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Macrocyclic Ring Closure of OH‐assisted Prins Reaction. A new and efficient synthesis of ( R , S )‐muscone
Author(s) -
SchulteElte Karl H.,
Hauser Arnold,
Ohloff Günther
Publication year - 1979
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19790620817
Subject(s) - chemistry , ring (chemistry) , yield (engineering) , prins reaction , catalysis , bicyclic molecule , closure (psychology) , hydrogen chloride , dihydropyran , organic chemistry , medicinal chemistry , market economy , materials science , economics , metallurgy
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.