O-Protected N-(2-Nitrophenylsulfonyl)hydroxylamines: Novel Reagents for the Synthesis of Hydroxamates

Abstract

Preparative methods for novel O-protected N-(2-nitrophenylsulfonyl)hydroxylamines (8a-e) are described. Their versatility as intermediates en route to polyhydroxamates is exemplified by the synthesis of a non-amide DFO analog 22.

A Mild and Modular Approach to the Total Synthesis of Desferrioxamine B

“…Installation of the key hydroxamic acid has conventionally been achieved by nucleophilic substitution of an alkyl halide precursor with N -Boc-protected O -benzyl­hydroxylamine. − The major drawbacks of this approach are the use of harsh reaction conditions, namely strong base and high temperature, ,,− and the potential for disubstitution in the case where dihaloalkanes are employed as the starting material . In addition, where a nitrile substrate is used to generate the protected hydroxamic acid intermediate, harsh reduction conditions are required (Raney Ni, Parr H 2 ) to liberate the amine for downstream coupling. − A mild alternative to these installations is a Mitsunobu reaction with a mild deprotection of the hydroxamic acid nitrogen. − Prior to undertaking the Mitsunobu protocol, O -benzyl­hydroxylamine hydrochloride 7 first required protection to generate a dual protected hydroxylamine reagent 8 . − This was achieved by installation of a nosyl unit with 2-nitrobenzyl­sulfonyl chloride in pyridine, generating 8 in a yield of 70%. The diamine containing substrate 9 was generated by treating the N -Boc-protected 5-aminopentan-1-ol 6 with the dual protected hydroxylamine reagent 8 under mild Mitsunobu conditions .…”