Spiroepoxycyclohexa-2,4-dienones in Organic Synthesis

Abstract

Cyclohexa-2,4-dienones have been known for many years. 1 However, their chemistry has been limited to dimerization and rearrangement 1 until recently. [2][3][4][5] This is presumably because of their instability and high reactivity toward themselves and their propensity to aromatization and rearrangement. 1 In context with a research program to develop a unified strategy for the synthesis of polyquinanes and protoilludanes which has generated considerable interest, 6,7 cycloaddition of in situ generated spiroepoxycyclohexa-2,4-dienones of type 1 was explored 4,5 and a route to a variety of annulated bicyclo[2.2.2]octenones of type 2 and 3 was developed. Chemical and photochemical reactions of the annulated bicyclo[2.2.2]octenones thus obtained were also investigated. This led to the development of routes to various carbocyclic structures of contemporary interest 6,7 such as linearly fused cis-anti-cis triquinanes 4, cis-syn-cis triquinanes 5, tetraquinanes 6 and 7, protoilludanes 8, and the oxa-sterpurane framework 9 (Figure 1). In this Account, we summarize developments in this area wherein the spiroepoxycyclohexa-2,4-dienones have played a very important and crucial role, in conjunction with the chemical and photochemical reactions of the resulting tricyclic frameworks.Generation of Spiroepoxycyclohexa-2,4-dienones In Situ and Intermolecular π 4s + π 2s Cycloaddition with Cyclic Dienes. (a) Synthesis of endo Tricyclo[5.2.2.0 2,6 ]-undecanes. Conceptually, the tricyclo[5.2.2.0 2,6 ]undecanes of type 2 should be directly accessible in a single step via cycloaddition of cyclohexa-2,4-dienones such as 10 or 11 (Scheme 1) with appropriate olefins. Although the parent cyclohexa-2,4-dienone 10 (the keto tautomer of phenol) is unknown, only a few methods are known 8-10 for the preparation of 6,6-dialkyl derivatives 11 such as alkylation of substituted phenols 8 and rearrangement 9 of the exocyclic epoxide derived from dimethylfulvene. However, these methods appeared to be unsuitable for the above purpose. Therefore, a new indirect sequence for the synthesis of tricyclo[5.2.2.0 2,6 ]undecanes of type 2 employing epoxycyclohexa-2,4-dienones of type 1 was developed. It was envisaged that cycloaddition of 1 with cyclopentadiene would furnish adducts of type 14 ( Figure 2) whose epoxyketone moiety and olefinic bond present in the five-membered ring would be readily manipulated to give a variety of tricyclo[5.2.2.0 2,6 ]undecanes of type 2. However, spiroepoxycyclohexadienones of type 1 have only a fleeting existence during the oxidation of ohydroxymethyl phenols and instantaneously dimerize. 11 Therefore, it was thought to generate the spiroepoxycyclohexa-2,4-dienones via a retro Diels-Alder reaction of the readily obtainable 11 epoxydimers 13, and intercept them with a suitable diene/olefin.Unfortunately, pyrolysis of dimers of type 13 in the presence of dienes/olefins failed to yield adducts of type 14 and gave the corresponding aldehyde instead (Scheme 2). This is apparently due to the thermal rearrangement of the oxira...

Reactive species from aromatics and oxa-di-π-methane rearrangement: a stereoselective synthesis of (±)-hirsutene from salicyl alcohol

“…[1][2][3][4][5] These methods provide efficient and stereoselective avenues for the creation of complex molecular structures that are not readily available otherwise, and also led to synthesis of various types of natural products. [1][2][3][4][5] Polyquinane sesquiterpenoids have stimulated a longstanding interest on account of their novel molecular architecture and interesting biological profiles. This led to the development of a plethora of methodologies involving a number of ways to create the triquinane ring systems.…”

“…9 Hirsutene has served as a popular target for synthesis because of its molecular structure and role in biogenesis, and considered as a test case for new methods of cyclopentanoid synthesis. 6,10 In view of the above and to demonstrate the potential of 6,6-spiroepoxycyclohexa-2,4-dienone 4, and photochemical reactions of b,genones in organic synthesis, 2 we developed a synthesis of hirsutene 1 from salicyl alcohol 3, and wish to report the details herein. 11 The key features of our approach are the cycloaddition of spiroepoxycyclohexadienone 4, a reactive species generated from salicyl alcohol 3, a photochemical 1,2-acyl shift and an unusual alkylation at ring junction of a bridged carbocyclic framework.…”

Oxidative Conversion of Arenols into ortho ‐Quinols and ortho ‐Quinone Monoketals – A Useful Tactic in Organic Synthesis

“…Some remarkable accomplishments have been highlighted in several review articles [3,5,6,120]. Among the most significant ones, one can cite rearrangements of bicyclo[2.2.2]octenone cycloadducts into decalins, ring-contractions to polyquinanes, ring-expansions to tropolones, intramolecular cycloadditions to isotwistanes, cationic annulations to benzofurans, and nucleophilic additions to biaryls, enediyne units, and benzannulated heterocycles of various sizes.…”

“…Photochemical transformations of bicyclo[2.2.2]octenones derived from Diels-Alder reaction of spiroepoxycyclohexa-2,4-dienones 116 have been exploited by Singh's group in their synthetic studies towards triquinane 119 and oxa-triquinane 121, protoilludane 120, and oxa-sterpurane 122 frameworks ( Figure 30) [120,154]. Spiroepoxycyclohexa-2,4- [155,156].…”

A simple synthesis of bis-annulated bicyclo[2.2.2]octenones containing a β,γ-enone chromophore and photochemical reactions: a new entry into angular tetraquinane and other polycyclic systems

“…[1][2][3] The reactions in excited states permit a smooth and stereoselective transformation of bridged structure into ring fused system present in a large number of naturally occurring compounds. 2 However, while there are some methods for the synthesis of simple bicyclo [2.2.2]octenones 4 and monoannulated homologue, 5 there are no methods for bis-annulated bicyclo [2.2.2]octenes of type 1 having a b,g-enone chromophore. Recently, the reactive species generated from aromatics such as cyclohexadienone ketals, o-imido quinones have received greater attention for creation of complex molecular structures.…”