Enantioselective Heck Arylation of Acyclic Alkenol Aryl Ethers: Synthetic Applications and DFT Investigation of the Stereoselectivity

Author(s)

Polo, Ellen Christine ^[1] ; Wang, Marti Fernandez ^[1] ; Angnes, Ricardo Almir ^[2] ; Braga, Ataualpa A. C. ^[2] ; Duarte Correia, Carlos Roque ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Quim, Dept Quim Organ, Rua Josue de Castro S-N, BR-13083970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, Ave Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: ADVANCED SYNTHESIS & CATALYSIS; v. 362, n. 4 DEC 2019.
• Web of Science Citations: 1

Abstract

Herein we report the enantioselective Heck-Matsuda arylation of acyclic E and Z-alkenyl aryl ethers. The reactions were carried out under mild conditions affording the enantioenriched benzyl ethers in a regioselective manner, moderate to good yields (up to 73%), and in good to excellent enantiomeric ratios (up to 97:3). The enantioselective Heck-Matsuda arylation has shown a broad scope (25 examples), and some key Heck-Matsuda adducts were further converted into more complex and valuable scaffolds including their synthetic application in the synthesis of (R)-Fluoxetine, (R)-Atomoxetine, and in the synthesis of an enantioenriched benzo{[}c]chromene. Finally, in silico mechanistic investigations into the reaction's enantioselectivity were performed using density functional theory. (AU)

• FAPESP's process: 19/02052-4 - Computational mechanistic studies of transition metal catalyzed functionalizations of alkenes: nonintuitive enantioselectivity induction modes applied on contiguos stereocenter formation and difunctionalizations.
• Grantee: Ricardo Almir Angnes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes
• Grantee: Carlos Roque Duarte Correia
• Support Opportunities: Research Projects - Thematic Grants
• 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: 15/01491-3 - Theoretical study of cross-coupling reactions: homogeneous and heterogeneous catalysis
• Grantee: Ataualpa Albert Carmo Braga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/21494-2 - Synthesis of pharmacologically active compounds by the enantioselective Heck-Matsuda reaction and novel studies concerning the enantioselective acylation of cyclopentenes and cyclohexene compounds
• Grantee: Martí Fernández Wang
• Support Opportunities: Scholarships in Brazil - Post-Doctoral