Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• the unsymmetrical salens with zinc, copper, and cobalt was studied and the chiral Co–salen complex 2f was obtained in 98% yield. Hydrolytic kinetic resolution (HKR) of epichlorohydrin with water catalyzed by complex 2f (0.5 mol %) was explored and resulted in 98% ee, suggesting complex 2f could serve

• as an enantioselective catalyst for the asymmetric ring opening of terminal epoxides by phenols. A library of α-aryloxy alcohols 3 was thereafter synthesized in good yield and high ee using 2f via the phenolic KR of epichlorohydrin. Keywords: α-aryloxy alcohols; chiral Co–salen; HKR

• ]. Since their discovery, researchers have investigated several Co–salen complexes for the KR of epoxides with phenols as nucleophiles (Figure 1) [18][19]. Kim et al. described a catalytic system of a chiral Co–salen immobilized on meso/macroporous silica monoliths for the ring opening of epoxides [20

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• using a silica-supported chiral Co(salen) complex [42]. Asymmetric cyclopropanation has also been studied in continuous flow, using monolithic reactors immobilized with chiral PyBox ligands [43][44]. The cyclopropanation of stryrene with ethyldiazoacetate was investigated as a model reaction for this

• Co(salen) complex 33 (Scheme 10) [41]. Three consecutive 1 mmol scale runs (20 h each), where a solution of epibromohydrin was continuously circulated through the reactor via a pump, were performed without any loss of enantioselectivity and catalyst activity (76–87% yield, 91–93% ee). A fourth

• co-workers have designed a continuous-flow reactor system, PASSflow [40], based on the use of a functionalizable monolithic rod derived from a glass/polymer composite. This device was used for the dynamic kinetic resolution of epibromohydrin 32, using a monolith reactor functionalized with a chiral