Christopher Beaudry

Bio-inspired oxidative phenolic coupling: Total synthesis of the diarylether heptanoid (±)-pterocarine

Co-reporter:M. Quamar Salih, Christopher M. Beaudry

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

Publication Date(Web):24 May 2017

DOI:10.1016/j.tetlet.2017.04.015

•A bio-inspired synthesis of (±)-pterocarine is reported.•An intramolecular oxidative phenolic coupling forms a diphenyl ether.•Oxidative phenolic coupling proceeds with benzene hydroxylation.The diaryletherheptanoid natural product, pterocarine, is expeditiously synthesized using a bioinspired intramolecular oxidative phenolic coupling of acerogenin G. The cyclization precursor is prepared from a simple cinnamic acid derivative in three high yielding synthetic operations. The key oxidative coupling is inspired by biosynthetic hypotheses; however, the oxidative coupling proceeds with concomitant hydroxylation of the diphenyl ether motif.Download high-res image (55KB)Download full-size image

Total Synthesis of (±)-Goniomitine via Radical Translocation

Co-reporter:Jessica K. Vellucci and Christopher M. Beaudry

Organic Letters 2015 Volume 17(Issue 18) pp:4558-4560

Publication Date(Web):September 8, 2015

DOI:10.1021/acs.orglett.5b02277

The aspidosperma alkaloid goniomitine was synthesized in six steps from 2-ethyl-δ-valerolactam. The convergent strategy features an Ullman coupling to assemble the required carbon atoms. A complexity-generating radical translocation reaction was used to build the indole architecture.

Regioselective Suzuki couplings of non-symmetric dibromobenzenes: alkenes as regiochemical control elements

Co-reporter:Peng Zhao, Marshall D. Young and Christopher M. Beaudry

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 22) pp:6162-6165

Publication Date(Web):07 May 2015

DOI:10.1039/C5OB00717H

The regiochemical outcome of Suzuki couplings of non-symmetric dibromobenzenes is investigated. Selectivities are dependent on the proximity of the bromine atom to alkene substituents, not on steric or electronic effects. Extension to a one-pot three-component Suzuki reaction leads to efficient terphenyl syntheses.

The development of carbon–carbon bond forming reactions of aminal radicals

Co-reporter:David A. Schiedler, Jessica K. Vellucci, Yi Lu, Christopher M. Beaudry

Tetrahedron 2015 Volume 71(Issue 9) pp:1448-1465

Publication Date(Web):4 March 2015

DOI:10.1016/j.tet.2014.12.067

Aminal radicals were generated and used in synthetic reactions for the first time. Aminal radicals are formed from aminals by radical translocation using AIBN and a stoichiometric hydrogen atom donor, or by SmI2 reduction of N-acyl amidines or amidinium ions in the presence of a proton source. Aminal radicals were found to participate in inter- and intramolecular C–C bond forming reactions with electron deficient alkenes. Chemical yields were as high as 99%.

Total Synthesis of Russuphelol: A Case of Mistaken Chirality

Co-reporter:M. Quamar Salih and Christopher M. Beaudry

Organic Letters 2014 Volume 16(Issue 18) pp:4964-4966

Publication Date(Web):September 10, 2014

DOI:10.1021/ol502459p

The chlorohydroquinone tetramer, russuphelol, does not have stereocenters; however, it was reported as a chiral optically active substance with stable enantiomeric conformations. The natural product is synthesized in six steps and 14% overall yield. Synthetic material was used to experimentally investigate its chiral properties.

Reductive Synthesis of Aminal Radicals for Carbon–Carbon Bond Formation

Co-reporter:David A. Schiedler, Yi Lu, and Christopher M. Beaudry

Organic Letters 2014 Volume 16(Issue 4) pp:1160-1163

Publication Date(Web):February 10, 2014

DOI:10.1021/ol500024q

Aminal radicals were generated by reduction of the corresponding amidine or amidinium ion. The intermediate radicals participate in C–C bond-forming reactions to produce fully substituted aminal stereocenters. No toxic additives or reagents are required. More than 30 substrate combinations are reported, and chemical yields are as high as 99%.

The nature of persistent conformational chirality, racemization mechanisms, and predictions in diarylether heptanoid cyclophane natural products

Co-reporter:Ommidala Pattawong, M. Quamar Salih, Nicholas T. Rosson, Christopher M. Beaudry and Paul Ha-Yeon Cheong

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 20) pp:3303-3309

Publication Date(Web):04 Apr 2014

DOI:10.1039/C3OB42550A

Restricted rotations of chemical bonds can lead to the presence of persistent conformational chirality in molecules lacking stereocenters. We report the development of first-of-a-kind predictive rules that enable identification of conformational chirality and prediction of racemization barriers in the diarylether heptanoid (DAEH) natural products that do not possess stereocenters. These empirical rules-of-thumb are based on quantum mechanical computations (SCS-MP2/∞//B3LYP/6-31G*/PCM) of racemization barriers of four representative DAEHs. Specifically, the local symmetry of ring B and the E/Z configuration of the vinylogous acid/ester are critical in determining conformational chirality in the DAEH natural product family.

Synthesis of Bis(indole) Alkaloids from Arundo donax: The Ynindole DielsAlder Reaction, Conformational Chirality, and Absolute Stereochemistry

Co-reporter:Dr. Jingjin Chen;Andrew J. Ferreira;Dr. Christopher M. Beaudry

Angewandte Chemie International Edition 2014 Volume 53( Issue 44) pp:11931-11934

Publication Date(Web):

DOI:10.1002/anie.201407336

Abstract

Bis(indole) alkaloids from Arundo donax were synthesized using the first ynindole Diels–Alder reaction. The alkaloids are chiral, having stable enantiomeric conformations with half-lives of racemization of t_1/2=4150–25100 seconds at room temperature. Their absolute stereochemistry was determined using the exciton chirality method.

Enantioselective and Regioselective Pyrone DielsAlder Reactions of Vinyl Sulfones: Total Synthesis of (+)-Cavicularin

Co-reporter:Peng Zhao ;Dr. Christopher M. Beaudry

Angewandte Chemie International Edition 2014 Volume 53( Issue 39) pp:10500-10503

Publication Date(Web):

DOI:10.1002/anie.201406621

Abstract

The total synthesis of (+)-cavicularin is described. The synthesis features an enantio- and regioselective pyrone Diels–Alder reaction of a vinyl sulfone to construct the cyclophane architecture of the natural product. The Diels–Alder substrate was prepared by a regioselective one-pot three-component Suzuki reaction of a non-symmetric dibromoarene.

Enantioselective and Regioselective Pyrone DielsAlder Reactions of Vinyl Sulfones: Total Synthesis of (+)-Cavicularin

Co-reporter:Peng Zhao ;Dr. Christopher M. Beaudry

Angewandte Chemie 2014 Volume 126( Issue 39) pp:10668-10671

Publication Date(Web):

DOI:10.1002/ange.201406621

Abstract

The total synthesis of (+)-cavicularin is described. The synthesis features an enantio- and regioselective pyrone Diels–Alder reaction of a vinyl sulfone to construct the cyclophane architecture of the natural product. The Diels–Alder substrate was prepared by a regioselective one-pot three-component Suzuki reaction of a non-symmetric dibromoarene.

Synthesis of Bis(indole) Alkaloids from Arundo donax: The Ynindole DielsAlder Reaction, Conformational Chirality, and Absolute Stereochemistry

Co-reporter:Dr. Jingjin Chen;Andrew J. Ferreira;Dr. Christopher M. Beaudry

Angewandte Chemie 2014 Volume 126( Issue 44) pp:12125-12128

Publication Date(Web):

DOI:10.1002/ange.201407336

Abstract

Bis(indole) alkaloids from Arundo donax were synthesized using the first ynindole Diels–Alder reaction. The alkaloids are chiral, having stable enantiomeric conformations with half-lives of racemization of t_1/2=4150–25100 seconds at room temperature. Their absolute stereochemistry was determined using the exciton chirality method.

Total Synthesis of (±)-Cavicularin: Control of Pyrone Diels–Alder Regiochemistry Using Isomeric Vinyl Sulfones

Co-reporter:Peng Zhao and Christopher M. Beaudry

Organic Letters 2013 Volume 15(Issue 2) pp:402-405

Publication Date(Web):January 9, 2013

DOI:10.1021/ol303390a

An intramolecular pyrone Diels–Alder reaction–elimination retro-Diels–Alder cascade of a vinyl sulfone was used in the synthesis of cavicularin, a molecule possessing conformational chirality. The vinyl sulfone substitution pattern allowed for regiocontrol in the Diels–Alder cascade event.

Enantioselective Ullmann Ether Couplings: Syntheses of (−)-Myricatomentogenin, (−)-Jugcathanin, (+)-Galeon, and (+)-Pterocarine

Co-reporter:M. Quamar Salih and Christopher M. Beaudry

Organic Letters 2013 Volume 15(Issue 17) pp:4540-4543

Publication Date(Web):August 15, 2013

DOI:10.1021/ol402096k

The first enantioselective Ullmann cross-coupling reactions to prepare diaryl ethers are reported. The reactions were used to prepare the diarylether heptanoid natural products (−)-myricatomentogenin, (−)-jugcathanin, (+)-galeon, and (+)-pterocarine.

Structural Revision of Garuganin IV and 1,9′-Didesmethylgaruganin III through Total Synthesis

Co-reporter:Zhi-Qiang Zhu and Christopher M. Beaudry

The Journal of Organic Chemistry 2013 Volume 78(Issue 7) pp:3336-3341

Publication Date(Web):March 12, 2013

DOI:10.1021/jo302723n

The chemical structures of garuganin IV and 1,9′-didesmethylgaruganin III were misassigned. The structures were revised on the basis of analysis of the NMR data, and the revisions were verified through total synthesis.

The Garuganin and Garugamblin Diarylether Heptanoids: Total Synthesis and Determination of Chiral Properties Using Dynamic NMR

Co-reporter:Zhi-Qiang Zhu, M. Quamar Salih, Edward Fynn, Alex D. Bain, and Christopher M. Beaudry

The Journal of Organic Chemistry 2013 Volume 78(Issue 7) pp:2881-2896

Publication Date(Web):March 5, 2013

DOI:10.1021/jo400157d

The synthesis of the garuganin and garugamblin diarylether heptanoids using an intramolecular Ullmann coupling is reported. Alkene stereoisomers, vinylogous ester regioisomers, and β-diketone congeners are also synthesized. The chiral properties and free energies of activation for racemization of the garuganin and garugamblin diarylether heptanoids and congeners are determined using dynamic NMR methods. A combination of techniques including coalescence measurements, line shape analysis, and selective inversion experiments are used to measure racemization barriers. None of the garuganin or garugamblin diarylether heptanoids are chiral, despite their reported specific rotation values.

Chirality in Diarylether Heptanoids: Synthesis of Myricatomentogenin, Jugcathanin, and Congeners

Co-reporter:M. Quamar Salih and Christopher M. Beaudry

Organic Letters 2012 Volume 14(Issue 15) pp:4026-4029

Publication Date(Web):July 17, 2012

DOI:10.1021/ol301893t

The syntheses of myricatomentogenin, jugcathanin, galeon, pterocarine, and acerogenin L are reported. Synthetic material was used to measure their optical activities and free energy of activation for racemization. The natural enantiomers of myricatomentogenin, jugcathanin, galeon, and pterocarine were determined to have the same pR absolute stereochemistry. Acerogenins L and C are achiral compounds.

Formation of Carbon–Carbon Bonds Using Aminal Radicals

Co-reporter:David A. Schiedler, Jessica K. Vellucci, and Christopher M. Beaudry

Organic Letters 2012 Volume 14(Issue 23) pp:6092-6095

Publication Date(Web):November 29, 2012

DOI:10.1021/ol3029912

Aminal radicals were generated by radical translocation processes. For the first time, it is shown that they participate in carbon–carbon bond forming reactions. Either stannane or silane hydrogen atom donors are suitable for the reaction. More than 30 substrate combinations are reported, and chemical yields are as high as 91%.

High-Yielding Oxidation of β-Hydroxyketones to β-Diketones Using o-Iodoxybenzoic Acid

Co-reporter:Samuel L. Bartlett and Christopher M. Beaudry

The Journal of Organic Chemistry 2011 Volume 76(Issue 23) pp:9852-9855

Publication Date(Web):October 24, 2011

DOI:10.1021/jo201810c

The oxidation of β-hydroxyketones to β-diketones was systematically investigated. o-Iodoxybenzoic acid (IBX) was found to be efficient, operationally easy, and superior to other common oxidants. The reaction is suitable for milligram- to gram-scale oxidations.

Synthesis of natural products containing fully functionalized cyclopentanes

Co-reporter:Andrew J. Ferreira, Christopher M. Beaudry

Tetrahedron (23 February 2017) Volume 73(Issue 8) pp:

Publication Date(Web):23 February 2017

DOI:10.1016/j.tet.2016.12.071

The nature of persistent conformational chirality, racemization mechanisms, and predictions in diarylether heptanoid cyclophane natural products

Co-reporter:Ommidala Pattawong, M. Quamar Salih, Nicholas T. Rosson, Christopher M. Beaudry and Paul Ha-Yeon Cheong

Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 20) pp:NaN3309-3309

Publication Date(Web):2014/04/04

DOI:10.1039/C3OB42550A

Restricted rotations of chemical bonds can lead to the presence of persistent conformational chirality in molecules lacking stereocenters. We report the development of first-of-a-kind predictive rules that enable identification of conformational chirality and prediction of racemization barriers in the diarylether heptanoid (DAEH) natural products that do not possess stereocenters. These empirical rules-of-thumb are based on quantum mechanical computations (SCS-MP2/∞//B3LYP/6-31G*/PCM) of racemization barriers of four representative DAEHs. Specifically, the local symmetry of ring B and the E/Z configuration of the vinylogous acid/ester are critical in determining conformational chirality in the DAEH natural product family.

Regioselective Suzuki couplings of non-symmetric dibromobenzenes: alkenes as regiochemical control elements

Co-reporter:Peng Zhao, Marshall D. Young and Christopher M. Beaudry

Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 22) pp:NaN6165-6165

Publication Date(Web):2015/05/07

DOI:10.1039/C5OB00717H

The regiochemical outcome of Suzuki couplings of non-symmetric dibromobenzenes is investigated. Selectivities are dependent on the proximity of the bromine atom to alkene substituents, not on steric or electronic effects. Extension to a one-pot three-component Suzuki reaction leads to efficient terphenyl syntheses.