Acid-catalyzed polycyclization

Knowledge regarding biosyntheses has induced several biomimetic approaches towards steroids, the first examples being described by van Tamelen [10] and Corey [11]. A more efficient process was developed by Johnson [12] who, to synthesize progesterone 0-10 used an acid-catalyzed polycyclization of the tertiary allylic alcohol 0-7 in the presence of ethylene carbonate, which led to 0-9 via 0-8 (Scheme 0.3). The cyclopentene moiety in 0-9 is then transformed into the cyclohexanone moiety in progesterone (0-10). 

The acid-catalyzed acylation was successfully applied to the synthesis of two types of polycyclic 2-benzopyrylium salts 67 and 69. The initial compounds in these cases were orf/i0-(3,4-dimethoxyphenyl)-substituted a-naphthols (66) or /3-naphthols (68), and the final salts were 5-oxoniachrysenes 67 (76KGS745 77KGS1176) and 6-oxoniabenz[a]anth-racenes 69 (89ZOR164), respectively. 

The most useful and general approach for the preparation of diamonoid molecules arises from Lewis acid catalyzed rearrangements of polycyclic hydrocarbons. The ubiquitiy of these rearrangements coupled with the availability of several highly selective direct substition reactions which may be subsequently applied to the rearranged hydrocarbons (see Section V.A. 1,2), makes a wide variety of diamonoid substrates readily available. The need for direct, multistep syntheses arises only when special substitution patterns not available via the substitution approach are required (see Section V.A. 3). 

In addition to the preparations of ethanoadamantane via Lewis acid catalyzed rearrangement of various polycyclic hydrocarbons described above (Section II. A.1), a ring closure reaction of a substituted adamantane has also been developed. Treatment of 2-adamantyl diazoketone with copper results in the intramolecular carbene insertion illustrated in Eq. (48) 14°1. 

Polycyclic aromatic nitrogen cations, 55,261 Polyfluoroheteroaromatic compounds, 28, I Polymerization of pyrroles and indoles, acid-catalyzed, 2, 1... 

The kinetic data for isomerization of a range of arene oxides in both the mono- and polycyclic aromatic series as a function of pH showed that the process can be acid-catalyzed (kn) in all cases. A pH-independent spontaneous aromati-zation in the neutral to alkaline region (ko) was also found for arene oxides (generally too slow to be observed for K-region arene oxides). The kinetics of these isomerizations obey the rate law ... 

The rapid, acid-catalyzed hydrolysis of the polycyclic phosphite 2,8,9-trioxa-l-phosphaadamantane (L) produces two isomeric hydrolysates, 3-a-oxo-3-fi-hydrido-7-fi-hydroxy-2,4-dioxa-3-phosphahicyclo (3.3.1) nonane (Isomer A), and 3-fi-oxo-3-a-hydrido-7-ff-hydroxy-2,4-dioxa-3-phosphabicyclo (3.3.1) nonane (Isomer B), the configurations of which were tentatively postulated on the basis of infrared and PNMR spectra. Each isomer dehydrates to L under vacuum at 120°C., as well as in the presence of Cu+ or PhiC+ ions to give [CWLJ+ and [P/i3CL]+, respectively. With hydrated metal ions, L forms complexes of the general formula [M(L -HiO)A](X ), where X = BFa or ClOi and M = Mn+, Zn+, Fe+, and Cd+. Of the isomers, only A forms the identical complexes with these ions as well as Ni+. Infrared evidence is presented which is consistent with the postulate that L HiO is an enolform of A bound to the metal through phosphorus. 

There are only a few synthetic approaches toward these polycyclic systems. The coupling product from diazotized anthranilic acid and 2-hydroxy-1,4-naphthoquinone is transformed into 372 by heating with acetic anhydride (83IJC(B)95). The same quinone reacts with citral and, depending on the reaction conditions, several products are formed. In a triethylamine-catalyzed reaction, the angular quinones 373 and 374 are formed, whereas acid-catalyzed condensation gives the linear compound 375 (82SC195 ... 

ABSTRACT In the synthesis of relevant organic compounds such as natural products and analogues, the proportion of the number of steps coupled with the increase of complexity is now a universal paradigm to ascertain the quality and efficiency of a process. Alongwith providing accessibility to a multitude of diversified classes of natural products such as alkaloids, terpenoids, steroids and others, these criteria have been addressed by us via the application of domino processes. The acid-catalyzed intermolecular cyclization has been used as a viable synthetic tool for the stereospecific formation of different classes of polycyclic natural products. 

Bradsher reaction. Acid-catalyzed cyclodehydration of o-acyldiarylalkanes to polycyclic hydrocarbons and their heterocyclic analogs. 

The two keto tautomers of phenol 3, i.e. 4 and 5, were generated by flash photolysis of polycyclic precursors 6-8 in aqueous solution, and the pH-rate profiles of their 4 3 and 5 3 enolization reactions were measured. The rates of the reverse reactions, 3 4 and 3 5, were determined from the rates of acid-catalyzed hydrogen exchange at the ortho- and para-positions of phenol 3 (equation 3). 

The kinetic characteristics were measured for the rearrangements of arene oxides of benzo[a]anthracene, its methyl-substituted derivatives as well as for other polycyclic arene oxides (for transformations of arene oxides into phenols, see Section VII.C). The mechanism of these acid-catalyzed rearrangements and the isotope effects in these reactions were discussed. ... 

Treatment of ketone 409 with lithium diisopropylamide (LDA) results in the ethyl 1,2-dihydroxybenzoate 410 in a 74% yield (equation 191) . The acid-catalyzed isomerization of diarene oxides derived from benz[a]anthracene, chrysene and benzo[c]phenanthrene gives mixtures of isomeric polycyclic phenols. Finally, it should be mentioned that dibenzo[i>, ]oxepin 411 undergoes an interesting rearrangement to 2-hydroxyphenylindene 412 (equation 192). 

Depending on whether or not p-toluenesulfonic acid was present, the polycycle dibenzotricyclo-[3.0.0.0 ]octadiene (22) reacted differently with benzenethiol. With p-toluenesulfonic acid both stereoisomers were formed. When the acid was omitted, the reaction rate dropped and the reaction mixture contained small amounts of the bridgehead-substituted 25 and the hydrogenated product 26 besides the products 23 and 24 obtained from the acid-catalyzed reaction. ... 

Acid Catalyzed Rearrangements. An example of a photoresist based on an acid catalyzed rearrangement is the diaryliodonium salt photoinduced cyclization of cis-1,4-polyisoprene shown in Equation 18. This facile cyclization which has been reported previously (11) by non-photochemical processes results in a polycyclic polymer whose physical properties and solubility characteristics are considerably different than the initial polymer. Exploitation of these differences in the exposed and unexposed regions of the polymer film permit their use as either positive or negative tone resists. 

The enzyme-catalyzed polycyclization of squalene 135 produces dammaradienol 138, which is known to be the precursor of cholesterol. In the process, squalene oxide is the intermediate, which adopts the conformation as shown in 137, and rearranges, under acid catalysis, to 138 [20, 21]. Note that in the transformations 131 —> 133 and 137 —> 138, many SN2 reactions take place in tandem for the sole reason of stereoelectronically driven well-organized geometrical orientations of the reacting functional groups. Note that all the double bonds are trans, and also that two such consecutive bonds are 1,5-related to each other. 

Type I ene reactions have been applied with good success to form polycyclic intermediates in total synthesis. SnCU-catalyzed cyclization of aldehyde (106) affords (107) as a mixture of isomers, one of which was converted to junenol. Similar mixtures were obtained in the cis series. Cyclization of (108) with 0.002 M HCl in CHCb provides (109), apparently as the cis isomer. Cyclization of (110) with zinc iodide in CH2CI2 gives a quantitative yield of a 1 3 mixture of (111) and (112). It is possible that (112) is not a primary product since it can be formed by the acid-catalyzed isomerization of (111). Oxi-... 

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