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. 2021 Nov 5;23(21):8194-8198.
doi: 10.1021/acs.orglett.1c02896. Epub 2021 Oct 12.

Chiral Bifunctional Phosphine Ligand Enables Gold-Catalyzed Asymmetric Isomerization and Cyclization of Propargyl Sulfonamide into Chiral 3-Pyrroline

Xinpeng Cheng  1 , Liming Zhang  1
Affiliations

Chiral Bifunctional Phosphine Ligand Enables Gold-Catalyzed Asymmetric Isomerization and Cyclization of Propargyl Sulfonamide into Chiral 3-Pyrroline

Xinpeng Cheng et al. Org Lett. .

Abstract

This work details an asymmetric gold-ligand cooperative catalysis that transforms readily accessible chiral/achiral propargylic sulfonamides into chiral 3-pyrrolines. A bifunctional biphenyl-2-ylphosphine ligand featuring a chiral tetrahydroisoquinoline fragment is essential for the observed metal-ligand cooperation and the asymmetric induction. 2,5-cis-3-Pyrrolines are formed with excellent diastereoselectivities in a "matched" scenario. The "mismatched" scenario by using the ligand enantiomer delivers 2,5-trans-3-pyrrolines with >5/1 diastereoselectivity. The synthetic utilities of this chemistry are demonstrated.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Reaction Design
Scheme 2.
Scheme 2.
Reaction Scopea aReaction was performed on a 0.2 mmol scale in a 2-dram sealed vial if not specified. Yields based on conversion are reported in parentheses. bToluene (0.2 M). cSecond batch of (R)-L1AuCl (5 mol %) and NaBArF4 (10 mol %) was added after 24 h. d10 mol % (R)-L1AuCl and 20 mol % NaBArF4. ePhCF3 (0.5 M) at 95 °C. f5 mol % (R)-L2AuCl and 10 mol % NaBArF4. g10 mol % (S)-L1AuCl and 20 mol % NaBArF4.
Scheme 3.
Scheme 3.
Synthetic Application
See this image and copyright information in PMC

References

    1. Cheng X; Zhang L Designed Bifunctional Ligands in Cooperative Homogeneous Gold Catalysis. CCS Chem. 2021, 3, 1989–2002.
    1. Grützmacher H Cooperating Ligands in Catalysis. Angew. Chem., Int. Ed 2008, 47, 1814–1818. - PubMed
    2. Askevold B; Roesky HW; Schneider S Learning from the Neighbors: Improving Homogeneous Catalysts with Functional Ligands Motivated by Heterogeneous and Biocatalysis. ChemCatChem 2012, 4, 307–320.
    3. Khusnutdinova JR; Milstein D Metal−Ligand Cooperation. Angew. Chem., Int. Ed 2015, 54, 12236–12273. - PubMed
    4. Zhang Z; Smal V; Retailleau P; Voituriez A; Frison G; Marinetti A; Guinchard X Tethered Counterion-Directed Catalysis: Merging the Chiral Ion-Pairing and Bifunctional Ligand Strategies in Enantioselective Gold (I) Catalysis. J. Am. Chem. Soc 2020, 142, 3797–3805. - PubMed
    5. Trincado M; Grützmacher H Cooperating Ligands in Catalysis. In Cooperative Catalysis; Wiley-VCH Verlag GmbH & Co. KGaA: 2015; pp 67–110.
    1. Campeau D; León Rayo DF; Mansour A; Muratov K; Gagosz F Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes. Chem. Rev 2021, 121, 8756–8867. - PubMed
    2. Zheng Z; Ma X; Cheng X; Zhao K; Gutman K; Li T; Zhang L Homogeneous Gold-Catalyzed Oxidation Reactions. Chem. Rev 2021, 121, 8979–9038. - PMC - PubMed
    3. Lu Z; Li T; Mudshinge SR; Xu B; Hammond GB Optimization of Catalysts and Conditions in Gold(I) Catalysis—Counterion and Additive Effects. Chem. Rev 2021, 121, 8452–8477. - PubMed
    4. Ye L-W; Zhu X-Q; Sahani RL; Xu Y; Qian P-C; Liu R-S Nitrene Transfer and Carbene Transfer in Gold Catalysis. Chem. Rev 2021, 121, 9039–9112. - PubMed
    5. Li D; Zang W; Bird MJ; Hyland CJT; Shi M Gold-Catalyzed Conversion of Highly Strained Compounds. Chem. Rev 2021, 121, 8685–8755. - PubMed
    6. Wang T; Hashmi ASK 1,2-Migrations onto Gold Carbene Centers. Chem. Rev 2021, 121, 8948–8978. - PubMed
    7. Mato M; Franchino A; García-Morales C; Echavarren AM Gold-Catalyzed Synthesis of Small Rings. Chem. Rev 2021, 121, 8613–8684. - PMC - PubMed
    1. Wang Y; Wang Z; Li Y; Wu G; Cao Z; Zhang L A General Ligand Design for Gold Catalysis Allowing Ligand-Directed Anti-Nucleophilic Attack of Alkynes. Nat. Commun 2014, DOI: 10.1038/ncomms4470. - DOI - PMC - PubMed
    2. Wang Z; Nicolini C; Hervieu C; Wong Y-F; Zanoni G; Zhang L Remote Cooperative Group Strategy Enables Ligands for Accelerative Asymmetric Gold Catalysis. J. Am. Chem. Soc 2017, 139, 16064–16067. - PubMed
    1. Wang Z; Wang Y; Zhang L Soft Propargylic Deprotonation: Designed Ligand Enables Au-Catalyzed Isomerization of Alkynes to 1,3-Dienes. J. Am. Chem. Soc 2014, 136, 8887–8890. - PMC - PubMed
    2. Li T; Cheng X; Qian P; Zhang L Gold-Catalysed Asymmetric Net Addition of Unactivated Propargylic C−H Bonds to Tethered Aldehydes. Nat. Catal 2021, 4, 164–171. - PMC - PubMed
    3. Li X; Ma X; Wang Z; Liu P-N; Zhang L Bifunctional Phosphine Ligand Enabled Gold-Catalyzed Alkynamide Cycloisomerization: Access to Electron-Rich 2-Aminofurans and Their Diels−Alder Adducts. Angew. Chem., Int. Ed 2019, 58, 17180–17184. - PMC - PubMed
    4. Cheng X; Wang Z; Quintanilla CD; Zhang L Chiral Bifunctional Phosphine Ligand Enabling Gold-Catalyzed Asymmetric Isomerization of Alkyne to Allene and Asymmetric Synthesis of 2,5-Dihydrofuran. J. Am. Chem. Soc 2019, 141, 3787–3791. - PMC - PubMed