Skip to main content

Steven Malcolmson

Associate Professor of Chemistry
Chemistry
Box 90346, Durham, NC 27708-0346
1103 French Science Center, Durham, NC 27708

Selected Publications


Catalysis-enabled amine sorting.

Journal Article Nature chemistry · December 2024 Full text Cite

Shattering the mirror with copper catalysis

Journal Article Nature Synthesis · September 1, 2024 Racemic ketones are converted to stereoisomerically enriched homoallylic alcohols by copper-catalysed enantioconvergent allylation. ... Full text Cite

Copper-Catalyzed Diastereo-, Enantio-, and (Z)-Selective Aminoallylation of Ketones through Reductive Couplings of Azatrienes for the Synthesis of Allylic 1,2-Amino Tertiary Alcohols.

Journal Article Journal of the American Chemical Society · July 2024 We introduce a method for the (Z)-selective aminoallylation of a range of ketones to prepare allylic 1,2-amino tertiary alcohols with excellent diastereo- and enantioselectivity. Copper-catalyzed reductive couplings of 2-azatrienes with aryl/alkyl a ... Full text Cite

Palladium-Catalyzed Regiodivergent Three-Component Alkenylamination of 1,3-Dienes with Alkyl and Aryl Amines.

Journal Article Journal of the American Chemical Society · December 2023 We report a palladium-catalyzed method for 4,3- or 4,1-selective alkenylamination of terminal dienes. Three-component couplings proceed with alkenyl triflates and several amines, giving vicinal carboamination with a Xantphos-supported catalyst and distal d ... Full text Cite

A Diastereodivergent and Enantioselective Approach to syn- and anti-Diamines: Development of 2-Azatrienes for Cu-Catalyzed Reductive Couplings with Imines That Furnish Allylic Amines.

Journal Article Journal of the American Chemical Society · September 2021 We introduce a new reagent class, 2-azatrienes, as a platform for catalytic enantioselective synthesis of allylic amines. Herein, we demonstrate their promise by a diastereodivergent synthesis of syn- and anti-1,2-diamines through their Cu-bi ... Full text Cite

A Diastereodivergent and Enantioselective Approach to syn- and anti-Diamines: Development of 2-Azatrienes for Cu-Catalyzed Reductive Couplings with Imines that Furnish Allylic Amines

Journal Article · July 26, 2021 We introduce a new reagent class, 2-azatrienes, as a platform for catalytic enantioselective synthesis of allylic amines. Herein, we demonstrate their promise by diasteredivergent and enantioselective synthesis of <i>syn</i>- and <i& ... Full text Cite

Racing against unwanted isomerization.

Journal Article Science (New York, N.Y.) · January 2021 Full text Cite

A Diastereodivergent and Enantioselective Approach to syn- and anti-Diamines: Development of 2-Azatrienes for Cu-Catalyzed Reductive Couplings with Imines that Furnish Allylic Amines

Journal Article · 2021 We introduce a new reagent class, 2-azatrienes, as a platform for catalytic enantioselective synthesis of allylic amines. Herein, we demonstrate their promise by diasteredivergent and enantioselective synthesis of syn - and anti -1,2-diamines by Cu-bis(pho ... Full text Cite

Strategies for the Catalytic Enantioselective Synthesis of α-Trifluoromethyl Amines.

Journal Article ACS catalysis · November 2020 The exploitation of the α-trifluoromethylamino group as an amide surrogate in peptidomimetics and drug candidates has been on the rise. In a large number of these cases, this moiety bears stereochemistry with the stereochemical identity having impor ... Full text Cite

Rational ligand choice extends the SABRE substrate scope.

Journal Article Chemical communications (Cambridge, England) · August 2020 Here we report on chelating ligands for Signal Amplification By Reversible Exchange (SABRE) catalysts that permit hyperpolarisation on otherwise sterically hindered substrates. We demonstrate 1H enhancements of ∼100-fold over 8.5 T thermal for 2 ... Full text Cite

Enantioselective Construction of Quaternary Stereogenic Centers by the Addition of an Acyl Anion Equivalent to 1,3-Dienes.

Journal Article Organic letters · March 2020 Featured Publication We report the enantioselective formation of quaternary stereogenic centers by the intermolecular addition of malononitrile, an acyl anion equivalent, and related pronucleophiles to several 1,3-disubstituted acyclic 1,3-dienes in the presence of a Pd-PHOX c ... Full text Cite

Enantio- and Diastereoselective Synthesis of Homoallylic α-Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes.

Journal Article Organic letters · February 2020 We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethyl-substituted isatin-derived azadienolate nucleophiles undergo γ-selective a ... Full text Cite

Catalytic Enantio- And Regioselective Addition of Nucleophiles in the Intermolecular Hydrofunctionalization of 1,3-Dienes

Journal Article ACS Catalysis · January 17, 2020 Featured Publication Catalytic enantioselective synthesis of small-molecule building blocks with allylic stereogenic centers is an important objective in organic synthesis, but preparing this motif wherein the adjacent olefin is 1,2-disubstituted in a single step is a tremendo ... Full text Cite

Enantio- and Diastereoselective Synthesis of Homoallylic α-Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes

Journal Article · 2020 We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethylsubstituted isatin-derived azadienolate nucleophiles undergo γ-selective al ... Full text Cite

Catalytic Enantio- and Diastereoselective Cyclopropanation of 2-Azadienes for the Synthesis of Aminocyclopropanes Bearing Quaternary Carbon Stereogenic Centers.

Journal Article Organic letters · September 2019 Featured Publication We report the catalytic enantio- and diastereoselective preparation of aminocyclopropanes by the cyclopropanation of terminal and (Z)-internal 2-azadienes with donor/acceptor carbenes derived from α-diazoesters. The resulting cyclopropanes bear quat ... Full text Cite

2-Azadienes as Enamine Umpolung Synthons for the Preparation of Chiral Amines.

Journal Article Synlett : accounts and rapid communications in synthetic organic chemistry · July 2019 The development of new strategies for the preparation of chiral amines is an important objective in organic synthesis. In this Synpacts, we summarize our approach for catalytically accessing nucleophilic aminoalkyl metal species from 2-azadienes, an ... Full text Cite

Preparation of Chiral Allenes through Pd-Catalyzed Intermolecular Hydroamination of Conjugated Enynes: Enantioselective Synthesis Enabled by Catalyst Design.

Journal Article Journal of the American Chemical Society · May 2019 In this study, we establish that conjugated enynes undergo selective 1,4-hydroamination under Pd catalysis to deliver chiral allenes with pendant allylic amines. Several primary and secondary aliphatic and aryl-substituted amines couple with a wide range o ... Full text Cite

Brønsted acid and Pd-PHOX dual-catalysed enantioselective addition of activated C-pronucleophiles to internal dienes.

Journal Article Chemical science · May 2019 We describe the development of Pd-PHOX-catalysed enantioselective couplings of internal dienes with malononitrile and other activated C-pronucleophiles. Reactions are dramatically accelerated by the addition of Et3N·HBArF 4 as a Brønsted acid co-catalyst, ... Full text Cite

Palladium-Catalyzed Synthesis of α-Trifluoromethyl Benzylic Amines via Fluoroarylation of gem-Difluoro-2-azadienes Enabled by Phosphine-Catalyzed Formation of an Azaallyl-Silver Intermediate.

Journal Article ACS catalysis · January 2019 We report the synthesis of α-trifluoromethyl benzylic amines through the vicinal fluoroarylation of gem-difluoro-2-azadienes. Our studies indicate that XPhos plays an important role as a phase transfer catalyst that promotes the addition of A ... Full text Cite

Development and Mechanistic Investigations of Enantioselective Pd-Catalyzed Intermolecular Hydroaminations of Internal Dienes

Journal Article ACS Catalysis · September 7, 2018 We report the development of highly enantio- and regioselective Pd-catalyzed intermolecular hydroaminations of challenging 1,4-disubstituted acyclic dienes. Several aryl/alkyl-disubstituted dienes and a sterically differentiated alkyl/alkyl-disubstituted d ... Full text Cite

Enantioselective Synthesis of anti-1,2-Diamines by Cu-Catalyzed Reductive Couplings of Azadienes with Aldimines and Ketimines.

Journal Article Journal of the American Chemical Society · June 2018 Here we report highly efficient and chemoselective azadiene-imine reductive couplings catalyzed by (Ph-BPE)Cu-H that afford anti-1,2-diamines. In all cases, reactions take place with either aldimine or ketimine electrophiles to deliver a single diastereome ... Full text Cite

Enantioselective Intermolecular Pd-Catalyzed Hydroalkylation of Acyclic 1,3-Dienes with Activated Pronucleophiles.

Journal Article Journal of the American Chemical Society · February 2018 We report a highly enantioselective Pd-PHOX-catalyzed intermolecular hydroalkylation of acyclic 1,3-dienes. Meldrum's acid derivatives and other activated C-pronucleophiles, such as β-diketones and malononitriles, react with a variety of aryl- and alkyl-su ... Full text Cite

2-Azadienes as Reagents for Preparing Chiral Amines: Synthesis of 1,2-Amino Tertiary Alcohols by Cu-Catalyzed Enantioselective Reductive Couplings with Ketones.

Journal Article Journal of the American Chemical Society · January 2018 We introduce a new strategy for synthesis of chiral amines: couplings of α-aminoalkyl nucleophiles generated by enantioselective migratory insertion of 2-azadienes to a Cu-H. In this report, we demonstrate its application in catalytic reductive coupling of ... Full text Cite

Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long‐Lived SABRE‐Induced Hyperpolarization

Journal Article Angewandte Chemie · September 25, 2017 AbstractDiazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, Full text Cite

Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long-Lived SABRE-Induced Hyperpolarization.

Journal Article Angewandte Chemie (International ed. in English) · September 2017 Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, 15 N2 -diazirine can be h ... Full text Cite

Diastereoselective and Enantiospecific Synthesis of 1,3-Diamines via 2-Azaallyl Anion Benzylic Ring-Opening of Aziridines.

Journal Article Organic letters · August 2017 The 1,3-diamine motif appears in numerous complex molecules, yet there are few methods for the stereoselective construction of this moiety. Herein, we demonstrate a stereocontrolled synthesis of 1,3-diamines, which bear up to three contiguous stereogenic c ... Full text Cite

Umpolung Synthesis of 1,3-Amino Alcohols: Stereoselective Addition of 2-Azaallyl Anions to Epoxides.

Journal Article Organic letters · July 2017 We report the direct preparation of 1,3-amino alcohols that contain up to three contiguous stereogenic centers by the umpolung coupling of imines and epoxides. Nucleophilic 2-azaallyl anions, generated from imines, are stereoselectively added to epoxides t ... Full text Cite

Direct Hyperpolarization of Nitrogen-15 in Aqueous Media with Parahydrogen in Reversible Exchange.

Journal Article Journal of the American Chemical Society · June 2017 Signal amplification by reversible exchange (SABRE) is an inexpensive, fast, and even continuous hyperpolarization technique that uses para-hydrogen as hyperpolarization source. However, current SABRE faces a number of stumbling blocks for translation to b ... Full text Cite

Enantioselective Intermolecular Addition of Aliphatic Amines to Acyclic Dienes with a Pd-PHOX Catalyst.

Journal Article Journal of the American Chemical Society · May 2017 We report a method for the catalytic, enantioselective intermolecular addition of aliphatic amines to acyclic 1,3-dienes. In most cases, reactions proceed efficiently at or below room temperature in the presence of 5 mol % of a Pd catalyst bearing a PHOX l ... Full text Cite

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange.

Journal Article The journal of physical chemistry. C, Nanomaterials and interfaces · March 2017 Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we fo ... Full text Cite

Hyperpolarization of Nitrogen-15 Schiff Bases by Reversible Exchange Catalysis with para-Hydrogen.

Journal Article Chemistry (Weinheim an der Bergstrasse, Germany) · July 2016 NMR with thermal polarization requires relatively concentrated samples, particularly for nuclei with low abundance and low gyromagnetic ratios, such as (15) N. We expand the substrate scope of SABRE, a recently introduced hyperpolarization method, to allow ... Full text Cite

Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal 15N2-diazirine molecular tags

Journal Article Science Advances · March 25, 2016 Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin li ... Full text Open Access Link to item Cite

Catalyst-Controlled Stereoselective Olefin Metathesis

Chapter · January 1, 2015 This chapter covers the advances made since 2003 in the development of catalysts that can control the stereochemical outcome of olefin metathesis reactions. Various enantioselective processes, such as enantioselective ring-opening/cross-metathesis (EROCM) ... Full text Cite

The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · May 2013 Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-ato ... Full text Cite

Bipyridine Adducts of Molybdenum Imido Alkylidene and Imido Alkylidyne Complexes.

Journal Article Organometallics · June 2012 Seven bipyridine adducts of molybdenum imido alkylidene bispyrrolide complexes of the type Mo(NR)(CHCMe(2)R')(Pyr)(2)(bipy) (1a-1g; R = 2,6-i-Pr(2)C(6)H(3) (Ar), adamantyl (Ad), 2,6-Me(2)C(6)H(3) (Ar'), 2-i-PrC(6)H(4) (Ar(iPr)), 2-ClC(6)H(4) (Ar(Cl)), 2-t- ... Full text Cite

Three ring posttranslational circuses: insertion of oxazoles, thiazoles, and pyridines into protein-derived frameworks.

Journal Article ACS chemical biology · March 2012 Nitrogen heterocycles are the key functional and structural elements in both RNA and DNA, in half a dozen of the most important coenzymes, and in many synthetic drug scaffolds. On the other hand, only 3 of 20 proteinogenic amino acids have nitrogen heteroc ... Full text Cite

Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis.

Journal Article Chemistry & biology · September 2011 2,5-Dihydrophenylalanine (H(2)Phe) is a multipotent nonproteinogenic amino acid produced by various Actinobacteria and Gammaproteobacteria. Although the metabolite was discovered over 40 years ago, details of its biosynthesis have remained largely unknown. ... Full text Cite

Nine enzymes are required for assembly of the pacidamycin group of peptidyl nucleoside antibiotics.

Journal Article Journal of the American Chemical Society · April 2011 Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted ... Full text Cite

Catalytic enantioselective olefin metathesis in natural product synthesis. Chiral metal-based complexes that deliver high enantioselectivity and more.

Journal Article Angewandte Chemie (International ed. in English) · January 2010 Chiral olefin metathesis catalysts enable chemists to access enantiomerically enriched small molecules with high efficiency; synthesis schemes involving such complexes can be substantially more concise than those that would involve enantiomerically pure su ... Full text Cite

The significance of degenerate processes to enantioselective olefin metathesis reactions promoted by stereogenic-at-Mo complexes.

Journal Article Journal of the American Chemical Society · November 2009 The present study provides spectroscopic and experimental evidence demonstrating that degenerate metathesis is critical to the effectiveness of this emerging class of chiral catalysts. Isolation and X-ray characterization of both diastereomeric complexes, ... Full text Cite

Design and stereoselective preparation of a new class of chiral olefin metathesis catalysts and application to enantioselective synthesis of quebrachamine: catalyst development inspired by natural product synthesis.

Journal Article Journal of the American Chemical Society · January 2009 A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of ... Full text Cite

Highly efficient molybdenum-based catalysts for enantioselective alkene metathesis.

Journal Article Nature · December 2008 Discovery of efficient catalysts is one of the most compelling objectives of modern chemistry. Chiral catalysts are in particularly high demand, as they facilitate synthesis of enantiomerically enriched small molecules that are critical to developments in ... Full text Cite

Enantioselective synthesis of cyclic enol ethers and all-carbon quaternary stereogenic centers through catalytic asymmetric ring-closing metathesis.

Journal Article Journal of the American Chemical Society · April 2006 The first examples of catalytic asymmetric ring-closing metathesis (ARCM) reactions of enol ethers are reported. To identify the most effective catalysts, various chiral Mo- and Ru-based catalysts were screened. Although chiral Ru catalysts (those that do ... Full text Cite