Ohyun Kwon

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Name: Kwon, Ohyun

Organization: University of California , USA

Department: Department of Chemistry and Biochemistry

Title: (PhD)

TOPICS

Organic Chemistry

Chemicals
References

Intramolecular Crossed [2+2] Photocycloaddition through Visible Light-Induced Energy Transfer

Co-reporter:Jiannan Zhao, Jonathan L. Brosmer, Qingxuan Tang, Zhongyue Yang, K. N. Houk, Paula L. Diaconescu, and Ohyun Kwon

Journal of the American Chemical Society July 26, 2017 Volume 139(Issue 29) pp:9807-9807

Publication Date(Web):July 6, 2017

DOI:10.1021/jacs.7b05277

Herein, we present the intramolecular [2+2] cycloadditions of dienones promoted through sensitization, using a polypyridyl iridium(III) catalyst, to form bridged cyclobutanes. In contrast to previous examples of straight [2+2] cycloadditions, these efficient crossed additions were achieved under irradiation with visible light. The reactions delivered desired bridged benzobicycloheptanone products with excellent regioselectivity in high yields (up to 96%). This process is superior to previous syntheses of benzobicyclo[3.1.1]heptanones, which are readily converted to B-norbenzomorphan analogues of biological significance. Electrochemical, computational, and spectroscopic studies substantiated the mechanism of triplet energy transfer and explained the unusual regiocontrol.

Total syntheses of heliotridane and pseudoheliotridane through nitrodiene–acrylate 6π-electrocyclization/[3+2] cycloaddition

Co-reporter:Esra Koc, Ohyun Kwon

Tetrahedron 2017 Volume 73, Issue 29(Issue 29) pp:

Publication Date(Web):20 July 2017

DOI:10.1016/j.tet.2016.12.056

The total syntheses of the pyrrolizidine alkaloids heliotridane and pseudoheliotridane have been accomplished in six steps (overall yields: 24 and 7%, respectively) using, for the first time, the tandem 6π-electrocyclization/[3+2] dipolar cycloaddition of an acyclic nitrodiene, 1-nitro-2-methyl-1,3-butadiene.Download high-res image (99KB)Download full-size image

Catalytic Asymmetric Total Synthesis of (−)-Actinophyllic Acid

Co-reporter:Lingchao Cai; Kui Zhang

Journal of the American Chemical Society 2016 Volume 138(Issue 10) pp:3298-3301

Publication Date(Web):February 24, 2016

DOI:10.1021/jacs.6b00567

Described herein is a catalytic asymmetric total synthesis of (−)-actinophyllic acid, with the key step being a chiral phosphine-catalyzed [3 + 2] annulation between an imine and an allenoate to form a pyrroline intermediate in 99% yield and 94% ee. The synthesis also features CuI-catalyzed coupling between a ketoester and a 2-iodoindole to shape the tetrahydroazocine ring; intramolecular alkylative lactonization; SmI2-mediated intramolecular pinacol coupling between ketone and lactone subunits to assemble the complex skeleton of (−)-actinophyllic acid; and an unprecedented regioselective dehydroxylation.

Phosphine-Catalyzed Intramolecular Cyclizations of α-Nitroethylallenoates Forming (Z)-Furanone Oximes

Co-reporter:Qing-Fa Zhou, Kui Zhang, Lingchao Cai, and Ohyun Kwon

Organic Letters 2016 Volume 18(Issue 12) pp:2954-2957

Publication Date(Web):May 27, 2016

DOI:10.1021/acs.orglett.6b01299

A novel and efficient phosphine-catalyzed intramolecular cyclization of α-nitroethylallenic esters is reported. This process appears to be practical for the stereoselective syntheses of (Z)-furan-2(3H)-one oxime derivatives in excellent yields. Mechanistically, the reaction involves a phosphine-catalyzed Michael addition of an alkylideneazinate and rearrangement of the cyclic nitronate to the α-nitrosodihydrofuran.

Nazarov cyclization of 1,4-pentadien-3-ols: preparation of cyclopenta[b]indoles and spiro[indene-1,4′-quinoline]s

Co-reporter:Zhiming Wang, Xingzhu Xu, Zhanshou Gu, Wei Feng, Houjun Qian, Zhengyi Li, Xiaoqiang Sun and Ohyun Kwon

Chemical Communications 2016 vol. 52(Issue 13) pp:2811-2814

Publication Date(Web):24 Dec 2015

DOI:10.1039/C5CC08596A

The first Lewis acid-catalyzed intramolecular interrupted Nazarov cyclization of 1,4-pentadien-3-ols is described. Using FeBr3 as the catalyst, a series of new substituted cyclopenta[b]indoles was prepared—through a sequence of Nazarov cyclization, nucleophilic amination, and isomerization—with good yields and high diastereo- and regioselectivities. A similar catalytic process was also developed for the synthesis of structurally interesting spiro[indene-1,4′-quinoline]s.

Phosphine-Mediated Iterative Arene Homologation Using Allenes

Co-reporter:Kui Zhang; Lingchao Cai; Xing Jiang; Miguel A. Garcia-Garibay

Journal of the American Chemical Society 2015 Volume 137(Issue 35) pp:11258-11261

Publication Date(Web):August 21, 2015

DOI:10.1021/jacs.5b07403

A PPh3-mediated multicomponent reaction between o-phthalaldehydes, nucleophiles, and monosubstituted allenes furnishes functionalized non-C2-symmetric naphthalenes in synthetically useful yields. When the o-phthalaldehydes were reacted with 1,3-disubstituted allenes in the presence of PPh2Et, naphthalene derivatives were also obtained in up to quantitative yields. The mechanism of the latter transformation is straightforward: aldol addition followed by Wittig olefination and dehydration. The mechanism of the former is a tandem γ-umpolung/aldol/Wittig/dehydration process, as established by preparation of putative reaction intermediates and mass spectrometric analysis. This transformation can be applied iteratively to prepare anthracenes and tetracenes using carboxylic acids as pronucleophiles.

Functionalized α,α-Dibromo Esters through Claisen Rearrangements of Dibromoketene Acetals

Co-reporter:Nathan J. Dupper and Ohyun Kwon

Organic Letters 2015 Volume 17(Issue 4) pp:1054-1057

Publication Date(Web):February 11, 2015

DOI:10.1021/acs.orglett.5b00209

Allylic alcohols can be transformed into γ,δ-unsaturated α,α-dibromo esters through a two-step process: formation of a bromal-derived mixed acetal, followed by tandem dehydrobromination/Claisen rearrangement. The scope and selectivity of both steps have been investigated. The product α,α-dibromo esters were subjected to various carbon–carbon bond-forming reactions, oxidations, and lactonizations.

Synthesis of Functionalized Alkylidene Indanes and Indanones through Tandem Phosphine–Palladium Catalysis

Co-reporter:Yi Chiao Fan and Ohyun Kwon

Organic Letters 2015 Volume 17(Issue 9) pp:2058-2061

Publication Date(Web):April 14, 2015

DOI:10.1021/acs.orglett.5b00554

Densely functionalized alkylidene indanes and indanones can be prepared efficiently in one pot, in high yields with good stereoselectivities (in some cases exclusively the Z-isomer), through a route involving phosphine-catalyzed Michael addition followed by palladium-catalyzed Heck cyclization. These transformations tolerate substrates bearing various substituents around the indane/indanone motif. Employing this technology, a concise formal synthesis of sulindac, a nonsteroidal anti-inflammatory drug, has been established.

Stereoselective syntheses of α,β-unsaturated γ-amino esters through phosphine-catalyzed γ-umpolung additions of sulfonamides to γ-substituted allenoates

Co-reporter:Qing-Fa Zhou, Kui Zhang, Ohyun Kwon

Tetrahedron Letters 2015 Volume 56(Issue 23) pp:3273-3276

Publication Date(Web):3 June 2015

DOI:10.1016/j.tetlet.2015.01.120

α,β-Unsaturated γ-amino esters can be synthesized efficiently and stereoselectively through phosphine-catalyzed γ-umpolung additions of sulfonamides to γ-substituted allenoates. The structures of the sulfonamide and γ-substituted allenoate partners can be varied to achieve a range of α,β-unsaturated γ-amino esters with potentially interesting chemical and biological properties.

Phosphine catalysis of allenes with electrophiles

Co-reporter:Zhiming Wang, Xingzhu Xu and Ohyun Kwon

Chemical Society Reviews 2014 vol. 43(Issue 9) pp:2927-2940

Publication Date(Web):24 Mar 2014

DOI:10.1039/C4CS00054D

Nucleophilic phosphine catalysis of allenes with electrophiles is one of the most powerful and straightforward synthetic strategies for the generation of highly functionalized carbocycle or heterocycle structural motifs, which are present in a wide range of bioactive natural products and medicinally important substances. The reaction topologies can be controlled through a judicious choice of the phosphine catalyst and the structural variations of starting materials. This Tutorial Review presents selected examples of nucleophilic phosphine catalysis using allenes and electrophiles.

Hydroxyproline-Derived Pseudoenantiomeric [2.2.1] Bicyclic Phosphines: Asymmetric Synthesis of (+)- and (−)-Pyrrolines

Co-reporter:Christopher E. Henry ; Qihai Xu ; Yi Chiao Fan ; Tioga J. Martin ; Lee Belding ; Travis Dudding

Journal of the American Chemical Society 2014 Volume 136(Issue 34) pp:11890-11893

Publication Date(Web):August 6, 2014

DOI:10.1021/ja505592h

We have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]heptanes from naturally occurring trans-4-hydroxy-l-proline in six chemical operations. These syntheses are concise and highly efficient, with straightforward purification. When we used these chiral phosphines as catalysts for reactions of γ-substituted allenoates with imines, we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities. These two diastereoisomeric phosphines functioned as pseudoenantiomers, providing their chiral pyrrolines with opposite absolute configurations.

Phosphine-Initiated General-Base-Catalyzed Quinolone Synthesis

Co-reporter:San Khong ;Dr. Ohyun Kwon

Asian Journal of Organic Chemistry 2014 Volume 3( Issue 4) pp:453-457

Publication Date(Web):

DOI:10.1002/ajoc.201402039

Abstract

Phosphinocatalysis provides a new approach toward 3-substituted-4-quinolones. A simple procedure, which uses Ph₃P as an inexpensive catalyst and S-phenyl 2-(N-tosylamido)benzothioates and activated alkynes as starting materials, provides direct access to several 3-aroyl-4-quinolones and methyl 4-quinolone-3-carboxylate esters. The reaction presumably occurs through general base catalysis, with the initial addition of Ph₃P to the activated alkyne generating the phosphonium enoate zwitterion, which acts as the strong base that initiates the reaction.

Origins of 1,6-Stereoinduction in Torquoselective 6π Electrocyclizations

Co-reporter:Ashay Patel ; Gregg A. Barcan ; Ohyun Kwon ;K. N. Houk

Journal of the American Chemical Society 2013 Volume 135(Issue 12) pp:4878-4883

Publication Date(Web):February 27, 2013

DOI:10.1021/ja400882y

A novel stereoselective electrocyclization developed for the total synthesis of reserpine has been explored by both experiment and theory. A stereocenter six atoms away from the newly forming chiral center is responsible for the diastereoselectivity of the ring closure. This stereogenic center, lying at the junction of two six-membered rings, defines the conformation of the substrates’ fused ring skeleton that ultimately distinguishes between the two allowed, disrotatory triene geometries at the transition state. The presence of allylic strain in the disfavored transition state results in a torquoselective ring closure (dr up to 15.7:1).

Synthesis of nitrodienes, nitrostyrenes, and nitrobiaryls through palladium-catalyzed couplings of β-nitrovinyl and o-nitroaryl thioethers

Co-reporter:Gardner S. Creech and Ohyun Kwon

Chemical Science 2013 vol. 4(Issue 6) pp:2670-2674

Publication Date(Web):09 Apr 2013

DOI:10.1039/C3SC50773D

A highly efficient, base-free, mild protocol for the palladium-catalyzed, copper-activated desulfitative couplings of vinyl and aryl β-nitrothioethers generates a wide variety of conjugated nitroorganics. Orthogonality to traditional Suzuki–Miyaura coupling is demonstrated, as well as synthetic utility, through reductive Cadogan cyclization, for the formation of indoles, carbazoles, and pyrroles.

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

Co-reporter:Yi Chiao Fan and Ohyun Kwon

Chemical Communications 2013 vol. 49(Issue 99) pp:11588-11619

Publication Date(Web):22 Oct 2013

DOI:10.1039/C3CC47368F

In nucleophilic phosphine catalysis, tertiary phosphines undergo conjugate additions to activated carbon–carbon multiple bonds to form β-phosphonium enolates, β-phosphonium dienolates, β-phosphonium enoates, and vinyl phosphonium ylides as intermediates. When these reactive zwitterionic species react with nucleophiles and electrophiles, they may generate carbo- and heterocycles with multifarious molecular architectures. This article describes the reactivities of these phosphonium zwitterions, the applications of phosphine catalysis in the syntheses of biologically active compounds and natural products, and recent developments in the enantioselective phosphine catalysis.

Enantioselective total synthesis of (+)-ibophyllidine via an asymmetric phosphine-catalyzed [3 + 2] annulation

Co-reporter:Ian P. Andrews and Ohyun Kwon

Chemical Science 2012 vol. 3(Issue 8) pp:2510-2514

Publication Date(Web):23 May 2012

DOI:10.1039/C2SC20468A

In this study we performed the total synthesis of the terpene indole alkaloid (+)-ibophyllidine through a pathway involving asymmetric phosphine catalysis, with our novel L-4-hydroxyproline-derived chiral phosphine mediating the key [3 + 2] annulation. Hydrogenation of the [3 + 2] adduct allowed the rapid formation of the stereochemically dense pyrrolidine ring of (+)-ibophyllidine in excellent yield with exceptionally high levels of both diastereo- and enantioselectivity. We constructed the remainder of the pentacyclic skeleton through an intramolecular alkylation and an intramolecular aza-Morita–Baylis–Hillman reaction.

A Torquoselective 6π Electrocyclization Approach to Reserpine Alkaloids

Co-reporter:Gregg A. Barcan, Ashay Patel, K. N. Houk, and Ohyun Kwon

Organic Letters 2012 Volume 14(Issue 21) pp:5388-5391

Publication Date(Web):October 5, 2012

DOI:10.1021/ol302265z

A highly torquoselective thermal triene 6π electrocyclization controls the relative stereochemistry between the C3 and C18 stereocenters of the dodecahydroindolo[2,3-a]benzo[g]quinolizine skeleton of reserpine-type alkaloids. Employing a tandem cross-coupling/electrocyclization protocol allowed us to form the requisite triene and ensure its subsequent cyclization. A novel low-temperature dibromoketene acetal Claisen rearrangement established the requisite exocyclic dienylbromide precursor for the palladium-catalyzed cross-coupling reaction.

Total Synthesis of (±)-Hirsutine: Application of Phosphine-Catalyzed Imine–Allene [4 + 2] Annulation

Co-reporter:Reymundo A. Villa, Qihai Xu, and Ohyun Kwon

Organic Letters 2012 Volume 14(Issue 17) pp:4634-4637

Publication Date(Web):August 24, 2012

DOI:10.1021/ol302077n

The total synthesis of the indole alkaloid hirsutine has been achieved, with a key step being the application of our phosphine-catalyzed [4 + 2] annulation of an imine with ethyl α-methylallenoate. From commercially available indole-2-carboxaldehyde, the target was synthesized in 14 steps and 6.7% overall yield.

Phosphine/Palladium-Catalyzed Syntheses of Alkylidene Phthalans, 3-Deoxyisoochracinic Acid, Isoochracinic Acid, and Isoochracinol

Co-reporter:Yi Chiao Fan and Ohyun Kwon

Organic Letters 2012 Volume 14(Issue 13) pp:3264-3267

Publication Date(Web):June 21, 2012

DOI:10.1021/ol301154f

In this study we used sequential catalysis—PPh3-catalyzed nucleophilic addition followed by Pd(0)-catalyzed Heck cyclization—to construct complex functionalized alkylidene phthalans rapidly, in high yields, and with good stereoselectivities (E/Z ratios of up to 1:22). The scope of this Michael–Heck reaction includes substrates bearing various substituents around the alkylidene phthalan backbone. Applying this efficient sequential catalysis, we accomplished concise total syntheses of 3-deoxyisoochacinic acid, isoochracinic acid, and isoochracinol.

Phosphine-catalyzed intramolecular γ-umpolung addition of α-aminoalkylallenic esters: facile synthesis of 3-carbethoxy-2-alkyl-3-pyrrolines

Co-reporter:Ian P. Andrews, Brian R. Blank and Ohyun Kwon

Chemical Communications 2012 vol. 48(Issue 43) pp:5373-5375

Publication Date(Web):23 Apr 2012

DOI:10.1039/C2CC31347B

An array of N-tosylated α-aminoalkylallenic esters was prepared and their cyclization under the influence of nucleophilic phosphine catalysts was explored. The α-aminoalkylallenic esters were prepared through aza-Baylis–Hillman reactions or novel DABCO-mediated decarboxylative rearrangements of allenylic carbamates. Conversion of these substrates to 3-carbethoxy-2-alkyl-3-pyrrolines was facilitated through Ph3P-catalyzed intramolecular γ-umpolung addition.

One-Pot Phosphine-Catalyzed Syntheses of Quinolines

Co-reporter:San Khong and Ohyun Kwon

The Journal of Organic Chemistry 2012 Volume 77(Issue 18) pp:8257-8267

Publication Date(Web):August 28, 2012

DOI:10.1021/jo3015825

In this study we developed an efficient one-pot procedure for the preparation of 3-substituted and 3,4-disubstituted quinolines from stable starting materials (activated acetylenes reacting with o-tosylamidobenzaldehydes and o-tosylamidophenones, respectively) under mild conditions. The reaction appears to operate under a general base catalysis mechanism, instigated by the β-phosphonium enoate α-vinyl anion generated in situ through nucleophilic addition of PPh3 to the activated alkyne. Michael addition of the deprotonated tosylamides to the activated alkynes and subsequent rapid aldol cyclization led to the formation of labile N-tosyldihydroquinoline intermediates. Driven by aromatization, detosylation of the dihydroquinoline intermediates occurred readily in the presence of dilute aqueous HCl to give the final quinoline products.

Phosphine-Catalyzed Annulations of Azomethine Imines: Allene-Dependent [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] Pathways

Co-reporter:Risong Na ; Chengfeng Jing ; Qihai Xu ; Hui Jiang ; Xi Wu ; Jiayan Shi ; Jiangchun Zhong ; Min Wang ; Diego Benitez ; Ekaterina Tkatchouk ; William A. Goddard ; III; Hongchao Guo

Journal of the American Chemical Society 2011 Volume 133(Issue 34) pp:13337-13348

Publication Date(Web):August 3, 2011

DOI:10.1021/ja200231v

In this paper we describe the phosphine-catalyzed [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] annulations of azomethine imines and allenoates. These processes mark the first use of azomethine imines in nucleophilic phosphine catalysis, producing dinitrogen-fused heterocycles, including tetrahydropyrazolo-pyrazolones, -pyridazinones, -diazepinones, and -diazocinones. Counting the two different reaction modes in the [3 + 3] cyclizations, there are five distinct reaction pathways—the choice of which depends on the structure and chemical properties of the allenoate. All reactions are operationally simple and proceed smoothly under mild reaction conditions, affording a broad range of 1,2-dinitrogen-containing heterocycles in moderate to excellent yields. A zwitterionic intermediate formed from a phosphine and two molecules of ethyl 2,3-butadienoate acted as a 1,5-dipole in the annulations of azomethine imines, leading to the [3 + 2 + 3] tetrahydropyrazolo-diazocinone products. The incorporation of two molecules of an allenoate into an eight-membered-ring product represents a new application of this versatile class of molecules in nucleophilic phosphine catalysis. The salient features of this protocol—the facile access to a diverse range of nitrogen-containing heterocycles and the simple preparation of azomethine imine substrates—suggest that it might find extensive applications in heterocycle synthesis.

Phosphine-Initiated General Base Catalysis: Facile Access to Benzannulated 1,3-Diheteroatom Five-Membered Rings via Double-Michael Reactions of Allenes

Co-reporter:Judy Szeto, Vardhineedi Sriramurthy, and Ohyun Kwon

Organic Letters 2011 Volume 13(Issue 20) pp:5420-5423

Publication Date(Web):September 20, 2011

DOI:10.1021/ol201730q

General base-catalyzed double-Michael reactions of allenes with various dinucleophiles are described. The reactions are facilitated most efficiently by a catalytic amount of trimethylphosphine, affording six types of C2-functionalized benzannulated five-membered heterocycles: benzimidazolines, benzoxazolines, benzothiazolines, 1,3-benzodioxoles, 1,3-benzoxathioles, and 1,3-benzodithioles. This atom-economical reaction is operationally simple and provides the product heterocycles in good to excellent yields. Careful mechanistic studies unveiled the phosphine-triggered general base catalysis pathway. Furthermore, the double-Michael reaction can serve as an alternative method for the selective monoketalization of β-diketones.

Diversity Through a Branched Reaction Pathway: Generation of Multicyclic Scaffolds and Identification of Antimigratory Agents

Co-reporter:Dr. Zhiming Wang;Dr. Sabrina Castellano;Dr. Sape S. Kinderman;Christian E. Argueta;Dr. Anwar B. Beshir; Gabriel Fenteany; Ohyun Kwon

Chemistry - A European Journal 2011 Volume 17( Issue 2) pp:649-654

Publication Date(Web):

DOI:10.1002/chem.201002195

Abstract

A library of 91 heterocyclic compounds composed of 16 distinct scaffolds has been synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels–Alder reactions, and, in some cases, hydrolysis. This effort in diversity-oriented synthesis produced a collection of compounds that exhibited high levels of structural variation both in terms of stereochemistry and the range of scaffolds represented. A simple but powerful sequence of reactions thus led to a high-diversity library of relatively modest size with which to explore biologically relevant regions of chemical space. From this library, several molecules were identified that inhibit the migration and invasion of breast cancer cells and may serve as leads for the development of antimetastatic agents.

Phosphine-Catalyzed [4+2] Annulations of 2-Alkylallenoates and Olefins: Synthesis of Multisubstituted Cyclohexenes

Co-reporter:Yang S. Tran;Tioga J. Martin ; Ohyun Kwon

Chemistry – An Asian Journal 2011 Volume 6( Issue 8) pp:2101-2106

Publication Date(Web):

DOI:10.1002/asia.201100190

Abstract

From our investigations on phosphine-catalyzed [4+2] annulations between α-alkyl allenoates and activated olefins for the synthesis of cyclohexenes, we discovered a hexamethylphosphorous triamide (HMPT)-catalyzed [4+2] reaction between α-alkyl allenoates 1 and arylidene malonates or arylidene cyanoacetates 2 that provides highly functionalized cyclohexenes 3 and 4 in synthetically useful yields (30–89 %), with moderate to exclusive regioselectivity, and reasonable diastereoselectivity. Interestingly, the [4+2] annulations between the α-alkyl allenoates 1 and the olefins 2 manifested a polarity inversion of the 1,4-dipole synthon 1, depending on the structure of the olefin, thus providing cyclohexenes 3 exclusively when using arylidene cyanoacetates. The polarity inversion of α-alkyl allenoates from a 1,4-dipole A to B under phosphine catalysis can be explained by an equilibrium between the phosphonium dienolate C and the phosphorous ylide D.

Diversity through phosphine catalysis identifies octahydro-1,6-naphthyridin-4-ones as activators of endothelium-driven immunity

Co-reporter:Robert Modlin;Jon Kibbie;Daniel Cruz;Zhiming Wang

PNAS 2011 Volume 108 (Issue 17 ) pp:6769-6774

Publication Date(Web):2011-04-26

DOI:10.1073/pnas.1015254108

The endothelium plays a critical role in promoting inflammation in cardiovascular disease and other chronic inflammatory conditions, and many small-molecule screens have sought to identify agents that prevent endothelial cell activation. Conversely, an augmented immune response can be protective against microbial pathogens and in cancer immunotherapy. Yet, small-molecule screens to identify agents that induce endothelial cell activation have not been reported. In this regard, a bioassay was developed that identifies activated endothelium by its capacity to trigger macrophage inflammatory protein 1 beta from primary monocytes. Subsequently, a 642-compound library of 39 distinctive scaffolds generated by a diversity-oriented synthesis based on the nucleophilic phosphine catalysis was screened for small molecules that activated the endothelium. Among the active compounds identified, the major classes were synthesized through the sequence of phosphine-catalyzed annulation, Tebbe reaction, Diels–Alder reaction, and in some cases, hydrolysis. Ninety-six analogs of one particular class of compounds, octahydro-1,6-naphthyridin-4-ones, were efficiently prepared by a solid-phase split-and-pool technique and by solution phase analog synthesis. Structure-function analysis combined with transcriptional profiling of active and inactive octahydro-1,6-naphthyridin-4-one analogs identified inflammatory gene networks induced exclusively by the active compound. The identification of a family of chemical probes that augment innate immunity through endothelial cell activation provides a framework for understanding gene networks involved in endothelial inflammation as well as the development of novel endothelium-driven immunotherapeutic agents.

Tandem 6π-Electrocyclization and Cycloaddition of Nitrodienes to Yield Multicyclic Nitroso Acetals

Co-reporter:Gardner S. Creech

Journal of the American Chemical Society 2010 Volume 132(Issue 26) pp:8876-8877

Publication Date(Web):June 17, 2010

DOI:10.1021/ja1038819

Upon heating, nitrodienes rearrange through 6π-electrocyclization to form nitronate intermediates, which can be captured through tandem [3 + 2] dipolar cycloadditions to form highly functionalized nitroso acetals. The one-pot, two-step domino process is highly efficient, proceeding with good facial selectivity and exoselectivity. Dipolarophiles featuring electron-rich, -neutral, and -deficient carbon−carbon double bonds are viable substrates for [3 + 2] cycloadditions with the in situ generated nitronates. In addition, the highly functionalized nitroso acetal products can be hydrogenolyzed selectively to form densely functionalized spirocyclic hydroxy amides or hydroxy γ-amino acids.

Diphosphine-Catalyzed Mixed Double-Michael Reaction: A Unified Synthesis of Indolines, Dihydropyrrolopyridines, Benzimidazolines, Tetrahydroquinolines, Tetrahydroisoquinolines, Dihydrobenzo-1,4-oxazines, and Dihydrobenzo-3,1-oxazines

Co-reporter:Vardhineedi Sriramurthy and Ohyun Kwon

Organic Letters 2010 Volume 12(Issue 5) pp:1084-1087

Publication Date(Web):February 9, 2010

DOI:10.1021/ol100078w

Seven different types of benzannulated N-heterocycles—indolines, dihydropyrrolopyridines, benzimidazolines, dihydrobenzo-3,1-oxazines, benzomorpholines, tetrahydroquinolines, and tetrahydroisoquinolines—can be obtained from simple dinucleophiles and electron-deficient acetylenes in one synthetic step. This powerful methodology was made possible through the use of diphenylphosphinopropane (DPPP) as the catalyst, with acetic acid and sodium acetate used as additives in some cases. The benzannulated N-heterocycles were isolated in excellent yields under mild metal-free conditions; they were purified without the need for aqueous workups.

Equilibrium between a vinylogous ylide and a phosphonium dienolate zwitterion: vinylogous Wittig olefination versus vinylogous aldol-type reaction

Co-reporter:San N. Khong, Yang S. Tran, Ohyun Kwon

Tetrahedron 2010 66(26) pp: 4760-4768

Publication Date(Web):

DOI:10.1016/j.tet.2010.03.044

Phosphine-Promoted [3 + 3] Annulations of Aziridines With Allenoates: Facile Entry Into Highly Functionalized Tetrahydropyridines

Co-reporter:Hongchao Guo ; Qihai Xu

Journal of the American Chemical Society 2009 Volume 131(Issue 18) pp:6318-6319

Publication Date(Web):April 17, 2009

DOI:10.1021/ja8097349

The phosphine-mediated [3 + 3] annulations of aziridines and allenes are experimentally simple reactions, run under very mild conditions, for the preparation of highly functionalized tetrahydropyridines in yields of up to 98% and trans/cis ratios of up to 97:3. In addition to steps that are typical of nucleophilic phosphine-catalyzed reactions of allenoates, the mechanism of this new reaction features apparent nucleophilic aromatic substitution and concomitant desulfonylation, processes hitherto unknown during phosphine-promoted cycloaddition reactions. Notably, these reactions are the first reported examples of aziridines as reaction partners in nucleophilic phosphine-catalyzed transformations.

Nazarov cyclization of 1,4-pentadien-3-ols: preparation of cyclopenta[b]indoles and spiro[indene-1,4′-quinoline]s

Co-reporter:Zhiming Wang, Xingzhu Xu, Zhanshou Gu, Wei Feng, Houjun Qian, Zhengyi Li, Xiaoqiang Sun and Ohyun Kwon

Chemical Communications 2016 - vol. 52(Issue 13) pp:NaN2814-2814

Publication Date(Web):2015/12/24

DOI:10.1039/C5CC08596A

Phosphine-catalyzed intramolecular γ-umpolung addition of α-aminoalkylallenic esters: facile synthesis of 3-carbethoxy-2-alkyl-3-pyrrolines

Co-reporter:Ian P. Andrews, Brian R. Blank and Ohyun Kwon

Chemical Communications 2012 - vol. 48(Issue 43) pp:NaN5375-5375

Publication Date(Web):2012/04/23

DOI:10.1039/C2CC31347B

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

Co-reporter:Yi Chiao Fan and Ohyun Kwon