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Open Access Publications from the University of California

Scholarly Works (9 results)

  • Thesis
  • Peer Reviewed
UC Santa Barbara Electronic Theses and Dissertations (2021)

Most ligands used in asymmetric gold(I) catalysis are directly adopted from palladium catalysis. These ligands were initially designed to facilitate the chemistry of square-planar Pd(II) complexes and hence are hardly optimal for Au(I) catalysis, in which the catalysts display linear geometry. For the past several years, the Zhang Lab has designed various bifunctional biphenyl-2-ylphosphine ligands featuring a remote basic group to harness the linear Au(I) structure and enable ligand-metal cooperation. During the research of this dissertation, a new type of bifunctional phosphine ligands possessing a chiral center and a fluxional biphenyl axis were developed to enable asymmetric isomerization of propargylic alcohols and sulfonamides into chiral 2,5-dihydrofurans and chiral 3-pyrrolines, respectively. The synthetic potential of this methodology was demonstrated in a total synthesis of diplobifuranylone B. Notably, this type of chiral ligands is also suitable for Ag(I) and Cu(I) catalysis. β, γ-Butenolides was isomerized into chiral α, β-butenolides with high enantiomeric excesses via enantioselective γ-protonation under Cu(I) catalysis.

    Cover page: Chiral Bifunctional Phosphine Ligand-Enabled Cooperative Asymmetric Coinage Metal Catalysis
    • Article
    • Peer Reviewed
    UC Santa Barbara Previously Published Works (2021)
    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.
      Cover page: Chiral Bifunctional Phosphine Ligand Enables Gold-Catalyzed Asymmetric Isomerization and Cyclization of Propargyl Sulfonamide into Chiral 3‑Pyrroline
      • Article
      • Peer Reviewed
      UC Santa Barbara Previously Published Works (2019)
      An asymmetric total synthesis of diplobifuranylone B was achieved in 10 steps for the longest linear sequence and in 15.8% overall yield from commercially available methyl (R)-(+)-lactate and l-glutamic acid. This synthesis features a stereoselective construction of the key 2,5-dihydrofuran ring in the natural product via a recently developed asymmetric gold catalysis. The stereochemical flexibility offered by the catalysis enables an expedient revision of the reported structure of diplobifuranylone B, where the relative stereochemistry of the 2,5-dihydrofuran moiety was previously misassigned as cis instead of trans.
        Cover page: Total Synthesis and Structure Revision of Diplobifuranylone B
        • Article
        • Peer Reviewed
        UC Santa Barbara Previously Published Works (2019)
        Gold-catalyzed oxidations of alkynes by N-oxides offer direct access to reactive α-oxo gold carbene intermediates from benign and readily available alkynes instead of hazardous diazo carbonyl compounds. Despite various versatile synthetic methods developed based on this strategy, one of the hallmarks of α-oxo carbene/carbenoid chemistry, that is, the Wolff rearrangement, has not been realized in this context. This study discloses the first examples that show the Wolff rearrangement can be readily realized by α-oxo gold carbenes oxidatively generated from TBS-terminated alkynes (TBS=tert-butyldimethylsilyl). The thus-generated silylketenes can be either isolated pure or subsequently trapped by various internal or external nucleophiles in one pot to afford α-silylated carboxylic acids, their derivatives, or TBS-substituted allenes.
          Cover page: Wolff Rearrangement of Oxidatively Generated α‐Oxo Gold Carbenes: An Effective Approach to Silylketenes
          • Article
          • Peer Reviewed
          UC Santa Barbara Previously Published Works (2019)
          The asymmetric isomerization of alkyne to allene is the most efficient and the completely atom-economic approach to this class of versatile axial chiral structure. However, the state-of-the-art is limited to tert-butyl alk-3-ynoate substrates that possess requisite acidic propargylic C-H bonds. Reported here is a strategy based on gold catalysis that is enabled by a designed chiral bifunctional biphenyl-2-ylphosphine ligand. It permits isomerization of alkynes with nonacidic α-C-H bonds and hence offers a much-needed general solution. With chiral propargylic alcohols as substrates, 2,5-disubstituted 2,5-dihydrofurans are formed in one step in typically good yields and with good to excellent diastereoselectivities. With achiral substrates, 2,5-dihydrofurans are formed with good to excellent enantiomeric excesses. A novel center-chirality approach is developed to achieve a stereocontrol effect similar to an axial chirality in the designed chiral ligand. The mechanistic studies established that the precatalyst axial epimers are all converted into the catalytically active cationic gold catalyst owing to the fluxional axis of the latter.
            Cover page: Chiral Bifunctional Phosphine Ligand Enabling Gold-Catalyzed Asymmetric Isomerization of Alkyne to Allene and Asymmetric Synthesis of 2,5-Dihydrofuran
            • Article
            • Peer Reviewed
            UC Santa Barbara Previously Published Works (2021)
            α,β-Butenolides with ≥96% enantiomeric excess are synthesized from β,γ-butenolides via a novel Cu(I)-ligand cooperative catalysis. The reaction is enabled by a chiral biphenyl-2-ylphosphine ligand featuring a remote tertiary amino group. Density functional theory studies support the cooperation between the metal center and the ligand basic amino group during the initial soft deprotonation and the key asymmetric γ-protonation. Remarkably, other coinage metals, that is, Ag and Au, can readily assume the same role as Cu in this asymmetric isomerization chemistry.
              Cover page: Chiral Bifunctional Phosphine Ligand-Enabled Cooperative Cu Catalysis: Formation of Chiral α,β-Butenolides via Highly Enantioselective γ‑Protonation
              • Article
              • Peer Reviewed
              UC Santa Barbara Previously Published Works (2021)
              The asymmetric one-step net addition of unactivated propargylic C-H bond to aldehyde leads to an atom-economic construction of versatile chiral propargylic alcohols but has not been realized previously. Here we show its implementation in an intramolecular manner under mild reaction conditions. Via cooperative gold catalysis enabled by a chiral bifunctional phosphine ligand, this chemistry achieves asymmetric catalytic deprotonation of propargylic C-H (pKa > 30) by a tertiary amine group (pKa ~ 10) of the ligand in the presence of much more acidic aldehydic α-hydrogens (pKa ~ 17). The reaction exhibits a broad scope and readily accommodates various functional groups. The 5-/6-membered ring fused homopropargylic alcohol products are formed with excellent enantiomeric excesses and high trans-selectivities with or without a preexisting substrate chiral center. DFT studies of the reaction support the conceived reaction mechanism and the calculated energetics corroborate the observed stereoselectivity and confirm an additional metal-ligand cooperation.
                Cover page: Gold-catalysed asymmetric net addition of unactivated propargylic C–H bonds to tethered aldehydes
                • Article
                • Peer Reviewed
                UC Santa Barbara Previously Published Works (2021)
                Homogeneous gold catalysis has experienced extraordinary development since the dawn of this millennium. Oxidative gold catalysis is a vibrant and fertile subfield and has over the years delivered a diverse array of versatile synthetic methods of exceptional value to synthetic practices. This review aims to cover this topic in a comprehensive manner. The discussions are organized by the mechanistic aspects of the metal oxidation states and further by the types of oxidants or oxidizing functional groups. Synthetic applications of oxidative gold catalysis are also discussed.
                  Cover page: Homogeneous Gold-Catalyzed Oxidation Reactions
                  • Article
                  • Peer Reviewed
                  UC Santa Barbara Previously Published Works (2018)
                  Using the previously designed biphenyl-2-ylphosphine ligand, featuring a remote tertiary amino group, the first gold-catalyzed intermolecular hydroalkenylation of alkynes has been developed. Synthetically valuable conjugated dienyl alcohols are formed in moderate to good yields. A range of alkenyltrifluoroborates are allowed as the alkenyl donor, and no erosion of alkene geometry and/or the propargylic configuration are detected. DFT calculations confirm the critical role of the remote basic group in the ligand as a general-base catalyst for promoting this novel gold catalysis with good efficiency.
                    Cover page: Bifunctional Ligand Enables Efficient Gold‐Catalyzed Hydroalkenylation of Propargylic Alcohol
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