Convergent Syntheses of N‐Boc‐Protected (2S,4R)‐4‐(Z)‐Propenylproline and 5‐Chloro‐1‐(methoxymethoxy)pyrrol‐2‐carboxylic Acid − Two Essential Building Blocks for the Signal Metabolite Hormaomycin

An efficient and scalable synthesis of enantiomerically pure N‐Boc‐protected 4‐(Z)‐propenylproline (15) using the conventional Wittig reaction to construct the double bond has been developed [11% yield over 8 steps from N‐Boc‐protected (2S,4R)‐4‐hydroxyproline, 7]. The O‐MOM‐protected 5‐chloro‐1‐hydroxypyrrole‐2‐carboxylic acid [Chpca(MOM)‐OH (29)] was prepared along a reasonably efficient synthetic route applying the thermal rearrangement of 2‐azido‐6‐chloropyridine N‐oxide (22) as a key step in fairly good overall yield [9% over 7 steps from easily accessible 2,6‐dichloropyridine N‐oxide (21)]. The suitability of the MOM‐protected N‐hydroxy group during the preparation of the N‐hydroxypyrroles functionalized at C‐2, was confirmed by the successful synthesis of Chpca‐(3‐Ncp)Ala‐OFM 33 obtained from the acylated amino ester Chpca(MOM)‐(3‐Ncp)Ala‐OFM 32, which was selectively deprotected leaving the sensitive N‐hydroxypyrrole unit intact. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)