The PGA Research Group

Suppachai Krajangsri

SK2

In my first year, I have participated in the development of chiral NHC, phosphine-Ir complexes. We have designed, synthesized and investigated a new library of chiral NHC, phosphine-Ir complexes in the hydrogenation of ketones. The results showed that chiral carbene phosphine-Ir complexes show excellent reactivity. The reaction was performed under mild conditions at room temperature, 1 bar of Hydrogen, without any acidic or basic additives as well as low catalyst loading (1 mol% of metal complexes) and led to completion within 30 minutes with up to 96% ee.
Then I started the new project, the development of pincer ligands which are composed of phosphine, N-heterocyclic carbene (NHCs), phosphine donor atoms (PNHCP) to complex with Iridium. In the beginning, we designed two achiral PNHCP ligands A and B (Scheme 1) which were successfully synthesized in high yields.


Scheme 1. The structure of pincer PNHCP ligands A and B.
The complexation method of pincer ligands with Iridium precursor from the reported procedure was modified. The Ir-PNHCP complexes were used to investigate the catalytic reactivity without further purification. No reactivity was obtained when the complexes were tested in the hydrogenation of alkenes. On the other hand, Ir-B complexes were found to be highly active in the hydrogen transfer reactions of ketones. The reaction could be conducted under nitrogen atmosphere (there was no need for hydrogen gas) at room temperature and a catalytic amount of base led to very high conversions, up to 98%, in 60 minutes. In comparison, Ir-A complexes had lower reactivity and only moderate conversions (49%) were obtained. Furthermore, heterocyclic aromatic compounds, quinolone and imidazoline derivatives were hydrogenated using 2 mol% Ir-B complexes under 50 bar H2 at room temperature with formic acid as an additive to provide the hydrogenated products with full conversions. These results inspired us to develop the chiral pincer (PNHCP) ligands for hydrogen transfer reaction of ketones and hydrogenation of heterocyclic aromatic compounds. The preliminary results from the new chiral pincer PNHCP ligand that we have designed and synthesized show high reactivity under the same conditions as described above with promising ee of up to 92%. We now want to investigate the role of the stereogenic center of the pincer PNHCP ligand and its effect on enantioselectivity. Unfortunately, we could not reproduce the reaction. We then stopped this project for a while.

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Scheme 2. Asymmetric Transfer Hydrogenation of Ketone.

In the second year, I have participated in the project, the asymmetric hydrogenation of allylic alcohol by Ir-N,P catalysts. High yield and excellent enantioselectivities were achieved for most of the allylic alcohols studied using various Ir-N,P-complexes. The challenging substrates, (Z)-allylic alcohols and γ,γ-dialkyl allylic alcohols were hydrogenate in excellent yield and enantioselectivities up to 98%ee. It was found that a certain class of substrates could be hydrogenated perfectly by the best one catalyst. However, it was difficult. Many substrates were required an appropriate catalyst for achieving high chemoselectivity as well as in satisfying enantioselectivity. The observed absolute configuration of products could be confirmed by using the selectivity model. This project was published in ACS catalysis (ACS Catal. 2016, 6, 8342−8349)

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Scheme 3. The asymmetric hydrogenation of allylic alcohol by Ir-N,P catalysts.

The following project, a study of the Dynamic Kinetic Resolution observed in the hydrogenation of some racemic allylic alcohols. In summary, we have reported the first dynamic kinetic resolution asymmetric hydrogenation of secondary allylic alcohols to yield chiral saturated alcohols in good yield with excellent diastereoselectivites (up to 95/5) and enantioselectivities (up to 98%) using highly efficient Ir-N,P catalysts. On-going work involves studying the mechanism of the reaction and extending the substrate scope to include more functionalized substrates which could be promoted in the DKRAH with iridium catalysts from our library as well as the development of new iridium complexes to improve efficiency. We have recently submitted manuscript .

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Scheme 4. DKR asymmetric hydrogenation of secondary allylic alcohols using chiral Ir-N,P catalyst.
We recently published our project, Regioselective Iridium-Catalyzed Asymmetric Monohydrogenation of 1,4-Dienes in  Journal of the American Chemical Society. In this project we developed the regioselective asymmetric hydrogenation of 1,4-diene which have two different olefins. Under optimized reaction we obtained desired product in moderate to good yields with excellent %ee. The hydrogenated product can be used to prepared useful intermediate.

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Scheme 5. Regioselective Iridium-Catalyzed Asymmetric Monohydrogenation of 1,4-Dienes
Currently, I am working on iridium-catalyzed asymmetric hydrogenation of beta-hydroxy silane via terminal olefin formation. In this project, we observed the Peterson olefination of beta-hydroxy silane under the hydrogenation reaction. It has been known that Ir-N,P catalysts generate the acidic reaction medium which can promote the formation of olefin from beta-hydroxy silane. The olefin the will be hydrogenated by iridium catalyst. By using the our developed iridium catalyst, we got high yield (up to 99%) and excellent ee (99%). We are still working on this project, study the competition reaction and develop new Ir catalysts.

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Scheme 6. Iridium-catalyzed Asymmetric hydrogenation of beta-hydroxy silane via terminal olefin formation.

References:
(1) W. A. Herrmann , Angew. Chem. Int. Ed. 2002, 41, 1290.
(2) N. Schneider et al. Eur. J. Inorg. Chem. 2009, 493.
(3) H. M. Lee et al. Inorganica Chimica Acta 357 (2004) 4313.
(4) Li, J.-Q; Andersson, P. G. Chem. Comm. 2013, 49, 6131.
(5) X. Quan, S. Kerdphon, P. G. Andersoon, Chem. Eur. J., 2015, 21, 3576
(6) S. Kerdphon, X. Quan, V. S. Parihar, P. G. Andersson, J. Org. Chem., Just Accepted Manuscript.
(7) a) Cheruku, P.; Paptchikhine, A.; Church, T. L.; Andersson, P. G., J. Am. Chem. Soc.  2009, 131, 8285-8289. c) Cheruku, P.; Diesen, J.; Andersson, P. G., J. Am. Chem. Soc. 2008, 130, 5595-5599. d) Källström, K.; Hedberg, C.; Brandt, P.; Bayer, A.; Andersson, P. G., J. Am. Chem. Soc. 2004, 126, 14308-14309. e) Verendel, J. J.; Li, J.-Q.; Quan, X.; Peters, B.; Zhou, T.; Gautun, O. R.; Govender, T.; Andersson, P. G., Chem. Eur. J. 2012, 18, 6507-6513.