THE TWO-PHASE REACTION OF HYPOCHLOROUS ACID WITH OLEFINIC COMPOUNDS; APPLICATION IN TERPENE SYNTHESIS
Abstract
The two-phase reaction of hypochlorous acid with trisubstituted and 1,1-disubstituted olefins affords allylic chlorides in high isolated yield. The absence of neighboring hydroxyl group has been demonstrated in the reaction of various olefinic alcohols with HOCl. (alpha)-Chloro-(beta),(gamma)-unsaturated ketones are obtained by the reaction of HOCl with more highly substituted conjugated ketones which can exist in an s-cis conformation. The formation of allylic chlorides is best accounted for by invoking the participation of entering chlorine with the carbocationic center in the chloronium ion intermediate. Vinyl chloride formation competing with the production of allyl chloride is observed in the reaction of HOCl with olefinic substrates containing a conjugating substituent such as a phenyl group or vinyl group. The methodology finds particular application in the functionalization of the isopropylidene terminus of various polyolefinic acyclic terpenoids. An efficient synthesis of rose oxide from citronellol is described which involves the dehydrochlorination of 3-chloro-2,6-dimethyl-1-octen-8-ol to 2,6-dimethyl-1,3-octadien-8-ol followed by acid-catalyzed cyclization. Menthofuran has been synthesized by a novel dehydrochlorination reaction of 4-chloroisopulegone in high yield and high optical purity. 10-Chloroisopulegone also undergoes dehydrochlorination under base catalysis to yield menthofuran. The reaction of HOCl with monocyclic monoterpenes containing an isopropenyl group affords allylic chlorides derived from a kinetically controlled elimination of the chloronium ion intermediate. Organozinc compounds derived from these allylic chlorides undergo facile addition to isovaleraldehyde to yield sesquiterpene alcohols with a bisabolane carbon skeleton. The application of this methodology in terpene synthesis has been illustrated in approaches to (+) bilobanone, a constituent of heartwood timber and juvabione, a juvenile hormone type compound. Cholesterol, an olefinic alcohol, is shown to undergo a novel fragmentation on treatment with HOCl to yield secochlorocholestenal which finds potential application in the synthesis of secosteroids.
Degree
Ph.D.
Subject Area
Organic chemistry
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