Stereochemical course of the [4+2] cycloaddition of 1-methoxybuta-1,3-diene to N-glyoxyloyl-(2R)-bornane-10,2-sultam. The formal synthesis of compactin and mevinolin

Article abstract of DOI:10.1016/0957-4166(96)00156-5

The chiral heterodienophile N-glyoxyloyl-(2R)-bornane-10,2-sultam 2, readily prepared from (2R)-bornane-10,2-sultam 1, was used in noncatalyzed atmospheric and high-pressure as well as in [Eu(fod)₃]-catalyzed [4+2] cycloadditions with 1-methoxybuta-1,3-diene 3. All the [4+2] cycloadditions studied led to diastereoisomeric mixtures of 6-substituted derivatives of 2-methoxy-5,6-dihydro-2H-pyran 4-7. The extent of asymmetric induction in these reactions was established by ¹H NMR analysis and the absolute configuration of the thermodynamically stable products 5 and 7 by X-ray analysis, and independently by chemical correlation. Stereochemical models for both noncatalyzed and [Eu(fod₃]-promoted reactions are proposed. The [4+2] cycloadduct 5 was then effectively transformed into (4R)-hydroxy-(6S)-hydroxymethyltetrahydropyrone-2 12, a key synthon for the lactone moiety of compactin 10 and mevinolin 11.