Macrocyclic Ring Closure of OH-assisted Prins Reaction. A new and efficient synthesis of (R,S)-muscone

✍ Scribed by Karl H. Schulte-Elte; Arnold Hauser; Günther Ohloff

• Publisher: John Wiley and Sons
• Year: 1979
• Tongue: German
• Weight: 489 KB
• Volume: 62
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19790620817

✦ Synopsis

Abstract

A new strategy for the synthesis of muscone (1) using the OH‐assisted Prins reaction for macrocyclic ring closure has been developed. The monoacetal 4 of (Z,E)‐4,8‐dodecadienedial (3), easily obtainable from (Z,E,E)‐1,5,9‐cyclododecatriene (2), is treated with methallylmagnesium chloride, and the resulting C~16~‐precursor 5 is subjected to acid‐catalyzed cyclization in dilute (⩽1%) solutions. This results in formation of the bicyclic dihydropyran derivatives 6 which directly yield muscone (1) on heating with a noble metal catalyst saturated with hydrogen. The five‐step pathway proceeds with readily available starting materials in conventional steps and excellent overall yield (∼40%). This new principle of macrocyclic ring formation has also been used successfully for the preparation of 3‐methylcyclotridecanone (34) and should be generally applicable for other suitable ring systems.