Stevens rearrangement
The Stevens rearrangement is an organic reaction in which nitrogen and sulfur ylides perform an intramolecular alkylation. The process usually begins with a persubstituted ammonium or sulfonium cation, in which case the net reaction is a 1,2-rearrangement as follows:
History
[edit]Thomas S. Stevens' original 1928 publication concerned the reaction of 1-phenyl-2-(N,N-dimethylamino)ethanone with benzyl bromide. The resulting ammonium salt reacted with aqueous sodium hydroxide to the rearranged amine:[1]
A 1932 publication described the corresponding sulfur reaction.[2]
Reaction mechanism
[edit]The Stevens rearrangement's mechanism is one of the most controversial in organic chemistry.[3] Certain is an initial deprotonation by a strong base: this yields an ylide stabilized by the electron-withdrawing substituent.[4][5]
The difficulty with the subsequent migration is that it exhibits retention of configuration. Retention is inconsistent with a concerted reaction, which would require an antarafacial transition state. But it is also inconsistent with diradical (3a) or ionic (3b) intermediates, unless those intermediates are trapped in a solvent cage:
Scope
[edit]Cationic reactants can be obtained through alkylation of the corresponding amines and sulfides.[6] The active ylide intermediate can be formed without deprotonation through rhodium(II)-acetate–catalyzed coordination of a diazo carbenoid:[7]
Competing reactions are the Sommelet-Hauser rearrangement and Hofmann elimination.
Enzymatic reaction
[edit]γ-butyrobetaine hydroxylase,[8][9] an enzyme on the human carnitine biosynthesis pathway, catalyzes a Stevens-like C-C bond formation[8][10] on meldonium.[11]
See also
[edit]- Sommelet–Hauser rearrangement
- Pummerer rearrangement, which may be thought of as a specific example of the Stevens rearrangement for the case of sulfonium acetates
- γ-Butyrobetaine hydroxylase
References
[edit]- ↑ Stevens TS, Creighton EM, Gordon AB, MacNicol M (1928). "CCCCXXIII.—Degradation of quaternary ammonium salts. Part I". J. Chem. Soc.: 3193–3197. doi:10.1039/JR9280003193.
- ↑ Stevens, T.S.; et al. (1932). "8. Degradation of quaternary ammonium salts. Part V. Molecular rearrangement in related sulphur compounds". J. Chem. Soc.: 69. doi:10.1039/JR9320000069.
- ↑ Bhakat, S (2011). "The controversial reaction mechanism of Stevens rearrangement: A review". J. Chem. Pharm. Res. 3 (1): 115–121.
- ↑ M B Smith, J March. March's Advanced Organic Chemistry (Wiley, 2001) (ISBN 0-471-58589-0)
- ↑ Strategic Applications of Named Reactions in Organic Synthesis Laszlo Kurti, Barbara Czako Academic Press (4 March, 2005) ISBN 0-12-429785-4
- ↑ Pine SH (2011). The Base-Promoted Rearrangements of Quaternary Ammonium Salts. Organic Reactions. pp. 403–464. doi:10.1002/0471264180.or018.04. ISBN 978-0471264187.
{{cite book}}:|journal=ignored (help) - ↑ Macrocycle Ring Expansion by Double Stevens RearrangementKeisha K. Ellis-Holder, Brian P. Peppers, Andrei Yu. Kovalevsky, and Steven T. Diver Org. Lett.; 2006; 8(12) pp. 2511–2514; (Letter) doi:10.1021/ol060657a
- 1 2 Leung IKH, Krojer TJ, Kochan GT, Henry L, von Delft F, Claridge TDW, Oppermann U, McDonough MA, Schofield CJ (December 2010). "Structural and mechanistic studies on γ-butyrobetaine hydroxylase". Chem. Biol. 17 (12): 1316–24. doi:10.1016/j.chembiol.2010.09.016. PMID 21168767.
- ↑ Tars K, Rumnieks J, Zeltins A, Kazaks A, Kotelovica S, Leonciks A, Sharipo J, Viksna A, Kuka J, Liepinsh E, Dambrova M (August 2010). "Crystal structure of human gamma-butyrobetaine hydroxylase". Biochem. Biophys. Res. Commun. 398 (4): 634–9. doi:10.1016/j.bbrc.2010.06.121. PMID 20599753.
- ↑ Henry L, Leung IKH, Claridge TDW, Schofield CJ (August 2012). "γ-Butyrobetaine hydroxylase catalyses a Stevens type rearrangement". Bioorg. Med. Chem. Lett. 22 (15): 4975–4978. doi:10.1016/j.bmcl.2012.06.024. PMID 22765904.
- ↑ Simkhovich BZ, Shutenko ZV, Meirena DV, Khagi KB, Mezapuķe RJ, Molodchina TN, Kalviņs IJ, Lukevics E (January 1988). "3-(2,2,2-Trimethylhydrazinium)propionate (THP)--a novel gamma-butyrobetaine hydroxylase inhibitor with cardioprotective properties". Biochem. Pharmacol. 37 (2): 195–202. doi:10.1016/0006-2952(88)90717-4. PMID 3342076.