Modularly Designed Supramolecular Catalytic Assembly for the Strategic
Enantioselective Borylation of Remote C–H Bonds
Ronald Lazo Reyes
Specially Appointed Assistant Professor
Affiliation: ICReDD and Faculty of Science, Hokkaido Universitye-mail: rlreyes@icredd.hokudai.ac.jp
Specialty: Organometallic Chemistry, Organic Synthesis
ABSTRACT
There exists in nature efficient catalytic systems that enable the challenging
functionalization of ubiquitous C–H bonds in diverse substrate classes. Enzymatic assemblies
have inspired the creation of wide-ranging synthetic supramolecular catalysts that mimic theirproficient activities. Despite the conceptual advances of these synthetic biomimetic systems, theelaborate preparations and limited substrate compatibility limit their utilities in organic synthesis.
With our interest in the development of novel methodologies for the transformation ofC–H bonds in readily available feedstock chemicals, we previously demonstrated the competentactivation and subsequent asymmetric borylation of C(sp3)–H bonds under Ir or Rh catalysts
utilizing a chiral monophosphite ligand system allowing the preparation of biologically-active
and synthetically useful organoboronates.1,2 Our collaboration with ICReDD scientists has given
us infinite opportunity to further extend the reactivity of our catalytic system. Thus, guided bycalculation derived transition-state models, we recently succeeded in the asymmetric borylationof remote -C–H bonds in aliphatic carboxylic amides and esters using a chiral, modular Irmonophosphite catalyst and a urea receptor ligand that recruits the substrate via noncovalentinteractions – a direct functionalization realized using a modularly designed supramolecularcatalytic assembly.3 In this aspect, the overall efficiency relies on the crucial interactions between
the catalytic system and the substrate within a reaction cavity or pocket that resembles the active
site of natural enzymes. Inspired and goal-driven by these results, further collaboration and joint
efforts has led us to the possibility of designing catalytic assemblies to target more distal C–H
bonds in the aliphatic hydrocarbon chain of common and readily available chemical feedstocks
including biomass resources allowing for a more sustainable and efficient organic synthesis.
In this presentation, the development of catalytic enantioselective borylation of C–Hbonds will be described in the context of reaction discovery, design, and utility. Strategic
convergence of experimental and theoretical studies will be outlined to emphasize our approachin targeting remote C–H bonds beyond the -position, further highlighting the need for thecreation of methodologies that will allow challenging transformations.

REFERENCES
1. R. L. Reyes, T. Iwai, S. Maeda, M. Sawamura, Iridium-catalyzed Asymmetric Borylation of
Unactivated Methylene C(sp3)–H Bonds. J. Am. Chem. Soc. 2019, 141, 6817–6821.
2. R. L. Reyes, M. Sato, T. Iwai, M. Sawamura, Asymmetric Synthesis of α-Aminoboronates via

Rhodium-Catalyzed Enantioselective C(sp3)–H Borylation. J. Am. Chem. Soc. 2020, 142,589–597.
3. R. L. Reyes, M. Sato, T. Iwai, K. Suzuki, S. Maeda, M. Sawamura, Asymmetric Remote C–H
Borylation of Aliphatic Amides and Esters with a Modular Iridium Catalyst. Science 2020,369, 970–974.