Craig S. Wilcox

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Name: Wilcox, Craig

Organization: University of Pittsburgh , USA

Department: Department of Chemistry

Title: Professor(PhD)

TOPICS

Organic Chemistry

Chemicals
References

Asymmetric solution-phase mixture aldol reaction using oligomeric ethylene glycol tagged chiral oxazolidinones

Co-reporter:Serhan Turkyilmaz, Craig S. Wilcox

Tetrahedron Letters 2017 Volume 58, Issue 21(Issue 21) pp:

Publication Date(Web):24 May 2017

DOI:10.1016/j.tetlet.2017.04.026

•Oligomeric ethylene glycol (OEG) derivatives act as chromatographic sorting tags.•Chiral oxazolidinones tagged with OEGs of varying length were synthesized.•4 aldol products were synthesized in one pot using tagged chiral oxazolidinones.•Products were easily separated using silica gel flash column chromatography.•Aldol products were obtained with good yield and enantioselectivity.Sorting tags are oligomeric structures that can be used as protecting groups or chiral auxiliaries enabling solution-phase mixture syntheses of multiple tagged compounds in one pot and allowing for facile and predictable chromatographic separation of products at the end of synthetic sequences. Perfluorinated hydrocarbon and oligomeric ethylene glycol (OEG) derivatives are known classes of sorting tags. Herein we describe the preparation of OEGylated chiral oxazolidinones and their use in asymmetric solution-phase mixture aldol reactions. Through the use of such oxazolidinones based on tyrosine four different individually tagged aldol adducts were obtained as a mixture, chromatographically demixed, detagged, and it was shown that these processes gave the desired aldol products in good yield and enantioselectivity.Download high-res image (96KB)Download full-size image

Synthesis and NMR Analysis of a Conformationally Controlled β-Turn Mimetic Torsion Balance

Co-reporter:Alyssa B. LypsonCraig S. Wilcox

The Journal of Organic Chemistry 2017 Volume 82(Issue 2) pp:

Publication Date(Web):January 10, 2017

DOI:10.1021/acs.joc.6b02307

The molecular torsion balance concept was applied to a new conformationally controlled scaffold and synthesized to accurately evaluate pairwise amino acid interactions in an antiparallel β-sheet motif. The scaffold’s core design combines (ortho-tolyl)amide and o,o,o′-trisubstituted biphenyl structural units to provide a geometry better-suited for intramolecular hydrogen bonding. Like the dibenzodiazocine hinge of the traditional torsion balance, the (ortho-tolyl)amide unit offers restricted rotation around an N-aryl bond. The resulting two-state folding model is a powerful template for measuring hydrogen bond stability between two competing sequences. The aim of this study was to improve the alignment between the amino acid sequences attached to the upper and lower aromatic rings in order to promote hydrogen bond formation at the correct distance and antiparallel orientation. Bromine substituents were introduced ortho to the upper side chains and compared to a control to test our hypothesis. Hydrogen bond formation has been identified between the NH amide proton of the upper side chain (proton donor) and glycine acetamide of the lower side chain (proton acceptor).

Rotational Isomers of N-Methyl-N-arylacetamides and Their Derived Enolates: Implications for Asymmetric Hartwig Oxindole Cyclizations

Co-reporter:Jérémie Mandel, Xiaohong Pan, E. Ben Hay, Steven J. Geib, Craig S. Wilcox, and Dennis P. Curran

The Journal of Organic Chemistry 2013 Volume 78(Issue 8) pp:4083-4089

Publication Date(Web):March 28, 2013

DOI:10.1021/jo400385t

The rotational preferences of N-(2-bromo-4,6-dimethylphenyl)-N-methyl 2-phenylpropanamide were studied as a model of precursors for Hartwig asymmetric oxindole cyclizations. The atropisomers of this compound were separated by flash chromatography, and then the enantiomers were resolved and the interconversions of the stereocenter and the N–Ar axis were studied. Under thermal conditions, the axis is very stable. Under the basic conditions of the Hartwig cyclization, both the stereocenter and the chiral axis equilibrate via enolate formation. The N–Ar rotation barrier of a 2-phenylacetamide analogue was reduced from 31 kcal mol–1 in the precursor to 17 kcal mol–1 in the enolate. Reasons for this dramatic barrier reduction and implications of both N–Ar and amide C–N rotations for Hartwig cyclizations are discussed.

Synthesis of Dibenzazepinones by Palladium-Catalyzed Intramolecular Arylation of o-(2′-Bromophenyl)anilide Enolates

Co-reporter:Xiaohong Pan and Craig S. Wilcox

The Journal of Organic Chemistry 2010 Volume 75(Issue 19) pp:6445-6451

Publication Date(Web):September 7, 2010

DOI:10.1021/jo101137r

A new approach for the convenient synthesis of dibenzazepinones is reported. The key step is the formation of the seven-membered ring through palladium-catalyzed intramolecular arylation of an anilide enolate. The reactions were completed in 10 min at 100 °C with moderate to excellent yields. Aminodibenzazepinone 1, the core structure in the γ-secretase inhibitor LY411575, can be prepared in five steps from 2-bromophenylboronic acid and 2-iodoaniline in 60% overall yield. The synthesis reported here compares favorably with presently available approaches to this interesting ring system.

A Minimal Protein Folding Model To Measure Hydrophobic and CH–π Effects on Interactions between Nonpolar Surfaces in Water

Co-reporter:Brijesh Bhayana;Craig S. Wilcox Dr.

Angewandte Chemie International Edition 2007 Volume 46(Issue 36) pp:

Publication Date(Web):3 AUG 2007

DOI:10.1002/anie.200700932

In the balance: A synthetic molecule that exhibits two-state folding behavior in water is described. Quantitative experiments reveal that the microscopic hydrophobic effect is similar in magnitude to the CH–π interaction. These forces may therefore be equally important in the folding of aromatic-rich regions of proteins. The method allows a new approach to the direct measurement of excess surface energy associated with nonpolar surfaces.

A Minimal Protein Folding Model To Measure Hydrophobic and CH–π Effects on Interactions between Nonpolar Surfaces in Water

Co-reporter:Brijesh Bhayana;Craig S. Wilcox Dr.

Angewandte Chemie 2007 Volume 119(Issue 36) pp:

Publication Date(Web):3 AUG 2007

DOI:10.1002/ange.200700932

Ausgeglichen: Ein synthetisches Molekül, das in Wasser zwischen zwei Zuständen faltet, wird beschrieben. Nach quantitativen Experimenten ist der mikroskopische hydrophobe Effekt ähnlich groß wie die CH-π-Wechselwirkung. Damit sind diese Kräfte möglicherweise gleich wichtig für das Falten arenreicher Proteinregionen. Die Methode bietet einen neuen Zugang zur direkten Messung der mit unpolaren Oberflächen verbundenen Überschussoberflächenenergie.

Solution-Phase Mixture Synthesis with Double-Separation Tagging: Double Demixing of a Single Mixture Provides a Stereoisomer Library of 16 Individual Murisolins

Co-reporter:Craig S. Wilcox Dr.;Venugopal Gudipati;Hejun Lu;Serhan Turkyilmaz;Dennis P. Curran Dr.

Angewandte Chemie 2005 Volume 117(Issue 42) pp:

Publication Date(Web):5 OCT 2005

DOI:10.1002/ange.200501989

Doppelt markiert hält besser: Sechzehn Stereoisomere von Murisolin (siehe Schema) wurden gemeinsam synthetisiert und rein isoliert; dabei half ein Verfahren mit doppelter Markierung und Trennung. Eine Strategie für die Synthese von Stereoisomeren in Lösung durch doppeltes Markieren und Entmischen setzt auf Fluoralkyl- und Oligo(ethylenglycol)-Marker ((OCH₂CH₂)_nOCH₃, OEG).

Solution-Phase Mixture Synthesis with Double-Separation Tagging: Double Demixing of a Single Mixture Provides a Stereoisomer Library of 16 Individual Murisolins

Co-reporter:Craig S. Wilcox, Venugopal Gudipati, Hejun Lu, Serhan Turkyilmaz,Dennis P. Curran

Angewandte Chemie International Edition 2005 44(42) pp:6938-6940

Publication Date(Web):

DOI:10.1002/anie.200501989

A novel precipitating auxiliary approach to the purification of Baylis–Hillman adducts

Co-reporter:Todd Bosanac and Craig S. Wilcox

Chemical Communications 2001 (Issue 17) pp:1618-1619

Publication Date(Web):09 Aug 2001

DOI:10.1039/B103969P

Diaryl alkene alcohol 1 is a ‘precipiton’, a precipitating auxiliary that is used to aid the isolation of Baylis–Hillman adducts.

Precipitons—Functional Protecting Groups to Facilitate Product Separation: Applications in Isoxazoline Synthesis

Co-reporter:Todd Bosanac;Jaemoon Yang Dr.

Angewandte Chemie 2001 Volume 113(Issue 10) pp:

Publication Date(Web):15 MAY 2001

DOI:10.1002/1521-3757(20010518)113:10<1927::AID-ANGE1927>3.0.CO;2-#

Stellen Sie sich mal vor, nach einer vollständigen homogenen Reaktion muss man, um das reine Produkt auszufällen, zu der Reaktionsmischung nur noch einen Katalysator geben oder die Mischung mit weichem UV-Licht bestrahlen. Dies gelingt mit Schutzgruppen, die kontrollierbare Löslichkeitszustände aufweisen, so genannten Präzipitonen. Hier werden die ersten Erfolge dieser Strategie beschrieben (siehe Bild).

Titelbild

Co-reporter:Todd Bosanac;Jaemoon Yang Dr.

Angewandte Chemie 2001 Volume 113(Issue 10) pp:

Publication Date(Web):15 MAY 2001

DOI:10.1002/1521-3757(20010518)113:10<1839::AID-ANGE1839>3.0.CO;2-S

Das Titelbild zeigt ein neues Konzept zur Lösung eines der ältesten und wichtigsten Probleme der Chemie: die Isolierung von reinen Substanzen aus komplexen homogenen Lösungen. Ein Produkt kann gezielt für die Isolierung vorbereitet werden, indem das entsprechende Edukt markiert wird. Die verwendeten Marker, so genannte Präzipitonen, sind ausgesprochen löslich in den verwendeten Lösungsmitteln und unterstützen so die homogenen Reaktionsbedingungen (12). Nach der Reaktion kann das markierte Produkt von der homogenen Mischung (4) aus Lösungsmittel, überschüssigen Reagentien, Katalysatoren und nichtmarkierten Nebenprodukten durch Aktivierung des Präzipitons getrennt werden (45). Die Trennung gelingt, weil die Präzipitonen isomerisieren, mit der Folge, dass das markierte Produkt in fast allen Lösungsmitteln unlöslich ist und nur das reine Produkt ausfällt (5). Das Produkt (6) kann dann durch Filtration oder Zentrifugieren isoliert werden und gegebenenfalls durch Pulverisierung weiter gereinigt werden. Manchmal ist es wünschenswert, unlösliche Katalysatoren oder Nebenprodukte zu entfernen oder das Lösungsmittel der Reaktion durch ein anderes zu ersetzen, bevor die Präzipitonen aktiviert werden (24). Diese geschickte Strategie, die auf einer geplanten Isomerisierung beruht, kann für Reaktionen in jeglichem Maßstab genutzt werden und die Reaktionen können automatisiert werden. Mehr über diese Methode finden Sie in der Zuschrift von Wilcox et al. auf S. 1927ff.