Iterative Synthesis of Pluripotent Thioethers through Controlled Redox Fluctuation of Sulfur

Dedicated to Prof. Kazuhiro Kobayashi

Published as part of the Special Section 9^th EuCheMS Organic Division Young Investigator Workshop

Abstract

Target- and diversity-oriented syntheses are based on diverse building blocks, whose preparation requires discrete design and constructive alignment of different chemistries. To enable future automation of the synthesis of small molecules, we have devised a unified strategy that serves the divergent synthesis of unrelated scaffolds such as carbonyls, olefins, organometallics, halides, and boronic esters. It is based on iterations of a nonelectrophilic Pummerer-type C–C coupling enabled by turbo-organomagnesium amides that we have recently reported. The pluripotency of sulfur allows the central building blocks to be obtained by regulating C–C bond formation through control of its redox state.

Key words

sulfur - Pummerer coupling - iterative synthesis - Grignard reagents

• References and Notes

• 1a Sans V. Cronin L. Chem. Soc. Rev. 2016; 45: 2032
• 1b Eastgate MD. Schmidt MA. Fandrick KR. Nat. Rev. Chem. 2017; 1: 0016
• 1c Peplow M. Nature 2014; 512: 20
• 2a Merrifield RB. Science 1965; 150: 178
• 2b Caruthers MH. Science 1985; 230: 281
• 2c Plante OJ. Palmacci ER. Seeberger PH. Science 2001; 291: 1523
• 2d Li J. Ballmer SG. Gillis EP. Fujii S. Schmidt MJ. Palazzolo AM. Lehmann JW. Morehouse GF. Burke MD. Science 2015; 347: 1221
• 2e Tsubogo T. Oyamada H. Kobayashi S. Nature 2015; 520: 329
• 2f Adamo A. Beingessner RL. Behnam M. Chen J. Jamison TF. Jensen KF. Monbaliu J.-CM. Myerson AS. Revalor EM. Snead DR. Stelzer T. Weeranoppanant N. Wong SY. Zhang P. Science 2016; 352: 61
• 3a Hartwig J. Kirschning A. Angew. Chem. Int. Ed. 2015; 54: 10412
• 3b Li J. Grillo AS. Burke MD. Acc. Chem. Res. 2015; 48: 2297
• 3c Xu L. Zhang S. Li P. Chem. Soc. Rev. 2015; 44: 8848
• 3d Jurjens G. Kirschning A. Candito DA. Nat. Prod. Rep. 2015; 32: 723
• 3e Vara BA. Jouffroy M. Molander GA. Chem. Sci. 2017; 8: 530
• 4a Burns M. Essafi S. Bame JR. Bull SP. Webster MP. Balieu S. Dale JW. Butts CP. Harvey JN. Aggarwal VK. Nature 2014; 513: 183
• 4b Bootwicha T. Feilner JM. Myers EL. Aggarwal VK. Nat. Chem. 2017; 9: 896
• 4c Battilocchio C. Feist F. Hafner A. Simon M. Tran DN. Allwood DM. Blakemore DC. Ley SV. Nat. Chem. 2016; 8: 360
• 4d Balieu S. Hallett GE. Burns M. Bootwicha T. Studley J. Aggarwal VK. J. Am. Chem. Soc. 2015; 137: 4398
• 4e Noble A. Roesner S. Aggarwal VK. Angew. Chem. Int. Ed. 2016; 55: 15920
• 5a Burke MD. Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
• 5b CJ OC. Beckmann HS. Spring DR. Chem. Soc. Rev. 2012; 41: 4444
• 5c Kato N. Comer E. Sakata-Kato T. Sharma A. Sharma M. Maetani M. Bastien J. Brancucci NM. Bittker JA. Corey V. Clarke D. Derbyshire ER. Dornan GL. Duffy S. Eckley S. Itoe MA. Koolen KM. Lewis TA. Lui PS. Lukens AK. Lund E. March S. Meibalan E. Meier BC. McPhail JA. Mitasev B. Moss EL. Sayes M. Van Gessel Y. Wawer MJ. Yoshinaga T. Zeeman AM. Avery VM. Bhatia SN. Burke JE. Catteruccia F. Clardy JC. Clemons PA. Dechering KJ. Duvall JR. Foley MA. Gusovsky F. Kocken CH. Marti M. Morningstar ML. Munoz B. Neafsey DE. Sharma A. Winzeler EA. Wirth DF. Scherer CA. Schreiber SL. Nature 2016; 538: 344
• 5d Nielsen TE. Schreiber SL. Angew. Chem. Int. Ed. 2008; 47: 48
• 6 Liebeskind LS. Srogl J. Org. Lett. 2002; 4: 979
• 7a Screttas CG. Micha-Screttas M. J. Org. Chem. 1978; 43: 1064
• 7b Haufe G. Hugenberg V. Synlett 2008; 106
• 7c Canestrari D. Lancianesi S. Badiola E. Strinna C. Ibrahim H. Adamo MF. Org. Lett. 2017; 19: 918
• 7d Abramovitch A. Varghese JP. Marek I. Org. Lett. 2004; 6: 621
• 7e Back TG. Baron DL. Yang K. J. Org. Chem. 1993; 58: 2407
• 7f Foubelo F. Yus M. Chem. Soc. Rev. 2008; 37: 2620
• 8a Feldman KS. Tetrahedron 2006; 62: 5003
• 8b Pulis AP. Procter DJ. Angew. Chem. Int. Ed. 2016; 55: 9842
• 8c Bur SK. Padwa A. Chem. Rev. 2004; 104: 2401
• 8d Gamba-Sánchez D. Garzón-Posse F. Pummerer-Type Reactions as Powerful Tools in Organic Synthesis . In Molecular Rearrangements in Organic ­Synthesis . John Wiley and Sons; Hoboken, NJ: 2015. Chap. 20, 66
• 9 Hoyle CE. Lowe AB. Bowman CN. Chem. Soc. Rev. 2010; 39: 1355
• 10 Smith LH. Coote SC. Sneddon HF. Procter DJ. Angew. Chem. Int. Ed. 2010; 49: 5832

For recent examples of Pummerer processes with electron-rich arenes, see:
• 11a Shrives HJ. Fernandez-Salas JA. Hedtke C. Pulis AP. Procter DJ. Nat. Commun. 2017; 8: 14801
• 11b Kobatake T. Fujino D. Yoshida S. Yorimitsu H. Oshima K. J. Am. Chem. Soc. 2010; 132: 11838
• 11c Yanagi T. Otsuka S. Kasuga Y. Fujimoto K. Murakami K. Nogi K. Yorimitsu H. Osuka A. J. Am. Chem. Soc. 2016; 138: 14582

For examples with enolate equivalents, see:
• 11d Shang L. Chang Y. Luo F. He JN. Huang X. Zhang L. Kong L. Li K. Peng B. J. Am. Chem. Soc. 2017; 139: 4211
• 11e Fernandez-Salas JA. Eberhart AJ. Procter DJ. J. Am. Chem. Soc. 2016; 138: 790
• 11f Kaldre D. Maryasin B. Kaiser D. Gajsek O. Gonzalez L. Maulide N. Angew. Chem. Int. Ed. 2017; 56: 2212
• 11g Huang X. Patil M. Fares C. Thiel W. Maulide N. J. Am. Chem. Soc. 2013; 135: 7312
• 11h Kaiser D. Veiros LF. Maulide N. Chem. Eur. J. 2016; 22: 4727
• 11i Peng B. Huang X. Xie LG. Maulide N. Angew. Chem. Int. Ed. 2014; 53: 8718

For examples with propargyl equivalents and silanes, see:
• 11j Fernandez-Salas JA. Eberhart AJ. Procter DJ. J. Am. Chem. Soc. 2016; 138: 790
• 11k Eberhart AJ. Procter DJ. Angew. Chem. Int. Ed. 2013; 52: 4008
• 11l Eberhart AJ. Imbriglio JE. Procter DJ. Org. Lett. 2011; 13: 5882

For a recent example with ene-donors, see:
• 11m Tamura Y. Maeda H. Choi HD. Ishibashi H. Synthesis 1982; 56
• 12a Suarez-Pantiga S. Colas K. Johansson MJ. Mendoza A. Angew. Chem. Int. Ed. 2015; 54: 14094
• 12b Otero-Fraga J. Suarez-Pantiga S. Montesinos-Magraner M. Rhein D. Mendoza A. Angew. Chem. Int. Ed. 2017; 56: 12962
• 13 Colas K. Martin-Montero R. Mendoza A. Angew. Chem. Int. Ed. 2017; 56: 16042
• 14a Kakarla R. Dulina RG. Hatzenbuhler NT. Hui YW. Sofia MJ. J. Org. Chem. 1996; 61: 8347

For a recent protocol for the oxidation of acid-sensitive thioethers, see:
• 14b Voutyritsa E. Triandafillidi I. Kokotos CG. Synthesis 2017; 49: 917
• 15 Bao RL. Zhao R. Shi L. Chem. Commun. 2015; 51: 6884
• 16 Small-scale experiments (Scheme 2, B) were run in a one-pot fashion. However, at larger scale took the precaution of filtering the silica gel used in the oxidation reaction before removal of the solvent. We have not studied the influence of this filtration in the efficiency of the coupling.
• 17 For a recently developed C–S cleavage reaction on thioethers, see: Lian Z. Bhawal BN. Yu P. Morandi B. Science 2017; 356: 1059