Department of Chemistry and Biochemistry

Faculty: Wei Li, Ph.D.

Associate Professor and Associate Chair
Email: wei.li@utoledo.edu
Office: WO 3269
Phone: (419) 530-1507
Fax: (419) 530-4033

Professional Background:
B.S., 2006, Univ. of North Carolina
Ph.D., 2011, Univ. of Michigan
Postdoctoral Fellow, 2012-2015, Princeton University 

Group Page
Publications

Research Interests:
Organic, organometallic and medicinal chemistry 

Research Synopsis:

The overarching goal of our program is to develop new catalytic reactions to facilitate the syntheses of medicinally valuable chemical motifs. In particular, we are interested in tackling the selectivity challenges often encountered in these reactions. Strategically, we aim to utilize classic intermediates as catalytic platforms and non-covalent interactions to design selective chemical reactions.

The research in our group is divided in the following categories:  

Program I. Alkene Sulfenoamination for the Syntheses of N- and S-containing Heterocycles.

• We have accomplished and published a series of alkene sulfenoamination protocols including: 1) a one-pot strategy for thiazoline synthesis from alkenes and thioamides (Org. Lett. 2017, 19, 930).Our group has published an initial one-pot oxidative alkene dibromination approach to generate thiazolines. Since then, several complementary thiazoline syntheses have been developed similar to our strategy. 2)an intermolecular regio- and stereoselective sulfenoamination of alkenes with thioimidazoles (Org. Lett. 2017, 19, 6204).We have published a concise synthesis of another S- and N-heterocycle, thiazolidine, from the couplings of alkenes and thioimidazoles. In this case, we have demonstrated that the thiol polarity can be inverted, from reacting with Selectfluor, to gain access to thiiranium intermediates following alkene additions. Interestingly, this approach is regiodivergent to an alternative dibromination protocol. 3) an iodide-catalyzed intermolecular alkene sulfenoamination for 1,4-benzothiazine synthesis.This published work demonstrates the feasibility of iodide catalysis in the synthesis of 1,4-benzothiazines with the direct couplings of alkenes and 2-aminothiophenols (Chem. Eur. J. 2019, 25, 6902). Most importantly, all our alkene sulfenoamination strategies utilize un-functionalized S- and N-precursors, which is an important and practical feature in our synthetic method development that is highlighted in green. Currently, we are working on refined procedures of thioamide and alkene coupling to generate thiazolines via radical processes (unpublished work). In addition, we have been collaborating with Dr. Ronning’s group (University of Nebraska Medical Center) on: 1) screening the S- and N-heterocycles for anti-tuberculosis activities of drug resistant mycobacterium; 2) development of firefly luciferin analogs to evaluate cytoplasmic bioaccumulation against Gram-negative bacteria.

Program II. Iodonium and Hypervalent iodine-Catalyzed Regioselective Alkene Oxyaminations.

•  We have reported the use of urea for the regioselective intermolecular oxyamination of both activated and un-activated olefins(Angew. Chem. Int. Ed. 2019, 58, 11676). Our approach utilizes inexpensive iodide catalyst LiI that was oxidized to an iodenium ion, which in turn coupled with an alkene to generate the iodonium. A subsequent formal [3+2] cyclization with urea regenerated the iodide catalyst while affording a valuable N- and O-based heterocycle.⁹ This reaction represents an unusual approach to intermolecular coupling of alkenes with bifunctional reagents via a formal [3+2] process for the regio- and stereoselective olefin oxyamination reaction. Through this reaction, we have 1) demonstrated the catalytic feasibility of iodonium for intermolecular alkene difunctionalizations, and 2) that the initial nucleophilic addition to the iodonium constitutes the key regiodetermining step. In addition, several other features are notable. First, simple feedstock urea can be directly used for this intermolecular oxyamination coupling reaction. Second, highly regioselective outcome is observed for both activated and un-activated olefins – a difficult feature in intermolecular alkene difunctionalizations. Third, the regioselectivities of the activated and un-activated olefins are reversed relative to the N- and O- additions. Finally, stereospecificity can be obtained to a certain degree under the currently conditions, providing a versatile strategy for stereoselective oxyamination based on olefin stereochemistry. We have also investigated potential aerobic processes for olefin oxyamination in intramolecular settings (ACS Catal. 2018, 8, 1921). In this regard, we have observed interesting triiodide formation that function as an iodine reservoir to minimize iodine concentration (Org. Lett. 2018, 20, 6462). Consequently, strong primary or secondary amines can be directly introduced in the copper-catalyzed oxyamination reaction to generate lactam or aminolactone, respectively (Org. Lett. 2020, 22, 884). We are currently working on the development of a regiodivergent approach to olefin oxyamination that can form both regioisomeric products (unpublished). In addition, we are evaluating chiral catalyst scaffolds to developing regio- and enantioselective alkene oxyamination protocols (unpublished).

Program III. Halogen-Bond Induced Nitrogen Radical Formation.

• Among the many facets of XB, our work in this area is inspired by the charge transfer component postulated by the works of Mulliken. We are curious if this XB character can, under visible-light-mediated conditions, elicit heteroatom radical formation with simple nitrogen sources for a variety of chemical reaction designs. We have demonstrated that a simple halogen bond donor such as NIS can be used to engage the Lewis basic sulfonamides in halogen bonding. Upon visible light irradiation, a halogen bonding charge transfer complex can induce a nitrogen centered radicalformation. The resulting nitrogen radical can either 1) undergo hydrogen atom transfer (HAT) in C–H functionalization reactions (Org. Lett. 2020, 22, 2135); or 2) initiate other interesting radical processes (unpublished). For the C–H abstraction work, we will explore a range of alkanes for C–N bond formation and a nitrogen relay strategy by merging with visible light mediated Hofmann–Löffler–Freytag (HLF) reaction. More importantly, the understanding and study of the charge transfer component of halogen bonding will be essential to provide mechanistic support for further chemical reaction engineering. Finally, the maturation of these chemical methods will enable us to target the synthesis of pyrrolidine-based natural products that are highly prevalent in medicinal agents and pharmaceuticals.