Phenanthrenones

Dihydro-1-vinylnaphthalene (67) as well as 3,4-dihydro-2-vinylnaphtha-lene (68) are more reactive than the corresponding aromatic dienes. Therefore they may also undergo cycloaddition reactions with low reactive dienophiles, thus showing a wider range of applications in organic synthesis. The cycloadditions of dienes 67 and 68 and of the 6-methoxy-2,4-dihydro-1-vinylnaphthalene 69 have been used extensively in the synthesis of steroids, heterocyclic compounds and polycyclic aromatic compounds. Some of the reactions of dienes 67-69 are summarized in Schemes 2.24, 2.25 and 2.26. In order to synthesize indeno[c]phenanthrenones, the cycloaddition of diene 67 with 3-bromoindan-l-one, which is a precursor of inden-l-one, was studied. Bromoindanone was prepared by treating commercially available indanone with NBS [64]. 

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho(2,3-a 2, 3 -c)carbazole-6,ll,12,17-tetrone in addition to 2-(3-indolyl)-1,4-naphthoquinone which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(lH-indol-3-yl)-9-phenanthrenol and 9,10-dihydro-9-(lH-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol or 10,10-di-lH-indol-3-yl-9(10H)-phenanthrenone, respectively. All of these products were only obtained in trace amounts in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(lH-indol-3-yl)-9(10H)-phenanthrenone obtained in the solution photoreaction (Wang et al., 1998). 

When the trifluoromethyl group is the only electron-withdrawing. substituent of the cyclic dienophilc, such as in 4-(trifluoromethyl)-1,2-dihydronaphthalene, high pressure is required for the reaction to occur. The yield is improved when the reaction is performed with the tricarbonyl chromium complex 21 of 4-(trifluoromethyl)-l,2-dihydronaphthalene. In the reaction with l-methoxy-.3-(trimethylsiloxy)buta-l,3-diene (Danishefsky s diene, 4), the cycloadducts are obtained as a 1 1 mixture ofcHr/o/c.vo-addition products. They are easily converted into the (trifluoroniethyl)phenanthrenone 22 by the action of bromotrimethylsilane. 

The irradiation of benzocyclobutanone and the phenanthrenone (4) at 77 K has been reported as a possible route to the corresponding arynes. Evidence for the formation of ketenes was obtained."... 

As with esters, the prevailing view held for many years was that ring reduction of aromatic ketones was not feasible. The first indication that this was incorrect was provided by the reduction of the hydro-phenanthrenone (149 Scheme 29). Further isolated examples of ring reduction in naphthyl ketones and molecules containing such moieties have been reported subsequently, but it is clear that these systems are much more easily reduced than simple benzenoid systems. Optimal procedures for the reduction and reductive alkylation of such systems were first established by Watanabe and Narisada for acetophenone and its methoxy derivatives. ... 

In the laboratory of J.D. White, the asymmetric total synthesis of (+)-codeine was accomplished. The Robinson annulation was the method of choice to build a phenanthrenone precursor starting from a substituted tetralone derivative. As it is usuaiiy the case, the isolation of the Michael adduct allowed the intramolecular aldol reaction to proceed cleanly and to afford a higher yield of the annulated product. 

Nimbiol. 2,3,4,4a, 10,1 Oa-Hexahydro-6-hydroxy-1.1,4a, 7-tetra methyl-9<, lH)-phenanthrenone 6-hyd roxy-7-raethyl-9-oxopodocarpane. mol wt 272.37- C... 

Photfrfysis of a-Diazo Carbonyl Compounds - Some recent advances in the matrix photochemistry of diazoketones, including some heterocyclic species, have been reviewed. Flash photolysis of 10-diazo-9(10//)-phenanthrenone (35) in aqueous solution led to the detection of two transient species on the pathway to the final product, fluorene-9-carboxylic acid. These were identified, from solvent isotope effects and the nature of the observed acid-base catalysis, as fluorenylideneketene (36, X = CO) and the enol of fluorene-9-carboxylic acid (36, X = C(0H)2), formed by hydration of the ketene. In related studies, fluorenylideneketene was found to react with amines to give ylides as intermediates on the route to the amide final products. The product distribution from the photochemical reactions of 2-diazo-3-oxo-5,10,15,20-tetraphenylchlorins with alcohols strongly depends on the central metal ion of the irradiated diazoketones. ... 

Mulzer J, Bats JW, List B, Opatz T, Trauner D (1997) The phenanthrenone approach to opium alkaloids formal total synthesis of morphine by sigmatropic rearrangement. Synlett 441 44... 

A similar reaction was used in the synthesis of phenanthrenone 118 from the readily available fluorenone derivative 117 (Scheme 3.47) [130]. 

Herein, three syntheses of morphine or related alkaloids are discussed in detail, which utilize completely different protocols for the coupling of the ring motifs of the alkaloid. Rice published a biomimetic approach with an acid-mediated electrophilic cyclization strategy as key step [144]. Mulzer employed a Friedel-Crafts acylation and a Robinson annulation to construct the phenanthrenone ring system [145]. The D ring of the alkaloid was elaborated with a 1,4-cuprate addition as key step. In his most recent contribution to morphine research, Hudlicky employed a Diels-Alder cycloaddition reaction to construct the ABCE ring system of the natural product. The requisite diene was obtained after oxidative dearomatization of the A ring precursor [146]. 

As outlined in Scheme 12.43, the initial steps of the synthesis were devoted to the elaboration of phenanthrenone 242, which served as substrate for the intended key cuprate addition reaction. Subsequent cuprate addition should then establish the quaternary C13 center and install the handle to establish the D ring of the alkaloid. 

Wilson, R.M., Romanova, T.N., Azadnia, A., Krause Bauer, I.A., and Johnson, R.P., The Argon Laser-Jet Initiated, Multiple-Photon (Reluctant), Electrocyclic Ring Opening of 10,10-Diphenyl-9-(10H)-phenanthrenone A Carbene and Biradical Modeling Study, Tetrahedron Lett., 35, 5401-5404,1994. 

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