O-nitrophenylacetaldehydes

Izumi used Pd(OAc)2 to effect the bis-alkoxylation of o-nitrostyrenes to form the corresponding o-nitrophenylacetaldehyde acetals, which, upon treatment with Fe/HOAc/HCl, give a variety of indoles (4-OMe, 5-OMe, 4-Me, 4-C1, 4-C02Me, 6-Me) in 63-86% yields [465]. Mori and coworkers employed a titanium-isocyanate complex to construct tetrahydroindolones 373 from cyclohexane-1,3-diones [466],... 

NITR0CYCL00CTENE, 50, 84 Nitrogen atmosphere, apparatus for maintaining, 52, 46 Nitrogen, purification, 50, 69 1-Nitro-l-octadecene, 50, 86 o-Nitrophenylacetaldehyde dimethyl acetal, 52, 139 4-p-Nitrophenyl-l,2,4-triazoline- 3, 5-dione, synthesis of, 51, 125... 

The ozonolysis reaction, followed by reductive workup with sulfur dioxide, as described in Part A of the present procedure, illustrates a general method which has been developed for the preparation of acetals. Application of the procedure is illustrated by conversion of the following olefins in alcoholic solution to the corresponding acetals (1) l-chloro-4-(o-nitrophenyl)-2-butene to o-nitrophenylacetaldehyde dimethyl acetal in 84% yield (2) l,4-dibromo-2-butene tobromoacetaldehyde dimethyl acetal in 67% yield (3) 3-butenoic acid to malonaldehydic acid diethyl acetal ethyl ester in 61% yield (4) cyclopentadiene to malonaldehyde bis(diethyl acetal) in 48% yield and (5)... 

Several versions of palladium-catalyzed coupling reactions have been used to convert o-nitroaryl halides to o-nitrophenylacetaldehydes or o-nitrobenzyl ketones. Coupling with trimethylsilylethyne gives aryl alkynes which can be converted to o-nitrophenylacetaldehyde enol ethers by sodium ethoxide (Scheme 21) <86CPB2362>. 

Meerwein arylation of vinyl acetate provides an alternative route to o-nitrophenylacetaldehydes. Reduction with iron/acetic acid provides indoles in 50-90% yield (Scheme 23) <83JOC2066>. 

The reductive cyclization of o-nitrophenylacetaldehydes presents the obvious problem in that the formyl group is susceptible to reduction. Nevertheless, several such successful indole ring formations are known. Moreover, the intermediate hydroxylamine can cyclize onto the formyl group to give an A-hydroxyindole. 

The reductive cyclization of o-nitrophenylacetaldehyde dialkyl acetals is a powerful indole synthesis as shown by many investigators (Table 1). The reaction presented in... 

Table 1 Reductive Cycllzatlon of o-NItrophenylacetaldehyde DIalkyl Acetals...

As alluded to earlier, the reductive cyclization of nitro ketones often leads to A-hydroxyindoles when the intermediate reduction prodnct, a hydroxylamine, undergoes cyclization. This path can be made dominant if desired. Thus, as shown in Scheme 12, several researchers have developed such a methodology. Acheson may have been the first chemist to achieve this reaction. A two-phase zinc reduction of o-nitrophenylacetaldehyde yields the unstable N-hydroxyindole, which was trapped as the more stable (distillable) A-acetoxyindole (equation 1) [85]. Wong and colleagues use a lead-promoted reductive cyclization approach to Al-hydroxyindoles in excellent yields (equation 2 and 34-37) [86]. Wojciechowski s team employed a VNS synthesis of the A-hydroxyindole precursors (equation 3) [87]. 

Dihydrothiophene 1,1-dioxide treated with ozone in abs. ethanol and methylene chloride wtih Dry Ice-methanol cooling and stirring until the soln. becomes blue, treated portionwise with liq. SOg during 10-15 sec., and after 2 min. allowed to warm to room temp, during 8-16 hrs. cis- and trfl -2,6-diethoxy-l,4-oxa-thiane 4,4-dioxide (Y 74-81%) mixed with NH4CI and glacial acetic acid, placed in an oil bath preheated to 125-130°, stirred and refluxed 25-35 min. 4H-1,4-thiazine 1,1-dioxide (Y 69-83%). - By the above ozonolysis process, acetals can be obtained from ethylene derivs. E l-Chloro-4-(o-nitrophenyl)-2-butene and methanol -> o-nitrophenylacetaldehyde dimethyl acetal. Y 84%. F. e. s. W. E. Noland and R. D. DeMaster, Org. Synth. 52, 135 (1972). 

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