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Synlett 2009(6): 1021-1022  
DOI: 10.1055/s-0028-1088201
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

2-(Trimethylsilyl)ethanesulfonamide (TMS(CH2)2SO2NH2 or SES-NH2) - A Sulfonamidation Agent With Multiple Qualities

Carmelita Gomes da Silva*
Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Avenida Athos da Silveira Ramos, Centro de Tecnologia, Bloco A, 6º andar. Ilha do Fundão, Cidade Universitária, Rio de Janeiro; RJ, CEP 21941-909, Brazil.
e-Mail: carmelita@iq.ufrj.br;
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Publication History

Publication Date:
16 March 2009 (online)

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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]

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.