Mild Deprotection of Primary N-(p-Toluenesulfonyl) Amides with SmI2 Following Trifluoroacetylation
Ziad Moussa, Daniel Romo*
*Department of Chemistry, Texas A&M University, P. O. Box 30012, College
Station, TX 77842-3012, USA, Email: romo
mail.chem.tamu.edu
Z. Moussa, D. Romo, Synlett, 2006, 3294-3298.
DOI: 10.1055/s-2006-951530
Abstract
A mild deprotection for notoriously difficult to unmask primary N-(p-toluenesulfonyl) amides occurs at low temperature by initial activation of the nitrogen with a trifluoroacetyl group, followed by reductive cleavage of the p-toluenesulfonyl group with samarium diiodide.
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Details
The document discusses a mild deprotection method for primary N-(p-toluenesulfonyl) amides, which are notoriously difficult to unmask. Developed during the total synthesis of the marine toxin gymnodimine, the method involves initial activation of the nitrogen with a trifluoroacetyl group, followed by reductive cleavage of the p-toluenesulfonyl group using samarium diiodide (SmI2) at low temperatures (-78°C). This approach builds on previous methods for cleaving nitrogen-heteroatom bonds and offers improved functional group compatibility and milder conditions compared to traditional harsh deprotection protocols. The method was tested on various substrates, demonstrating good to excellent yields and compatibility with a wide range of functional groups. The process involves a one-pot procedure where the N-monosubstituted sulfonamides are first acylated with trifluoroacetic anhydride (TFAA) and then treated with SmI2. This method is particularly useful for synthesizing complex molecules where functional group tolerance is crucial. The authors acknowledge financial support from the NIH, the Robert A. Welch Foundation, and the NSF for the purchase of NMR instrumentation.
Key Words
toluenesulfonamides, samarium diiodide, reductive cleavage, trifluoroacetylation
ID: J60-Y2006-4800
