Synthesis of Spirocyclic β- and γ-Sultams by One-Pot Reductive Cyclization of Cyanoalkylsulfonyl Fluorides

被引：13

作者：

Stepannikova, Kateryna O. ^{[1
]}

Vashchenko, Bohdan V. ^{[1
,2
]}

Grygorenko, Oleksandr O. ^{[1
,2
]}

Gorichko, Marian, V ^{[2
]}

Cherepakha, Artem Yu ^{[1
]}

Moroz, Yurii S. ^{[2
,3
]}

Volovenko, Yulian M. ^{[2
]}

Zhersh, Serhii ^{[1
,2
]}

机构：

[1] Enamine Ltd, Chervonotkatska St 78, UA-02094 Kiev, Ukraine

[2] Taras Shevchenko Natl Univ Kyiv, Volodymyrska St 60, UA-01601 Kiev, Ukraine

[3] Chemspace, Ilukstes Iela 38-5, LV-1082 Riga, Latvia

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2021年 / 2021卷 / 47期

关键词：

Reduction; Spirocycles; Sulfonylation; Sultams; Synthetic methods; SUBSTITUTED 1,2-THIAZETIDINE 1,1-DIOXIDES; ASYMMETRIC-SYNTHESIS; INHIBITORS; DERIVATIVES; SCAFFOLDS; DISCOVERY; CLEAVAGE; PRODRUG; DESIGN; DRUG;

D O I：

10.1002/ejoc.202000351

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

One-pot intramolecular cyclization of novel sp(3)-enriched cyanoalkylsulfonyl fluorides into spirocyclic beta- or gamma-sultams is disclosed. The method relies on nitrile group reduction followed by sulfonylation of amino group thus formed upon mild conditions (NaBH4, NiCl2 center dot 6H(2)O in MeOH). Cyclization proceeds smoothly with considerable efficiency (48-84 %, 10 examples) on up to 30 g scale. The cyanoalkylsulfonyl fluoride intermediates can be obtained via S-nucleophilic substitution in beta-functionalized alkanenitriles or double alkylation of alpha-alkylthioacetonitrile, followed by oxidative chlorination with Cl-2 and further reaction with KHF2. The title mono- and bifunctional sultams are advanced sp(3)-enriched building blocks for drug discovery and organic synthesis providing novel substitution patterns and frameworks mimicking saturated nitrogen heterocycles such as pyrrolidine/pyrrolidone.

引用

页码：6530 / 6540

页数：11

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