Integrated Synthesis Using Isothiocyanate-Substituted Aryllithiums by Flow Chemistry

Hyune-Jea Lee; Daiki Torii; Yongju Jeon; Jun-ichi Yoshida; Heejin Kim

doi:10.1055/s-0040-1707251

Synlett, Inhaltsverzeichnis

Synlett 2020; 31(19): 1899-1902
DOI: 10.1055/s-0040-1707251

cluster

Integrated Synthesis Using Isothiocyanate-Substituted Aryllithiums by Flow Chemistry

Hyune-Jea Lee

^aDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea eMail: heejinkim@korea.ac.kr

,

Daiki Torii

^bDepartment of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

,

Yongju Jeon

^aDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea eMail: heejinkim@korea.ac.kr

,

Jun-ichi Yoshida∗

^bDepartment of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

^cNational Institute of Technology, Suzuka College, Shiroko-cho, Suzuka, Mie 510-0294, Japan

,

Heejin Kim∗

^aDepartment of Chemistry, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea eMail: heejinkim@korea.ac.kr

^bDepartment of Synthetic Chemistry and Biological Chemistry, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Dedicated to Prof. Jun-ichi Yoshida (1952–2019) for his pioneering work on flow chemistry

Published as part of the Cluster Integrated Synthesis Using Continuous-Flow Technologies

Abstract

The isothiocyanate (NCS) group is an attractive functional group in the field of organic and pharmaceutical chemistry. It can be transformed into other heteroatomic functional groups. It usually acts as the inductive group of biological activity and has also been traditionally used as the fluorescent-labeling reagent. However, it is not compatible with strong bases. When the NCS group is at para position in halobenzenes, it generally undergoes nucleophilic additions upon reaction with strong bases. To the best of our knowledge, there is currently no general methodology for the formation and reactions of NCS-functionalized aryllithiums for meta and para substituents. Herein, we report the continuous-flow generation of NCS-substituted aryllithiums from the corresponding haloarenes via a selective halogen–lithium exchange reaction and its reaction with various electrophiles to yield NCS-containing products. We also achieved an integrated synthesis through sequential reactions of the NCS-containing compounds with additional nucleophiles using the continuous-flow reactors.

Key words

isothiocyanate - organolithium - flow chemistry - microreactor - integrated synthesis

Volltext

Referenzen

References

1a Browne DL, O’Brien M, Koos P, Cranwell PB, Polyzos A, Ley SV. Synlett 2012; 23: 1402
1b Pace V, Castoldi L, Monticelli S, Safranek S, Roller A, Langer T, Holzer W. Chem. Eur. J. 2015; 21: 18966
1c Prevost JR. C, Kozlova A, Saadi BE, Yildiz E, Modaffari S, Lambert DM, Pochet L, Wouters J, Dolušić E, Frédérick R. Tetrahedron Lett. 2018; 59: 4315
1d Lu C, Hu L, Zhao B, Yao Y. Organometallics 2019; 38: 2167

2a Klayman DL, Bartosevich JF, Griffin TS, Mason CJ, Scovill JP. J. Med. Chem. 1979; 22: 855
2b Ejim L, Farha MA, Falconer SB, Wildenhain J, Coombes BK, Tyers M, Brown ED, Wright GD. Nat. Chem. Biol. 2011; 7: 348
2c Lee C.-M, Lee D.-S, Jung W.-K, Yoo JS, Yim M.-J, Choi YH, Park S, Seo S.-K, Choi JS, Lee Y.-M, Park WS, Choi I.-W. Int. J. Mol. Med. 2016; 38: 912
2d Stone LK, Baym M, Lieberman TD, Chait R, Clardy J, Kishony R. Nat. Chem. Biol. 2016; 12: 902
2e Kjaerulff L, Sikandar A, Zaburannyi N, Adam S, Herrmann J, Koehnke J, Müller R. ACS Chem. Biol. 2017; 12: 2837

3a Coons AH, Creech HJ, Jones RN, Berliner E. J. Immunol. 1942; 45: 159
3b The TH, Feltkamp TE. W. Immunology 1970; 18: 875
3c Christensen PJ, Goodman RE, Pastoriza L, Moore B, Toews GB. Am. J. Pathol. 1999; 155: 1773
3d Hermanson GT. Bioconjugate Techniques, 3rd ed. 2013; 395

4a Parham WE, Bradsher CK. Acc. Chem. Res. 1982; 15: 300
4b Parham WE, Sayed YA. J. Org. Chem. 1974; 39: 2053
4c Parham WE, Jones LD. J. Org. Chem. 1976; 41: 2704

5 Kim H, Lee H.-J, Kim D.-P. Angew. Chem. Int. Ed. 2015; 54: 1877

6a Nagaki A, Kim H, Yoshida J. Angew. Chem. Int. Ed. 2008; 47: 7833
6b Nagaki A, Kim H, Yoshida J. Angew. Chem. Int. Ed. 2009; 48: 8063
6c Nagaki A, Kim H, Usutani H, Matsuo C, Yoshida J. Org. Biomol. Chem. 2010; 8: 1212
6d Nagaki A, Kim H, Moriwaki Y, Matsuo C, Yoshida J. Chem. Eur. J. 2010; 16: 11167
6e Kim H, Nagaki A, Yoshida J. Nat. Commun. 2011; 2: 264
6f Yoshida J, Kim H, Nagaki A. ChemSusChem 2011; 4: 331
6g Ren W, Kim H, Lee H.-J, Wang J, Wang H, Kim D.-P. Lab Chip 2014; 14: 4263

7a Kim H, Lee H.-J, Kim D.-P. Angew. Chem. Int. Ed. 2016; 55: 1422
7b Kim H, Min K.-I, Inoue K, Im DJ, Kim D.-P, Yoshida J. Science 2016; 352: 691
7c Kim H, Inoue K, Yoshida J. Angew. Chem. Int. Ed. 2017; 56: 7863
7d Lee H.-J, Kim H, Yoshida J, Kim D.-P. Chem. Commun. 2018; 54: 547
7e Kim H, Yonekura Y, Yoshida J. Angew. Chem. Int. Ed. 2018; 57: 4063
7f Kim H, Yin Z, Sakurai H, Yoshida J. React. Chem. Eng. 2018; 3: 635
7g Lee H.-J, Kim H, Kim D.-P. Chem. Eur. J. 2019; 25: 11641
7h Lee H.-J, Roberts RC, Im DJ, Yim S.-J, Kim H, Kim JT, Kim D.-P. Small 2019; 15: 1905005

8a Newman SG, Jensen KF. Green Chem. 2013; 15: 1456
8b Pastor JC, Browne DL, Ley SV. Chem. Soc. Rev. 2013; 42: 8849
8c Fukuyama T, Totoki T, Ryu I. Green Chem. 2014; 16: 2042
8d Ley SV, Fitzpatrick DE, Myers RM, Battilocchio C, Inham RJ. Angew. Chem. Int. Ed. 2015; 54: 10122
8e Kobayashi S. Chem. Asian J. 2016; 11: 425
8f Cambié D, Bottecchia C, Straathof NJ. W, Hessel V, Noel T. Chem. Rev. 2016; 116: 10276
8g Plutschack MB, Pieber B, Gilmore K, Seeberger PH. Chem. Rev. 2017; 117: 11796
8h Shen G, Osako T, Nagaosa M, Uozumi Y. J. Org. Chem. 2018; 83: 7380
8i Arakawa Y, Ueta S, Okamoto T, Minagawa K, Imda Y. Synlett 2020; 31: 866

9 Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Cara CL, Basso G, Viola G, Khedr M, Balzarini J, Mahboobi S, Sellmer A, Brancale A, Hamel E. J. Med. Chem. 2009; 52: 5551

10a Teng X, Degterev A, Jagtap P, Xing X, Choi S, Denu R, Yuan J, Cuny GD. Bioorg. Med. Chem. Lett. 2005; 15: 5039
10b Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J. Nat. Chem. Biol. 2008; 4: 313

Zusatzmaterial

Supporting Information