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CC BY 4.0 · Synlett
DOI: 10.1055/a-2702-3605
DOI: 10.1055/a-2702-3605
Synpacts
Enantiocontrol in Radical Coupling Reactions: A Catalytic [1,2]-Rearrangement of Allylic Ammonium Ylides
Authors
Funding Information A.D.S. and K.K. thank the EPSRC Programme Grant “Boron: Beyond the Reagent” (EP/W007517) for support.
Abstract
The [1,2]-rearrangement of ammonium ylides is a fascinating reaction that has captivated the mechanistically inclined for almost a century. Allylic migration of these ylides is dominated by a thermally allowed concerted [2,3]-rearrangement, with the [1,2]-process usually absent or a minor pathway. As such, development of a [1,2]-selective reaction within allylic systems is an uphill battle. Decades of mechanistic insights have not settled the debate on the true pathway for [1,2]-rearrangement, with a C–N homolysis step followed by a radical coupling within a solvent cage commonly accepted. Herein, we describe our journey through the development of such a process and opine on the broader context in which this chemistry may currently rest.
Keywords
Radical coupling - Rearrangement - Enantioselective organocatalysis - Ylide - Solvent cage - Recombination - Ammonium ylidePublication History
Received: 21 July 2025
Accepted after revision: 14 September 2025
Accepted Manuscript online:
15 September 2025
Article published online:
03 November 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
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References
- 1a Vanecko JA, Wan H, West FG. Tetrahedron 2006; 62: 1043-1062
- 1b West TH, Spoehrle SSM, Kasten K, Taylor JE, Smith AD. ACS Catal 2015; 5: 7446-7479
- 1c Wu H, Wang Q, Zhu J. Eur J Org Chem 2019; 2019: 1964-1980
- 1d Schwartz Z, Valiton C, Lovasz M, Roberts AG. Synthesis 2024; 56: 87-106
- 2a Stevens TS, Creighton EM, Gordon AB, MacNicol M. J Chem Soc 1928; 3193-3197
- 2b Stevens TS. J Chem Soc 1930; 2107-2119
- 3a Sommelet M, Hebd CR. Seances Acad Sci 1937; 205: 56
- 3b Nair VN, Tambar UK. Org Biomol Chem 2022; 20: 3427-3439
- 3c Tayama E. Synthesis 2022; 53: 5385-5399
- 4a Kantor SW, Hauser CR. J Am Chem Soc 1951; 73: 4122-4131
- 4b Heard GL, Yates BF. J Org Chem 1996; 61: 7276-7284
- 4c Ghigo G, Cagnina S, Maranzana A, Tonachini G. J Org Chem 2010; 75: 3608-3617
- 5a West FG, Clark JS. In: Nitrogen, Oxygen and Sulfur Ylide Chemistry: A Practical Approach in Chemistry. Clark JS. ed. Oxford University Press; 2002
- 5b Pine SH. Organic Reactions. John Wiley & Sons, Inc.; 2004
- 5c Sweeney JB. Chem Soc Rev 2009; 38: 1027-1038
- 5d Bach R, Harthong S, Lacour J. In: Comprehensive Organic Synthesis. Knochel P. ed. 2nd ed Amsterdam: Elsevier; 2014: 992-1037
- 6a Zhang C, Maeda Y, Sato Y. Chem Pharm Bull 1998; 46: 572-576
- 6b Ghisu L, Melis N, Secci F, Caboni P, Frongia A. Tetrahedron 2016; 72: 8201-8209
- 7a Hauser CR, Kantor SW. J Am Chem Soc 1951; 73: 1437-1441
- 7b Schöllkopf U, Ludwig U, Ostermann G, Patsch M. Tetrahedron Lett 1969; 10: 3415-3418
- 7c Schöllkopf U. Angew Chem Int Ed 1970; 9: 763-773
- 7d Chantrapromma K, Ollis WD, Sutherland IO. J Chem Soc Chem Commun 1977; 97-99
- 7e Chantrapromma K, Ollis WD, Sutherland IO. J Chem Soc Chem Commun 1978; 673-675
- 7f Ollis WD, Rey M, Sutherland IO. J Chem Soc Perkin Trans 1983; 1: 1009-1027
- 8a Woodward RB, Hoffmann R. Angew Chem Int Ed 1969; 8: 781-853
- 8b Dewar MJS, Ramsden CA. J Chem Soc Perkin Trans 1974; 1: 1839-1844
- 9a Mageswaran S, Ollis WD, Sutherland IO. J Chem Soc Perkin Trans 1981; 1: 1953-1962
- 9b Ollis WD, Sutherland IO, Thebtaranonth Y. J Chem Soc Perkin Trans 1981; 1: 1963-1968
- 9c Couty F, Durrat F, Evano G, Prim D. Tetrahedron Lett 2004; 45: 7525-7528
- 9d Drouillat B, d'Aboville E, Bourdreux F, Couty F. Eur J Org Chem 2014; 2014: 1103-1109
- 9e Wang K, Yang L, Li Y. et al. Angew Chem Int Ed 2023; 62: e202307249
- 9f De Oliveira Silva A, Masand SA, Farah AO. et al. J Org Chem 2024; 89: 9063-9067
- 10a Marmsäter FP, Vanecko JA, West FG. Org Lett 2004; 6: 1657-1660
- 10b Xu B, Tambar UK. J Am Chem Soc 2016; 138: 12073-12076
- 10c Xu B, Gartman JA, Tambar UK. Tetrahedron 2017; 73: 4150-4159
- 10d Nair VN, Kojasoy V, Laconsay CJ, Kong WY, Tantillo DJ, Tambar UK. J Am Chem Soc 2021; 143: 9016-9025
- 11a Jemison RW, Laird T, Ollis WD, Sutherland IO. J Chem Soc Perkin Trans 1980; 1: 1450-1457
- 11b Jonczyk A, Zdrojewski T, Grzywaca P, Balcerzak P. J Chem Soc Perkin Trans 1996; 1 (25) 2919-2923
- 12a Jemison RW, Laird T, Ollis WD, Sutherland IO. J Chem Soc Perkin Trans 1980; 1: 1436-1449
- 12b Jemison RW, Laird T, Ollis WD, Sutherland IO. J Chem Soc Perkin Trans 1980; 1 (09) 1458-1461
- 12c Doyle MP, Tamblyn WH, Bagheri V. J Org Chem 1981; 46: 5094-5102
- 12d Roy T, Gaykar RN, Bhattacharjee S, Biju AT. Chem Commun 2019; 55: 3004-3007
- 13a Giumanini AG, Trombini C, Lercker G, Lepley AR. J Org Chem 1976; 41: 2187-2193
- 13b Biswas B, Collins SC, Singleton DA. J Am Chem Soc 2014; 136: 3740-3743
- 14a Chantrapromma K, Ollis WD, Sutherland IO. J Chem Soc Chem Commun 1978; 670-671
- 14b Nishimura T, Zhang C, Maeda Y, Shirai N, Ikeda S-i, Sato Y. Chem Pharm Bull 1999; 47: 267-272
- 15 Biswas B, Singleton DA. J Am Chem Soc 2015; 137: 14244-14247
- 16 Hare SR, Tantillo DJ. Pure Appl Chem 2017; 89: 679-698
- 17a Campbell A, Houston AHJ, Kenyon J. J Chem Soc 1947; 93-95
- 17b Jenny EF, Druey J. Angew Chem Int Ed 1962; 1: 155-156
- 17c Hill RK, Chan T-H. J Am Chem Soc 1966; 88: 866-867
- 17d JH, Jones Jr RS. J Org Chem 1969; 34: 354-358
- 17e Baldwin JE, Erickson WF, Hackler RE, Scott RM. J Chem Soc D: Chem Commun 1970; 576b-578b
- 18a Ollis WD, Rey M, Sutherland IO, Closs GL. J Chem Soc Chem Commun 1975; 543-545
- 18b Ollis WD, Rey M, Sutherland IO. J Chem Soc Chem Commun 1978; 675-676
- 19 Schöllkopf U, Walter D. Liebigs Ann Chem 1962; 654: 27-38
- 20a Chantrapromma K, Ollis WD, Sutherland IO. J Chem Soc Perkin Trans 1983; 1: 1049-1061
- 20b Braden DA, Parrack EE, Tyler DR. Coord Chem Rev 2001; 211: 279-294
- 20c Barry JT, Berg DJ, Tyler DR. J Am Chem Soc 2016; 138: 9389-9392
- 20d Barry JT, Berg DJ, Tyler DR. J Am Chem Soc 2017; 139: 14399-14405
- 20e Li X, Ogihara T, Abe M, Nakamura Y, Yamago S. Chem Eur J 2019; 25: 9846-9850
- 21a Glaeske KW, West FG. Org Lett 1999; 1: 31-34
- 21b Tayama E, Nanbara S, Nakai T. Chem Lett 2006; 35: 478-479
- 21c Tayama E, Orihara K, Kimura H. Org Biomol Chem 2008; 6: 3673-3680
- 21d Tayama E, Otoyama S, Tanaka H. Tetrahedron Asymmetry 2009; 20: 2600-2608
- 21e Tuzina P, Somfai P. Org Lett 2009; 11: 919-921
- 22 Krusic PJ, Meakin P. J Am Chem Soc 1976; 98: 228-230
- 23a Ma J, Harms K, Meggers E. Chem Commun 2016; 52: 10183-10186
- 23b Wang C, Qin J, Shen X, Riedel R, Harms K, Meggers E. Angew Chem Int Ed 2016; 55: 685-688
- 23c Huang X, Li X, Xie X, Harms K, Riedel R, Meggers E. Nat Commun 2017; 8: 2245
- 23d Ma J, Rosales AR, Huang X. et al. J Am Chem Soc 2017; 139: 17245-17248
- 24a Li C, Cheng J, Wan X. et al. J Am Chem Soc 2024; 146: 19909-19918
- 24b Li T, Xu Z, Huang Y, Zu W, Huo H. J Am Chem Soc 2025; 147: 10999-11009
- 25a Pirnot MT, Rankic DA, Martin DBC, MacMillan DWC. Science 2013; 339: 1593-1596
- 25b Silvi M, Verrier C, Rey YP, Buzzetti L, Melchiorre P. Nat Chem 2017; 9: 868-873
- 25c Bonilla P, Rey YP, Holden CM, Melchiorre P. Angew Chem Int Ed 2018; 57: 12819-12823
- 25d Mazzarella D, Crisenza GEM, Melchiorre P. J Am Chem Soc 2018; 140: 8439-8443
- 25e Berger M, Carboni D, Melchiorre P. Angew Chem Int Ed 2021; 60: 26373-26377
- 25f Byun S, Hwang MU, Wise HR, Bay AV, Cheong PH-Y, Scheidt KA. Angew Chem Int Ed 2023; 62: e202312829
- 26 Uraguchi D, Kinoshita N, Kizu T, Ooi T. J Am Chem Soc 2015; 137: 13768-13771
- 27a Li J, Kong M, Qiao B, Lee R, Zhao X, Jiang Z. Nat Commun 2018; 9: 2445
- 27b Liu Y, Liu X, Li J, Zhao X, Qiao B, Jiang Z. Chem Sci 2018; 9: 8094-8098
- 27c Li Y, Han C, Wang Y. et al. J Am Chem Soc 2022; 144: 7805-7814
- 28a Biegasiewicz KF, Cooper SJ, Gao X. et al. Science 2019; 364: 1166-1169
- 28b Black MJ, Biegasiewicz KF, Meichan AJ. et al. Nat Chem 2020; 12: 71-75
- 28c Page CG, Cooper SJ, DeHovitz JS. et al. J Am Chem Soc 2021; 143: 97-102
- 28d Zhou Q, Chin M, Fu Y, Liu P, Yang Y. Science 2021; 374: 1612-1616
- 28e Fu H, Cao J, Qiao T. et al. Nature 2022; 610: 302-307
- 28f Cheng L, Li D, Mai BK. et al. Science 2023; 381: 444-451
- 28g Fu H, Qiao T, Carceller JM, MacMillan SN, Hyster TK. J Am Chem Soc 2023; 145: 787-793
- 28h Page CG, Cao J, Oblinsky DG. et al. J Am Chem Soc 2023; 145: 11866-11874
- 28i Fu W, Fu Y, Zhao Y, Wang H, Liu P, Yang Y. Nat Chem 2024; 16: 1999-2008
- 28j Ju S, Li D, Mai BK. et al. Nat Chem 2024; 16: 1339-1347
- 28k Wang T-C, Mai BK, Zhang Z. et al. Nature 2024; 629: 98-104
- 28l Liu F, Peng X, Yu J, Huang X. Org Chem Front. 2025
- 28m Raps FC, Rivas-Souchet A, Jones CM, Hyster TK. Nature 2025; 637: 362-368
- 29 Capone M, Dell’Orletta G, Page CG, Hyster TK, Scholes GD, Daidone I. ACS Catal 2024; 14: 16488-16496
- 30a Tseliou V, Kqiku L, Berger M. et al. Nature 2024; 634: 848-854
- 30b Xu Y, Chen H, Yu L. et al. Nature 2024; 625: 74-78
- 31 Leifert D, Studer A. Angew Chem Int Ed 2020; 59: 74-108
- 32 Miller DC, Lal RG, Marchetti LA, Arnold FH. J Am Chem Soc 2022; 144: 4739-4745
- 33a West TH, Daniels DSB, Slawin AMZ, Smith AD. J Am Chem Soc 2014; 136: 4476-4479
- 33b West TH, Walden DM, Taylor JE. et al. J Am Chem Soc 2017; 139: 4366-4375
- 33c Kasten K, Slawin AMZ, Smith AD. Org Lett 2017; 19: 5182-5185
- 33d West TH, Spoehrle SSM, Smith AD. Tetrahedron 2017; 73: 4138-4149
- 34 Hartley WC, Kasten K, Greenhalgh MD. et al. J Am Chem Soc 2025; 147: 1101-1111
- 35 Hartley WC, O'Riordan TJC, Smith AD. Synthesis 2017; 49: 3303-3310