Synthesis of Optically Active, Cyclic α‐Hydroxy Ketones and 1,2‐Diketones from Verbenone Epoxide

Abstract

The reactivity of verbenone epoxide (5), a terpenoid from the pinane series, towards different aliphatic and aromatic aldehydes in the presence of natural montmorillonite (askanite-bentonite) clay has been studied. A series of mechanistically different transformations afforded a number of new, optically active, polyfunctional compounds (7, 8, 10 -14, 16). These products are potentially interesting synthons in asymmetric synthesis.Introduction. -Oxygen-containing monoterpenes from the pinane series are commercially available compounds of high optical purity, and may serve as precursors of biologically active compounds [1] and intermediates in asymmetric synthesis [2]. In acidic media, they generally easily undergo numerous transformations, affording complex mixtures of products [3]. As shown previously, the natural montmorillonite clay askanite-bentonite and its synthetic analog K-10 can be used as catalysts for the transformation of pinane terpenoids, which facilitates the synthetic procedure and improves the ecological aspects of such chemical processes. Moreover, the use of clays also occasionally allows the selective synthesis of complex products. For example, the reaction of a-pinene epoxide (1) with aliphatic or aromatic aldehydes gave the new polyheterocyclic compounds 2 and 3 [4] (Scheme 1).

Reactions of Allyl Alcohols of the Pinane Series and of Their Epoxides in the Presence of Montmorillonite Clay

“…According to GC/MS data, storage of (+)-trans-verbenol ((+)-12) on askanite-bentonite clay for 40 min at room temperature afforded para-cymene (13; 39%), 2-(4-methylcyclohexa-2,4-dienyl)propan-2-ol (14; 20%) and 2-(2-methylcyclohexa-2,4-dienyl)propan-2-ol (15; 15%) as the major products (Scheme 4). These results are in good agreement with the literature data on the behavior of verbenol in various acids (storage in the presence of sulfuric acid [19], treatment with acetic anhydride in the presence of clay K-10 [20]) 6 ).…”

“…The hypothetical mechanism leading to (À)-23 includes protonation and cleavage of the oxirane ring, skeletal rearrangement into a cation with a para-menthane framework, and its subsequent interaction with aldehyde (Scheme 5). Interestingly, at the last stage of this mechanism, heterocyclization in the resulting cation E is preferable to carbocyclization, as previously observed in reactions of other O-containing terpenoids of the pinane series [6] [21]. When performed on synthetic montmorillonite clay K-10, this reaction gave the same products (GC/MS data) as in the case of the reaction carried out on an askanite-bentonite clay, but the product ratio changed, the content of the intermolecular-reaction product (À)-23 increasing substantially and hydroxy ketone (À)-22 being prevalent among isomerization products.…”

“…The interesting and unexpected data obtained in our previous study of the behavior of (À)-verbenone epoxide (1) in the presence of montmorillonite clay [6] 1 ) prompted us to investigate transformations of other compounds of the pinane series under the same conditions. For the object of this investigation, we took a number of accessible optically active alcohols: (+)-trans-pinocarveol ((+)-2), (À)-myrtenol ((À)-3a), and verbenols (+)-12 and (À)-16.…”

“…Thus the relative arrangement of the OH group in the starting verbenol did not affect the occurrence and direction of intermolecular reactions. Moreover, replacement of the OH group by a MeO group in passing from (+)-trans-verbenol ((+)-12) to (À)-trans-verbe- 6 ) Previously, we showed that on askanite-bentonite clay, (+)-trans-verbenol ((+)-12) undergoes unusual reactions with aliphatic and aromatic aldehydes, resulting in heterocyclic compounds [21]. These transformations were accompanied by a skeletal rearrangement of the starting alcohol (+)-12, presumably forming a carbocation with a para-menthane framework which reacted with aldehydes.…”

Unusual α-hydroxyaldehyde with a cyclopentane framework from verbenol epoxide

“…The mechanism suggested led to the formation of cation 7 at the key stage of the process. [a] 20 580 -44 (c 12, CHCl 3 )}, obtained from (-)-verbenone by oxidation with aqueous H 2 O 2 and further reduction with LiAlH 4 according to published procedures, 5,9 was added with stirring to a suspension of K10 clay (30.0 g, Fluka), preliminarily calcinated for 3 h at 120°C, in CH 2 Cl 2 (200 ml). The reaction mixture was stirred for 1 h at room temperature.…”