9.10- Dihydrophenanthrene synthesis

Dihydrophenanthrene synthesis. Evans et al. have reported a new route to dihydrophenanthrene derivatives based on the condensation of p-quinone mono-ketals (1) or monosilyl cyanohydrin derivatives (5, 721-722) with the enolate of methyl 3-(3,4,5-trimethoxyphenyl)propionate (2) to give p-quinol ketals (3). These undergo acid-catalyzed cyclization to dihydrophenanthrene derivatives (4). A typical example is formulated in equation (I). The choice of the Lewis acid catalyst is sometimes critical for the cyclization. In the case of the cyclization shown above, use of SnCL, CF3COOH and BF3 etherate resulted in much lower... 

The photochemical isomerization of E-stilbenes has been applied in the preparation of phenanthrenes, as Z-stilbenes undergo electrocyclie ring closure (cf. chapter 3.1.3) to dihydrophenanthrenes which in turn are easily oxidized to phenanthrenes (3.1) 305). This sequence has also been employed in the synthesis of benzoquinolines 306) or of benzoquinolizines (3.2) 307). 

Uses Explosives dyestuffs biochemical research synthesis of drugs preparation of 9,10-phen-anthrenequinone, 9,10-dihydrophenanthrene, 9-bromophenanthrene, 9,10-dibromo-9,10-dihydro-phenanthrene, and many other organic compounds. 

The iV-aminopyrrole - benzene ring methodology has been applied to a synthesis of the 9,10-dihydrophenanthrene juncusol (218) (81TL1775). Condensation of the tetralone (213) with pyrrolidine and reaction of the enamine with ethyl 3-methoxycarbonylazo-2-butenoate gave pyrrole (214). Diels-Alder reaction of (214) with methyl propiolate produced a 3 1 mixture of (215) and its isomer in 70% yield. Pure (215) was reduced selectively with DIBAL to the alcohol, reoxidized to aldehyde, and then treated with MCPBA to generate formate (216). Saponification to the phenol followed by O-methylation and lithium aluminum hydride reduction of the hindered ester afforded (217), an intermediate which had been converted previously to juncusol (Scheme 46). 

The synthesis of 9-phenylphenanthrene (Expt 6.14) illustrates the formation of the phenanthrene system by the cyclisation of a 1,2-diphenylethylene (stilbene). The process involves an allowed photochemical cyclisation which gives initially a dihydrophenanthrene. This is readily dehydrogenated in situ by molecular oxygen in the presence of iodine. 

This reaction has been used in a regiospecific synthesis of juncusol (1) (a natural dihydrophenanthrene), as outlined in Scheme I.3 O... 

This reaction has been used for synthesis of juncunone (1), an unusual natural neclyl-9,10-dihydrophenanthrene.3... 

Irurre, J. Riera, M. Guixa, M. Gram-scale synthesis of (+)- and (-)-trans-10-amino-9-hydroxy-9,10-dihydrophenanthrene by enzymic hydrolysis. Chirality 2002, 14 490-494. 

One process which is related to the photocyclization of stilbene-like substrates is the conversion of 2-vinyl biphenyls to 8,9a-dihydrophenanthrenes, which undergo a facile thermal isomerization to 9,10-dihydrophenanthrenes (Scheme 9.24) [36]. For the synthesis of 5,6-dihydro- 1,10-phenanthroline and 1,10-phenanthroline derivatives, metal-chelation of the nitrogen atoms has shown to be productive (Scheme 9.25) [37]. 

Further investigations on the field of oxidative bond cleavage even made single bonds accessible. Thus, biaryls 10 and 11 were similarly obtained by electrooxidation of 9,10-dihydrophenanthrene. Moreover, the cleaving reaction of benzylic carbons was also exploited in the synthesis p-tert-butylbenzaldehyde dimethyl acetale (3) starting from l,2-di-(p-ferf-butylphenyl)ethane (4, 1,2-DPTE) (Fig. 5.8) (Zollinger et al. 2004b). 

There are two types of enamides readily available for the simple synthesis of protoberberine alkaloids via the route involving photocyclization. One is the 2-acyl-1-benzylideneisoqui noline-type enamide that has a stilbene structure in the molecule and is known to undergo a six -electron conrota-tory electrocyclic cyclization to a dihydrophenanthrene and subsequent dehydrogenation (103), and thus provides a useful synthetic route to apor-phine alkaloids. The second is the 2-aroyl-l-methyleneisoqui noline-type enamide that gives the 8-oxoberbine in good yields on irradiation. 

Fluorene has been reported to afford the 3,9a-dihydro product, but it is almost certain that this is the 2,4a-dihydro isomer (55 = 1) by analogy with biphenyl. 9,10-Dihydrophenanthrene (56) is reduced as expected to (55 n = 2), but spontaneously reverts to the starting material on standing. These systems do not require the presence of alcohol for reduction and it is consequently possible to alkylate the intermediate anions with alkyl halides, as (56) gives (57). These products are much more stable and structural analysis is simplified accordingly oxidation of the doubly allylic methylene occurs readily to afford the dienone (58 Scheme 7). Dienones of this type have potential as intermediates for the synthesis of natural products. Anthracene and phenanthrene are both readily reduced in the central ring to form the 9,10-di-hydro derivatives as might be expected, but to avoid further reduction it is necessary to have an iron salt present. Further examples are reviewed elsewhere. ... 

Both anthracene and phenanthrene undergo electrophilic substitution, with a few exceptions, liowevcr, these reactions are of little value in synthesis because of the formation of mixtures and polysubstitution products. Derivatives of these two hydrocarbons are usually obtained in other ways by electrophilic substitution in 9.10-aiithraquinone or 9,10-dihydrophenanthrene, for example, or by ring closure methods (Secs. 30.18 and 30.19). 

Removing hydrogen atoms from adjacent carbon atoms, as shown above for stilbene, is generally difficult synthetically. Preliminary work (28) has shown that dianions of acenaphthalene can be prepared by treating acenaphthene with n-BuLi in THF. Unfortunately the technique has limited applicability—for example, similar treatment of 9,10-dihydrophenanthrene does not give dianion formation (28). We have routinely used a modified version of this reaction with the base TMED for years (24, 25)—as above in the synthesis of naphthalene dianion. The dianion of phenanthrene with TMED can also be readily prepared by this reaction ... 

Ishigaki Y, Suzuki T, Nishida J et al (2011) Hysteietic tricolor electrochromic systems based on the dynamic redox properties of imsymmetrically substituted dihydrophenanthrenes and biphenyl-2,2 -diyl dications efficient precursor synthesis by a flow micTOTeactor method. Materials 4 1906-1926... 

Della Greca M, Fiorentino A, Monaco P, Pinto G, Previtera L, Zarrelli A (2001) Synthesis and antialgal activity of dihydrophenanthrenes and phenanthrenes 11 mimics of naturally occurring compounds in Juncus effusus. J Chem Ecol 27 257-271... 

SCHEME 5.11 (a) Tsuji-Trost asymmetric allyUc alkylation applied to the total synthesis of vinyl or isopro-penyl chiral dihydrophenanthrenes. (h) Stereoselective synthesis of the (-)-cedril A precursor 36b. 

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