Research

Synergistic catalysis

Synergistic catalysis, in which two catalytic cycles involving two separate catalysts work in concerted fashion to create a single new bond, has emerged as a powerful approach for the development of new reactions. The concurrent activation of both nucleophile and electrophile using distinct catalytic species facilitates the enhancement of inherent chemical reactivity and allows for the synthesis of complex scaffolds that might be difficult to obtain otherwise (Figure 1). While synergistic catalysis is more prevalent in nature, the principle has now begun to emerge as a recognized and valued approach to bond-forming processes in organic chemistry.

Figure 1: Traditional and synergistic catalysis

Some examples of our work in Synergistic Catalysis is the developemnt of an enantioselective synthesis of dihydro acridines[1], a Conia -Ene reaction with pyrazolones[2] a enantioselective ring contraction to form spiropyrazolones[4]. or a ring expansion for the synthesis of spiro compounds [5] among others.

Figure 2 : Synergistic highly diastereoselective addition of benzoxazoles to MBH-carbonates

 

 

Figure 3 : Synergistic Ring expansion for the synthesis of spiropyrazolones.

 

Some older example: We developed the first highly cis-cyclopropanation of enals via a Synergistic catalysis. For first time an organocascade reaction was coupled with a synergistic activation of benzoxazoles.

 

We have developed an expedited method has been developed for the diastereoselective synthesis of highly functionalized alkyl-azaarene systems with good yields and high diastereoselectivities (> 15:1 dr). The methodology includes a synergistic catalysis event involving organometallic (10 mol% AgOAc) activation of an alkyl azaarene and Lewis base (10 mol% DABCO) activation of a Morita–Baylis–Hillman carbonate. The structure and relative configuration of a representative product were confirmed by X-ray analysis (1).

Figure 4 : Synergistic highly diastereoselective addition of benzoxazoles to MBH-carbonates

We extended this type of chemistry to the enantioselective addition of benzoxazole to enals. Achieving the final products in good yields and reasonable stereochemistries (2).

Figure 5 : Synergistic enantioselective addition of benzoxazoles to enals

 

Related Publications:

1 “Synergistic Catalysis: Highly Enantioselective Cascade Reaction for the Synthesis of Dihydroacridines” Sara Meninno, Marta Meazza, Jung Woon Yang, Tomas Tejero, Pedro Merino and Ramon Rios; Chem. Eur. J. 2019, 25, 7623-7627.

2 “Proline Bulky Substituents Consecutively Act as Steric Hindrances and Directing Groups in a Michael/Conia-Ene Cascade Reaction under Synergistic Catalysis” Salil Putatunda, Juan V. Alegre-Requena, Marta Meazza, Dominika Rohaľová, Pooja Vemuri, Ivana Císařová, Raquel, P. Herrera, Ramon Rios, and Jan Veselý Chem. Sci.  2019, 10, 4107-4115.

3 “Synergistic Catalysis: Highly Enantioselective Acetyl Azaarenes Addition to Enals” Marta Meazza,  Gabriela Sitinova, Cecilia Poderi, Michele Mancinelli, Kaiheng Zhang, Andrea Mazzanti and Ramon Rios Chem. Eur. J. 2018, 24, 13306-13310.

4 “Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones” Marta Meazza, Martin Kamlar, Lucie Jašíková, Bedřich Formánek, Andrea Mazzanti, Jana Roithová, Jan Veselý and Ramon Rios, Chem. Sci.  2018, 9, 6368-6373

5 “Synergistic Catalysis: Enantioselective Ring Expansion of Vinyl Cyclopropanes combining 4 catalytic cycles. Synthesis of Highly substituted cyclopentanes bearing 3 stereocenters” Marta Meazza, and Ramon Rios* Chem. Eur. J. 2016, 22, 9923-9928.

6 “Synergistic Catalysis: cis-Cyclopropanation of benzoxazoles” Marta Meazza, Mark E. Light, Andrea Mazzanti and Ramon Rios* Chem. Sci. 2016, 7, 984-988.

1- “Synergistic catalysis: Highly diastereoselective benzoxazole addition to Morita–Baylis-Hillman carbonates” Victor Ceban, Piotr Putaj, Marta Meazza, Mateusz B. Pitak, Simon J. Coles, Jan Vesely, and Ramon Rios* Chem. Commun. 2014, 7447-7450.

2- "Synergistic catalysis: Enantioselective addition of alkylbenzoxazoles to enals" Marta Meazza, Victor Ceban, Mateusz B. Pitak, Simon J. Coles, Ramon Rios Chem. Eur. J. 2014, 20, 16853-16857 (Highlighted in Synfacts Synfacts; 01, 2015).

3- “Synergistic Catalysis: cis-Cyclopropanation of benzoxazoles” Marta Meazza, Mark E. Light, Andrea Mazzanti and Ramon Rios* Chem. Sci. 2016, 7, 984-988.

4- “Merging transition metal activation and aminocatalysis” Marta Meazza and Ramon Rios* Synthesis 2016, 48, 960-973.