A5038661637- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Catalytic C–H Functionalization Methods
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- Catalytic Cross-Coupling Reactions
- Asymmetric Hydrogenation and Catalysis
- Radical Photochemical Reactions
- Alkaloids: synthesis and pharmacology
- Oxidative Organic Chemistry Reactions
- Advanced Synthetic Organic Chemistry
- Traditional and Medicinal Uses of Annonaceae
- Marine Sponges and Natural Products
- Cyclopropane Reaction Mechanisms
- Bioactive Natural Diterpenoids Research
- Plant-based Medicinal Research
- Crystallography and molecular interactions
- Machine Learning in Materials Science
- Synthesis and Biological Activity
- Computational Drug Discovery Methods
- Synthesis and Catalytic Reactions
- Biological Activity of Diterpenoids and Biflavonoids
- Catalytic Alkyne Reactions
- Axial and Atropisomeric Chirality Synthesis
California Institute of Technology
2016-2025
Division of Chemistry
2021
Pasadena City College
2018-2021
University of California, Berkeley
2021
Colorado State University
2010
Yale University
2004-2008
Harvard University
2008
Sterling Research Group
2004
Connecticut College
2000-2002
Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These proven particularly useful for the coupling of sec-alkyl electrophiles form stereogenic centers; however, development enantioselective variants remains challenging. In this Perspective, we summarize progress that has been made toward Ni-catalyzed reactions.
Asymmetric, catalytic reactions of oxocarbenium ions are reported. Simple, chiral urea and thiourea derivatives shown to catalyze the enantioselective substitution silyl ketene acetals onto 1-chloroisochromans. A mechanism involving anion binding by catalyst generate a reactive ion is invoked. Catalysts bearing tertiary benzylic amide groups afforded highest enantioselectivities, with optimal structure being derived from enantioenriched 2-arylpyrrolidine derivatives.
The first enantioselective Ni-catalyzed reductive acyl cross-coupling has been developed. Treatment of acid chlorides and racemic secondary benzyl with a Ni(II)/bis(oxazoline) catalyst in the presence Mn(0) as stoichiometric reductant generates acyclic α,α-disubstituted ketones good yields high enantioselectivity without requiring chiral auxiliaries or pregeneration organometallic reagents. mild, base-free reaction conditions are tolerant variety functional groups on both coupling partners.
A Ni-catalyzed asymmetric reductive cross-coupling between vinyl bromides and benzyl chlorides has been developed. This method provides direct access to enantioenriched products bearing aryl-substituted tertiary allylic stereogenic centers from simple, stable starting materials. broad substrate scope is achieved under mild reaction conditions that preclude the pregeneration of organometallic reagents regioselectivity issues commonly associated with arylation.
An asymmetric Ni-catalyzed reductive cross-coupling of (hetero)aryl iodides and benzylic chlorides has been developed to prepare enantioenriched 1,1-diarylalkanes. As part these studies, a new chiral bioxazoline ligand, 4-heptyl-BiOX (L1), was in order obtain products synthetically useful yield enantioselectivity. The reaction tolerates variety heterocyclic coupling partners, including pyridines, pyrimidines, indoles, piperidines.
An electrochemically-driven enantioselective nickel-catalyzed reductive cross-coupling of alkenyl bromides and benzyl chlorides is reported. The reaction forms products bearing allylic stereogenic centers with good enantioselectivity under mild conditions in an undivided cell. Electrochemical activation turnover the catalyst mitigate issues posed by metal powder reductants. This report demonstrates that Ni-catalyzed cross-electrophile couplings can be driven electrochemically.
A Ni-catalyzed asymmetric reductive cross-coupling of heteroaryl iodides and α-chloronitriles has been developed. This method furnishes enantioenriched α,α-disubstituted nitriles from simple organohalide building blocks. The reaction tolerates a variety heterocyclic coupling partners, including pyridines, pyrimidines, quinolines, thiophenes, piperidines. proceeds under mild conditions at room temperature precludes the need to pregenerate organometallic nucleophiles.
An asymmetric Ni-catalyzed reductive cross-coupling has been developed to prepare enantioenriched allylic silanes. This enantioselective alkenylation proceeds under mild conditions and exhibits good functional group tolerance. The chiral silanes prepared here undergo a variety of stereospecific transformations, including intramolecular Hosomi–Sakurai reactions, set vicinal stereogenic centers with excellent transfer chirality.
An enantioselective Ni-catalyzed cross-coupling of N-hydroxyphthalimide esters with vinyl bromides is reported. The reaction proceeds under mild conditions and uses tetrakis(N,N-dimethylamino)ethylene as a terminal organic reductant. Good functional group tolerance demonstrated, over 20 examples reactions that proceed >90% ee.
One of the most oft-employed methods for C–C bond formation involving coupling vinyl-halides with aldehydes catalyzed by Ni and Cr (Nozaki–Hiyama–Kishi, NHK) has been rendered more practical using an electroreductive manifold. Although early studies pointed to feasibility such a process, those precedents were never applied others due cumbersome setups limited scope. Here we show that carefully optimized procedure can enable sustainable approach NHK, even in asymmetric fashion on highly...
Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation
ConspectusAfter decades of palladium dominating the realm transition-metal-catalyzed cross-coupling, recent years have witnessed exciting advances in development new nickel-catalyzed cross-coupling reactions to form C(sp3) centers. Nickel possesses distinct properties compared with palladium, such as facile single-electron transfer electrophiles and rapid C–C reductive elimination from NiIII. These properties, among others, make nickel particularly well-suited for (RCC) which two are coupled...
Ni-catalyzed asymmetric reductive cross-coupling reactions provide rapid and modular access to enantioenriched building blocks from simple electrophile precursors. Reductive coupling that can diverge through a common organometallic intermediate two distinct families of products are particularly versatile but underdeveloped. Here, we describe the development bis(oxazoline) ligand enables desymmetrization meso-anhydrides. When secondary benzylic electrophiles employed, doubly stereoselective...
The development of machine learning models to predict the regioselectivity C(sp3)-H functionalization reactions is reported. A data set for dioxirane oxidations was curated from literature and used generate a model C-H oxidation. To assess whether smaller, intentionally designed sets could provide accuracy on complex targets, series acquisition functions were developed select most informative molecules specific target. Active learning-based that leverage predicted reactivity uncertainty...
(R)-BINOL·SnCl(4) was found to catalyze a formal [3 + 2] cycloaddition reaction between C(3)-substituted indoles and 2-amidoacrylates provide pyrroloindolines. A variety of pyrroloindolines were prepared with high enantioselectivity in one step from simple precursors. This methodology is expected facilitate the total synthesis pyrroloindoline alkaloids, an important class biologically active natural products.
Pyrroloindoline alkaloids constitute a large family of natural products that has inspired the development an impressive array new reactions to prepare key heterocyclic motif. This synopsis will address catalytic, asymmetric developed synthesize pyrroloindolines bearing C3a all-carbon quaternary stereocenters. The methods described herein include both transition-metal-catalyzed and organocatalyzed have been demonstrated be suitable for synthesis pyrroloindoline framework.
An efficient and highly stereoselective total synthesis of the natural product (±)-welwitindolinone A isonitrile (1) is described. The bicyclo[4.2.0]octane core 1 was established by a regio- diastereoselective [2+2] ketene cycloaddition. C12 quaternary center vicinal stereogenic chlorine were installed in single operation with excellent stereocontrol via chloronium ion mediated semipinacol rearrangement. Described strategies for construction spiro-oxinole include SmI2−LiCl reductive...
Buchner and Curtius first reported the cyclopropanation of arenes in 1885. Since initial discovery, reaction has been subject significant research by both physical synthetic organic chemists. Described herein is a brief overview related arene processes, with an emphasis on their application to natural product total synthesis.
The first total synthesis of (-)-maoecrystal Z is described. key steps the include a diastereoselective Ti(III)-mediated reductive epoxide coupling reaction and Sm(II)-mediated cascade cyclization reaction. These transformations enabled preparation in only 12 from (-)-γ-cyclogeraniol.
The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features include (1) preparation a key cyclobutane intermediate by tandem Wolff rearrangement/asymmetric ketene addition, (2) directed C(sp3)–H alkenylation reaction to strategically forge C1–C2 bond, and (3) ring-closing metathesis build bridging bicyclo[4.3.1]decane terpene framework.
A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials. utility this transformation highlighted the five-step syntheses natural (+)-naseseazine B.
The tandem Friedel–Crafts conjugate addition/asymmetric protonation reaction between 2-substituted indoles and methyl 2-acetamidoacrylate is reported. catalyzed by (R)-3,3′-dibromo-BINOL in the presence of stoichiometric SnCl4, first example a using BINOL·SnCl4 complex as catalyst. A range furnished synthetic tryptophan derivatives good yields high levels enantioselectivity, even on preparative scale. convergent nature this transformation should lend itself to preparation unnatural for use...