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Sodium Borohydride Reduction of Carbamoyl Azide Function: A Synthesis of N ‐Protected N′ ‐Formyl‐ gem ‐diaminoalkyl Derivatives
Author(s) -
Verardo Giancarlo,
Gorassini Andrea
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300442
Subject(s) - chemistry , sodium borohydride , azide , conformational isomerism , epimer , formamides , sodium azide , borohydride , stereochemistry , specific rotation , medicinal chemistry , organic chemistry , molecule , catalysis
A simple, efficient two‐step synthesis of N ‐protected N′ ‐formyl‐ gem ‐diaminoalkyl derivatives is reported. The procedure involves the unprecedented reduction of the carbamoyl azide of α‐ N ‐Boc/Fmoc/Z‐protected amino acids and dipeptides (Boc = tert ‐butoxycarbonyl, Fmoc = 9‐fluorenylmethoxycarbonyl, Z = benzyloxycarbonyl) by treatment with NaBH 4 at room temperature. The reaction proceeds rapidly (45 min) without detectable epimerization (by HPLC‐ESI‐MS analysis) and is not influenced by the nature of the starting carbamoyl azide. The 1 H and 13 C NMR analyses of the synthesized N ‐protected N′ ‐formamides were carried out in [D 6 ]DMSO. The spectra exhibited the presence of two rotameric forms in solution as a result of the restricted rotation around the N–CO formyl bond. The integration of the N–CH–N protons of the two isomers showed that the cis isomer (rotamer B) was the more abundant conformer by 60 to 78 %. The reported synthesis represents the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes.