Mild deprotection of primary N-(p-toluenesulfonyl) amides with SmI ₂ following trifluoroacetylation

A mild deprotection method for notoriously difficult to unmask primary N-(p-toluenesulfonyl) amides was developed during our total synthesis studies toward the marine toxin, gymnodimine. The deprotection occurs at low temperature (-78 °C) under mild conditions by initial activation of the nitrogen with a trifluoroacetyl group, followed by reductive cleavage of the p-toluenesulfonyl group with samarium diiodide. The substrate scope and functional group tolerance of this useful N-S cleavage process, which builds on related cleavage processes of other nitrogen-heteroatom bonds, is explored.