaction chamber. Using a human DGAT1 cryo‐EM structure in complex with an oleoyl‐CoA substrate, we designed two different all‐atom molecular dynamics (MD) simulation systems: DGAT1away(both acyl‐CoA and DAG away from the reaction chamber) and DGAT1bound(acyl‐CoA bound in and DAG away from the reaction chamber). Our DGAT1awaysimulations reveal that acyl‐CoA approaches the reaction chamber via interactions with positively charged residues in transmembrane helix 7. DGAT1boundsimulations show DAGs entering into the reaction chamber from the cytosol leaflet. The bound acyl‐CoA's fatty acid lines up with the headgroup of DAG, which appears to be competent to TAG formation. We then converted them into TAG and coenzyme (CoA) and used adaptive biasing force (ABF) simulations to explore the egress pathways of the products. We identify their escape routes, which are aligned with their respective entry pathways. Visualization of the substrate and product pathways and their interactions with DGAT1 is expected to guide future experimental design to better understand DGAT1 structure and function. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; (, Molecules)
    null (Ed.)
    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. 
    more » « less
  4. ; ; ; ; ; ; ; ; (, Chemical Science)
    A versatile Rh( i )-catalyzed C6-selective decarbonylative C–H alkenylation of 2-pyridones with readily available, and inexpensive alkenyl carboxylic acids has been developed. This directed dehydrogenative cross-coupling reaction affords 6-alkenylated 2-pyridones that would otherwise be difficult to access using conventional C–H functionalization protocols. The reaction occurs with high efficiency and is tolerant of a broad range of functional groups. A wide scope of alkenyl carboxylic acids, including challenging conjugated polyene carboxylic acids, are amenable to this transformation and no addition of external oxidant is required. Mechanistic studies revealed that (1) Boc 2 O acts as the activator for the in situ transformation of the carboxylic acids into anhydrides before oxidative addition by the Rh catalyst, (2) a decarbonylation step is involved in the catalytic cycle, and (3) the C–H bond cleavage is likely the turnover-limiting step. 
    more » « less
  5. ; ; ; ; (, Journal of Polymer Science)
    Abstract DMSO, an interesting solvent for copper‐catalyzed living radical polymerization (LRP) mediated by disproportionation, does not exhibit the greatest disproportionation of Cu(I)X into Cu(0) and Cu(II)X2. Under suitable conditions, DMSO provides 100% conversion and absence of termination, facilitating the development of complex‐architecture methodologies by living and immortal polymerizations. The mechanism yielding this level of precision is being investigated. Here we compare Cu(0)‐wire‐catalyzed LRP of methyl acrylate mediated by disproportionating ligands tris(2‐dimethylaminoethyl)amine, Me6‐TREN, tris(2‐aminoethyl)amine, TREN, and Me6‐TREN/TREN = 1/1 in presence of eight disproportionating solvents, some more efficient than DMSO in disproportionation. Unexpectedly, we observed that all solvents increased the rate of polymerization when monomer concentration decreased. This reversed trend from that of conventional LRPs demonstrates catalytic effect for disproportionating solvents. Above a certain concentration, the classic concentration‐rate dependence was observed. The external order of reaction of the apparent rate constant of propagation,kpappon solvent concentration demonstrated the highest order of reaction for the least disproportionating DMSO. Of all solvents investigated, DMSO has the highest ability to stabilize Cu(0) nanoparticles and therefore, yields the highest activity of Cu(0) nanoparticles rather than their greatest concentration. The implications of the catalytic effect of solvent in this and other reactions were discussed. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email