C‐Glycosyl Styrene Type Compounds by Pd‐Catalyzed Cross‐Coupling Reactions of Anhydro‐Aldose Tosylhydrazones with Benzyl Bromides

Abstract

C-Glycopyranosyl styrene type compounds are valuable synthetic intermediates whose syntheses are known in rather lengthy procedures. Herein palladium-catalyzed cross-couplings of O-peracylated 2,6anhydro-aldose tosylhydrazones with benzyl bromides were studied under thermic conditions in the presence of LiOtBu. The reactions gave the corresponding C-glycopyranosyl styrenes in up to 59% yields. The transformations represent a new, short synthetic sequence to get this type of glycomimetic compounds in 4-5 steps from a free aldose.

Coupling Reactions of Anhydro-Aldose Tosylhydrazones with Boronic Acids

“…13 C NMR (100 MHz, CDCl3) δ 167.3, 166.7, 165.6, 165.4 (4 × CO), 136.8 (C-1), 139.5-126.1 (aromatics), 120.9 (C-2), 74.0 (C-3), 73.4 (C-4), 71.4 (C-5), 68.6 (C-6), 65.5 (C-7), 3d: 1 H NMR (400 MHz, CDCl 3 ) δ 8.20-7.81 (8H, m, aromatics), 7.64-7.01 (16H, m, aromatics), 6.74 (1H, d, J 1,2 15.9 Hz, H-1), 6.26 (1H, dd, J 2,3 6.7 Hz, H-2), 6.12-6.02 (2H, m, H-3, H-4), 5.75 (1H, dd, J 4,5 1.1, J 5,6 8.9 Hz, H-5), 4.52 (1H, dd, J 6,7a 2.9, J 7a,7b 11.9 Hz, H-7 a ), 4.34 (1H, dd, J 6,7b 5.9 Hz, H-7 b ), 4.20-4.10 (1H, m, H-6), 3.60 (1H, d, J 6,OH 5.2 Hz, OH), 2.33 (3H, s, CH 3 ). 13 14.9 Hz, H-1), 6.25 (1H, dd, J 2,3 6.6 Hz, H-2), 6.21 (1H, pseudo t, J 3,4 8. 6 Hz, H-3), 5.81 (1H, dd, J 4,5 1.…”

“…We began a systematic study aimed at the investigation of the applicability of anhydro-aldose-tosylhydrazones 1 [ 7 , 8 , 9 ] in coupling reactions. In this project C-O [ 10 ], C-S [ 11 ], and C-N [ 12 ] bonds were successfully formed under metal-free conditions, while C-C bonds [ 13 , 14 ] were obtained in Pd-catalyzed reactions ( Scheme 1 ).…”

New syntheses towards C-glycosyl type glycomimetics

“…Rearrangements of such carbene complexes and subsequent reductive elimination may lead to various products depending on other compounds present in the coordination sphere of the metal. Thus, the reactions of 65 with aryl bromides in the presence of Pd 2 (dba) 3 resulted in aryl-substituted exo-glycals 82 [107], while with benzyl bromides C-glycopyranosyl styrenes 83 were formed [108] (Scheme 9). In these transformations several pathways are open both for the deprotonated tosylhydrazone and the carbene intermediate and, as a consequence, the formation of 81 by a nucleophilic substitution of the tosylhydrazone on the benzyl bromide as well as that of exo-glycals 74 due to intramolecular insertion can be observed and the by-products can be isolated.…”

Synthesis of Five-Membered exo-Glycals from Six-Membered 2-Iodo-endo-glycals

“…Addition of Organometallic Reagents to Ketone 3Determined by1 H NMR. b Due to the presence of the THP group.After purification, 4f was contaminated by 4-chlorophenol and used in the next step as such.…”

“…exo -Glycals are sugars with an exocyclic double bond at the C-1 position. These compounds are frequently used as synthetic intermediates, but they can also be used as final molecules for their biological properties . The first synthesis of an exo -glycal was reported in 1975 by Bischofberger et al to access glycosyl α-amino acids .…”