Development of a Kilogram-Scale Process for the Enantioselective Synthesis of 3-Isopropenyl-cyclohexan-1-one via Rh/DTBM-SEGPHOS-Catalyzed Asymmetric Hayashi Addition Enabled by 1,3-Diol Additives

Autor:	Boguslaw Mudryk, Yuping Qiu, Eric M. Simmons, Yi Hsiao, Andrew G. Lee, Thomas M. Razler
Rok vydání:	2017
Předmět:	Heptane SEGPHOS 010405 organic chemistry Pinacol Ligand Organic Chemistry Diol Enantioselective synthesis 010402 general chemistry 01 natural sciences Neopentyl glycol 0104 chemical sciences Catalysis chemistry.chemical_compound chemistry Organic chemistry Physical and Theoretical Chemistry
Zdroj:	Organic Process Research & Development. 21:1659-1667
ISSN:	1520-586X 1083-6160
DOI:	10.1021/acs.oprd.7b00253
Popis:	The development of a scalable process for the Rh-catalyzed asymmetric 1,4-addition of (isopropenyl)pinacolboronate to 2-cyclohexen-1-one is reported. High-throughput ligand screening and initial optimization studies identified DTBM-SEGPHOS as an effective ligand along with a heptane/MeOH mixed solvent system. An inhibitory effect of the pinacol byproduct was identified, which could be mitigated by the addition of a 1,3-diol such as neopentyl glycol (npg). This process was demonstrated on 1 kg scale with 0.6 mol % Rh, producing (S)-1 in 82% yield and 99.6% ee, and was successfully scaled up at a vendor on 100 kg scale.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::d81c6f62720517a1425e25ea53b69aea https://doi.org/10.1021/acs.oprd.7b00253 Zobrazit plný text záznamu