Several research directions in our lab:
1) One of our main research interests is the direct coupling of organic molecules through transition-metal-catalyzed C-H activation. We are especially interested in developing catalytic systems that recognize/activate the substrate and enable site-selective functionalization.
2) We pursue the development of sustainable organic synthesis using Earth-abundant metals as catalysts.
3) We believe in the renaissance of organosodium chemistry, and we explore the synthesis and synthetic applications of organosdium compounds, as a sustainable alternative to organolithium.
Recent Research Results
ACS Catal. 2021, 11, 5968–5973. link
Fluoroarenes are important compounds for drug discovery, and late-stage selective functionalization of these compounds allows structure-bioactivity relationship studies. We developed a new terpyridine ligand, which in combination with an iridium salt catalyzes the stoichiometric borylation of various fluoroarenes with high ortho-selectivity to fluorine. The catalytic system tolerates sensitive functional groups, and thus could be used for the selective functionalization of a complex drug molecule such as haloperidol. Preliminary mechanistic studies by experiment and calculation suggested that the terpyridine ligand does not coordinate iridium through the typical N, N, N-coordination mode, but instead undergoes rollover cyclometalation to generate an N, N, C-coordinated iridium complex.
Commun. Chem. 2021, 4, 76. link
Review: Synthesis 2021, DOI: 10.1055/a-1478-7061. link
Halogen–lithium exchange has been extensively used in organic synthesis because it allows rapid preparation of a large variety of organolithium compounds from (hetero)aryl or alkenyl bromides or iodides, typically using butyllithium or tert-butyllithium under cryogenic conditions. From a sustainability point of view, there is a growing demand for alternatives to the less abundant and increasingly expensive lithium. Sodium is an attractive candidate, but attempts at halogen–sodium exchange using alkylsodiums such as butylsodium and pentylsodium have met with significant challenges, such as low yields and formation of byproducts.
We discovered that the use of a primary and bulky alkylsodium lacking β-hydrogens retards undesired reactions and enables efficient halogen–sodium exchange. The alkylsodium is readily prepared in situ from neopentyl chloride and an easy-to-handle sodium dispersion, and allows us to prepare a large variety of (hetero)aryl- and alkenylsodium compounds including tri- and tetrasodioarenes, many of them previously inaccessible by other methods.
We believe that this reaction has the potential to replace the textbook halogen–lithium exchange, and open new frontiers for establishing organosodium-based organic chemistry.