Research

Research Interests

We are a young and dynamic research group engaged in organic synthesis. Particularly, we are interested in the following field:

1) New strategies for deuterium labeling

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Generally, three strategies are employed in the synthesis of deuterated compounds: (a) synthesis from deuterated precursors; the feasibility of this strategy, however, highly depends on the availability of starting materials and long synthetic routes must often be considered; (b) postsynthetic hydrogen/deuterium exchange, including metal-catalyzed and pH-dependent protocols; however, a vast majority of reactions of this type require either expensive catalysts or harsh reaction conditions and suffer from limited scope, low levels of deuterium incorporation, and poor selectivity; and (c) reductive deuteration, including reductions mediated by alkali metal deuterides, such as sodium borodeuteride and lithium aluminum deuteride. Reductive methods of this type can selectively introduce deuterium into the targeted position and generally result in high levels of deuterium incorporation. However, the widespread application of these methods is restricted by the requirement of expensive pyrophoric alkali metal deuterides.

AJ research group has demonstrated the single electron transfer reduction as an emerging strategy for reductive deuterations. In our work, a cheap and bench stable reagent, sodium dispersions in oil (particle size 5−10 μm) was employed as the single electron donor. And EtOD-d1 or D2O was used as the deuterium donor. Synthetic methods of this type are highly regioselective and lead to excellent deuterium incorporations.

Key publications:

J. Org. Chem. 2018, 83, 6006–6014

Org. Lett. 2018, 20, 8–11

Tetrahedron Lett. 2017, 58, 2757–2760

Org. Chem. 2017, 82, 1285–1290.

2) Ammonia Free Birch Reductions

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The reduction and dearomatization of aromatic compounds to produce unconjugated cyclohexadienes, is a key synthetic transformation in organic synthesis, with wide application and scope. Despite being developed over 70 years ago, the classic Birch reduction, involving dissolving metal in liquid ammonia, is still the most common method available. Although quite a few research groups have been working on ammonia free Birch reductions, the reduction of benzene and electron rich benzenoid aromatic compounds under ammonia and amine-free conditions is still a formidable challenge

we address this challenge and report the development of a new electride-based Birch reduction that is practical, green and wide in scope.  This ammonia free system is amenable to scale-up, using only bench-stable and commercially available sodium dispersions, recoverable 15-crown-5 and i-PrOH.

Key publication:

Org. Lett. 2018, 20, 3439-3442

3) Deuterium labeled bio-active compounds

Selective deuterium substitution of physiologically-active compounds can result in longer half-lives and improve safety due to higher stability of C–D bonds than C–H bonds. With the recent renaissance of deuterated drugs, a considerable amount of deuterium-containing agents have entered clinical trials. In 2017, the US Food and Drug Administration (FDA) awarded a new chemical entity to the first deuterated drug, deutetrabenazine, which is recognized as a different orphan drug for the treatment of chorea versus tetrabenazine. In addition, deuterium labeled compounds have been widely used as metabolic or pharmacokinetic probes, internal standards in analytical chemistry, and tools for elucidation of reaction mechanisms.

Our group is interested in the synthesis of deuterium labeled bio-active compounds. For example, we have synthesized a series of deuterium labeled pefurazoate. We would be very happy to collaborate with analytical chemist and biologist who may need those deuterated compounds as internal standards or probes.

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