Synthesis, Table of Contents Synthesis 2019; 51(12): 2579-2583DOI: 10.1055/s-0037-1610703 paper © Georg Thieme Verlag Stuttgart · New YorkReactions of t-Boc-Protected Amines with Difluorocarbene Authors Author Affiliations Andrii Gerasov a Life Chemicals Inc., Murmanska st. 5, Kyiv, 02660, Ukraine Email: A.Shivanyuk@lifechemicals.com Alexander Shivanyuk* a Life Chemicals Inc., Murmanska st. 5, Kyiv, 02660, Ukraine Email: A.Shivanyuk@lifechemicals.com b The Institute of High Technologies, Taras Shevchenko National University of Kyiv, 4 Glushkov st.5, Kyiv, 03187, Ukraine Volodymyr Fetyukhin a Life Chemicals Inc., Murmanska st. 5, Kyiv, 02660, Ukraine Email: A.Shivanyuk@lifechemicals.com Oleg Lukin a Life Chemicals Inc., Murmanska st. 5, Kyiv, 02660, Ukraine Email: A.Shivanyuk@lifechemicals.com Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract The reactions of t-Boc-protected secondary and primary amines with difluorocarbene generated from trimethylsilyl (fluorosulfonyl)difluoroacetate [Me3SiOC(O)CF2SO2F] (TFDA) in toluene at 110 °C results in the replacement of t-Bu by difluoromethyl in the t-Boc group. This reaction can be carried out in the presence of CH2Br and COOMe moieties in the structure of the protected amine. In the example of a t-Boc-protected amine containing a C=C double bond, replacement of the t-Bu group and/or cyclodifluoropropanation takes place. Difluoromethyl esters are shown to react with primary and secondary amines yielding the corresponding ureas. Key words Key words t-Boc group - trimethylsilyl (fluorosulfonyl)difluoroacetate - t-Bu/CHF2 replacement - difluoromethylcarbamate - acylation - urea Full Text References References 1 Schelhaas M, Waldmann H. Angew. Chem., Int. Ed. Engl. 1996; 35: 2056 2 Ashworth IW, Cox BG, Meyrick B. J. Org. Chem. 2010; 75: 8117 3a Brahms DL. S, Dailey WP. Chem. Rev. 1996; 96: 1585 3b Ni C, Hu J. Synthesis 2014; 46: 0842 3c Dilman AD, Levin VV. Acc. Chem. Res. 2018; 51: 1272 4 Cai X, Zhai Y, Ghiviriga I, Abboud KA, Dolbier WR. J. Org. Chem. 2004; 69: 4210 5 Dolbier WR, Tiana F, Duana JX, Li A.-R, Ait-Mohanda S, Bautista O, Buathong S, Baker JM, Crawford J, Anselme P, Cai XH, Modzelewska A, Koroniak H, Battiste MA, Chen Q.-Y. J. Fluorine Chem. 2004; 125: 459 6 Wang F, Luo T, Hu J, Wang Y, Krishnan HS, Jog PV, Ganesh SK, Prakash GK. S, Olah GA. Angew. Chem. Int. Ed. 2011; 50: 7153 7 Chandrasekhar S, Babu BN, Reddy ChR. Tetrahedron Lett. 2003; 44: 2057 8 To the best of our knowledge only one difluoromethylcarbamate has been described in the literature which was isolated in 15% yield as a side product of the reaction between HO(O)CCF2SO2F and the sodium salt of benzimidazole: Qingyun C, Guoying Y, Shengwen W. Chin. J. Chem. 1992; 10: 350 9 Nosik PS, Gerasov AO, Boiko RO, Rusanov E, Ryabukhin SV, Grygorenko OO, Volochnyuk DM. Adv. Synth. Catal. 2017; 359: 3126 10 Ghosh S, Kinney WA, Gauthier DA, Lawson EC, Hudlicky T, Maryanoff BE. Can. J. Chem. 2006; 84: 555 11a Sheldrick G. Acta. Crystallogr., Sect. A. 2008; 64: 112 11b CCDC 184669 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. 12 Kim M, Chang S. Org. Lett. 2010; 12: 1640 13 Jeong BH, Kim LH, Thompson DH. Aust. J. Chem. 2016; 69: 805 14 Jollie DM, Harrison PG. J. Chem. Soc., Perkin Trans. 2 1997; 1571 15 Olah GA, Prakash GK. S, Wang Q, Li X. Formyl Fluoride . In Encyclopedia of Reagents for Organic Synthesis . Paquette L. J. Wiley & Sons; New York: 2001 16 Christe KO, Wilson WW. J. Fluorine Chem. 1990; 46: 339 17a Bogolubsky AV, Ryabukhin SV, Pipko SE, Lukin O, Shivanyuk A, Mykytenko D, Tolmachev A. Tetrahedron 2011; 67: 3619 17b Gallou I. Org. Prep. Proced. Int. 2007; 39: 355 17c Majer P, Randad RS. J. Org. Chem. 1994; 59: 1937 17d Thavonecham B. Synthesis 1997; 1189 17e Lemoucheux L, Rouden J, Ibazizene M, Sobrio F, Lasne M.-C. J. Org. Chem. 2003; 68: 7289 Supplementary Material Supplementary Material Supporting Information (PDF)
