Hetero-Diels-Alder Additions of α,β-Unsaturated-Acyl Cyanides. Part 3. Syntheses of 3-Bromo-2-ethoxy-3,4-dihydro-3H-pyran-6-carbonitriles, and about Their Transformation to 2-Ethoxy-2H-pyrans

Article abstract of DOI:10.1002/hlca.19950780115

Cycloadditions of the α,β-unsaturated-acyl cyanides 1-3 with (Z)-or (E)-1-bromo-2-ethoxyethene (4) may be performed at moderate temperatures and provide in good yields the 3-bromo-2-ethoxy-3,4-dihydro-2H-pyran-6-carbonitriles 5-7, respectively (Scheme 1).Diastereomeric pairs of products result at room temperature merely from the "endo"- and "exo"-transition states; more complex mixtures appear above 60 deg C as a consequence of (Z)/(E)-isomerization of 4.The relative stability of the anomers of 5 and 6 is explored by treatment with BF3*Et2O.Acid alcoholysis (MeOH or EtOH) of 5 leads to acetals 9a, b of 4-bromo-5-oxopentanoate.Alkyl (2Z,4E)-5-ethoxypenta-2,4-dienoates 12, 17, and 20, are formed in alcoholic alkoxide solutions from 5,6,and 7, respectively, which is compatible with the intermediacy of 2-alkoxy-2H-pyrans and their valence tautomers, α,β-unsaturated-acyl cyanides.Methoxide addition to the CN group competes with dehydrobromination in case of 5; it leads to 3-bromo-3,4-dihydro-2H-pyran-6-carboximidate 13 (ca. 50percent at -20 deg C) which can be hydrolyzed to the methyl carboxylate 14.DBU (1,8-diazabicyclo<5.4.0>undec-7-ene) in benzene converts 5 to 6-ethoxy-2-oxohexa-3,4-dienenitrile (11), the ring-opening product of an obviously unstable 2-ethoxy-2H-pyran; the same reagent dehydrobrominates 6 to 2-ethoxy-4-methyl-2H-pyran-6-carbonitrile (15).HBr Elimination from 7 takes place with great ease in presence of pyridine, or even during chromatography on alumina, and leads to the stable ethyl 6-cyano-2-ethoxy-2H-pyran-4-carboxylate (18); this dimerizes at room temperature to give a 1:3 mixture of tricyclic adducts "endo"-21 and "exo"-21.The structure of the latter is established by an X-ray crystallographic analysis.