Stereospecific Conversion of Boronic Esters into Enones using Methoxyallene: Application in the Total Synthesis of 10‐Deoxymethynolide

• Published in: Angewandte Chemie International Edition Vol. 62; no. 50; pp. e202312054 - n/a
• Main Authors: Chambers, Kristian J., Sanghong, Patthadon, Carter Martos, Daniel, Casoni, Giorgia, Mykura, Rory C., Prasad Hari, Durga, Noble, Adam, Aggarwal, Varinder K.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 11.12.2023; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Communication; Communications; Complex formation; Direct conversion; Enones; Esters; Functional groups; Lithiation-Borylation; Molecular biology; Organoboron Compounds; Oxidation; Physical Sciences; Protonation; Science & Technology; Stereospecificity; Substrates; Total Synthesis; TARGET; SITE; ASYMMETRIC CONJUGATE ADDITION; SECONDARY; ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; PROTEIN-KINASES; Total Synthesis; ALCOHOLS; Enones; Lithiation-Borylation; Organoboron Compounds; Stereospecificity; STEREOSELECTIVE-SYNTHESIS; DERIVATIVES
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202312054

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three‐carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated‐methoxyallene, protonation triggers a stereospecific 1,2‐migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2‐migration and give a much broader range of α‐functionalized enones. Finally, the methodology was applied to a 14‐step synthesis of the enone‐containing polyketide 10‐deoxymethynolide. A one‐pot strategy for the stereospecific conversion of boronic esters into enones has been developed using methoxyallene as a commercially available, three‐carbon building block. The methodology is suitable for primary, secondary, and tertiary boronic esters and has been applied to a 14‐step total synthesis of the polyketide 10‐deoxymethynolide.