Conversion of aliphatic amides into amines with [I,I-bis(trifluoroacetoxy)iodo]benzene. 2. Kinetics and mechanism

Synthesis of retro-inverso peptides employing isocyanates of Nα-Fmoc-amino acids/peptide acids catalyzed by DMAP

“…5,6 The more commonly used route involves a Hofmann rearrangement of N a -protected amino acid amides using iodobenzene bis(trifluoroacetate) (IBTFA) as an oxidizing agent to obtain mono N-acetylated, gem-diaminoalkyl trifluoroacetates as key intermediates. [7][8][9] As concluded recently by Chorev, rigorous purification is required for building blocks; thus selection of protecting groups and the presence of reactive side-chains are key factors which cannot be overlooked. 3 Further, IBTFA oxidation is not compatible with Fmoc chemistry.…”

Hypervalent iodine reagents in the total synthesis of natural products

“…This transformation has been described with DIB, 397 PIFA, 398,399 and HTIB. 400 An important feature of this rearrangement is the retention of configuration of the migrating…”

“…399 The first step is the formation of a dimer of PIFA (although the reaction could also take place by PIFA itself), on which the amide displaces one of the ligands to give a mixed dimer.…”

Carbocyclic galanthamine analogs: Incorporating the phenethylamine motif

“…The conversion of 7 into the amide (8) was performed by successive treatment with thionyl chloride in dry dichloromethane and ammonia in dry formamide and gave 8 in 92% yield. Isopropyl ether cleavage of 8 using boron trichloride in dry dichloromethane afforded the diphenol (9) in 88% yield, which was then subjected to a K 3 [Fe(CN) 6 ] induced tandem cyclization. After chromatographic purification (4aR*,8aR*)-1-bromo-4a,5,9,10, 11 , 1 2 -h e x a h y d r o -3 -m e t h o x y -6 -o x o -6H-b e n z o [a] c y c l ohepta[hi]benzofuran-11-carboxamide (10) was isolated as a mixture of diastereomeric amides with a total yield of 19% and was used directly in the next reaction steps (see Scheme 1).…”

“…Due to the presence of the cyclohexene ring the degradation of the amide (11) required very mild reaction conditions to avoid epoxide formation. Applying phenyliodisyl bis(trifluoroacetate) (PIFA) [8,9] in acetonitrile/water as the selective oxidant led to the desired amine (12) in 75% yield without formation of major byproducts. After debromination using a freshly prepared copper-zinccouple [10] the diastereomeric galanthamine analogs 2 a and 2b were separated by medium pressure liquid chromatography (MPLC) (see Scheme 2) and were both obtained as colorless solids.…”