Enantioselective Synthesis of 2-Alkyl-5-methylene-1,3-dioxolan-4-ones and Exo-Selective Diels-Alder Reactions with Cyclopentadiene

Article abstract of DOI:10.1021/jo00038a028

Highly stereoselective syntheses of chiral dienophiles (R)-1 and (R)-2 are described.Diazotization of L-serine in the presence of HCl and then treatment of the resulting β-hydroxy-α-chloropropionic acid (S)-7 with KOH provides potassium glycidate ((R)-8) in good yield and high enantiomeric purity.Treatment of (R)-8 with PhSH in MeOH then provides α-hydroxy acid (S)-10 that can be purified by recrystallization.Condensation of (S)-10 with either pivalaldehyde or cyclohexanecarboxaldehyde followed by oxidation to the sulfone and DBU-promoted elimination of benzenesulfinic acid then provides dienophiles (R)-1 and (R)-2, respectively.Highly exo-selective Diels-Alder reactions of (R)-1 and (R)-2 with cyclopentadiene are also described.The major cycloadduct (-)-15 (94percent of total) from the Diels-Alder reaction of 1 was shown to have an enantiomeric purity of <*> 99percent ee.This figure defines the lower limit of enantiomeric purity of (R)-1.The diastereofacial selectivity of the Diels-Alder reactions of 1 in the exo manifold (50:1) is greater than that of 2 (20:1), as would be expected on the basis of the different steric requirements of the tert-butyl and cyclohexyl substituents of the two reagents.Consequently, dienophile 1 is the preferred reagent for complex synthetic applications, either as a chiral ketene equivalent or in contexts in which the α-hydroxy acid funtionality will be preserved in the ultimate synthetic target.Finally, the possible role of dipole effects on the exo selectivity of the Diels-Alder reactions of these and related dienophiles are briefly discussed.