An Improved Protocol for the Morita-Baylis-Hillman Reaction Allows Unprecedented Broad Synthetic Scope

Author(s):Show less -

Camilo, Nilton S. ; Santos, Hugo ; Zeoly, Lucas A. ; Fernandes, Fabio S. ; Rodrigues Jr, Manoel T. ; Silva, Thiago S. ; Lima, Samia R. ; Serafim, Jose Claudio ; de Oliveira, Aline S. B. ; Carpanez, Arthur G. ; Amarante, Giovanni W. ; Coelho, Fernando

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY; v. N/A, p. 9-pg., 2022-01-19.

Abstract

The Morita-Baylis-Hillman (MBH) reaction has been stablished as an important C-C bond-forming transformation between carbonyl-containing compounds and activated olefins. However, the slow reaction rate usually observed with electron-rich electrophilic partners hinders a more widespread use of this reaction. In order to overcome this drawback, the effects of several Bronsted acids on the rate of DABCO-catalyzed MBH reactions were evaluated. The protocol is operationally simple, involving neat and open-flask conditions, and is compatible with a wide range of reagents. We suggest a general acid catalysis mechanism to be responsible for the rate increase. The synthetic versatility of the MBH adducts is exemplified with a two-steps diastereoselective synthesis of the natural product (+/-)-sitophilure. We hope this acid-mediated protocol to have potential use as a general methodology for the MBH reaction. (AU)

• FAPESP's process: 18/00299-0 - Halo-etherification reactions of Morita-Baylis-Hillman adducts and derivatives: synthesis of epoxides and oxetanes
• Grantee: Aline Silva Barroso de Oliveira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/02611-0 - Post-Functionalization of Small Ply-functionalized Molecules: A Robust Approach to the Synthesis of New Structural Patterns with POtential Biological Activity
• Grantee: Fernando Antonio Santos Coelho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/23005-6 - Synthesis of new heterocycles exhibiting potential biological activities by exploring the Morita-Baylis-Hillman adducts as building blocks
• Grantee: Fábio de Souza Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/09205-0 - New frontiers of the Morita-Baylis-Hillman reaction: 1) New applications of a bifunctional catalyst derived from imidazole. 2) Studies on the asymmetric synthesis of a natural high-potency sweetener
• Grantee: Hugo dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)