A study of the Claisen—Eschenmoser reaction for hydroxymethylbenzofurans and-indoles

The Synthesis of Certain Derivatives and Analogues of (−)- and (+)-Galanthamine and an Assessment of their Capacities to Inhibit Acetylcholine Esterase

“…This was contaminated by small amounts (7%) of its chromatographically inseparable C5 epimer. “Thwarted E-C rearrangements” of this type have been reported previously and in this instance the process may be driven by electron-rich arene residues facilitating ionization of the intermediate mixed acetal with the ensuing and extensively stabilized cation then undergoing nucleophilic capture by 1-methoxy- N , N -dimethylethen-1-amine that is itself generated through thermal cracking of the starting dimethyl acetal. The basic structure of product 39 follows from the observation that the diastereotopic methylene hydrogens of the acetamide side-chain both show vicinal couplings to the adjacent allylic hydrogen.…”

“…2, 118.8, 111.0, 80.3, 77.5, 77.2, 72.5, 57.5, 28.1, 25.9; IR ν max 3453,2987,2934,2826,1646,1457,1381,1217,1164,1074, 869 cm −1 ; MS (EI, 70 eV) m/z 280 and 278 (M +• , both 3%), 265 and 263 (both 35%), 101 (100); HRMS (EI, 70 eV) M +• calcd for C 10 H 15 79 BrO 4 278.0154, found 278.0148. 4-Hydroxy-3-((3aR,6S,7R,7aS)-7-hydroxy-6-methoxy-2,2-dimethyl-3a,6,7,7a-tetrahydrobenzo [d][1,3]dioxol-4-yl)-5-methoxybenzaldehyde (32). A magnetically stirred solution of compound 31 (150 mg, 0.54 mmol), ester 27 (180 mg, 0.65 mmol), PdCl 2 dppf•CH 2 Cl 2 (31.5 mg, 0.04 mmol), and triethylamine (3 mL) in THF/water (18 mL of a 9:1 v/v mixture) was purged with nitrogen for 0.5 h and then heated under reflux for 2 h before being cooled, poured into water (50 mL), and extracted with ethyl acetate (3 × 30 mL).…”

Claisen Rearrangements of Benzyl Vinyl Ethers and Heterobenzyl Vinyl Ethers

“…In addition to indole examples discussed above, the Claisen rearrangement of other fused heterocycles (such as benzofurans) has also been investigated by Mukhanova and co-workers. 54 A range of (hydroxymethyl)benzofurans 197a-e, when subjected to standard Eschenmoser-Claisen conditions, generated the rearranged products 198a-e in 22-81% yield (Scheme 40). Notably, methoxy-substituted benzofurans 197b and 197c produced the respective product in significantly higher yields (~80%) than the unsubstituted parent 197a (22%).…”