Synthesis of Tryptamines through a Novel Brønsted Acid Mediated Tandem Reaction Initiated by α-Iminol Rearrangement of Transient 2-Substituted 2-Hydroxycyclobutylimines

Abstract

A novel Brønsted acid promoted condensation reaction between a primary aniline and 2-hydroxycyclobutanone provides access to diverse tryptamine derivatives in moderate to good yields. The proposed mechanism involves an α-iminol rearrangement, ring expansion, ring closure, and a depart-and-return rearrangement process.

Key words

tandem reaction - carbocycles - nitrogen heterocycles - synthetic methods - α-iminol rearrangement

• References


For selected reviews on cyclobutanes, see:
• 1a Namsylo JC, Kaufmann DE. Chem. Rev. 2003; 103: 1485
• 1b Lee-Ruff E, Mladenova G. Chem. Rev. 2003; 103: 1449
• 1c Fu N.-Y, Chan S.-H. In The Chemistry of Cyclobutanes . Rappoport Z, Liebman JF. Wiley; Chichester: 2005: 357
• 1d Lee-Ruff E. In The Chemistry of Cyclobutanes . Rappoport Z, Liebman JF. Wiley; Chichester: 2005: 281
• 1e Salaün J. In Science of Synthesis, Vol. 26. Cossy J. Thieme; Stuttgart: 2004: 557-606
• 1f Secci F, Frongia A, Piras PP. Molecules 2013; 18: 15541
• 2a Aitken DJ, Capitta F, Frongia A, Ollivier J, Piras PP, Secci F. Synlett 2012; 727
• 2b Aitken DJ, Capitta F, Frongia A, Gori D, Guillot R, Ollivier J, Piras PP, Secci F, Spiga M. Synlett 2011; 712
• 3 Capitta F, Frongia A, Ollivier J, Piras PP, Secci F. Synlett 2011; 89
• 4a Cuccu F, Serusi L, Luridiana A, Secci F, Caboni P, Aitken DJ, Frongia A. Org. Lett. 2019; 21: 7755
• 4b Porcu S, Luridiana A, Martis A, Frongia A, Sarais G, Aitken DJ, Boddaert T, Guillot R, Secci F. Chem. Commun. 2018; 54: 13547

For a comprehensive review on Favorskii or pinacol type ring contractions, see:
• 4c Conia JM, Robson MJ. Angew. Chem. Int. Ed. 1975; 14: 473
• 5a Aitken DJ, Caboni P, Eijsberg H, Frongia A, Guillot R, Ollivier J, Piras PP, Secci F. Adv. Synth. Catal. 2014; 356: 941
• 5b Frongia A, Melis N, Serra I, Secci F, Piras PP, Caboni P. Asian J. Org. Chem. 2014; 3: 378
• 5c Melis N, Ghisu L, Guillot R, Caboni P, Secci F, Aitken DJ, Frongia A. Eur. J. Org. Chem. 2015; 4358
• 6 Melis N, Secci F, Boddaert T, Aitken DJ, Frongia A. Chem. Commun. 2015; 51: 15272
• 7a Wang Z. Comprehensive Organic Name Reactions and Reagents. Wiley; New York: 2010: 74
• 7b Li L.-Y, Zeng Q.-L, Li G.-X, Tang Z. Synlett 2019; 30: 694
• 7c Chanda D, Harohally NV. Tetrahedron Lett. 2018; 59: 2983
• 7d Frongia A, Secci F, Capitta F, Piras PP, Sanna ML. Chem. Commun. 2013; 49: 8812
• 7e Guzi TG, Macdonald TL. Tetrahedron Lett. 1996; 37: 2939
• 7f Wrodnigg TM, Stütz AE. Angew. Chem. Int. Ed. 1999; 38: 827

For critical assessments of strategies for indole synthesis, see:
• 8a Inman M, Moody CJ. Chem. Sci. 2013; 4: 29
• 8b Taber DF, Tirunahari PK. Tetrahedron 2011; 67: 7195
• 9a Paquette LA, Hofferberth JE. Org. React. 2003; 62: 477
• 9b Movassaghi M, Schmidt MA, Ashenhurst JA. Org. Lett. 2008; 10: 4009
• 9c Zhang X, Staples RJ, Rheingold AL, Wulff WD. J. Am. Chem. Soc. 2014; 136: 13971
• 9d Zhang X, Dai Y, Wulff WD. Synlett 2018; 29: 2015
• 9e Li G, Piemontesi C, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2019; 58: 2870
• 9f Stevens CL, Ash AB, Thuillier A, Amin JH, Balys A, Dennis WE, Dickerson JP, Glinski RP, Hanson HT, Pillai MD, Stoddard JW. J. Org. Chem. 1966; 31: 2593
• 9g Stevens CL, Thuillier A, Taylor KG, Daniher FA, Dickerson JP, Hanson HT, Nielsen NA, Tikotkar NA, Weier RM. J. Org. Chem. 1966; 31: 2601
• 9h Stevens CL, Klundt IL, Munk ME, Pillai MD. J. Org. Chem. 1965; 30: 2967
• 10a Weier RM. Ph.D. Dissertation . Wayne State University; Detroit: 1967
• 10b Stevens CL, Pillai PM, Munk ME, Taylor KG. In Mechanisms of Molecular Migrations, Vol. 3. Thyagarajan BS. Wiley Interscience; New York: 1971: 271
• 10c Serusi L, Soddu F, Cuccu F, Peretti G, Luridiana A, Secci F, Caboni P, Aitken DJ, Frongia A. Adv. Synth. Catal. 2020; 362: 4159

For ring expansions related to B → C, see:
• 11a Vergne F, Partogyan K, Aitken DJ, Husson H.-P. Tetrahedron 1996; 52: 2421
• 11b Methot JL, Dunstan TA, Mampreian DM, Adams B, Altman MD. Tetrahedron Lett. 2008; 49: 1155
• 12 PTSA was selected as the catalyst for this reaction on the basis of our previous investigations on related transformations; see reference 6.
• 13 The use of PTSA under these reaction conditions led to extensive decomposition of the reaction components.