Biomimetic Cyclization of Small Terpenoids Promoted by Zeolite NaY: Tandem Formation of α‐Ambrinol from Geranyl Acetone

Abstract

Zeolite NaY promotes efficiently the biomimetic cyclization of small acyclic terpenes. Geranyl and neryl acetone undergo a novel tandem 1,5-diene cyclization/carbonyl-ene reaction to form the natural product a-ambrinol isolated in > 65% yield.

En route to terpene natural products utilizing supramolecular cyclase mimetics

“…Geraniol or geranyl acetate (7) produced cyclogeranyl derivatives 8 as main products employing either zeolites or chlorosulfuric acid. [20][21][22] Related head-to-tail cyclizations have also been observed with sesquiterpene substrates using the conditions reported for monoterpenes 20,22 or employing superacids. 23 Strong acids seem to favor protonation of the head olen in solution.…”

Acid‐Catalyzed Cyclization of Terpenes Under Homogeneous and Heterogeneous Conditions as Probed Through Stereoisotopic Studies: A Concerted Process with Competing Preorganized Chair and Boat Transition States

“…The cyclization of [D 3 ]-17 under zeolite confinement conditions was achieved by using the highly dealuminated zeolite HY (Si/Al = 30:1) as a catalyst at ambient temperature. This relatively mildly acidic zeolite, in contrast to NaY [13] and HY (Si/Al = 2.7:1), promotes the cyclization of farnesyl to drimenyl acetate in good yield, without forming hydrocarbon byproducts (resulting from an acid-catalyzed elimination of the acetate in the starting material). [37] In the presence of dealuminated HY, [D 3 ]-17 afforded a mixture of 22/23 in 72 % isolated yield and in a relative ratio of approximately 92:8 (Scheme 10).…”

“…[12] We were pleased to find that small acyclic terpenes undergo a clean cyclization reaction under essentially mild and environmentally friendly conditions (Scheme 2). [13] Furthermore, NaY promotes the selective monocyclization of epoxy polyene terpenoids, [14] as a unique methodology for the synthesis of a series of incompletely cyclized naturally occurring terpenols. [15] For example, geranyl acetate (1) forms at the initial reaction stages primarily g-cyclogeranyl acetate (1 a), which on prolonged reaction time isomerizes to the thermodynamically more stable a-cyclogeranyl acetate (1 b).…”

“…The aldehyde was coupled with isopropylidenetriphenylphosphorane to produce the TBDPS-protected alkene 9. Finally, alkene 9 was deprotected with tetrabutylammonium fluoride (TBAF) and the resulting alcohol 10 (6-[D]-geraniol) was acetylated with acetic anhydride to form [D]-1, in 14 % overall isolated yield from geraniol.The cyclization of [D]-1 under zeolite confinement conditions [13] afforded a-cyclogeranyl acetate as a mixture of the two diastereomers 11 and 12 in a relative ratio of 86:14 (Scheme 5). The reaction was almost exclusively driven to a-cyclogeranyl acetate (70 8C, 3 h) to avoid the interfering absorptions in the aliphatic region of the initially formed isomeric g-cyclogeranyl acetate.…”

“…A remarkable result among those studies was the cyclization of geranylacetone (2) [13] and its derivatives, [16] which provide a direct one-pot cascade route to the synthesis of a-ambrinol (2 b); a valuable compound in the fragrance industry. A unique tandem dicyclization pathway was also uncovered for the case of farnesal adsorbed within NaY.…”