Timothy Clark

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Organization: University of San Diego

Department: Department of Chemistry and Biochemistry

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TOPICS

Organic Chemistry

suzuki-miyaura Coupling

Chemicals
References

-Hydroxyboronate Esters: Formation and Synthetic Applications

Co-reporter:Timothy B. Clark

Asian Journal of Organic Chemistry 2016 Volume 5( Issue 1) pp:31-42

Publication Date(Web):

DOI:10.1002/ajoc.201500284

Abstract

The synthesis of α-oxyboronate esters by the copper-catalyzed diboration of carbonyls provides a facile method to access these versatile intermediates. The evolution of diboration conditions and approaches to allow the isolation of products derived from α-hydroxyboronate esters is discussed. Both experimental and computational evidence for the mechanism of the copper-catalyzed diboration reaction distinguishes the potential pathways of the key migratory insertion of the carbonyl into the copper–boron bond. α-Hydroxyboronate esters and their derivatives have been used in a number of synthetic transformations, including homologation, coupling, and elimination reactions.

Synthesis of Biaryl Ethers by the Copper-Catalyzed Chan–Evans–Lam Etherification from Benzylic Amine Boronate Esters

Co-reporter:Justin S. Marcum, Kathryn A. McGarry, Carl J. Ferber, and Timothy B. Clark

The Journal of Organic Chemistry 2016 Volume 81(Issue 17) pp:7963-7969

Publication Date(Web):August 4, 2016

DOI:10.1021/acs.joc.6b01254

The copper-catalyzed etherification of ortho-borylated benzylic amines with phenols has been achieved to provide biaryl ethers that are prevalent in biologically active compounds. A variety of substitution patterns on the aryl boronate ester and the phenol are tolerated under the reaction conditions, providing moderate to high yields. A competition reaction between phenol and aniline revealed condition-dependent selectivity in which the phenol could be highly favored over the aniline.

Role of Hemilabile Diamine Ligands in the Amine-Directed C–H Borylation of Arenes

Co-reporter:Lillian V. A. Hale, Kathryn A. McGarry, Marissa A. Ringgold, and Timothy B. Clark

Organometallics 2015 Volume 34(Issue 1) pp:51-55

Publication Date(Web):December 30, 2014

DOI:10.1021/om5007837

A study of the role played by the bidentate ligand used in amine-directed C–H borylation is described. Both reaction conversion and selectivity were significantly impacted when steric congestion and electronic perturbations of the bidentate diamine ligand were made, but a more significant influence was imparted by reducing the bite angle of the ligand. N-Benzylaminopyridine was identified as a general ligand that improves both selectivity and yield for most problematic substrates previously reported with picolylamine as ligand.

Selective Formation of ortho-Aminobenzylamines by the Copper-Catalyzed Amination of Benzylamine Boronate Esters

Co-reporter:Kathryn A. McGarry, Alexi A. Duenas, and Timothy B. Clark

The Journal of Organic Chemistry 2015 Volume 80(Issue 14) pp:7193-7204

Publication Date(Web):June 12, 2015

DOI:10.1021/acs.joc.5b01074

The copper-catalyzed coupling between benzylamino boronate esters and aryl amines has been investigated. Formation of ortho-aminobenzylamines was achieved under oxidative conditions in the presence of copper(II) acetate. The major side product of the transformation is the homocoupling of the aryl boronate ester. The formation of the desired diamines was found to be improved in the absence of base, increasing selectivity over the homocoupled product. Both electron-donating and electron-withdrawing substituents are tolerated on both the boronate ester substrate and the aniline coupling partner under the reaction conditions. The presence of the adjacent benzylamine moiety appears to enhance the reactivity of the boronate ester and influence the resulting product distribution, likely by affecting the competing rates of transmetalation in the catalytic cycles.

Facile Formation of β-Hydroxyboronate Esters by a Cu-Catalyzed Diboration/Matteson Homologation Sequence

Co-reporter:Cameron M. Moore, Casey R. Medina, Peter C. Cannamela, Melissa L. McIntosh, Carl J. Ferber, Andrew J. Roering, and Timothy B. Clark

Organic Letters 2014 Volume 16(Issue 23) pp:6056-6059

Publication Date(Web):November 20, 2014

DOI:10.1021/ol502767m

The copper-catalyzed diboration of aldehydes was used in conjunction with the Matteson homologation, providing the efficient synthesis of β-hydroxyboronate esters. The oxygen-bound boronate ester was found to play a key role in mediating the homologation reaction, which was compared to the α-hydroxyboronate ester (isolated hydrolysis product). The synthetic utility of the diboration/homologation sequence was demonstrated through the oxidation of one product to provide a 1,2-diol.

Phosphine-Directed CH Borylation Reactions: Facile and Selective Access to Ambiphilic Phosphine Boronate Esters

Co-reporter:Kristina M. Crawford;Timothy R. Ramseyer;Christopher J. A. Daley ;Timothy B. Clark

Angewandte Chemie 2014 Volume 126( Issue 29) pp:7719-7723

Publication Date(Web):

DOI:10.1002/ange.201402868

Abstract

Ambiphilic ligands have received considerable attention over the last two decades due to their unique reactivity as organocatalysts and ligands. The iridium-catalyzed CH borylation of phosphines is described in which the phosphine is used as a directing group to provide selective formation of arylboronate esters with unique scaffolds of ambiphilic compounds. A variety of aryl and benzylic phosphines were subjected to the reaction conditions, selectively providing stable, isolable boronate esters upon protection of the phosphine as the borane complex. After purification, the phosphine-substituted boronate esters could be deprotected and isolated in pure form.

Phosphine-Directed CH Borylation Reactions: Facile and Selective Access to Ambiphilic Phosphine Boronate Esters

Co-reporter:Kristina M. Crawford;Timothy R. Ramseyer;Christopher J. A. Daley ;Timothy B. Clark

Angewandte Chemie International Edition 2014 Volume 53( Issue 29) pp:7589-7593

Publication Date(Web):

DOI:10.1002/anie.201402868

Abstract

Stereoselective Formation of Trisubstituted Vinyl Boronate Esters by the Acid-Mediated Elimination of α-Hydroxyboronate Esters

Co-reporter:Weiye Guan, Alicia K. Michael, Melissa L. McIntosh, Liza Koren-Selfridge, John P. Scott, and Timothy B. Clark

The Journal of Organic Chemistry 2014 Volume 79(Issue 15) pp:7199-7204

Publication Date(Web):June 10, 2014

DOI:10.1021/jo500773t

The copper-catalyzed diboration of ketones followed by an acid-catalyzed elimination leads to the formation of 1,1-disubstituted and trisubstituted vinyl boronate esters with moderate to good yields and selectivity. Addition of tosic acid to the crude diboration products provides the corresponding vinyl boronate esters upon elimination. The trisubstituted vinyl boronate esters are formed as the (Z)-olefin isomer, which was established by subjecting the products to a Suzuki–Miyaura coupling reaction to obtain alkenes of known geometry.

Iridium-Catalyzed, Substrate-Directed C–H Borylation Reactions of Benzylic Amines

Co-reporter:Andrew J. Roering, Lillian V. A. Hale, Phillip A. Squier, Marissa A. Ringgold, Emily R. Wiederspan, and Timothy B. Clark

Organic Letters 2012 Volume 14(Issue 13) pp:3558-3561

Publication Date(Web):June 25, 2012

DOI:10.1021/ol301635x

The iridium-catalyzed arene C–H borylation reaction of benzylic amines has been developed, which inverts the typical steric-controlled product distribution to provide ortho-substituted boronate esters. Picolylamine was found to be an ideal ligand to replace 4,4′-di-tert-butylbipyridine to induce the directing effect. Preliminary experiments are consistent with a mechanism involving dissociation of one amine of the hemilabile diamine ligand.

Alkoxide-Catalyzed Reduction of Ketones with Pinacolborane

Co-reporter:Ian P. Query, Phillip A. Squier, Emily M. Larson, Nicholas A. Isley, and Timothy B. Clark

The Journal of Organic Chemistry 2011 Volume 76(Issue 15) pp:6452-6456

Publication Date(Web):June 24, 2011

DOI:10.1021/jo201142g

The reduction of ketones with pinacolborane (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) is catalyzed by 5 mol % NaOt-Bu at ambient temperature. The reaction is high yielding and general, providing complete conversion of aryl and dialkyl ketones. Although spectroscopic studies of the active hydride source in benzene-d6 were complicated due to poor solubility, the data are consistent with the active hydride source being the trialkoxyborohydride, which is believed to be present in low concentration under the reaction conditions. Performing analogous studies in tetrahydrofuran resulted in a complex equilibrium between several different boron-containing species in which the trialkoxyborohydride compound was the major species.

An ortho-directed C–H borylation/Suzuki coupling sequence in the formation of biphenylbenzylic amines

Co-reporter:Lillian V. A. Hale, David G. Emmerson, Emma F. Ling, Andrew J. Roering, Marissa A. Ringgold and Timothy B. Clark

Inorganic Chemistry Frontiers 2015 - vol. 2(Issue 6) pp:NaN664-664

Publication Date(Web):2015/02/17

DOI:10.1039/C4QO00348A

A C–H borylation/Suzuki–Miyaura coupling sequence is reported using benzylic amines to direct the C–H borylation to the ortho C–H bond. Both aryl bromides and iodides were coupled to the resulting arylboronate esters. A series of biphenylbenzylic amines are reported, requiring a single purification in the two-step reaction sequence.