Development of a Scalable Synthesis toward a KRAS G12C Inhibitor Building Block Bearing an All-Carbon Quaternary Stereocenter, Part 2: Asymmetric Synthesis via Shi Epoxidation
ORGANIC PROCESS RESEARCH & DEVELOPMENT(2024)
Abstract
The development of a scalable asymmetric synthesis of KRAS G12C inhibitor building block 1 is described. The all-carbon quaternary stereocenter was installed enantioselectively via Shi epoxidation, followed by a newly discovered regioselective LaCl3 center dot 2LiCl-catalyzed epoxide opening. Subsequent organocatalyzed oxidation provided the requisite ketone, which underwent the final assembly of the heterocyclic core, delivering 1 with high chemical and enantiomeric purities in 40% overall yield in only five steps, enabling robust and rapid manufacturing of over 300 kg of 1.
MoreTranslated text
Key words
enyne,Shi epoxidation,LaCl3 center dot 2LiCl,epoxide opening,pre-IBS,organocatalyst
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined