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Wills Group Research Interests

You can download a recent Research Presentation on the work of the group.


commercially available. (search for 'teth').

A video of how to run an ATH reaction is below:


Recent applications of tethered catalyst by other groups, in industry and academia. If you'd like any advice on this don't hesistate to contact me (email is best):

An excellent ATH/DKR application using the 3C catalyst:

Enantioselective synthesis of chiral multicyclic γ-lactones via dynamic kinetic resolution of racemic γ-keto carboxylic acids, Zhichao Xiong, Jiangyan Tian, Peng Xue, Xumu Zhang and Hui Lv, Org. Chem. Front., 2020,7, 104-108. The tethered catalyst used for same application as DENEB in JACS 2019, 141, 16354-16361.

An excellent application to an ATH-DKR of a complex substrate using the 3C catalyst:

Synthesis of MeBmt and related derivatives via syn-selective ATH-DKR, Adam Rolt, Paul M. O’Neill, T. Jake Liang and Andrew V. Stachulski, RSC Advances, 2019, 9, 40336 - 40339.

An elegant application of the 3C-tethered catayst to the reduction of a cyclic ketone, with it outperfoming other ATH catalysts:

Enantioselective Synthesis of (S)-Ketamine and (S)-Norketamine, Cheng-Yi Chen and Xiaowei Lu, Org. Lett. 2019, 21, 6575-6578.

Jason Burch et al (Genentech and Pharmaron Beijing) reported an elegant synthesis of a selective interleukin-2 inducible T-cell kinase (ITK) inhibitor using the 3C tethered catalyst at a key point:

Enantioselective synthesis of GNE-6688, a potent and selective inhibitor of interleukin-2 inducible T-cell kinase (ITK). Jared Moore, Kevin Lau, Xiaofeng Xu, Yamin Zhang and Jason D.Burch, Tetrahedron Lett. 2019, 60, 785-788.

Xumu Zhang et al. used the 3C catalyst in a fantastic dynamic kinetic resolution application:

Highly enantioselective transfer hydrogenation of racemic α-substituted β-keto sulfonamides via dynamic kinetic resolution by Zhichao Xiong, Chengfeng PEi, Peng Xue, Hui Lv and Xumu Zhang, Chem. Commun. 2018, 54, 3883-3886.

Developing an Asymmetric Transfer Hydrogenation Process for (S)-5-Fluoro-3-methylisobenzofuran-1(3H)-one, a Key Intermediate to Lorlatinib,

Shengquan Duan* , Bryan Li, Robert W. Dugger, Brian Conway, Rajesh Kumar, Carlos Martinez, Teresa Makowski, Robert Pearson, Mark Olivier, and Roberto Colon-Cruz (Pfizer) Org. Process Res. Dev., 2017, 21, 1340–1348. Use of the tethered catalysts, alongside other ATH catalysts, in a fantastic industrial application which highlights the tremedous value of this class of catalyst in industrial applications. Although not selected for final use in the preparation of 400 kg of intermediate, it gave an excellent result in the screen (99.9% conv and 99.7% ee - the highest ee of the set.

Use of the 3C tethered catalyst in a Dynamic Kinetic Resolution Reaction:

Kinetic Resolution Driven Diastereo- and Enantioselective Synthesis of cis-β-Heteroaryl Amino Cycloalkanols by Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation, Vijyesh K. Vyas and Bhalchandra M. Bhanage, Organic Letters 2016, 18, 8436-6439.

Use of the 3C tethered catalyst with 1,4-butanediol as a reducing agent:

Alternative Hydrogen Source for the Asymmetric Transfer Hydrogenation in the Reduction of ketones.

Russell J. Wakeham, James A. Morris and Jonathan M. J. Williams, ChemCatChem 2015, 7, 4039-4041. Use of the tethered catalyst inketone reduction, with 1,4-butenediol used as a hydrogen source.

An application of the 3C tethered catalyst in C=N reduction by Merck:

'Enantioselective Synthesis of an HCV NS5a Antagonist'

Ian K. Mangion , Cheng-yi Chen, Hongmei Li , Peter Maligres , Yonggang Chen , Melodie Christensen , Ryan Cohen , Ingyu Jeon , Artis Klapars , Shane Krska , Hoa Nguyen , Robert A. Reamer , Benjamin D. Sherry , and Ilia Zavialov, Org. Lett., 2014, 16, 2310–2313 - a synthesis of MK-8742 by Merck uses tethered catalyst in a C=N reduction.

An application to asymmetric lactone synthesis using the 3C catalyst:

'Preparation of Enantioenriched gamma-Substituted Lactones via Asymmetric Transfer Hydrogenation of beta-Azidocyclopropane Carboxylates Using the Ru-TsDPEN catalyst' Yan Su, Yong-Qiang Tu, and Peiming Gu, Org. Lett., 2014, 16 (16), pp 4204–4207A study of a combined cyclopropane opening / asymmetric reduction / cyclisation in one pot using the tethered catalyst.

An application to azido acrylate reduction usign the 3C catalyst:

'Asymmetric transfer hydrogenation of a-azido acrylates' by J Ji, P. Xue, D.-D. Ma, X.-Q. Li, P. Gu and R. Li Tetrahedron Lett. 2015, 56, 192-194.

The tethered catalyst has also been used by several companies in work reported in patents.