Skip to content

Research at St Andrews

Enantioselective synthesis of α-aryl-β2-amino-esters by cooperative isothiourea and Brønsted acid catalysis

Research output: Contribution to journalArticlepeer-review

Author(s)

Feng Zhao, Chang Shu, Claire M. Young, Cameron Carpenter-Warren, Alexandra M. Z. Slawin, Andrew David Smith

School/Research organisations

Abstract

The synthesis of α‐aryl‐β2 ‐amino esters through enantioselective aminomethylation of an arylacetic acid ester in high yields and enantioselectivity via cooperative isothiourea and Brønsted acid catalysis is demonstrated. The scope and limitations of this process are explored (25 examples, up to 94% yield and 96:4 er), with applications to the synthesis of (S)‐Venlafaxine·HCl and (S)‐Nakinadine B. Mechanistic studies are consistent with a C(1)‐ammonium enolate pathway being followed rather than an alternative dynamic kinetic resolution process. Control studies indicate that (i) a linear effect between catalyst and product er is observed; (ii) an acyl ammonium ion can be used as a precatalyst; (iii) reversible isothiourea addition to an in situ generated iminium ion leads to an off‐cycle intermediate that can be used as a productive precatalyst.
Close

Details

Original languageEnglish
Pages (from-to)11892-11900
Number of pages10
JournalAngewandte Chemie International Edition
Volume60
Issue number21
Early online date4 May 2021
DOIs
Publication statusPublished - 11 May 2021

    Research areas

  • Isothiourea, Cooperative catalysis, Mechanistic study, Enantioselective aminomethylation, b2-amino acid

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones

    Zhang, S., Bacheley, L., Young, C. M., Stark, D. G., O'Riordan, T., Slawin, A. M. Z. & Smith, A. D., Oct 2020, In: Asian Journal of Organic Chemistry. 9, 10, p. 1562-1566 5 p.

    Research output: Contribution to journalArticlepeer-review

  2. Isothiourea-catalyzed synthesis of pyrrole- and indole-functionalized tetrasubstituted pyridines

    Zhang, S., Hartley, W., Greenhalgh, M. D., Ng, S., Slawin, A. M. Z. & Smith, A. D., 18 Sep 2020, In: ChemCatChem. 12, 18, p. 4522-4525 5 p.

    Research output: Contribution to journalArticlepeer-review

  3. NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

    Davies, A., Greenhalgh, M. D., Slawin, A. M. Z. & Smith, A. D., 30 Jun 2020, In: Beilstein Journal of Organic Chemistry. 16, p. 1572-1578

    Research output: Contribution to journalArticlepeer-review

  4. Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives

    Bitai, J., Slawin, A. M. Z., Cordes, D. B. & Smith, A. D., 25 May 2020, In: Molecules. 25, 10, 13 p., 2463.

    Research output: Contribution to journalArticlepeer-review

  5. Tandem sequential catalytic enantioselective synthesis of highly-functionalised tetrahydroindolizine derivatives

    Zhang, S., Greenhalgh, M. D., Slawin, A. M. Z. & Smith, A. D., 12 Mar 2020, In: Chemical Science. Advance Article, 8 p.

    Research output: Contribution to journalArticlepeer-review

Related by journal

  1. Cu(OTf)2-mediated cross-coupling of nitriles and N-heterocycles with arylboronic acids to generate nitrilium and pyridinium products

    Bell, N., Xu, C., Fyfe, J., Vantourout, J. C., Brals, J., Chabbra, S., Bode, B. E., Cordes, D. B., Slawin, A. M. Z., McGuire, T. M. & Watson, A. J. B., 29 Mar 2021, In: Angewandte Chemie International Edition. 60, 14, p. 7935-7940 7 p.

    Research output: Contribution to journalArticlepeer-review

  2. Engineering of a peptide α-N-methyltransferase to methylate non-proteinogenic amino acids

    Naismith, J. H., Song, H., Burton, A. J., Shirran, S. L., Fahrig-Kamarauskaitė, J., Kaspar, H., Muir, T. W. & Künzler, M., 14 Apr 2021, (Accepted/In press) In: Angewandte Chemie International Edition.

    Research output: Contribution to journalArticlepeer-review

  3. Using the mechanical bond to tune the performance of a thermally activated delayed fluorescence emitter

    Rajamalli, P., Rizzi, F., Li, W., Jinks, M. A., Gupta, A. K., Laidlaw, B., Samuel, I. D. W., Penfold, T. J., Goldup, S. M. & Zysman-Colman, E., 11 May 2021, In: Angewandte Chemie International Edition. 60, 21, p. 12066-12073 9 p.

    Research output: Contribution to journalArticlepeer-review

  4. Controlling single molecule conductance by a locally induced chemical reaction on individual thiophene units

    Michnowicz, T., Borca, B., Pétuya, R., Schendel, V., Pristl, M., Pentegov, I., Kraft, U., Klauk, H., Wahl, P., Mutombo, P., Jelínek, P., Arnau, A., Schlickum, U. & Kern, K., 18 Feb 2020, In: Angewandte Chemie International Edition. In press, 7 p.

    Research output: Contribution to journalArticlepeer-review

ID: 273137136

Top