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

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). Diastereoisomeric pairs of products result at room temperature merely from the ‘endo’- and ‘exo’-transition states; more complex mixtures appear above 60° 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-unsaturatedacyl 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. 50% at ?20°) which can be hydrolyzed to the methyl carboxylate 14 . DBU (1,8-diazabicyclo5,4,0]undec-7-ene) in benzene converts 5 to 6-ethoxy-2-oxohexa-3,5-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.