Our research program is aimed at discovering new modes of catalytic reactivity, studying their mechanisms, and using them to solve problems in organic synthesis. We focus on carbohydrates, nucleosides and heterocycles because they present fundamental challenges in site-selectivity, regioselectivity and stereoselectivity, and have translational importance. Organoboron catalysis, hydrogen atom transfer and photocatalysis are among the group's research themes. Students develop expertise in the core techniques of organic synthesis, along with quantitative skills in kinetics, computation and data science.
Taking advantage of the reversible covalent interactions between organoboron compounds and diols, we have developed catalytic processes for site-selective OH-functionalizations of sugars. This mode of reactivity enabled us to achieve catalyst-controlled glycosylations, an important challenge in the carbohydrate field. Activation of nucleophiles by tetracoordinate organoboron complex formation has proved to be a broadly useful concept in catalysis, and has been adapted and extended by groups around the world. More recently, we have pioneered methods for site-selective hydrogen atom transfer from sugars, enabling homologations and redox manipulations of the carbon backbone. Catalytic activation of organic substrates towards HAT shows promise as a general approach to achieving site-selective C–H functionalizations of complex molecules. In another line of ongoing research, we have shown that interactions of organoboron catalysts with azoles enable regioselective N-functionalizations of these important heterocyclic compounds.
Our approach to reaction development relies on mechanistic analysis via state-of-the-art experimental and computational methods, including kinetics, quantum chemical calculations and, increasingly, high-throughput computation and statistical analysis.
Representative publications.
Site-selective OH-functionalization of sugars:
Catalysis based on reversible interactions of organoboron compounds. Taylor, M. S. Acc. Chem. Res. 2015, 48, 295–305.
Borinic acid catalyzed stereo- and regioselective couplings of glycosyl methanesulfonates. D'Angelo, K.; Taylor, M. S. J. Am. Chem. Soc. 2016, 138, 11058–11066.
Site-selective hydrogen atom transfer:
Site-selective and stereoselective C–H alkylations of carbohydrates via combined diarylborinic acid and photoredox catalysis. Dimakos, V.; Su, H. Y.; Garrett, G. E.; Taylor, M. S. J. Am. Chem. Soc. 2019, 141, 5149–5153.
Synthesis of ketodeoxysugars from acylated pyranosides using photoredox catalysis and hydrogen atom transfer. Turner, J. A.; Rosano, N.; Gorelik, D. J.; Taylor, M. S. ACS Catal. 2021, 11, 11171–11179.
Regioselective activation of azoles:
Borinic acid-catalyzed regio- and stereoselective N-glycosylations of purines and other azole heterocycles: access to nucleoside analogues. J. Am. Chem. Soc. 2024, 146, 4973–4984.
Mechanistic and computational analysis:
Synergistic organoboron/palladium cocatalyzed dehydrative couplings of azoles with allylic alcohols: a combined experimental and computational mechanistic investigation. ACS Catal. 2024, 14, 6728–6739.
Funding
We are grateful to the following agencies for supporting our research.
NSERC (Discovery Grants and Canada Research Chairs Programs)
Digital Research Alliance of Canada
A. P. Sloan Research Foundation
ACS Petroleum Research Fund (New Directions Program)
Boehringer Ingelheim (Canada) Ltd.
Ontario Ministry of Research and Innovation
Merck Research Laboratories
Canada Foundation for Innovation