Bicyclic Pyrrolidines for Medicinal Chemistry via [3+2]-Cycloaddition

被引：23

作者：

Savych, Vladimir, I ^{[1
]}

Mykhalchuk, Vladimir L. ^{[1
]}

Melnychuk, Pavlo, V ^{[1
]}

Isakov, Andrii O. ^{[1
]}

Savchuk, Taras ^{[1
]}

Timoshenko, Vadim M. ^{[2
]}

Siry, Sergiy A. ^{[2
]}

Pavlenko, Sergiy O. ^{[1
]}

Kovalenko, Dmytro, V ^{[1
]}

Hryshchuk, Oleksandr, V ^{[1
]}

Reznik, Vitalii A. ^{[1
]}

Chalyk, Bohdan A. ^{[1
,2
]}

Yarmolchuk, Vladimir S. ^{[1
]}

Rusanov, Eduard B. ^{[2
]}

Mykhailiuk, Pavel K. ^{[1
]}

机构：

[1] Enamine Ltd, UA-02094 Kiev, Ukraine

[2] Natl Acad Sci Ukraine, Inst Organ Chem, UA-02094 Kiev, Ukraine

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2021年 / 86卷 / 19期

关键词：

ADVANCED BUILDING-BLOCKS; PHOTOCHEMICAL-SYNTHESIS; LEAD OPTIMIZATION; AZOMETHINE; CYCLOADDITION; POTENT; DISCOVERY; FUNCTIONALIZATION; DEAROMATIZATION; DERIVATIVES;

D O I：

10.1021/acs.joc.1c01327

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A general approach to bicyclic fused pyrrolidines via [3 + 2]-cycloaddition between nonstabilized azomethyne ylide and endocyclic electron-deficient alkenes was elaborated. "Push-pull" alkenes and CF3-alkenes did not react with the azomethyne ylide under the previously reported conditions, and we developed a superior protocol (LiF, 140 degrees C, no solvent). Among obtained products were medchem-relevant bicyclic sulfones, monofluoro-, difluoro-, and trifluoromethyl-substituted pyrrolidines. This approach not only allowed preparation of novel molecules but also significantly simplified synthesis of the existing ones (e.g., sofinicline).

引用

页码：13289 / 13309

页数：21

共 69 条

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