Tricyclic ketones with

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

The research team of G. Prater investigated the acid catalyzed rearrangement of p-monocyclofamesol for the synthesis of tricyclic ketones with sesquiterpene skeleton. The substrate p-monocyclofamesol, prepared from dihydro-P-ionone in two steps, was exposed to concentrated formic acid, which resulted in the formation of a mixture of three different formates. 

Tricyclic ketones with well-defined all-m ring connections are easily prepared from alcohols of the following type184. 

After considerable experimentation, a similar hydrosilylation protocol was used as a key step for the syntheses of jatrophatrione and citlalitrione by Paquette and co-workers.32 Following the stereoselective reduction of a tricyclic ketone with lithium aluminum hydride to provide alochol 28, silylation and platinum catalyzed hydrosilylation were effected to produce 29. Finally, the carbon-silicon bond was successfully cleaved to generate diol 30 in an impressive 93% yield. 

Tricyclic ketones with an angular methyl group have been obtained from readily available 1,2-diphenylethane derivatives in superacidic medium . ... 

Carbonylation of five-membered zirconacycles has been applied for synthesis of complexed and natural products. Stereocontrolled one-pot synthesis of tricyclic ketone with only cis isomer was achieved by Negishi and coworkers (Eq.43) [45]. 

In a more general approach toward pentacyclic heteroaromatics from tricyclic ketones, treatment of the N-methylated derivative of 112 with p-tolylhydrazine, followed by Fischer indolization of the resulting phenylhydrazone in a mixture of trifluoroacetic acid and acetic acid, produced only a low yield of 114, although this method proved to be considerably mrae efficient for synthesis of analogous systems containing other heteroatoms than nitrogen (98SC1239). 

Preparation of the key intermediate to this series begins by reduction of the methylene phthalide, 12a, with hydriodic acid and red phosphorus. Cyclization of the acid (26) thus obtained affords the tricyclic ketone, 27. Reaction with the Grignard reagent from 3-dimethylamino-2-methylpropyl chloride affords the... 

Schemes 3-7 describe the synthesis of cyanobromide 6, the A-D sector of vitamin Bi2. The synthesis commences with an alkylation of the magnesium salt of methoxydimethylindole 28 to give intermediate 29 (see Scheme 3a). The stereocenter created in this step plays a central role in directing the stereochemical course of the next reaction. Thus, exposure of 29 to methanol in the presence of BF3 and HgO results in the formation of tricyclic ketone 22 presumably through the intermediacy of the derived methyl enol ether 30. It is instructive to point out that the five-membered nitrogen-containing ring in 22, with its two adjacent methyl-bearing stereocenters, is destined to become ring A of vitamin Bi2. A classical resolution of racemic 22 with a-phenylethylisocyanate (31) furnishes tricyclic ketone 22 in enantiomerically pure form via diaster-eomer 32.

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

One of the compounds shown below undergoes intramolecular cyclization to give a tricyclic ketone on being treated with NaHMDS, but the other does not cyclize. Indicate which compound will cyclize more readily and offer and explanation. 

A similar sequence starting with the acylation product (76) from metachlorophenylacetonitrile gives the halogenated tricyclic ketone 83. Condensation of that intermediate with ethyl bromoacetate in the presence of zinc (Reformatsky reaction) gives the hydroxyester 84. This product is then in turn dehydrated under acid conditions (85), saponified to the corresponding acid (86), and converted to the dimethyl-amide (87) by way of the acid chloride. The amide function is then reduced to the amine (88) with lithium aluminum hydride catalytic hydrogenation of the exocyclic double bond completes the synthesis of closiramine (89). This compound also exhibits antihistaminic activity. 

The tandem Michael and cyclopropanation reaction of lithium enolates with nitroalkenes gives tricyclic ketones in one pot, as shown in Eq. 7.42.43... 

Formation of this ring system was also reported in the reaction of a,/3-unsaturated ketones with substituted pyrrol-5-ones, giving the tricyclic products in 41—46% yield <2004PS(179)61>. 4-Thienyl and 4-furyl derivatives of a dihydropyrano[2,3- 5,6-c]dipyrazole were also obtained via the heterocycle-substituted acrylonitrile in 77% and 74% yield, respectively <2005RJ0742>. 

Synthetic applications of other decarbonylation reactions are found in the conversion of cyclooctatetraene to barrelene 250), with the photodecarbonyla-tion of a Diels-Alder adduct as key step (2.31) and the preparation of tetrathioesters from 1,3-dithioles (2.32) 251). The most remarcable application of such a reaction up to date is the synthesis of tetra t.butyltetrahedrane from a tricyclic ketone precursor (2.33) 252). 

The acid-catalysed ring-closure of divinyl ketones to cyclopentenones (equation 6), the Nazarov reaction6-8, represents a conrotatory electrocyclization of 4jr-cyclopentadienyl cations. The conrotatory course of the reaction was confirmed for the case of the dicyclo-hexenyl ketone 7, which yielded solely the tricyclic ketone 8 on treatment with phosphoric acid (equation 7)3b. Cycloalkanocyclopentenones 10 with c/s-fused rings are obtained from the trimethylsilyl-substituted ketones 9 (n = 1, 2 or 3) and iron(III) chloride and... 

Photoaddition of the enol acetate (48) in hexane resulted in the intramolecular [2 + 2]cycloaddition with the production of a 2 3 mixture of the isomeric tricyclic ketones (49) and (50). (Upon hydrolytic cleavage, the mixture was converted to the compounds (51) and (52) 18,22). 

Additions to Vinylphosphonium Salts. Vinyltriphenylphosphonium bromide reacts with the enolate (141) to give a one-stage synthesis of the tricyclic ketone (142) (Scheme 6).135... 

These transformations were applied to develop a new promising method for synthesis of various bridged polycyclic systems66, viz. ketones 160 and 161. Tropone reacts with butenyl magnesium bromide (—78 °C, 75%) to form a mixture of 2-(3-butenyl)dihydrotropones 158 and 159, the pyrolysis of which (200-210 °C, neat or in heptane solution) leads to 60% total yield of the isomeric homoprotoadamantenones 160 and 161 and the tricyclic ketone 162 in a ratio of 58 18 24, respectively (equation 49)66. 

The use of lithium in liquid ammonia to reduce enones is a well-known, well-established procedure which has seen widespread use. The nucleophilic character of the -carbon is clear, and has been demonstrated in many ways. For example, reduction of enone 253 leads to displacement of tosylate and formation of the tricyclic ketone 254 [68,69]. It is interesting to note that the yield for formation of 254 is a function of the nature of the reducing agent. For example, using Li/NH3, a 45% yield is obtained, while with lithium dimethylcuprate, it is 96% [70], and via cathodic reduction, 98%. 

Snider and Kwon use either cupric triflate and cuprous oxide or ceric ammonium nitrate and sodium bicarbonate as single-electron oxidants to convert d,s- and ,C-unsaturated enol silyl ethers 9 stereoselectively to the tricyclic ketones 14 in excellent yields [83, 84]. Based on comparison with other experimental data and literature results, the authors try to distinguish between several possible intermediates and propose the following mechanism with a very electrophilic radical cation 10 as the key intermediate. 

In contrast to the preceding syntheses of kelsoene. Piers and Orellana used ethylene 8 in the [2-1-2]-photocycloaddition key step to furnish tricyclic ketone rac-lO diastereoselectively (Scheme 2) [11]. In accordance with the report by Srinivas and Mehta, attempts to homologate the sterically encumbered ketone rac-lO using the Wittig, Magnus [18, 19] or Taguchi [20] pro-... 

The intermediate tricyclic ketones 495 and 496 have been transformed to the methoxy-substituted derivative 97284,285) latter ketone is subject to hydrogen-deuterium exchange only under basic conditions and appears to exist entirely in the keto form despite the ready formation of its anion and successful methylation on oxygen . In agreement with the aromatic nature of 490, the hydrocarbon undergoes electrophilic substitution reactions... 

A regio- and stereospecific synthesis of modhephene has also been achieved beginning with the Weiss-Cook reaction As illustrated in Scheme XCVII, cyclo-pentai -l,2-dione can be readily crait l into a-diazo ketone 8(M), copper-catalyz l decomposition of which delivers tricyclic ketone 801. Following the dimethylation of this intermediate, carbomethoxylation was accomplished to give 802 and provide... 

This reaction in the presence of base was applied to a tandem cyclization. When bis-alkynyl silyl enol ether 93a was irradiated in toluene in the presence of 10 mol % W(CO)6 and DABCO with 1 equiv of H2O, the expected tricyclic ketone 94a was obtained in 80% yield. The five-membered substrate 93b also gave the corresponding tricyclic ketone 94b having the basic carbon skeleton of the cedranes. Thus we can prepare synthetically useful tricyclic compounds utilizing this W (CO)5(L)-catalyzed tandem cyclization in the presence of DABCO [25c] (Scheme 5.29). 

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