skip to main content

Explore Research Products in the NSF-PAR

Title: Fe-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and Grignard reagents
A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp 2 -hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp 2 -hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C–C bonds.  more » « less
Award ID(s):
1751568
NSF-PAR ID:
10214131
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Chemical Science
Volume:
11
Issue:
31
ISSN:
2041-6520
Page Range / eLocation ID:
8301 to 8305
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; ; ; et al ( , Asian Journal of Organic Chemistry)
    Abstract

    A direct and convenient method for the palladium‐catalyzed reductive cross‐coupling of aryl iodides or alkenyl bromides and secondary benzyl halides under ambient CO pressure to generate a diverse array of aryl/alkenyl alkyl ketones has been developed. This strategy successfully achieves a three‐component carbonylative reaction with Zn as the reducing agent for C−C bond formation, overcoming the well‐known homocoupling of aryl or alkenyl halides, direct cross‐coupling between two different electrophiles and other carbonylative coupling reactions. In addition, this method avoids use of preformed organometallic nucleophiles, such as organo‐magnesium, zinc and boron reagents. This approach enables the construction of valuable aryl alkyl/alkenyl ketone derivatives (60 examples, 56–95% yields). Reactivity studies indicate that in situ formed benzylic zinc reagents are intermediates in the catalytic system.

     
    more » « less
  2. ; ; ; ( , Chemical Communications)
    An iron-catalyzed regioselective dicarbofunctionalization of electron-rich alkenes is described. In particular, aryl- and alkyl vinyl ethers are used as effective linchpins to couple alkyl or (fluoro)alkyl halides and sp 2 -hybridized Grignard nucleophiles. Preliminary results demonstrate the ability to engage thioethers as linchpins and control enantioselectivity in these transformations, an area which is largely unexplored in iron-catalyzed three-component cross-coupling reactions. 
    more » « less
  3. ; ; ; ; ; ; ( , Chemical Science)
    null (Ed.)
    Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized via a mechanistically driven approach. Mechanistic studies support the diffusion of alkyl radical intermediates out of the solvent cage to participate in an intra- or intermolecular radical cascade with a range of VCPs followed by re-entering the Fe radical cross-coupling cycle to undergo (stereo)selective C(sp 2 )–C(sp 3 ) bond formation. This work provides a proof-of-concept of the use of vinyl cyclopropanes as synthetically useful 1,5-synthons in Fe-catalyzed conjunctive cross-couplings with alkyl halides and aryl/vinyl Grignard reagents. Overall, we provide new design principles for Fe-mediated radical processes and underscore the potential of using combined computations and experiments to accelerate the development of challenging transformations. 
    more » « less
  4. ; ; ; ; ; ; ( , Nature Communications)
    null (Ed.)
    Abstract Despite remarkable recent advances in transition-metal-catalyzed C(sp 3 )−C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary -C(sp 3 )−C bonds, presumably due to unfavorable steric interactions and competing isomerizations of tertiary alkyl metal intermediates. Reported herein is a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary centers. This approach enables the facile construction of otherwise difficult to prepare all-carbon quaternary centers. Key to the success of this transformation is an unusual remote functionalization via chain walking to the most sterically hindered tertiary C(sp 3 ) center of the substrate. Preliminary mechanistic and radical trapping studies with primary alkyl bromides suggest a unique mode of tertiary C-radical generation through chain-walking followed by Ni–C bond homolysis. This strategy is complementary to the existing coupling protocols with tert -alkyl organometallic or -alkyl halide reagents, and it enables the expedient formation of quaternary centers from easily available starting materials. 
    more » « less
  5. ; ; ; ( , Advanced Synthesis & Catalysis)
    Abstract

    Aryl tosylates are an attractive class of electrophiles for cross‐coupling reactions due to ease of synthesis, low price, and the employment of C−O electrophiles, however, the reactivity of aryl tosylates is low. Herein, we report the Ni‐catalyzed C(sp2)−C(sp3) Kumada cross‐coupling of aryl tosylates with primary and secondary alkyl Grignard reagents. The method delivers valuable alkyl arenes by cross‐coupling with challenging alkyl organometallics possessing β‐hydrogens that are prone to β‐hydride elimination and homo‐coupling. The reaction is catalyzed by an air‐ and moisture stable‐Ni(II) precatalyst. A broad range of electronically‐varied aryl tosylates, including bis‐tosylates, underwent this transformation, and many examples are suitable at mild room temperature conditions. The combination of Ar−X cross‐coupling with the facile Ar−OH activation/cross‐coupling strategy permits for orthogonal cross‐coupling with challenging alkyl organometallics. Furthermore, we demonstrate that the method operates with TON reaching 2000, which is one of the highest turnovers observed to date in Ni‐catalyzed cross‐couplings.

    magnified image

     
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email