ChemInform Abstract: ACID‐CATALYZED ANNELATION OF α‐ALKYLALDEHYDES AND α,β‐UNSATURATED KETONES. A ONE‐POT SYNTHESIS OF 4,4‐DIMETHYL‐2‐CYCLOHEXEN‐1‐ONE

Design and Pharmacological Characterization of Inhibitors of Amantadine-Resistant Mutants of the M2 Ion Channel of Influenza A Virus

“…Intermediate spiro[5.5]undec-1-en-3-one 1 was prepared both from acid-catalyzed one-pot Robinson annulation reaction and through a Diels−Alder adduct followed by acid hydrolysis and aldol ring formation. The acid-catalyzed annulation often led to low yields (≤62%) due to acid-catalyzed polymerization of methyl vinyl ketone as evidenced by a black oily substance formed in the reaction flask . While catalysis with proline derivatives might allow circumvention of these problems, we found the alternative Diels−Alder route provided better overall yields (75%) .…”

Novel S1P1 Receptor Agonists - Part 2: From Bicyclo[3.1.0]hexane-Fused Thiophenes to Isobutyl Substituted Thiophenes

“…The precursor of 59 , 4,5,6,7-tetrahydro­benzo[ c ]thiophene-1-carboxylic acid 58 (for target compounds 45 and 54 ), is commercially available. Preparation of 62 (for 47 and 55 ) relied on 4,4-diethylcyclohexanone 61 . , Spiro[2.5]octan-6-one 65 needed for the preparation of 66 (for 48 and 56 ) was prepared starting from acetal 64 following literature procedures. − The starting material for thiophenecarboxylic acid 69 (for 49 and 57 ), spiro[4.5]decan-8-one 68 , was also prepared following literature procedures. , 4-Methylcyclohexanone 71 needed for the synthesis of thiophene 72 (for 50 ) is commercially available. The carboxylic acids 59 , 62 , 66 , 69 , and 72 were then transformed to the corresponding ketones 60 , 63 , 67 , 70 , and 73 , respectively, by treating them with methyllithium.…”

“… a Reagents and conditions: (a) t BuLi, THF, EtI, −100 to −70 °C, 2–18 h, 31–85%; (b) MeLi, diethyl ether, 20–30 °C, 1–2 h, 33–66%; (c) H 2 SO 4 , rt, 24 h, 70%, then 1 bar of H 2 , Pd/C, EA, rt, 24 h, quantitative; , (d) ethyl formate, KO t Bu, THF, rt, 24 h; (e) oxalyl chloride, DCM or CHCl 3 , 0–30 °C, 1–18 h; (f) (1) NaOEt, HSCH 2 COOEt, EtOH, rt, 1 h; (2) NaOEt, EtOH, 65–75 °C, 18 h; (3) 2 N aqueous LiOH or NaOH, H 2 O, 70 °C, 2–3 h; 23–47% (over steps d, e, f, b); (g) (1) Ph 3 PMeBr, NaH, toluene, DMSO, rt, 1 h, quantitative (crude); , (2) Et 2 Zn, CH 2 I 2 , toluene, −40 °C to rt, 18 h, then TFA, H 2 O, rt, 30 min, 90% (crude); , (h) (1) piperidine, ethanol, 85 °C, 24 h, then NaOAc, HOAc, 85 °C, 24 h, 63%; (2) 1 atm of H 2 , Pd/C, EA, rt, 90 min, 97%. , . …”