Approaches to the Synthesis of Cytochalasans. Part 4 . Improved Synthesis of the Tetrahydroisoindoline Subunits Related to the Cytochalasins and Aspochalasins

A general scheme for the synthesis of the tetrahydroisoindolinone moiety of naturally occurring cytochalasans and unnatural analogs was developed. The key‐step consists of the inter molecular [2+4]cycloaddition of 4‐methylsorbinol (7) to an alkylidene malonic ester derivative such as 6, 9 or 10 , obtained from the corresponding amino acids. The products obtained, 4a, 17 , and 18 were converted to the desired lactams 5, 21 , and 22. Cycloaddition of the diene alcohol 7 to the optically active alkylidene malonic ester derivative 9b (s. Footnote 5) prepared from L ‐leucine gave compound 17b with 98% enantiomeric excess. The optical activity was retained during the conversion of 17b to the lactam 21b . The latter is a subunit for the synthesis of the aspochalasins.