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.

Attention:

The NSF Public Access Repository (PAR) system and access will be unavailable from 9:30 PM ET on Friday, January 23 until 7:00 AM ET on Saturday, January 24 due to maintenance. We apologize for the inconvenience.

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


Title: Palladium-catalyzed benzylic C(sp 3 )–H carbonylative arylation of azaarylmethyl amines with aryl bromides
A highly selective palladium-catalyzed carbonylative arylation of weakly acidic benzylic C(sp 3 )–H bonds of azaarylmethylamines with aryl bromides under 1 atm of CO gas has been achieved. This work represents the first examples of use of such weakly acidic pronucleophiles in this class of transformations. In the presence of a NIXANTPHOS-based palladium catalyst, this one-pot cascade process allows a range of azaarylmethylamines containing pyridyl, quinolinyl and pyrimidyl moieties and acyclic and cyclic amines to undergo efficient reactions with aryl bromides and CO to provide α-amino aryl-azaarylmethyl ketones in moderate to high yields with a broad substrate scope and good tolerance of functional groups. This reaction proceeds via in situ reversible deprotonation of the benzylic C–H bonds to give the active carbanions, thereby avoiding prefunctionalized organometallic reagents and generation of additional waste. Importantly, the operational simplicity, scalability and diversity of the products highlight the potential applicability of this protocol.  more » « less
Award ID(s):
1902509
PAR ID:
10348058
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Chemical Science
Volume:
12
Issue:
32
ISSN:
2041-6520
Page Range / eLocation ID:
10862 to 10870
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; ; (, Chemical Science)
    A unique C(sp 3 )–H/C(sp 3 )–H dehydrocoupling of N -benzylimines with saturated heterocycles is described. Using super electron donor (SED) 2-azaallyl anions and aryl iodides as electron acceptors, single-electron-transfer (SET) generates an aryl radical. Hydrogen atom transfer (HAT) from saturated heterocycles or toluenes to the aryl radical generates alkyl radicals or benzylic radicals, respectively. The newly formed alkyl radicals and benzylic radicals couple with the 2-azaallyl radicals with formation of new C–C bonds. Experimental evidence supports the key hydrogen-abstraction by the aryl radical, which determines the chemoselectivity of the radical–radical coupling reaction. It is noteworthy that this procedure avoids the use of traditional strong oxidants and transition metals. 
    more » « less
  2. ; ; ; ; (, Chemistry – A European Journal)
    Palladium‐catalyzed aryl amination and Heck arylation reactions are complementary transformations, generally requiring a suitable catalyst combination and a base. With substrates containing both an amino group and a vinyl moiety, control of C─N versus C─C reactivity can lead to regiodivergent functionalizations. With this focus, reactions of silyl‐protected 8‐vinyl 2'‐deoxyadenosine and adenosine with aryl bromides and iodides have been studied. Pd(OAc)2, Pd2(dba)3, and preformed dichloro[1,1′‐bis(di‐t‐butylphosphino)ferrocene]palladium (II) (Pd‐118) were evaluated as metal sources. Ligands tested were Xantphos, DPEphos, BIPHEP, and DPPF, with Cs2CO3and K3PO4as bases. In toluene as solvent, the Pd(OAc)2/Xantphos/Cs2CO3combination was uniquely capable of predominantN6arylation. Aryl bromides and iodides gave comparable product yields. Replacement of Cs2CO3with K3PO4redirected arylation from the nitrogen atom to the vinyl carbon atom, and all other catalyst, ligand, and base combinations gave Cvinylarylation as well. Simply switching from Pd(OAc)2to Pd2(dba)3resulted in loss of theN6‐selectivity and Cvinylarylation was favored. Based upon these results, using two structurally similar catalytic systems sequential CvinylandN6arylations of the nucleosides were accomplished. Some of the products were converted to other novel nucleoside analogues. Because some compounds were fluorescent, their photophysical properties were assessed experimentally and computationally. 
    more » « less
  3. ; ; ; (, Organic Letters)
    Herein we report the palladium-catalyzed borylation of aryl halides (iodides or bromides) under base-free conditions utilizing a commercially available Lewis acidic mediator, Zn(OTf)2. Under these conditions, an array of electronically and functional group-diverse aryl iodides and bromides undergo borylation to afford the corresponding aryl boronic esters in up to 82% isolated yield. Mechanistic investigations are consistent with Zn(OTf)2 enabling transmetalation between a cationic Pd(II)-Ar intermediate and B2pin2 via halide abstraction. Furthermore, stabilization of the cationic [ArPdII]+ complex with added [BArF4]– significantly improves reaction efficiency with electron-poor arenes. 
    more » « less
  4. ; ; ; ; ; ; ; ; (, Organic Chemistry Frontiers)
    The activation of C–O bonds in aryl methyl ethers is a fundamental method for the cross-coupling of carbon–oxygen bonds; however, this process is highly challenging due to the high dissociation energy compared with other phenol derivatives. Herein, we report a mild Ru(0)-catalyzed cleavage of C(aryl)–O bonds enabled by a combination of a Ru 3 (CO) 12 catalyst and an imine auxiliary. This method offers rapid entry to synthetically valuable biaryl aldehydes from abundant anisoles. Broad functional group tolerance is observed using this strategy, including unprecedented tolerance towards aryl bromides. The synthetic utility of this strategy has been demonstrated in sequential processes to construct complex biaryls, exploiting the orthogonal selectivity of C–O bond activation. DFT studies were conducted to provide insight into the selectivity of C–O bond cleavage. This method establishes the mildest approach to C–OMe cross-coupling reported to date. 
    more » « less
  5. ; ; (, Angewandte Chemie International Edition)
    Abstract Electrochemical approaches to form C(sp2)−C(sp3) bonds have focused on coupling C(sp3) electrophiles that form stabilized carbon‐centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp3) coupling partners owing to their availability and cost‐effectiveness, their tendency to undergo radical‐radical homocoupling makes them challenging substrates for electroreductive cross‐coupling. Herein, we disclose a metal‐free regioselective cross‐coupling of 1,4‐dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4‐dicyanobenzene radical anions, leading to negligible homocoupling and high cross‐selectivity to form 1,4‐alkyl cyanobenzenes. The cross‐coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp3) precursors. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Text Encoded Conversion
  • XML
  • Save / Share this Record
  • Send to Email