Regioselective and Stereoselective Heck Matsuda Arylations of Trisubstituted Allylic Alkenols and Their Silyl and Methyl Ether Derivatives To Access Two Contiguous Stereogenic Centers: Expanding the Redox-Relay Process and Application in the Total Synthesis of meso-Hexestrol

Author(s)

Frota, Carlise ^[1] ; Polo, Ellen Christine ^[1] ; Esteves, Henrique ^[1] ; Duarte Correia, Carlos Roque ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Chem, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Journal of Organic Chemistry; v. 83, n. 4, p. 2198-2209, FEB 16 2018.
• Web of Science Citations: 7

Abstract

Novel palladium-catalyzed redox-relay Heck arylation reactions of trisubstituted allylic alkenols were developed employing silyl and methyl ethers. The reactions proceeded under mild conditions in moderate to high yields in an excellent anti diastereoselectivity to form alpha,beta-disubstituted methyl ketones containing two contiguous stereocenters. The new redox-relay arylations using silyl and methyl ethers of the starting alkenols demonstrate that the presence of a free hydroxyl group is not a sine qua non condition for an effective redox-relay process as previously thought. Deuterium-labeled alkenols 2-d-10a, 2-d-10b, and 2-d-10c permitted tracking the palladium-hydride reinsertion steps in the conversion of the starting free alcohols, silyl, and methyl ethers into the corresponding methyl ketone 3-d-11a, with >98% deuterium retention. Moreover, the synthetic potential of the method was demonstrated with a straightforward synthesis of the meso-hexestrol in 4 steps, in 41% overall yield from alkenol 10a. (AU)

• FAPESP's process: 13/10639-9 - Studies on the intermolecular enantioselective Heck-Matsuda reaction of complex acyclic olefins and synthetic applications.
• Grantee: Carlise Frota
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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: 16/18061-4 - Heck-Matsuda Arylation of Alkenyl Ethers and Derivatives: Expansion, Mechanistic Studies and Synthetic Applications of the Redox-Relay Strategy
• Grantee: Henrique Esteves
• Support Opportunities: Scholarships in Brazil - Doctorate