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

共 76 条

[51] Expected and unforeseen reactions of 2,3,3-trimethyl-1λ6- isothiazolidine-1,1,4-trione and their Spiro derivative [J].

Popova, Maria, V ;

Dobrydnev, Alexey, V ;

Dyakonenko, Viktoriya V. ;

Konovalova, Irina S. ;

Shishkina, Svitlana, V ;

Volovenko, Yulian M. .

TETRAHEDRON, 2019, 75 (09) :1231-1245

[52] Synthetic approaches to 1,3-propanesultams (microreview) [J].

Popova, Maria V. ;

Dobrydnev, Alexey V. .

CHEMISTRY OF HETEROCYCLIC COMPOUNDS, 2017, 53 (05) :492-494

[53] Synthesis of a series of tetraminic acid sulfone analogs [J].

Popova, Maria V. ;

Dobrydnev, Alexey V. ;

Dyachenko, Maksim S. ;

Duhayon, Carine ;

Listunov, Dymytrii ;

Volovenko, Yulian M. .

MONATSHEFTE FUR CHEMIE, 2017, 148 (05) :939-946

[54] Synthesis and selected reactions of a bicyclic sultam having sulfur at the apex position [J].

Preston, Adam J. ;

Gallucci, Judith C. ;

Paquette, Leo A. .

JOURNAL OF ORGANIC CHEMISTRY, 2006, 71 (17) :6573-6578

[55] SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation factor Xa [J].

Qlao, Jennifer X. ;

Chang, Chong-Hwan ;

Cheney, Daniel L. ;

Morin, Paul E. ;

Wang, Gren Z. ;

King, Sarah R. ;

Wang, Tammy C. ;

Rendina, Alan R. ;

Luettgen, Joseph M. ;

Knabb, Robert M. ;

Wexler, Ruth R. ;

Lam, Patrick Y. S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (16) :4419-4427

[56] Synthesis of sultams by cycloalkylation of (alkoxycarbonylmethane)sulfonanilides [J].

Rassadin, V. A. ;

Tomashevskii, A. A. ;

Sokolov, V. V. ;

Potekhin, A. A. .

CHEMISTRY OF HETEROCYCLIC COMPOUNDS, 2008, 44 (04) :474-485

[57] Methods of Sultam Synthesis [J].

Rassadin, V. A. ;

Grosheva, D. S. ;

Tomashevskii, A. A. ;

Sokolov, V. V. .

CHEMISTRY OF HETEROCYCLIC COMPOUNDS, 2013, 49 (01) :39-65

[58] Access to a Wide Range of Sultams by Cyclodialkylation of α-Substituted Methanesulfonanilides [J].

Rassadin, Valentin A. ;

Grosheva, Daria S. ;

Arefeva, Irina A. ;

Tomashevskiy, Aleksandr A. ;

Sokolov, Victor V. ;

de Meijere, Armin .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2012, 2012 (26) :5028-5037

[59] Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11β-HSD1 inhibitors [J].

Rew, Yosup ;

McMinn, Dustin L. ;

Wang, Zhulun ;

He, Xiao ;

Hungate, Randall W. ;

Jaen, Juan C. ;

Sudom, Athena ;

Sun, Daqing ;

Tu, Hua ;

Ursu, Stefania ;

Villemure, Elisia ;

Walker, Nigel P. C. ;

Yan, Xuelei ;

Ye, Qiuping ;

Powers, Jay P. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (06) :1797-1801

[60] A Modular Reaction Pairing Approach to the Diversity-Oriented Synthesis of Fused- and Bridged-Polycyclic Sultams [J].

Samarakoon, Thiwanka B. ;

Loh, Joanna K. ;

Rolfe, Alan ;

Le, Lisa S. ;

Yoon, Sun Young ;

Lushington, Gerald H. ;

Hanson, Paul. R. .

ORGANIC LETTERS, 2011, 13 (19) :5148-5151

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