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DOI: 10.1055/s-0028-1088201
2-(Trimethylsilyl)ethanesulfonamide (TMS(CH2)2SO2NH2 or SES-NH2) - A Sulfonamidation Agent With Multiple Qualities
Publication History
Publication Date:
16 March 2009 (online)
Biographical Sketches
![](https://www.thieme-connect.de/media/synlett/200906/v279_gomes.jpg)
Introduction
Sulfonamides act as protecting and activating groups in the synthesis of amines [¹] and they are among the most stable amine protecting groups under a wide range of conditions. [²] SES-NH2 plays this role in synthesis and can be used alternatively to introduce a SES-protected amine functionality directly into a molecule. [²]
Weinreb and co-workers prepared sulfonamides from a primary or secondary amine using the previously unknown β-(trimethylsilyl)ethanesulfonyl chloride (SES-Cl). [³]
In 1996, Griffith and Danishefsky synthesized 2-(trimethylsilyl)ethanesulfonamide (SES-NH2) by bubbling ammonia gas through a stirred solution of SES-Cl in dichloromethane at 0 ˚C. The reaction occurs with good yield of 70% over a period of one hour (Scheme [¹] ). [4]
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Scheme 1
Nosyl, tosyl and mesyl groups would perform the same role as the SES group, however, tosyl and mesyl groups are usually troublesome to deprotect. [¹] [²] Although SES-protected amines are stable compounds, they can be readily cleaved under mild conditions using fluoride sources (CsF or TBAF) to generate the parent amine. [²] [5]
On deprotection, the fluoride ion attacks the silicon atom leading to the free amine and to volatile products such as ethylene, fluorotrimethylsilane and sulfur dioxide through β-elimination. [6]
SES-NH2 is considered as an ammonia surrogate for the palladium-catalyzed amination of aryl bromides and aryl chlorides. [6] Moreover, this reagent can be used in iminations reaction, [7] synthesis of azamacrocycles, [8] aza-Baylis-Hillman reaction, [9] [¹0] synthesis of the aziridines [¹¹] [¹²] and important biologically compounds. [¹²] [¹³]
The reagent is commercially available as a white solid (mp 86-89 ˚C). [4] It should be used with carefull precaution, because it can be irritating to the eyes, the skin and the respiratory system.
Abstracts
(A) The SES-NH2 can be used as an ammonia substitute in the palladium-catalyzed synthesis of primary arylamines from aryl halides. This reaction, known by Buchwald-Hartwig method, works well with aryl bromides, aryl chlorides and heterocyclic chlorides to produce high yields of the adducts with different substituents such as cyano, ester, keto, nitro and aldehyde. [6] |
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(B) The stereospecific imination of various sulfoxides has been achieved under mild conditions (room temperature) using the inexpensive Fe(acac)3 as a catalyst. Sulfonamide in combination with iodosylbenzene is a nonhazardous nitrogen source for this reaction in substitution of potentially explosive azides. [7] |
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(C) SES-NH2 offers a convenient access to the synthesis of linear and cyclic triamines with control over the carbon-bridge architecture. Masllorens et al. proposed the synthesis of 15-membered triolefinic azamacrocycles using SES-NH2 as an amine protecting group [example a)]. An example of removal of the protecting group by fluoride can be verified on second stage of the reaction supplying a good yield of 81% [example b)]. [8] |
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(D) An attractive method for the synthesis of β-aminoesters is the 3-component aza version of Baylis-Hillman reaction. Reaction of furfural at 70 ˚C and 6 h have showed high selectivity, yielding 71% (example a). [9] Ribière et al. reported the first nitrogen-anchored polymer-supported aza-Baylis-Hillman reaction, by means of PEG-SES-NH2. [¹0] This support allows the use of large excess of reactants that is easily removed after precipitation by filtration and washing. In the case of benzaldehyde a quantitative conversion was achieved in 3 h and in the absence of solvent (example b). [¹0] |
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(E) A series of olefins reacts to afford N-sulfonylated aziridines in moderate yields. This reaction is a direct copper-catalyzed nitrogen transfer mediated by the iodosylbenzene, a powerful oxygen atom donor (example a). [¹¹] Example b) shows an diastereoselective aziridination which provided a 7:3 ratio of the (2R,4R) and (2R,4S) isomers, with yield 40% of the major diastereomer. This reaction was an important stage on the synthesis of enduracididine, an α-amino acid isolated from Streptomyces fungicidicus in 1968. [¹²] Moreover, the comercial availability of easy-to-handle copper(II) complexes as catalyst makes this reaction highly practical. [¹¹-¹³] |
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(F) Wang et al. used SES-NH2 in a stage to the synthesis of an N-linked glycopeptide presenting the H-type 2 human blood group determinant. The iodosulfonamidation was followed by thiolysis and release of iodide, providing a thioglycoside at room temperature in 85% yield. [¹4] |
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- 1
Mayer AC. Synlett 2008, 945 - 2
Ribière P.Declerck V.Martinez J.Lamaty F. Chem. Rev. 2006, 106: 2249 - 3
Weinreb SM.Demko DM.Lessen TA. Tetrahedron Lett. 1986, 27: 2099 - 4
Griffith DA.Danishefsky SJ. J. Am. Chem. Soc. 1996, 118: 9526 - 5
Hoye RC.Richman JE.Dantas GA.Lightbourne MF.Shinneman LS. J. Org. Chem. 2001, 66: 2722 - 6
Anjanappa P.Mullick D.Selvakumar K.Sivakumar M. Tetrahedron Lett. 2008, 49: 4585 - 7
Mancheño OG.Bolm C. Org. Lett. 2006, 8: 2349 - 8
Masllorens J.Moreno-Mañas M.Roglans A. Tetrahedron 2005, 61: 10105 - 9
Declerck V.Ribière P.Martinez J.Lamaty F. J. Org. Chem. 2004, 69: 8372 - 10
Ribière P.Enjalbal C.Aubagnac J.-L.Yadav-Bhatnagar N.Martinez J.Lamaty F. J. Comb. Chem. 2004, 6: 464 - 11
Dauban P.Sanière L.Tarrade A.Dodd RH. J. Am. Chem. Soc. 2001, 123: 7707 - 12
Sanière L.Leman L.Bourguignon J.-J.Dauban P.Dodd RH. Tetrahedron 2004, 60: 5889 - 13
Leman L.Sanière L.Dauban P.Dodd RH. ARKIVOC 2003, (νi): 126 - 14
Wang Z.-G.Warren JD.Dudkin VY.Zhang X.Iserloh U.Visser M.Eckhardt M.Seeberger PH.Danishefsky SJ. Tetrahedron 2006, 62: 4954
References
- 1
Mayer AC. Synlett 2008, 945 - 2
Ribière P.Declerck V.Martinez J.Lamaty F. Chem. Rev. 2006, 106: 2249 - 3
Weinreb SM.Demko DM.Lessen TA. Tetrahedron Lett. 1986, 27: 2099 - 4
Griffith DA.Danishefsky SJ. J. Am. Chem. Soc. 1996, 118: 9526 - 5
Hoye RC.Richman JE.Dantas GA.Lightbourne MF.Shinneman LS. J. Org. Chem. 2001, 66: 2722 - 6
Anjanappa P.Mullick D.Selvakumar K.Sivakumar M. Tetrahedron Lett. 2008, 49: 4585 - 7
Mancheño OG.Bolm C. Org. Lett. 2006, 8: 2349 - 8
Masllorens J.Moreno-Mañas M.Roglans A. Tetrahedron 2005, 61: 10105 - 9
Declerck V.Ribière P.Martinez J.Lamaty F. J. Org. Chem. 2004, 69: 8372 - 10
Ribière P.Enjalbal C.Aubagnac J.-L.Yadav-Bhatnagar N.Martinez J.Lamaty F. J. Comb. Chem. 2004, 6: 464 - 11
Dauban P.Sanière L.Tarrade A.Dodd RH. J. Am. Chem. Soc. 2001, 123: 7707 - 12
Sanière L.Leman L.Bourguignon J.-J.Dauban P.Dodd RH. Tetrahedron 2004, 60: 5889 - 13
Leman L.Sanière L.Dauban P.Dodd RH. ARKIVOC 2003, (νi): 126 - 14
Wang Z.-G.Warren JD.Dudkin VY.Zhang X.Iserloh U.Visser M.Eckhardt M.Seeberger PH.Danishefsky SJ. Tetrahedron 2006, 62: 4954
References
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Scheme 1
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