Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug 7;10(15):8237-8246.
doi: 10.1021/acscatal.0c01842. Epub 2020 Jun 24.

Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions

Kelsey E Poremba  1 , Sara E Dibrell  1 , Sarah E Reisman  1
Affiliations

Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions

Kelsey E Poremba et al. ACS Catal. .

Abstract

Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging. In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Proposed mechanistic hypotheses.
Scheme 1.
Scheme 1.
Seminal reports of Ni-mediated reductive homocoupling.
Scheme 2.
Scheme 2.
First reports of Ni-catalyzed cross-coupling of C(sp2) and C(sp3) electrophiles with metal reductants.
Scheme 3.
Scheme 3.
First report of enantioconvergent RCC.
Scheme 4.
Scheme 4.
Enantioconvergent RCCs of alkenyl bromides.
Scheme 5.
Scheme 5.
Enantioconvergent reductive decarboxylative cross-coupling.
Scheme 6.
Scheme 6.
Enantioconvergent RCC of α-chloronitriles.
Scheme 7.
Scheme 7.
Enantioconvergent RCCs with a novel BiOX ligand.
Scheme 8.
Scheme 8.
Enantioconvergent RCC with Ni/Ti co-catalysis.
Scheme 9.
Scheme 9.
Enantioselective RCCs of olefins and C(sp2) electrophiles.
Scheme 10.
Scheme 10.
Enantioselective RCCs of olefins and C(sp3) electrophiles.
Scheme 11.
Scheme 11.
Enantioselective reductive intermolecular cross-coupling of olefins.
See this image and copyright information in PMC

References

    1. Rudolph A; Lautens M Secondary Alkyl Halides in Transition-Metal-Catalyzed Cross-Coupling Reactions. Angew. Chem. Int. Ed 2009, 48 (15), 2656–2670. - PubMed
    2. Jana R; Pathak TP; Sigman MS Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-Organometallics as Reaction Partners. Chem. Rev 2011, HI (3), 1417–1492. - PMC - PubMed
    1. Tasker SZ; Standley EA; Jamison TF Recent Advances in Homogeneous Nickel Catalysis. Nature 2014, 509 (7500), 299–309. - PMC - PubMed
    1. For selected reviews of reductive cross-couplings, see: Knappke CEI; Grupe S; Gartner D; Corpet M; Gosmini C; Jacobi von Wangelin A Reductive Cross-Coupling Reactions between Two Electrophiles. Chem. Eur. J 2014, 20 (23), 6828–6842. - PubMed
    2. Weix DJ Methods and Mechanisms for Cross-Electrophile Coupling of Csp2 Halides with Alkyl Electrophiles. Acc. Chem. Res 2015, 48 (6), 1767–1775. - PMC - PubMed
    3. Gu J; Wang X; Xue W; Gong H Nickel-Catalyzed Reductive Coupling of Alkyl Halides with Other Electrophiles: Concept and Mechanistic Considerations. Org. Chem. Front 2015, 2, 1411–1421.
    4. Wang X; Dai Y; Gong H Nickel-Catalyzed Reductive Couplings. Top. Curr. Chem 2016, 374 (4), 43. - PubMed
    5. Lucas EL; Jarvo ER Stereospecific and Stereoconvergent Cross-Couplings between Alkyl Electrophiles. Nat. Rev. Chem 2017, 1 (9), 0065.
    6. Richmond E; Moran J Recent Advances in Nickel Catalysis Enabled by Stoichiometric Metallic Reducing Agents. Synthesis 2018, 50 (3), 499–513.
    7. Goldfogel MJ; Huang L; Weix DJ Cross-Electrophile Coupling: Principles and New Reactions In Nickel Catalysis in Organic Synthesis; Ogoshi S, Ed.; Wiley, 2020; pp 183–222.
    1. Dombrowski AW; Gesmundo NJ; Aguirre AL; Sarris KA; Young JM; Bogdan AR; Martin MC; Gedeon S; Wang Y Expanding the Medicinal Chemist Toolbox: Comparing Seven C(Sp2)-C(Sp3) Cross-Coupling Methods by Library Synthesis. ACS Med. Chem. Lett 2020, 11 (4), 597–604. - PMC - PubMed
    1. For selected examples of Ni-catalyzed intramolecular RCCs, see: Yan C-S; Peng Y; Xu X-B; Wang Y-W Nickel-Mediated Inter- and Intramolecular Reductive Cross-Coupling of Unactivated Alkyl Bromides and Aryl Iodides at Room Temperature. Chem. Eur. J 2012, 18 (19), 6039–6048. - PubMed
    2. Xue W; Xu H; Liang Z; Qian Q; Gong H Nickel-Catalyzed Reductive Cyclization of Alkyl Dihalides. Org. Lett 2014, 16 (19), 4984–4987. - PubMed
    3. Konev MO; Hanna LE; Jarvo ER Intra- and Intermolecular Nickel-Catalyzed Reductive Cross-Electrophile Coupling Reactions of Benzylic Esters with Aryl Halides. Angew. Chem. Int. Ed 2016, 55 (23), 6730–6733. - PubMed
    4. Lucas EL; Hewitt KA; Chen P-P; Castro AJ; Hong X; Jarvo ER Engaging Sulfonamides: Intramolecular Cross-Electrophile Coupling Reaction of Sulfonamides with Alkyl Chlorides. J. Org. Chem 2020, 85 (4), 1775–1793. - PubMed
    5. Sanford AB; Thane TA; McGinnis TM; Chen P-P; Hong X; Jarvo ER Nickel-Catalyzed Alkyl–Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes. J. Am. Chem. Soc 2020, 142 (11), 5017–5023. - PMC - PubMed