A Mild Heteroatom (O-, N-, and S-) Methylation Protocol Using Trimethyl Phosphate (TMP)–Ca(OH)₂Combination

Abstract

A mild heteroatom methylation protocol using trimethyl phosphate (TMP)–Ca(OH)₂ combination has been developed, which proceeds in DMF, or water, or under neat conditions, at 80 °C or at room temperature. A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, are suitable substrates for this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmentally friendly nature of this protocol make it an attractive alternative to the conventional base-promoted heteroatom methylation procedures.

Key words

trimethyl phosphate - calcium hydroxide - heteroatom methylation - aqueous S-methylation - N-sulfonamide methylation

Publikationsverlauf

Eingereicht: 16. Dezember 2021

Angenommen nach Revision: 04. Januar 2022

Accepted Manuscript online:
04. Januar 2022

Artikel online veröffentlicht:
03. März 2022

• References

• 1 Smith M. B., March J.; In March’s Advanced Organic Chemistry. Reactions, Mechanisms, and Structure; John Wiley and Sons:  New York, 2007; 425–656.

For recent reviews, see:
• 2a Steverlynck J, Sitdikov R, Rueping M. Chem. Eur. J. 2021; 27: 11751
• 2b Sun Q, Soulé J.-F. Chem. Soc. Rev. 2021; 50: 10806
• 2c Chen Y. Chem. Eur. J. 2019; 25: 3405

For some recent reports on heteroatom methylation, see:
• 3a Rooney CL, Wu Y, Tao Z, Wang H. J. Am. Chem. Soc. 2021; 143: 19983
• 3b Bartlett ME, Zhu Y, Gaffney UB, Lee J, Wu M, Sharew B, Chavez AK, Gorin DJ. Eur. J. Org. Chem. 2021; 5661
• 4a Lissel M, Schmidt S, Neumann B. Synthesis 1986; 382
• 4b Tundo P, Selva M. Acc. Chem. Res. 2002; 35: 706
• 5 Bergman J, Norrby P.-O, Sand P. Tetrahedron 1990; 46: 6113
• 6 Fevig JM. Trimethyl Phosphate in Encyclopedia of reagents for Organic Synthesis. Charette A. John Wiley & Sons. Ltd.; 2001

For toxicity study of TMP, see:
• 7a Jackson H, Jones AR. Nature 1968; 220: 591
• 7b Hanna PJ, Kerr JB. Experientia 1981; 37: 999
• 8a Noller CR, Dutton GR. J. Am. Chem. Soc. 1933; 55: 424
• 8b Nelson RB. US 4453017A, 1984
• 8c Saidi MR, Rajabi F. Phosphorus, Sulfur Silicon Relat. Elem. 2003; 178: 2343
• 8d Duval A, Avérous L. Green Chem. 2020; 22: 1671
• 9 Duclos M.-C, Herbinski A, Mora A.-S, Métay E, Lemaire M. ChemSusChem 2018; 11: 547
• 10a Billman JH, Radike A, Mundy BW. J. Am. Chem. Soc. 1942; 64: 2977
• 10b Thomas DG, Billman JH, Davis CE. J. Am. Chem. Soc. 1946; 68: 895
• 10c Gray MD. M, Smith DJ. H. Tetrahedron Lett. 1980; 21: 859
• 11a Asai S, Ban K, Monguchi Y, Sajiki H, Sawama Y. Synlett 2018; 29: 322
• 11b Banerjee A, Hattori T, Yamamoto H. Synthesis 2021; in press, DOI:
• 12a Yamauchi K, Kinoshita M. J. Chem. Soc., Perkin Trans. 1 1973; 391
• 12b Yamauchi K, Kinoshita M. J. Chem. Soc., Perkin Trans. 1 1973; 2506
• 12c Yamauchi K, Hayashi M, Kinoshita M. J. Org. Chem. 1975; 40: 385
• 12d Tanabe T, Yamauchi K, Kinoshita M. Bull. Chem. Soc. Jpn. 1976; 49: 3224
• 12e Frank J, Mészáros Z, Dutka F, Kömives T, Márton AF. Tetrahedron Lett. 1977; 4545
• 13a Yamauchi K, Sugimae T, Kinoshita M. Tetrahedron Lett. 1977; 1199
• 13b Hayashi M, Hisanaga Y, Yamauchi K, Kinoshita M. Synth. Commun. 1980; 10: 791
• 13c Mentz M, Modro AM, Modro TA. Can. J. Chem. 1994; 72: 1933
• 14 Recently, TMP/LiI combination has been disclosed as an effective reagent for the C-methylation of arylboronic esters; see: He Z.-T, Li H, Haydl AM, Whiteker GT, Hartwig JF. J. Am. Chem. Soc. 2018; 140: 17197
• 15 To the best of our knowledge, there are no reported examples of base-promoted methylation reactions using Ca(OH)2 as the base. Of the alkali earth metal hydroxide series, only Ba(OH)2 has occasionally been used; for example, see: Gelling OJ, Feringa BL. J. Am. Chem. Soc. 1990; 112: 7599

Ca(OH)₂ has occasionally been used as a base in organic synthesis. For examples, see:
• 16a Lee YR, Hari GS. Bull. Korean Chem. Soc. 2011; 32: 2949
• 16b Wadzinski TJ, Steinauer A, Hie L, Pelletier G, Schepartz A, Miller SJ. Nat. Chem. 2018; 10: 644
• 16c Zhang G.-L, Gadi MR, Cui X, Liu D, Zhang J, Saikam V, Gibbons C, Wang PG, Li L. Green Chem. 2021; 23: 2907
• 16d Wen P, Jia P, Fan Q, McCarty BJ, Tang W. ChemSusChem 2022; 15: e202102483
• 17 Massah AR, Mosharafian M, Momeni AR, Aliyan H, Naghash HJ, Adibnejad M. Synth. Commun. 2007; 37: 1807
• 18 Šterk D, Časar Z, Jukič M, Košmrlj J. Tetrahedron 2012; 68: 155
• 19 Naidu AB, Jaseer EA, Sekar G. J. Org. Chem. 2009; 74: 3675
• 20 Hipwell VM, Garcia-Garibay MA. J. Org. Chem. 2019; 84: 11103
• 21 Luo B, Gao J.-M, Lautens M. Org. Lett. 2016; 18: 4166
• 22 Jiang Z.-J, Li Z.-H, Yu J.-B, Su W.-K. J. Org. Chem. 2016; 81: 10049
• 23 Chen H, Dong W, Hu J, Rao L, Wang P, Wang S, Xiang Y, Yang Y. Green Chem. 2021; 23: 5797
• 24 Li C, Song Z.-Q, Wang D.-H, Wang J.-R. Org. Lett. 2021; 23: 8450
• 25 Alonso-Alijaa C, Michels M, Peilstöcker K, Schirok H. Tetrahedron Lett. 2004; 45: 95
• 26 Yang Y.-M, Yao J.-F, Yan W, Luo Z, Tang Z.-Y. Org. Lett. 2019; 21: 8003
• 27 Sang D, Yue H, Zhao Z, Yang P, Tian J. J. Org. Chem. 2020; 85: 6429
• 28 Anugu RR, Chandra D, Falck JR, Jat JL, Munnuri S, Verma S. Synthesis 2019; 51: 3709
• 29 Taniguchi T, Curran DP. Org. Lett. 2012; 14: 4540
• 30 Jaita S, Phakhodee W, Chairungsi N, Pattarawarapan M. Tetrahedron Lett. 2018; 59: 3571
• 31 Guo H, Liu D, Butt NA, Liu Y, Zhang W. Tetrahedron 2012; 68: 3295
• 32 Wu Z, Wei F, Wan B, Zhang Y. J. Am. Chem. Soc. 2021; 143: 4524
• 33 Fu Y, Wu Q.-K, Du Z. Eur. J. Org. Chem. 2021; 1896
• 34 Blieck R, Perego LA, Ciofini I, Grimaud L, Taillefer M, Monnier F. Synthesis 2019; 51: 1225
• 35 Pan X, Gao J, Liu J, Lai J, Jiang H, Yuan G. Green Chem. 2015; 17: 1400
• 36 Baker DC, Jiang B. US 6353112B1, 2002
• 37 Roth GJ, Heckel A, Colbatzky F, Handschuh S, Kley J, Lehmann-Lintz T, Lotz R, Tontsch-Grunt U, Walter R, Hilberg F. J. Med. Chem. 2009; 52: 4466
• 38 Urlam MK, Pireddu R, Ge Y, Zhang X, Sun Y, Lawrence HR, Guida WC, Sebti SM, Lawrence NJ. MedChemComm 2013; 4: 932
• 39 Zhao X, Chen M, Huang B, Yang C, Gao Y, Xia W. Synthesis 2018; 50: 2981
• 40 Li G, Ji C.-L, Hong X, Szostak M. J. Am. Chem. Soc. 2019; 141: 11161
• 41 Tapa P, Corral E, Sardar S, Pierce BS, Foss FW. J. Org. Chem. 2019; 84: 1025
• 42 Blanco MM, Levin GJ, Schapira CB, Perillo IA. Heterocycles 2002; 57: 1881
• 43 Laursen SR, Jensen MT, Lindhardt AT, Jacobsen MF, Skrydstrup T. Eur. J. Org. Chem. 2016; 1881
• 44 Tsuchiya D, Moriyama K, Togo H. Synlett 2011; 2701
• 45 Tolstikov AG, Biktimirova LA, Tolstikova OV, Shmakov VS, Vyrypaev EM, Tolstikov GA. Chem. Nat. Compd. 1992; 28: 85
• 46 Winter M, Furrer A, Willhalm B, Thommen W. Helv. Chim. Acta 1976; 59: 1613
• 47 Melzig L, Diene CR, Rohbogner CJ, Knochel P. Org. Lett. 2011; 13: 3174
• 48 Kong Z, Pan C, Li M, Wen L, Guo W. Green Chem. 2021; 23: 2773
• 49 Huang D, Wu X. J. Fluorine Chem. 2021; 245: 109778
• 50 Blank L, Fagnoni M, Protti S, Rueping M. Synthesis 2019; 51: 1243
• 51 Wang Y.-Y, Wu X.-M, Yang M.-H. Synlett 2020; 31: 1226
• 52 Uetake Y, Niwa T, Hosoya T. Org. Lett. 2016; 18: 2758
• 53 Hari DP, Hering T, Koenig B. Org. Lett. 2012; 14: 5334
• 54 Kathe PM, Berkefeld A, Fleischer I. Synlett 2021; 32: 1629
• 55 Smith DJ, Yap GP. A, Kelley JA, Schneider JP. J. Org. Chem. 2011; 76: 1513
• 56 Zhang Y, Zhang H, Gao K. Org. Lett. 2021; 23: 8282
• 57 Toyooka G, Tuji A, Fujita K.-I. Synthesis 2018; 50: 4617
• 58a Zhang Z, Liu Y.-H, Zhang X, Wang X.-C. Tetrahedron 2019; 75: 2763
• 58b Heredia MD, Guerra WD, Barolo SM, Fornasier SJ, Rossi RA, Budén ME. J. Org. Chem. 2020; 85: 13481
• 59 Kiran YB, Ikeda R, Sakai N, Konakahara T. Synthesis 2010; 276
• 60 Mitchell LJ, Moody CJ. J. Org. Chem. 2014; 79: 11091
• 61 Dai C, Xu Z, Huang F, Yu Z, Gao Y.-F. J. Org. Chem. 2012; 77: 4414
• 62 Zhu X, Li W, Luo X, Deng G, Liang Y, Liu J. Green Chem. 2018; 20: 1970
• 63 Siddaraju Y, Prabhu KR. Org. Biomol. Chem. 2015; 13: 11651
• 64 Ross J, Xiao J. Green Chem. 2002; 4: 129
• 65 Cleland D, McCluskey A. Org. Biomol. Chem. 2013; 11: 4646
• 66 Wessels M, König GM, Wright AD. J. Nat. Prod. 2001; 64: 1556
• 67 Zhang B, Fan Z, Guo Z, Xi C. J. Org. Chem. 2019; 84: 8661
• 68 Barbero N, Martin R. Org. Lett. 2012; 14: 796
• 69 Delcaillau T, Bismuto A, Lian Z, Morandi B. Angew. Chem. Int. Ed. 2020; 59: 2110
• 70 Yuan L.-Z, Zhao G, Hamze A, Alami M, Provot O. Adv. Synth. Catal. 2017; 359: 2682
• 71 Ye Y.-H, Ma L, Dai Z.-C, Xiao Y, Zhang Y.-Y, Li D.-D, Wang J.-X, Zhu H.-L. J. Agric. Food Chem. 2014; 62: 4063
• 72 Philippe B, Martin B, Wilhelm S. Tetrahedron 1993; 49: 595
• 73 Bhabak KP, Mugesh G. Chem. Eur. J. 2010; 16: 1175