The PGA Research Group

Cristiana Margarita

Cristiana

Part of my research is focused on the preparation of chiral Ir-N,P complexes to be employed as catalysts in the asymmetric hydrogenation of various classes of olefins. Thiazole and imidazole based ligands have been synthesized and were successfully used in the enantioselective hydrogenation of allylic alcohols.

Other projects cover the application of these procedures as key steps in the preparation of intermediates for the total synthesis of natural substances.
For example, the Ir-catalysed hydrogenation of two allylic alcohol fragments, giving 97 and 93 % ee, has been recently employed to obtain a late stage intermediate of the renin-inhibitor drug Aliskiren.[1]

We have then reported the asymmetric hydrogenation of prochiral 1,4-dienes generated by Birch reduction of readily available aromatic compounds. Several substitution patterns and different functionalities on the aromatic source were tolerated and demonstrated the wide applicability of this specific route towards chiral molecules of interest.[2]

I was later involved in the regioselective and asymmetric hydrogenation of cyclohexadienes containing an allyl silane moiety, whose reactivity can be employed in the Hosomi-Sakurai reaction with various electrophiles. A newly developed imidazole-based iridium catalyst proved to be highly efficient and enantioselective towards this type of substrates. The Hosomi-Sakurai reaction employing different aldehydes was then optimized, providing adducts with multiple stereogenic centers in high diastereoselectivity.[3]

 

The most recent project concerned the preparation of the natural sesquiterpene Juvabione via sequential asymmetric and regioselective hydrogenations. Two adjacent stereogenic centers were constructed, the first generated by hydrogenation of a styrene-type double bond (99% ee). Successively, the mono-hydrogenation of a diene intermediate was employed as key step, granting high levels of regio- and stereocontrol (94:6 dr). This strategy allowed to obtain (−)-juvabione from simple starting materials in 9 steps and 17% total yield.[4]

 

References:
[1]. Peters, B. K.; Liu, J.; Margarita, C.; Andersson, P. G. Chem. Eur. J., 2015, 21, 7292–7296.
[2]. Peters, B. K.; Liu, J.; Margarita, C.; Rabten, W.; Kerdphon, S.; Orebom, A.; Morsch, T.; Andersson, P. G. J. Am. Chem. Soc. 2016, 138, 11930 – 11935.
[3]. Rabten, W.; Margarita, C.; Eriksson, L.; Andersson, P. G. Chem. Eur. J. 2018, 24, 1681-1685.
[4]. Zheng, J.; Margarita, C.; Krajangsri, S.; Andersson, P. G. Org. Lett. 2018, 20, 5676-5679.