Multigram Synthesis of Heterabicyclo[n.1.0]alkan-1-yl Trifluoroborates

被引:11
作者
Kleban, Ihor [1 ,2 ]
Krokhmaliuk, Yevhen [1 ,3 ]
Reuti, Sofiia [1 ,3 ]
Shuvakin, Serhii [1 ,3 ]
Pendyukh, Vyacheslav V. [1 ]
Khyzhan, Oleksandr, I [1 ]
Yarmoliuk, Dmytro S. [1 ]
Tymtsunik, Andriy, V [1 ,4 ]
Rassukana, Yuliya, V [2 ,4 ]
Grygorenko, Oleksandr O. [1 ,3 ]
机构
[1] Enamine Ltd, Chervonotkatska 78, UA-02094 Kiev, Ukraine
[2] Natl Acad Sci Ukraine, Inst Organ Chem, Murmanska St 5, UA-02094 Kiev, Ukraine
[3] Taras Shevchenko Natl Univ Kyiv, Volodymyrska St 60, UA-01601 Kiev, Ukraine
[4] Natl Tech Univ Ukraine Igor Sikorsky Kyiv Polytec, Prospect Peremogy 37, UA-03056 Kiev, Ukraine
关键词
Organoboron compounds; Cyclopropanes; Heteroaliphatic compounds; Bicyclic compounds; Suzuki-Miyaura reaction; C-H BORYLATION; SUZUKI-MIYAURA; CATALYZED CYCLOPROPANATION; COUPLING REACTIONS; BUILDING-BLOCKS; ACID; ALKYLATION; CONVENIENT; GENERATION; CHEMISTRY;
D O I
10.1002/ejoc.202000977
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
An approach to the synthesis of oxa- and azabicyclo[n.1.0]alkan-1-yl trifluoroborates on a multigram scale was developed. Two synthetic strategies were evaluated: the first based on the lithiation-borylation of the corresponding 2-bromoallyl derivatives, and the other relying on regioselective hydroboration of the appropriate hetera-substituted enynes. The second method appeared to be more efficient in terms of scalability and substrate scope. Further steps included ring closing-metathesis, mild palladium-catalyzed cyclopropanation with diazomethane, and reaction with KHF(2)and furnished the title compounds in up to 50 g scale in a single run (10-41 % overall yield, 4-5 steps).
引用
收藏
页码:6551 / 6560
页数:10
相关论文
共 65 条
[1]   Two-and Three-dimensional Rings in Drugs [J].
Aldeghi, Matteo ;
Malhotra, Shipra ;
Selwood, David L. ;
Chan, Ah Wing Edith .
CHEMICAL BIOLOGY & DRUG DESIGN, 2014, 83 (04) :450-461
[2]   Synergistic Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic Ketones via N-C Cleavage of Imides [J].
Amani, Javad ;
Alam, Rauful ;
Badir, Shorouk ;
Molander, Gary A. .
ORGANIC LETTERS, 2017, 19 (09) :2426-2429
[3]  
[Anonymous], 2015, Angew. Chem
[4]  
[Anonymous], 2012, ANGEW CHEM
[5]  
Arndt F, 1935, ORG SYNTH, V15, P3
[6]   Diastereoselective Borocyclopropanation of Allylic Ethers Using a Boromethylzinc Carbenoid [J].
Benoit, Guillaume ;
Charette, Andre B. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2017, 139 (04) :1364-1367
[7]  
Bhat L, 2001, EUR J ORG CHEM, V2001, P1673
[8]   Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone? [J].
Brow, Dean G. ;
Bostrom, Jonas .
JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (10) :4443-4458
[9]  
Carreras J., 2018, ANGEW CHEM, V130, P2358
[10]   Enantio- and Diastereoselective Cyclopropanation of 1-Alkenylboronates: Synthesis of 1-Boryl-2,3-Disubstituted Cyclopropanes [J].
Carreras, Javier ;
Caballero, Ana ;
Perez, Pedro J. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2018, 57 (09) :2334-+