Programming Selectivity of Aliphatic C-H Bond Functionalization through Innovative Auxiliary Reagents

Samenvatting

Currently, organic synthesis relies on sequential transformations of functional groups, which typically generate stoichiometric amounts of non-productive waste. Consequently, fine-chemical production involves tedious multi-step procedures with poor atom-economy and low energy efficiency. The selective functionalization of C-H bonds has the potential to revolutionize synthetic planning, allowing for dramatic simplification of complex-molecule synthesis. However, the low reactivity of C-H bonds imposes significant obstacles to develop such transformations, with the improvement of selectivity as the main focus of the current efforts.
In this project, I propose to develop an innovative strategy to develop site-selective reactions for challenging unactivated C(sp3)-H bonds. The strategy relies on the use of ?auxiliary reagents? that bear (i) a substrate-binding site that binds to a functional group of a substrate, and (ii) a directing group for coordination to a catalyst. Upon formation of the substrate-auxiliary reagent architecture, and its coordination to the catalyst, one specific C-H bond will be selectively activated and functionalized. Importantly, site-selectivity can be controlled by crafting the auxiliary reagent framework. Furthermore, the chiral auxiliaries will allow for unprecedented enantioselective functionalization of unactivated C(sp3)-H bonds. This will significantly contribute to the development of sustainable methods for synthesis of fine-chemicals, such as pharmaceuticals, agrochemicals and materials.

Output

Wetenschappelijk artikel

  • D. S. Clark, J. F. Hartwig, H. M. Key, P. Dydio(2016): Artificial Catalysis by Heme Proteins Containing Noble Metal Porphyrins Nature pp. 534 - 537
  • J.F. Hartwig, P.F. Dydio, H.M. Key(2016): An artificial metalloenzyme with the kinetics of native enzymes. Science pp. 102 - 106
  • H.M. Key, J.F. Hartwig, P.F. Dydio(2017): Chemoselective, Enzymatic C–H Bond Amination Catalyzed by a Cytochrome P450 Containing an Ir(Me)-PIX Cofactor J. Am. Chem. Soc., 2017, 139 (5), pp 1750–1753 pp. 1750 - 1753
  • P.F. Dydio, H.M. Key, J.F. Hartwig(2017): Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes ACS Cent. Sci., 2017, 3 (4), pp 302–308 10.1021/acscentsci.6b00391 pp. 302 - 308

Kenmerken

Projectnummer

680-50-1306

Hoofdaanvrager

Dr. P.F. Dydio

Verbonden aan

Universiteit van Amsterdam, Faculteit der Natuurwetenschappen, Wiskunde en Informatica, Van 't Hoff Institute for Molecular Sciences (HIMS)

Uitvoerders

Dr. P.F. Dydio

Looptijd

19/06/2014 tot 03/11/2016