Of diquinanes

The first total synthesis of kelsoene was achieved by Mehta and Srinivas [7, 8]. The tricyclic scaffold was established by an intermolecular [2+2]-photocycloaddition of diquinane enone rac-6 and 1,2-dichloroethylene (7) as the key step (Scheme 2). As a consequence of the steric hindrance implemented... 

An enriched 1,3-diene as in substrates 149 can act as a nucleophile towards an activated alkyne. Iwasawa has reported an elegant synthesis of diquinane frameworks 150 that operates with various metals, out of which rhenium(I) appears to be the best [94], Minor products 152 presumably result from insertion of a carbenoid entity into the neighboring activated benzylic C - H bond. The same carbenoid species can undergo a 1,2-H shift to give 151 (Scheme 48). 

Scheme 19. Oxidative C-C bond cleavage in housane 11 leads to the formation of diquinane 12 [106cj.

Certain carbobicyclic rings systems can also be constructed in a stereoselective fashion using this approach. The stereoselective formation of diquinanes and hydrindanes, in which the relative stereochemistry between three contiguous stereogenic centers is controlled, has recently been reported152 135. Photolysis of 4-pyranone 36 presumably affords the intermediate ally-loxy zwitterion 37. Capture by a pendant alkene leads to formation of the diquinane 38. 

Radical cyclization reactions have found widespread use in the preparation of polyqui-nanes. A highly functionalized diquinane framework was prepared by Malacria and coworkers using a radical cascade process [66], It was anticipated that the (bromomethyl)-silyl ether 161 would serve as a suitable radical trigger. Thus, a solution of PhjSnH and AIBN was added over 5 h to a benzene solution of 161 and 10 equiv of acrylonitrile at reflux. Further heating for 5 h followed by Tamao oxidation of the crude product mixture allowed isolation of diquinane 162 in 51% yield as a single stereoisomer (by H-NMR) (Scheme 10-53). 

West FG, Fisher PV, Arif AM. Intramolecular alkene trapping of pyran-4-one-derived zwitterions a novel synthesis of diquinanes and hydrindans. ]. Am. Chem. Soc. 1993 115 1595-1597. 

In the construction of carbocycles, five-membered ring formation has been used for preparing fused cyclic compounds, such as functionalized diquinanes. ° The reaction of 36 with (TMSlsSiH furnished the expected product 37 in 80% yield and in a or.fi ratio of 82 18, as the result of a kinetic controlled reaction (Reaction 43). 

More recently, the bis-cyclopropanation of dienyne 325 has also been investigated by Fensterbank, Malacria, and Marco-Contelles to construct highly strained cyclopropyl-substituted diquinane frameworks 327 in a completely diastereoselective manner (Scheme 84). 3 It is noteworthy that the formal metathesis product was also observed in these reactions, albeit as a minor product, and that a simple introduction of a methyl group to one of the two ene moieties substantially affects the reaction. 

The homoenolate conjugate addition has been used very recently by Paquette and Cheney [17] to synthesise the key diquinane intermediate 18 in their studies directed towards the total synthesis of trixikingolide (Scheme 5.13). 

From an exhaustive retrosynthetic analysis and from the experimental work performed by Curran [29] [32], it was clear that the synthesis of modhephene required an elaborate strategy. In the first place, the tandem radical cyclisation should be conducted individually rather than just in one step since it allows more flexibility. In the second place, Curran s observation that the precursor of modhephene (54) could be the olefmic exocyclic derivative 55 allows the application of a series of heuristic principles already familiar to us, which greatly simplifies the retrosynthetic analysis and leads to diquinane and, finally, through a second radical retroannulation to the very simple cyclopentanone derivative (Scheme 7.24). 

In the first total synthesis of kelsoene (rac-l) [7, 8], commercially available 1,5-cyclooctadiene (11) was chosen as the starting material (Scheme 3). Oxidative cyclization with a mixture of PdCl2 and Pb(OAc)4 in acetic acid led to the formation of a diquinane diacetate [13] that was saponified to give... 

In a succeeding publication, the same authors reported on an enantiose-lective approach to diquinane enones 6 and ent-6 by combining the above-described synthesis with an enzymatic kinetic resolution (Scheme 4) [12]. After lipase-catalyzed enantioselective transesterification of diol rac-12. 

The approach of Schulz et al. to enantiomerically pure diquinane enone ent-6 employed (i )-(+)-pulegone (17) as chiral pool starting material [9, 10] (Scheme 5). Bromination and Favorskii rearrangement of 17 generated a... 

Racemic diquinane enone rac-6 was prepared by Piers and Orellana starting from cyclopentenone (Scheme 6) [11]. After the preparation of the heterocuprate from stannane 20, conjugate addition to cyclopentenone in the presence of BF3 Et20 provided carbonyl compound 21. It was expected that conversion of 21 by intramolecular alkylation and subsequent hydrogenation should provide the desired endo-substituted diquinane rac-13. While other hydrogenation methods proved to be rather unselective, reduction in the presence of Wilkinson s catalyst finally resulted in the formation of rac-13 with good facial diastereoselectivity [11]. 

In a study which was conducted simultaneously to the work in the Mehta group and which also aimed to prove the absolute configuration of natural kelsoene (1), Schulz et al. used a stereoselective approach starting from the enantiomerically pure chiral pool material (i )-pulegone 17 [9, 10] (see above). The final steps of their synthesis of the unnatural enantiomer of kelsoene (ent-l) were similar to the above-described first total synthesis of natural kelsoene (1) (Scheme 8). Taking into account the steric limitations of the system as communicated by Srinivas and Mehta, diquinane enone ent-6... 

Gymnomitrol (579), a tricyclic sesquiterpenoid which occurs as a major metabolite of the liverwort Gyrmomitrion obtusum (Lindb.) Pears, contains a rare 4,8-methano-azulene (diquinane) carbon skeleton with five adjacent chiral centers, three of them... 

The quite different route implemented by Schlessinger commences with an expedient construction of the diquinane nucleus 594. This accomplishment is followed by an interclude of functional group reorganization. The concluding steps are concerned with appropriate introduction of carbon atoms 14 and 10 (Scheme L). 

The Kojima-Sakai approach, which makes use of trans-cis diester 626, is summarized in Scheme LVII This intermediate was homologated by the Arndt-Eistert method, converted to olefin 627, and oxidatively cleaved to produce ultimately the diester 628. Dieckmann condensation was used to construct the diquinane core which was subsequently transformed to 623 by standard reactions. 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

In an aldol condensation an enolate adds to a carbonyl group. Among the various methods which have been developed to achieve regioselectivity those involving polarity alternation accentuation are a time-honored technique. For example, the closure of a more strained diquinane nucleus rather than a hydrindane system is possible by installing a phosphoryl group in the a-position of the appropriate ketone [148]. 

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