Tetracyclic ketone

An alternative new synthetic approach to chrysene 1,2-dihydro-diol based on Method IV has recently been developed (60). This method (Figure 12) entails synthesis of 2-chrysenol via alkylation of 1-1ithio-2,5-dimethoxy-1,4-cyclohexadiene with 2-(1-naphthyl) e-thyl bromide followed by mild acid treatment to ge nerate the diketone 12. Acid-catalyzed cyclization of 12 gave the unsaturated tetracyclic ketone 13 which was transformed to 2-chrysenol via dehydrogenation of its enol acetate with o-chloranil followed by hydrolysis. Oxidation of 2-chrysenol with Fremy s salt gave chrysene... 

On the other hand, upon heating, the ketone (314) gave the intermediate (315) at temperatures between 150-170 °C. The diene (315) would react with 1,4-naphthoquinone (316) and afforded the tetracyclic ketone (317) after treatment with oxygen and sodium methoxide 110). 

Synthesis ofLysergic Acid, By reacting N-benzoyl-3-(B-carboxyethyl)-dihydroindole (see JCS, 3158 (1931) for the preparation of this compound) with thionyl chloride, followed by aluminum chloride gives l-benzoyl-5-keto-l,2,2a,3,4,5-hexahydrobenzindole. This is then brominated to give the 4-bromo-derivative, which is converted to the ketol-ketone by reacting with methylamine acetone ethylene ketol. This is then hydrolized by acid to yield the diketone and treated with sodium methoxide to convert it to the tetracyclic ketone. Acetylate and reduce this ketone with sodium borohydride to get the alcohol, which is converted to the hydrochloride form, as usual. 

Wender and Dreyer have demonstrate that meta-areiw photocycloaddition chemistry can lead expediently to modhephene A( tate 7S>5, a photoproduct derived from indane and vinyl acetate was converted to tetracyclic ketone 797 (Scheme XCVI). Because the enolate of 797 partakes of the dynamic behavior of semibuUvalenes, it proved possible to trimethylate the substance to produce 798. A fourth methyl group was introduced by conjugate addition and the carbonyl was simultaneously converted to an olefinic center. Selective hydrogenation of799 provided modhephene in seven steps. 

Though the reaction is not general, certain cyclic ketones can be photolyzed to give ring-contracted products.455 In the example above, the tetracyclic ketone 56 was photolyzed to give 57.456 This reaction was used to synthesize tetra-f-butyltetrahedrane 457... 

By utilizing the above methods, a convenient route to the tetracyclic ketone 240, a derivative of the benzobicyclo[3.2.1]octane skeleton, has been developed847 using 2,-methoxy-5,-methyl-1,3-diphenylpropane 239 (Scheme 5.85). 

Umezawa and co-workers9 have reported a new synthesis of the tetracyclic lactam (19), which is a key intermediate in Torssell s synthesis of lycorine (cf. Vol. 9, p. 139) the Japanese work (Scheme 2), therefore, represents a formal synthesis of the alkaloid. The cyclohexyl isocyanate (15) (trans-diequatorial aryl and isocyanate groups) cyclized to a tricyclic lactam, which by reduction with a hydride and hydrolysis gave the ketone (18). The tetracyclic ketone (16) was converted into the 2,3-ene (17) by a Cope elimination reaction, and the synthesis of compound (19) was completed by transposition of the lactam carbonyl group from C-5 to C-7. 

To begin with the more classic transformations, the total synthesis of a clavine alkaloid, (+ )-isosetoclavine (24) reported by Kornfeld and Bach (27) deserves mention. Using the same tetracyclic ketone (23) as starting material as in their famous synthesis (28) of lysergic acid (43) (cf. Vol. VIII) 24 was built up stereospecifically in two steps as demonstrated below. 

A total synthesis of ( )-royleanone from 5,7,8-trimethoxy-l-tetralone (123) has been described.129 The tetralone was converted into the tricyclic ketone (124), which was in turn converted into 11,12,14-trimethoxypodocarpatriene (125). Demethyla-tion and oxidation afforded the quinone (126 R = H) which was alkylated to give royleanone (126 R = Pr ). Synthetic studies in the resin acid series have led130 to the preparation of the dicarboxylic acid (127) with a cis a/b ring junction. The preparation of some tetracyclic ketones as intermediates for gibberellin synthesis has been described.131 132 The key reaction involves photolysis of a diazoketone (128) to afford the tetracyclic system (129). In a synthesis of phyllocladene from abietic acid... 

In recent years, Ireland and his colleagues have made a major contribution to the total synthesis of tetra- and penta-cyclic triterpenoids. The details of some of this work have been published in a series of papers.55-58 The tetracyclic ketone (75) was conceived as a key intermediate in the synthesis of shionone (76). Three routes to (75) were undertaken.55 The most efficient involved a triethylaluminium-catalysed conjugate addition of cyanide to the enone (77) (see Vol. 5, p. 135). The second... 

An impressive cationic domino polycyclization has been developed by Corey and coworkers in their short and efficient enantioselective total synthesis of aegicer-adienol (1-150), a naturally occurring pentacyclic nor-triterpene belonging to the 3-amyrin family [42]. Thus, the treatment of the enantiopure monocyclic epoxy tet-raene 1-147 with catalytic amounts of methylaluminum dichloride induces a ca-tion-JT-tricyclation by initial opening of the epoxide to form the tetracyclic ketone 1-148 in 52 % yield, and its C-14 epimer 1-149 in 23 % yield, after silylation and chromatographic separation (Scheme 1.37). Further transformations led to aegicer-adienol (1-150) and its epimer 1-151. 

This cyclization has obvious applications to the synthesis of steroids and indeed Johnson et al. applied this reaction to a synthesis of dZ-progcsterone. The key step in the synthesis involves the cyclization of (3) to give (4). This reaction was carried out with trifluoroacetic acid as above, but ethylene carbonate was added to the reaction to trap the vinyl cation. After cyclization potassium carbonate was added to hydrolyze the enol complex. In this way (3) was converted into (4) in 71 % yield. The tetracyclic ketone (4) was converted into progesterone (6) by ozonization followed by intramolecular aldol condensation. Nole that (4) is a 5 1 mixture of the 17/7- and 17a-epimeric ketones. The mixture was converted into (6) and then separated by fractional crystallization. 

The synthesis of alnusenone (119) utilized a different method of assembling the pentacyclic skeleton. Condensation of the ketones (120) and (121) led via the tetracyclic ketone (122) to two pentacyclic ethers (123) and (124). The trans,anti,cis-stereochemistvy of (123) was confirmed by X-ray analysis. The desired trans,anti,trans-ether (124) was transformed into alnusenone (119). 

Johnson et al. have investigated the use of alkynylsilanes as terminators in the synthesis of steroids and triterpenes through biomimetic polyene cyclizations. This strategy was used in the stereospecific synthesis of the tetracyclic ketone (81) using an alkynylsilane as a terminator. Thus, treatment of (80) with trifluoroacetic acid under carefully optimized reaction conditions yielded, after hydrolysis of the ortho ester, the tetracyclic ketone (81 Scheme 39). 

When 3,3-dimethylcyclopropene is exposed to carbon monoxide under pressure in the presence of tetrakis(triphenylphosphane)palladium as catalyst, 3,3,6,6,10,10-hexamethyl-exo,enrfo-tet-racyclo[7.1.0.0 " .0 ]decan-8-one (hexamethyl-tris-cr-homotropone, 10) is formed as the main product (72.2%) along with carbonyl-free di- and oligomerization products. At ambient pressure with an in situ generated palladium(O) catalyst, only a 20% yield of the tetracyclic ketone 10 is obtained. 

Molecules containing a bicyclo[2.2.2]octen-2-one subunit fused or bridged to an additional ring have been investigated in detail, as their oxa-7c-methane rearrangements afford tetracyclic ketones, usually in very good yields. The commonest examples are 7,8-fused substrates 33 which afford 6,7-exo-fused tricyclo[3.3.0.0 ]octan-3-ones 34. 

Acetone- or acetophenone-sensitized irradiation of the enones yields the reeurranged ketones (213, 214) which are described as useful substrates for the synthesis of polyquinane natural products. The enones (215) can be converted by photosensitized irradiation into the diquinanediones (216). Irradiation of (215) in acetone gives a low yield of the tricyclic ketone (217). This ketone, while stable in the dark, is photochemically converted into the diquinanedione (215). The authors present evidence that this conversion results from fission of the cyclopropyl bond to yield the biradical (218). Demuth and Hinsken have reported the use of the oxardi-ir-methane rearrangement in the synthesis of annelated triquinanes. Thus the photo conversion of the enone (219) affords the tetracyclic ketone (220,72%). In an analogous reaction the enone (221) is converted into the isomeric ketone (222,70%). ... 

We recently reported (1) a new approach to the stereoselective construction of polycyclic systems, illustrated by the cyclozirconation/carbonylation (2) of a computationally designed diene 1 (Scheme 1) to give the tetracyclic ketone 2. Ketone 2 was converted over several steps to (-)-androst-4-ene-3,16-dione (3). 

Kraus and Zhao described the total synthesis of G-2N (48), an angnlarly fused quinone natural product, using a Diels-Alder reaction between an outerring bicyclic diene and a p-benzoquinone derivative. Sahagdn and colleagues reported the synthesis of tetracyclic ketone 49 nsing a Diels-Alder approach. Ketone 49 was intended to be used in the synthesis of new anthracychne analogs. 

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