Insights into the Reactivity of 2-Hydroxycyclobutanones with Thiols Corroborated by Quantum Chemical DFT Investigations and NMR and Raman Analysis

Abstract

A general strategy for the synthesis of 2-substituted cyclobutanone sulfides via a tandem Brønsted acid-catalyzed nucleophile addition/ring contraction/C3-C4 ring expansion reaction sequence has been exploited. The procedure led to a wide panel of four-membered cyclic ketones in good to excellent yields and with broad substrate scope. Mechanistic aspects and kinetic parameters were investigated by quantum chemical DFT calculations, allowing us to rationalize the different reactivity of 2-aryl- and 2-alkyl-substituted 2-hydroxycyclobutanones towards thiol nucleophiles in reactions mediated by sulfonic acids. NMR and in situ Raman techniques were employed to better understand the reaction kinetics and parameters that affect the desired outcome.

Key words

cyclobutanones - thiols - ring contraction - ring expansion - Brønsted acid catalysis - transposition - quantum chemical DFT

Publication History

Received: 30 June 2022

Accepted after revision: 28 July 2022

Accepted Manuscript online:
28 July 2022

Article published online:
10 October 2022

• References

• 1a Bloomfield JJ, Nelke JM. Org. Synth. 1988; 6: 167
• 1b Secci F, Porcu S, Luridiana A, Frongia A, Ricci PC. Org. Biomol. Chem. 2020; 18: 3684
• 2a Namsylo JC, Kaufmann DE. Chem. Rev. 2003; 103: 1485
• 2b Lee-Ruff E, Mladenova G. Chem. Rev. 2003; 103: 1449
• 2c Lee-Ruff E. The Chemistry of Cyclobutanes . Rappoport Z, Liebman JF. Wiley; Chichester: 2005: 281
• 2d Salaün J. In Science of Synthesis, Vol. 26. Cossy J. Thieme; Stuttgart: 2004: 557
• 2e Secci F, Frongia A, Piras PP. Molecules 2013; 18: 15541
• 2f Chen S, Shan G, Nie P, Rao Y. Asian J. Org. Chem. 2015; 4: 16
• 2g Stadler H. Helv. Chim. Acta 2015; 98: 1189
• 2h Snider BB, Walner M. Tetrahedron 1989; 45: 3171
• 2i Harding KE, Strickland JB, Pommerville J. J. Org. Chem. 1988; 53: 4877
• 2j Conia JM, Salaün J. Acc. Chem. Res. 1972; 5: 33
• 3 Porcu S, Demuro S, Luridiana A, Cocco A, Frongia A, Aitken DJ, Guillot FC.-P. R, Sarais G, Secci F. Org. Lett. 2018; 23: 7699
• 4a Melis N, Secci F, Boddaert T, Aitken DJ, Frongia A. Chem. Commun. 2015; 51: 15272
• 4b Serusi L, Cuccu F, Secci F, Aitken DJ, Frongia A. Synthesis 2021; 53: 673
• 5 Cuccu F, Serusi L, Luridiana A, Secci F, Cadoni P, Aitken DJ, Frongia A. Org. Lett. 2019; 21: 7755
• 6a Turnu F, Luridiana A, Cocco A, Porcu S, Frongia A, Sarais G, Secci F. Org. Lett. 2019; 21: 7329
• 6b Porcu S, Rodriguez CA, Frongia A, Secci F. Synthesis 2021; 53: 925
• 7 Porcu S, Luridiana A, Martis A, Frongia A, Sarais G, Aitken DJ, Boddaert T, Guillot R, Secci F. Chem. Commun. 2018; 54: 13547
• 8 Martis A, Luridiana A, Frongia A, Arca M, Sarais G, Aitken DJ, Guillot R, Secci F. Org. Biomol. Chem. 2017; 15: 10053
• 9a Aitken DJ, Capitta F, Frongia A, Ollivier J, Piras PP, Secci F. Synlett 2011; 712
• 9b Aitken DJ, Capitta F, Frongia A, Ollivier J, Piras PP, Secci F. Synlett 2012; 23: 727
• 10a Aitken DJ, Caboni P, Eijsberg H, Frongia A, Guillot R, Ollivier J, Piras PP, Secci F. Adv. Synth. Catal. 2014; 356: 941
• 10b Frongia A, Melis N, Serra I, Secci F, Piras PP, Caboni P. Asian J. Org. Chem. 2014; 3: 378
• 10c Melis N, Ghisu L, Guillot R, Caboni P, Secci F, Aitken DJ, Frongia A. Eur. J. Org. Chem. 2015; 20: 4358
• 11a Aitken DJ, Frongia A, Secci F. Vietnam J. Chem. 2019; 57: 661
• 11b Ghisu L, Melis N, Secci F, Caboni P, Frongia A. Tetrahedron 2016; 72: 8201
• 12 Luridiana A, Frongia A, Aitken DJ, Guillot R, Sarais G, Secci F. Org. Biomol. Chem. 2016; 14: 3394
• 13 Vaquer AF, Frongia A, Secci F, Tuveri E. RSC Adv. 2015; 5: 96695
• 14 Danheiser RL, Martinez-Davilla C, Sard H. Tetrahedron 1981; 37: 3943
• 15a Trost BM, Vladuchick WC, Bridges AJ. J. Am. Chem. Soc. 1980; 102: 3548
• 15b Trost BM, Jungheim L. J. Am. Chem. Soc. 1980; 102: 7910
• 16 Aprà E, Bylaska EJ, De Jong WA, Govind N, Kowalski K, Straatsma TP, Valiev M, Van Dam HJ. J, Alexeev Y, Anchell J, Anisimov V, Aquino FW, Atta-Fynn R, Autschbach J, Bauman NP, Becca JC, Bernholdt DE, Bhaskaran-Nair K, Bogatko S, Borowski P, Boschen J, Brabec J, Bruner A, Cauët E, Chen Y, Chuev GN, Cramer CJ, Daily J, Deegan MJ. O, Dunning TH, Dupuis M, Dyall KG, Fann GI, Fischer SA, Fonari A, Früchtl H, Gagliardi L, Garza J, Gawande N, Ghosh S, Glaesemann K, Götz AW, Hammond J, Helms V, Hermes ED, Hirao K, Hirata S, Jacquelin M, Jensen L, Johnson BG, Jónsson H, Kendall RA, Klemm M, Kobayashi R, Konkov V, Krishnamoorthy S, Krishnan M, Lin Z, Lins RD, Littlefield RJ, Logsdail AJ, Lopata K, Ma W, Marenich AV, Martin Del Campo J, Mejia-Rodriguez D, Moore JE, Mullin JM, Nakajima T, Nascimento DR, Nichols JA, Nichols PJ, Nieplocha J, Otero-De-La-Roza A, Palmer B, Panyala A, Pirojsirikul T, Peng B, Peverati R, Pittner J, Pollack L, Richard RM, Sadayappan P, Schatz GC, Shelton WA, Silverstein DW, Smith DM. A, Soares TA, Song D, Swart M, Taylor HL, Thomas GS, Tipparaju V, Truhlar DG, Tsemekhman K, Van Voorhis T, Vázquez-Mayagoitia A, Verma P, Villa O, Vishnu A, Vogiatzis KD, Wang D, Weare JH, Williamson MJ, Windus TL, Woliński K, Wong AT, Wu Q, Yang C, Yu Q, Zacharias M, Zhang Z, Zhao Y, Harrison RJ. J. Chem. Phys. 2020; 152: 184102
• 17 Weigend F, Ahlrichs R. Phys. Chem. Chem. Phys. 2005; 7: 3297
• 18 Adamo C, Barone VJ. Chem. Phys. 1999; 110: 6158
• 19 Grimme S, Antony J, Ehrlich S, Krieg H. J. Chem. Phys. 2010; 132: 154104
• 20 York DM, Karplus M. J. Phys. Chem. A 1999; 103: 11060
• 21 Gurke J, Budzák S, Schmidt BM, Jacquemin D, Hecht S. Angew. Chem. Int. Ed. 2018; 57: 4797
• 22 Aue DH. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2011; 1: 487
• 23 Johnson BG, Fisch MJ. J. Chem. Phys. 1998; 100: 7429