A continuous flow bromodimethylsulfonium bromide generator: application to the synthesis of 2-arylaziridines from styren
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A continuous flow bromodimethylsulfonium bromide generator: application to the synthesis of 2-arylaziridines from styrenes Michael Prieschl 1,2 & David Cantillo 1,2
&
C. Oliver Kappe 1,2
Received: 13 October 2020 / Accepted: 26 October 2020 # Akadémiai Kiadó 2020
Abstract A continuous flow procedure for the synthesis of aziridines from alkenes based on the in situ generation and utilization of bromodimethylsulfonium bromide (BDMS) is presented. In this process, BDMS was generated from hydrogen bromide and dimethylsulfoxide in the presence of the olefin, ensuing the corresponding 1,2-bromodimethylsulfonium bromide addition product. The solution containing this intermediate was mixed with a primary amine in flow, resulting in a rapid aziridination in a fast 3-step telescoped process. Notably, the exothermic formation of BDMS could be readily controlled in flow mode at room temperature, rendering a safe and reliable process. The complete sequence only required 7 min of total residence time, and provided a variety of 2-aryl aziridines in synthetically useful yields. Keywords Bromodimethylsulfonium bromide . Continuous flow . Chemical generators . Aziridines
Introduction Bromodimethylsulfonium bromide (BDMS) is a useful and versatile reagent with a wide range of applications in organic synthesis [1]. Since its discovery in 1965 by Meerwein [2], BDMS has often been employed both as a stoichiometric reagent and as a catalyst, owing to its attractive properties as an oxiziding agent, as well as a source of bromonium ion. Thus, it can readily transform alcohols to bromides [3] and generate αbromo enones [4]. BDMS can also be utilized for the bromination of aromatic compounds [5] and the synthesis of αbromoketones [6]. With alkenes as the coupling partner, the corresponding 1,2-addition bromosulfonium bromides are
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s41981-02000125-2. * David Cantillo [email protected] * C. Oliver Kappe [email protected] 1
Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria
2
Center for Continuous Flow Synthesis and Processing (CCFLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, Austria
formed, which can be used for further derivatization and the generation of 1,2-funtionalized scaffolds [7]. Other uses of BDMS include deprotection of thioacetals [8] and the ring opening of aziridines [9]. As a catalyst, it has been shown useful for the tetrahydropyranylation of alcohols [10] as well as Michael additions [11], Beckmann rearrangements [12] and the synthesis of α-aminophosphonates (Fig. 1) [13]. Although BDMS can be isolated as a solid and it is commercially available, its transport and storage in large amounts can be hazardous. BDMS is corrosive and heat and moisture sensitive, releasing molecular bromine (Br2) in contact with water. Thus, for safety reasons, the reagent is often prepared on site before its utiliz
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