Hien M. Nguyen

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Name: Nguyen, Hien M.

Organization: University of Iowa , USA

Department: Department of Chemistry

Title: Associate(PhD)

TOPICS

Organic Chemistry

Amination Oligosaccharide Synthesis

Chemicals
References

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers

Co-reporter:Eric T. Sletten, Ravi S. Loka, Fei Yu, and Hien M. Nguyen

Biomacromolecules October 9, 2017 Volume 18(Issue 10) pp:3387-3387

Publication Date(Web):August 28, 2017

DOI:10.1021/acs.biomac.7b01049

We report herein the first-time exploration of the attachment of well-defined saccharide units onto a synthetic polymer backbone for the inhibition of a glycosidase. More specifically, glycopolymers endowed with heparan sulfate (HS) disaccharides were established to inhibit the glycosidase, heparanase, with an IC50 value in the low nanomolar range (1.05 ± 0.02 nm), a thousand-fold amplification over its monovalent counterpart. The monomeric moieties of these glycopolymers were designed in silico to manipulate the well-established glycotope of heparanase into an inhitope. Studies concluded that (1) the glycopolymers are hydrolytic stable toward heparanase, (2) longer polymer length provides greater inhibition, and (3) increased local saccharide density (monoantennary vs diantennary) is negligible due to hindered active site of heparanase. Furthermore, HS oligosaccharide and polysaccharide controls illustrate the enhanced potency of a multivalent scaffold. Overall, the results on these studies of the multivalent presentation of saccharides on bottlebrush polymers serve as the platform for the design of potent glycosidase inhibitors and have potential to be applied to other HS-degrading proteins.

Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity

Co-reporter:Ravi S. Loka;Fei Yu;Eric T. Sletten

Chemical Communications 2017 vol. 53(Issue 65) pp:9163-9166

Publication Date(Web):2017/08/10

DOI:10.1039/C7CC04156J

Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics. This glycopolymer also lacks anticoagulant activity.

Utilization of bench-stable and readily available nickel(II) triflate for access to 1,2-cis-2-aminoglycosides

Co-reporter:Eric T. Sletten, Sai Kumar Ramadugu, Hien M. Nguyen

Carbohydrate Research 2016 Volume 435() pp:195-207

Publication Date(Web):29 November 2016

DOI:10.1016/j.carres.2016.10.008

•Commercial Ni(OTf)2 is an effective catalyst to form α-glycosidic bonds.•Comparison of Ni(OTf)2 and in-house prepared Ni(4-F-PhCN)4(OTf)2 is discussed.•Ni(OTf)2 prepared several bioactive motifs difficult under traditional methods.•Investigatory studies of solvent effects on Tn-antigen hydrogen bonding network.The utilization of substoichiometric amounts of commercially available nickel(II) triflate as an activator in the reagent-controlled glycosylation reaction for the stereoselective construction of biologically relevant targets containing 1,2-cis-2-amino glycosidic linkages is reported. This straightforward and accessible methodology is mild, operationally simple and safe through catalytic activation by readily available Ni(OTf)2 in comparison to systems employing our previously in-house prepared Ni(4-F-PhCN)4(OTf)2. We anticipate that the bench-stable and inexpensive Ni(OTf)2, coupled with little to no extra laboratory training to set up the glycosylation reaction and no requirement of specialized equipment, should make this methodology be readily adopted by non-carbohydrate specialists. This report further highlights the efficacy of Ni(OTf)2 to prepare several bioactive motifs, such as blood type A-type V and VI antigens, heparin sulfate disaccharide repeating unit, aminooxy glycosides, and α-GalNAc-Serine conjugate, which cannot be achieved in high yield and α-selectivity utilizing in-house prepared Ni(4-F-PhCN)4(OTf)2 catalyst. The newly-developed protocol eliminates the need for the synthesis of Ni(4-F-PhCN)4(OTf)2 and is scalable and reproducible. Furthermore, computational simulations in combination with 1H NMR studies analyzed the effects of various solvents on the intramolecular hydrogen bonding network of tumor-associated mucin Fmoc-protected GalNAc-threonine amino acid antigen derivative, verifying discrepancies found that were previously unreported.

Iridium-Catalyzed Enantioselective Fluorination of Racemic, Secondary Allylic Trichloroacetimidates

Co-reporter:Qi Zhang; David P. Stockdale; Jason C. Mixdorf; Joseph J. Topczewski

Journal of the American Chemical Society 2015 Volume 137(Issue 37) pp:11912-11915

Publication Date(Web):September 8, 2015

DOI:10.1021/jacs.5b07492

The Ir-catalyzed enantioselective fluorination of racemic, branched allylic trichloroacetimidates with Et3N·3HF is a mild and efficient route for selective incorporation of fluoride ion into allylic systems. We herein describe the asymmetric fluorination of racemic, secondary allylic electrophiles with Et3N·3HF using a chiral-diene-ligated Ir complex. The methodology enables the formation of acyclic fluorine-containing compounds in good yields with excellent levels of asymmetric induction and overcomes the limitations previously associated with the enantioselective construction of secondary allylic fluorides bearing α-linear substituents.

Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and TN Antigen via Nickel Catalysis

Co-reporter:Fei Yu, Matthew S. McConnell, and Hien M. Nguyen

Organic Letters 2015 Volume 17(Issue 8) pp:2018-2021

Publication Date(Web):April 8, 2015

DOI:10.1021/acs.orglett.5b00780

The highly α-selective and scalable synthesis of the Fmoc-protected GalNAc-threonine amino acid and TN antigen in gram scale (0.5–1 g) is described. The challenging 1,2-cis-2-amino glycosidic bond is addressed through a coupling of threonine residues with C(2)-N-ortho-(trifluoromethyl)benzylidenamino trihaloacetimidate donors mediated by Ni(4-F-PhCN)4(OTf)2. The desired 1,2-cis-2-amino glycoside was obtained in 66% yield (3.77 g) with α-only selectivity and subsequently transformed into the Fmoc-protected GalNAc-threonine and TN antigen. This operationally simple procedure no longer requires utilization of the commonly used C(2)-azido donors and overcomes many of the limitations associated with the synthesis of 1,2-cis linkage.

Studies of Highly-Ordered Heterodiantennary Mannose/Glucose-Functionalized Polymers and Concanavalin A Protein Interactions Using Isothermal Titration Calorimetry

Co-reporter:Ravi S. Loka, Matthew S. McConnell, and Hien M. Nguyen

Biomacromolecules 2015 Volume 16(Issue 12) pp:

Publication Date(Web):November 18, 2015

DOI:10.1021/acs.biomac.5b01380

Preparations of the highly ordered monoantennary, homofunctional diantennary, and heterofunctional diantennary neoglycopolymers of α-d-mannose and β-d-glucose residues were achieved via ring-opening metathesis polymerization. Isothermal titration calorimetry measurements of these synthetic neoglycopolymers with Concanavalin A (Con A), revealed that heterofunctional diantennary architectures bearing both α-mannose and nonbinding β-glucose units, poly(Man-Glc), binds to Con A (Ka = 16.1 × 106 M–1) comparably to homofunctional diantennary neoglycopolymer (Ka = 30 × 106 M–1) bearing only α-mannose unit, poly(Man-Man). In addition, poly(Man-Glc) neoglycopolymer shows a nearly 5-fold increasing in binding affinity compared to monoantennary neoglycopolymer, poly(Man). Although the exact mechanism for the high binding affinity of poly(Man-Glc) to Con A is unclear, we hypothesize that the α-mannose bound to Con A might facilitate interaction of β-glucose with the extended binding site of Con A due to the close proximity of β-glucose to α-mannose residues in the designed polymerizable scaffold.

Rhodium-catalyzed benzylic fluorination of trichloroacetimidates

Co-reporter:Qi Zhang, Jason C. Mixdorf, Gilbert J. Reynders III, Hien M. Nguyen

Tetrahedron 2015 Volume 71(Issue 35) pp:5932-5938

Publication Date(Web):2 September 2015

DOI:10.1016/j.tet.2015.04.066

Benzylic fluorides were synthesized via rhodium-catalyzed nucleophilic fluorination of benzylic trichloroacetimidates. A variety of naphthyl, phenyl, and pyridinyl trichloroacetimidates were fluorinated with Et3N·3HF reagent to provide fluorine-containing compounds in moderate to high yields under mild and operationally simple conditions. Preliminary mechanistic studies suggest that benzylic fluorination of trichloroacetimidate substrates are more likely to proceed through a discrete benzylic cation, generated by rhodium catalyst.

Rhodium-catalyzed regioselective opening of vinyl epoxides with Et3N·3HF reagent – formation of allylic fluorohydrins

Co-reporter:Qi Zhang and Hien M. Nguyen

Chemical Science 2014 vol. 5(Issue 1) pp:291-296

Publication Date(Web):03 Oct 2013

DOI:10.1039/C3SC51949J

A highly regioselective rhodium-catalyzed ring-opening of vinyl epoxides with Et3N·3HF reagent to form branched allylic fluorohydrins is described. The reaction occurs at room temperature under ambient air and relies on RhCOD2BF4 as an effective catalyst, providing the desired 1,2-addition allylic fluorohydrins in moderate to good yields with excellent levels of regioselectivity. Mechanistic studies demonstrate that the regioselective ring-opening of enantiopure vinyl epoxide occurs with inversion of stereochemistry.

Transition-Metal-Catalyzed Allylic Substitutions of Trichloroacetimidates

Co-reporter:Jeffrey S. Arnold;Qi Zhang

European Journal of Organic Chemistry 2014 Volume 2014( Issue 23) pp:4925-4948

Publication Date(Web):

DOI:10.1002/ejoc.201402097

Abstract

With the development of practical methods for their preparation, trichloroacetimidates have proven to be valuable substrates for use in carbohydrate and organic synthesis. The broad utility of allyl trichloroacetimidates for the construction of carbon-heteroatom bonds is the result of the unique features of the trichloroacetimidate nitrogen functionality as a directing, nucleophilic, and leaving group. In this review we describe the expansion of Overman's [3,3]-rearrangement of allyl trichloroacetimidates to allylic substitution reactions for regio- and enantioselective C–N, C–O, and C–F bond-forming methodologies.

Recent developments in glycosyl urea synthesis

Co-reporter:Matthew J. McKay, Hien M. Nguyen

Carbohydrate Research 2014 Volume 385() pp:18-44

Publication Date(Web):19 February 2014

DOI:10.1016/j.carres.2013.08.007

•Replacing the native O- & N-glycosidic linkage with urea may increase stability.•Glycosyl urea containing compounds display remarkable biological activity.•Chemical synthesis of glycosyl urea is necessary to facilitate additional research.•There are only a handful of reports for stereoselective synthesis of glycosyl urea.•β-Urea is easier to attain than α-urea and there are more synthetic options available.The area of sugar urea derivatives has received considerable attention in recent years because of the unique structural properties and activities that these compounds display. The urea-linkage at the anomeric center is a robust alternative to the naturally occurring O- and N-glycosidic linkages of oligosaccharides and glycoconjugates, and the natural products that have been identified to contain these structures show remarkable biological activity. While methods for installing the β-urea-linkage at the anomeric center have been around for decades, the first synthesis of α-urea glycosides has been much more recent. In either case, the selective synthesis of glycosyl ureas can be quite challenging, and a mixture of α- and β-isomers will often result. This paper will provide a comprehensive review of the synthetic approaches to α- and β-urea glycosides and examine the structure and activity of the natural products and their analogues that have been identified to contain them.Graphical abstract

Investigations of Scope and Mechanism of Nickel-Catalyzed Transformations of Glycosyl Trichloroacetimidates to Glycosyl Trichloroacetamides and Subsequent, Atom-Economical, One-Step Conversion to -Urea-Glycosides

Co-reporter:Dr. Matthew J. McKay;Nathaniel H. Park;Dr. Hien M. Nguyen

Chemistry - A European Journal 2014 Volume 20( Issue 28) pp:8691-8701

Publication Date(Web):

DOI:10.1002/chem.201402433

Abstract

The development and mechanistic investigation of a highly stereoselective methodology for preparing α-linked-urea neo-glycoconjugates and pseudo-oligosaccharides is described. This two-step procedure begins with the selective nickel-catalyzed conversion of glycosyl trichloroacetimidates to the corresponding α-trichloroacetamides. The α-selective nature of the conversion is controlled with a cationic nickel(II) catalyst, [Ni(dppe)(OTf)₂] (dppe=1,2-bis(diphenylphosphino)ethane, OTf=triflate). Mechanistic studies have identified the coordination of the nickel catalyst with the equatorial C₂-ether functionality of the α-glycosyl trichloroacetimidate to be paramount for achieving an α-stereoselective transformation. A cross-over experiment has indicated that the reaction does not proceed in an exclusively intramolecular fashion. The second step in this sequence is the direct conversion of α-glycosyl trichloroacetamide products into the corresponding α-urea glycosides by reacting them with a wide variety of amine nucleophiles in presence of cesium carbonate. Only α-urea-product formation is observed, as the reaction proceeds with complete retention of stereochemical integrity at the anomeric CN bond.

Rhodium-Catalyzed Sequential Allylic Amination and Olefin Hydroacylation Reactions: Enantioselective Synthesis of Seven-Membered Nitrogen Heterocycles

Co-reporter:Jeffrey S. Arnold;Edward T. Mwenda;Dr. Hien M. Nguyen

Angewandte Chemie International Edition 2014 Volume 53( Issue 14) pp:3688-3692

Publication Date(Web):

DOI:10.1002/anie.201310354

Abstract

Dynamic kinetic asymmetric amination of branched allylic acetimidates has been applied to the synthesis of 2-alkyl-dihydrobenzoazepin-5-ones. These seven-membered-ring aza ketones are prepared in good yield with high enantiomeric excess by rhodium-catalyzed allylic substitution with 2-amino aryl aldehydes followed by intramolecular olefin hydroacylation of the resulting alkenals. This two-step procedure is amenable to varied functionality and proves useful for the enantioselective preparation of these ring systems.

Rhodium-Catalyzed Sequential Allylic Amination and Olefin Hydroacylation Reactions: Enantioselective Synthesis of Seven-Membered Nitrogen Heterocycles

Co-reporter:Jeffrey S. Arnold;Edward T. Mwenda;Dr. Hien M. Nguyen

Angewandte Chemie 2014 Volume 126( Issue 14) pp:3762-3766

Publication Date(Web):

DOI:10.1002/ange.201310354

Abstract

Nickel-catalyzed α-glycosylation of C(1)-hydroxyl D-myo-inositol: a formal synthesis of mycothiol

Co-reporter:Matthew S. McConnell, Fei Yu and Hien M. Nguyen

Chemical Communications 2013 vol. 49(Issue 39) pp:4313-4315

Publication Date(Web):03 Sep 2012

DOI:10.1039/C2CC35823A

Formal synthesis of mycothiol has been developed via nickel-catalyzed α-glycosylation of the C(1)-hydroxyl group of D-myo-inositols with C(2)-N-substituted benzylideneamino N-phenyl trifluoroacetimidate donors. The pseudo-oligosaccharides were obtained in good yield and with excellent α-selectivity. Removal of the C(2)-N-2-trifluoromethylphenyl-benzylidene group under mild conditions provides a pseudo-disaccharide, completing the formal synthesis of mycothiol.

Stereoselective α-glycosylation of C(6)-hydroxyl myo-inositols via nickel catalysis—application to the synthesis of GPI anchor pseudo-oligosaccharides

Co-reporter:Matthew S. McConnell, Enoch A. Mensah, Hien M. Nguyen

Carbohydrate Research 2013 Volume 381() pp:146-152

Publication Date(Web):15 November 2013

DOI:10.1016/j.carres.2013.09.006

•Ni(4-F-PhCN)4(OTf)2 is an effective catalyst in forming α-linked glycosidic bonds.•A comparison of Lewis acids with the Ni catalyst is discussed.•The scope and limitations of Ni(4-F-PhCN)4(OTf)2 are examined.•Two routes for the stereoselective synthesis of GPI anchor analogs are provided.Glycosylphosphatidyl inositol (GPI) anchors play a key role in many eukaryotic biological pathways. Stereoselective synthesis of GPI anchor analogues have proven to be critical for probing the biosynthesis, structure, and biological properties of these compounds. Challenges that have emerged from these efforts include the preparation of the selectively protected myo-inositol building blocks and the stereoselective construction of glucosamine α-linked myo-inositol containing pseudodisaccharide units. Herein, we describe the effectiveness of the cationic nickel(II) catalyst, Ni(4-F-PhCN)4(OTf)2, at promoting selective formation of 1,2-cis-2-amino glycosidic bonds between the C(2)-N-substituted benzylideneamino trihaloacetimidate donors and C(6)-hydroxyl myo-inositol acceptors. This catalytic coupling process allows rapid access to pseudosaccharides of GPI anchors in good yields and with excellent levels of α-selectivity (α:β = 10:1–20:1). In stark contrast, activation of trichloroacetimidate donors containing the C(2)-N-substituted benzylidene group with TMSOTf and BF3.OEt2 provided the desired pseudodisaccharides as a 1:1 mixture of α- and β-isomers.

Rhodium-Catalyzed Dynamic Kinetic Asymmetric Transformations of Racemic Tertiary Allylic Trichloroacetimidates with Anilines

Co-reporter:Jeffrey S. Arnold

Journal of the American Chemical Society 2012 Volume 134(Issue 20) pp:8380-8383

Publication Date(Web):May 7, 2012

DOI:10.1021/ja302223p

The rhodium-catalyzed regio- and enantioselective amination of racemic tertiary allylic trichloroacetimidates with a variety of aniline nucleophiles is a direct and efficient route to chiral α,α-disubstituted allylic N-arylamines. We describe the first dynamic kinetic asymmetric transformations of racemic tertiary allylic electrophiles with anilines utilizing a chiral diene-ligated rhodium catalyst. The method allows for the formation of α,α-disubstituted allylic N-arylamines in moderate to good yields with good to excellent levels of regio- and enantioselectivity.

Recent Advances in Transition Metal-Catalyzed Glycosylation

Co-reporter:Matthew J. McKay and Hien M. Nguyen

ACS Catalysis 2012 Volume 2(Issue 8) pp:1563

Publication Date(Web):June 14, 2012

DOI:10.1021/cs3002513

Having access to mild and operationally simple techniques for attaining carbohydrate targets will be necessary to facilitate advancement in biological, medicinal, and pharmacological research. Even with the abundance of elegant reports for generating glycosidic linkages, stereoselective construction of α- and β-oligosaccharides and glycoconjugates is by no means trivial. In an era when expanded awareness of the impact we are having on the environment drives the state-of-the-art, synthetic chemists are tasked with developing cleaner and more efficient reactions for achieving their transformations. This movement imparts the value that prevention of waste is always superior to its treatment or cleanup. This review will highlight recent advancement in this regard by examining strategies that employ transition metal catalysis in the synthesis of oligosaccharides and glycoconjugates. These methods are mild and effective for constructing glycosidic bonds with reduced levels of waste through utilization of substoichiometric amounts of transition metals to promote the glycosylation.Keywords: anomeric selectivity; carbohydrates; glycosylation; transition metals

Rhodium-catalyzed regio- and enantioselective amination of racemic secondary allylic trichloroacetimidates with N-methyl anilines

Co-reporter:Jeffrey S. Arnold, Gregory T. Cizio, Drew R. Heitz and Hien M. Nguyen

Chemical Communications 2012 vol. 48(Issue 94) pp:11531-11533

Publication Date(Web):28 Sep 2012

DOI:10.1039/C2CC36961C

We report the chiral diene ligated rhodium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of racemic secondary allylic trichloroacetimidates with a variety of N-methyl anilines, providing allylic N-methyl arylamines in high yields, regioselectivity, and enantiomeric excess. The rhodium-catalyzed DYKAT method addresses limitations previously associated with this particular class of aromatic nitrogen nucleophiles.

Studies on the Selectivity Between Nickel-Catalyzed 1,2-cis-2-Amino Glycosylation of Hydroxyl Groups of Thioglycoside Acceptors with C(2)-Substituted Benzylidene N-Phenyl Trifluoroacetimidates and Intermolecular Aglycon Transfer of the Sulfide Group

Co-reporter:Fei Yu and Hien M. Nguyen

The Journal of Organic Chemistry 2012 Volume 77(Issue 17) pp:7330-7343

Publication Date(Web):July 30, 2012

DOI:10.1021/jo301050q

The stereoselective synthesis of saccharide thioglycosides containing 1,2-cis-2-amino glycosidic linkages is challenging. In addition to the difficulties associated with achieving high α-selectivity in the formation of 1,2-cis-2-amino glycosidic bonds, the glycosylation reaction is hampered by undesired transfer of the anomeric sulfide group from the glycosyl acceptor to the glycosyl donor. Overcoming these obstacles will pave the way for the preparation of oligosaccharides and glycoconjugates bearing the 1,2-cis-2-amino glycosidic linkages because the saccharide thioglycosides obtained can serve as donors for another coupling iteration. This approach streamlines selective deprotection and anomeric derivatization steps prior to the subsequent coupling event. We have developed an efficient approach for the synthesis of highly yielding and α-selective saccharide thioglycosides containing 1,2-cis-2-amino glycosidic bonds, via cationic nickel-catalyzed glycosylation of thioglycoside acceptors bearing the 2-trifluoromethylphenyl aglycon with N-phenyl trifluoroacetimidate donors. The 2-trifluoromethylphenyl group effectively blocks transfer of the anomeric sulfide group from the glycosyl acceptor to the C(2)-benzylidene donor and can be easily installed and activated. The current method also highlights the efficacy of the nickel catalyst selectively activating the C(2)-benzylidene imidate group in the presence of the anomeric sulfide group on the glycosyl acceptors.

Iridium-Catalyzed Allylic Fluorination of Trichloroacetimidates

Co-reporter:Joseph J. Topczewski ; Timothy J. Tewson

Journal of the American Chemical Society 2011 Volume 133(Issue 48) pp:19318-19321

Publication Date(Web):November 7, 2011

DOI:10.1021/ja2087213

A rapid allylic fluorination method utilizing trichloroacetimidates in conjunction with an iridium catalyst has been developed. The reaction is conducted at room temperature under ambient air and relies on Et3N·3HF reagent to provide branched allylic fluorides with complete regioselectivity. This high-yielding reaction can be conducted on a multigram scale and shows considerable functional group tolerance. The use of [18F]KF·Kryptofix allowed 18F– incorporation in 10 min.

Nickel-Catalyzed Stereoselective Glycosylation with C(2)-N-Substituted Benzylidene d-Glucosamine and Galactosamine Trichloroacetimidates for the Formation of 1,2-cis-2-Amino Glycosides. Applications to the Synthesis of Heparin Disaccharides, GPI Anchor Pseudodisaccharides, and α-GalNAc

Co-reporter:Enoch A. Mensah ; Fei Yu

Journal of the American Chemical Society 2010 Volume 132(Issue 40) pp:14288-14302

Publication Date(Web):September 22, 2010

DOI:10.1021/ja106682m

The 1,2-cis-2-amino glycosides are key components found within a variety of biologically important oligosaccharides and glycopeptides. Although there are remarkable advances in the synthesis of 1,2-cis-2-amino glycosides, disadvantages of the current state-of-the-art methods include limited substrate scope, low yields, long reaction times, and anomeric mixtures. We have developed a novel method for the synthesis of 1,2-cis-2-amino glycosides via nickel-catalyzed α-selective glycosylation with C(2)-N-substituted benzylidene d-glucosamine and galactosamine trichloroacetimidates. These glycosyl donors are capable of coupling to a wide variety of alcohols to provide glycoconjugates in high yields with excellent levels of α-selectivity. Additionally, only a substoichiometric amount of nickel (5−10 mol %) is required for the reaction to occur at 25 °C. The current nickel method relies on the nature of the nickel−ligand complex to control the α-selectivity. The reactive sites of the nucleophiles or the nature of the protecting groups have little effect on the α-selectivity. This methodology has also been successfully applied to both disaccharide donors and acceptors to provide the corresponding oligosaccharides in high yields and α-selectivity. The efficacy of the nickel procedure has been further applied toward the preparation of heparin disaccharides, GPI anchor pseudodisaccharides, and α-GluNAc/GalNAc. Mechanistic studies suggest that the presence of the substituted benzylidene functionality at the C(2)-amino position of glycosyl donors is crucial for the high α-selectivity observed in the coupling products. Additionally, the α-orientation of the C(1)-trichloroacetimidate group on glycosyl donors is necessary for the coupling process to occur.

Rhodium-Catalyzed Regioselective Amination of Secondary Allylic Trichloroacetimidates with Unactivated Aromatic Amines

Co-reporter:Jeffrey S. Arnold, Robert F. Stone, and Hien M. Nguyen

Organic Letters 2010 Volume 12(Issue 20) pp:4580-4583

Publication Date(Web):September 15, 2010

DOI:10.1021/ol1019025

The use of unactivated aromatic amines in the rhodium-catalyzed regioselective amination of secondary allylic trichloroacetimidates is explored. The desired N-arylamines are obtained in high yields and regioselectivity, favoring the branched amination products. The presence of the trichloroacetimidate leaving group was found to be critical for successful regioselective amination reactions with unactivated aromatic amines. Control studies show that rhodium is not simply acting as a Lewis acid to activate the trichloroacetimidate leaving group.

Rhodium-catalyzed regio- and enantioselective amination of racemic secondary allylic trichloroacetimidates with N-methyl anilines

Co-reporter:Jeffrey S. Arnold, Gregory T. Cizio, Drew R. Heitz and Hien M. Nguyen

Chemical Communications 2012 - vol. 48(Issue 94) pp:NaN11533-11533

Publication Date(Web):2012/09/28

DOI:10.1039/C2CC36961C

Rhodium-catalyzed regioselective opening of vinyl epoxides with Et3N·3HF reagent – formation of allylic fluorohydrins

Co-reporter:Qi Zhang and Hien M. Nguyen

Chemical Science (2010-Present) 2014 - vol. 5(Issue 1) pp:NaN296-296

Publication Date(Web):2013/10/03

DOI:10.1039/C3SC51949J

Nickel-catalyzed α-glycosylation of C(1)-hydroxyl D-myo-inositol: a formal synthesis of mycothiol

Co-reporter:Matthew S. McConnell, Fei Yu and Hien M. Nguyen