Spiro oxides rearrangement

The palladium-catalyzed reductive N-heteroannulation using carbon monoxide has been reported (Scheme 102). As part of this study, substrate 551 was examined in an attempt to synthesize 552. However, 552 was found to be unstable and underwent further oxidative rearrangement in air to form spiro compound 555 via intermediates 553 and 554 <2006T10829>. 

Oxidative rearrangements of tetrahydrobenzimidazoles 300-304 on treatment with dimethyldioxirane (DM DO) provided spiro-5-imidazolones 305-311 selectively in good yields. Moderate to excellent stereoselectivity was achieved via preferential oxidation at the less sterically hindered face (Scheme 73) <20040L735>. 

Oxidation of the carbinol (4) with periodate does not give the expected spiro-epoxy compound but the benzaldehyde acetal of 3,5-di-r-butylcatechol (5). This oxidative rearrangement is apparently limited to o-hydroxy-substituted diaryl- and triaryl-carbinols.3... 

In their further studies [95], the synthesis of spiro-p-lactams 84 (Scheme 22) were carried out by unusual oxidative rearrangement of monocarboxylates of 3-methyli-dene-p-lactams 83 with different oxidizing reagents such as H2O2 in alkali, f-BuOOH, or KOCl. The reaction always resulted in the single isolated crystalline spiro-p-lactam 84 whose stereochemistry was established by single X-ray crystallography. 

An interesting strategy for the synthesis of pyrrolizidines and indolizidines has been developed by Brandi and co-workers. Cycloaddition between nitrones or nitrile oxides with methylenecyclopropanes generates strained tricyclic spiro compounds, which are prone toward further transformations, such as rearrangement, ring opening, and new ring closure (Scheme 10.17).116... 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

Halogen substitution is expected to increase the electrophilicity of the carbenes, and in particular lh with four fluorine substituents is expected to be highly electrophilic and of unusual reactivity. All the carbenes le-g could be matrix-isolated by irradiation of their corresponding quinone diazides 2 in argon at 8-10 K.24 68,62 Again, the thermal reaction in (Vdoped matrices results in the formation of quinone oxides 7, which show the expected photochemical rearrangement to the spiro dioxiranes 8 and finally lactones 9. 

Reactions of arylsulfonylallenes with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide (227) proceed in a manner similar to that of the above-mentioned sulfides. Probably, both 4- and 5-alkylidene-4,5-dihydroisoxazole cycloadducts are initially formed which then undergo different transformations. 4-Alkylidene isomers give spiro adducts such as 60 with an additional molecule of nitrile oxide, while 5-isomers convert to isoxazoles 61, products of their prototropic rearrangement. 

In 2001, Albrecht Berkessel and Nadine Vogl reported on the Baeyer-Villiger oxidation with hydrogen peroxide in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent in the presence of Brpnsted acid catalysts such as para-toluenesulfonic acid (equation 85) . Under these conditions cyclohexanone could be selectively transformed into the corresponding lactone within 40 min at 60 °C with a yield of 92%. Mechanistic investigations of Berkessel and coworkers revealed that this reaction in HFIP proceeds by a new mechanism, via spiro-bisperoxide 234 as intermediate, which then rearranges to form the lactone. The study illustrates the importance of HFIP as solvent for the reaction, which presumably allows the cationic rearrangement of the tetroxane intermediates. 

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

Iy2-Acyl rearrangement of a, -epoxy ketones. This rearrangement can be used for synthesis of cyclic spiro-1,3-ketones. Thus the 2-cycloheptylidenecyclopenta-none oxide 1 rearranges in the presence of BF3 etherate at 25° within one minute to the spiro-1,3-diketone 2 in 91% yield.1... 

The reaction of 7-chloro-4,6-dinitrobenzofurazan with 2-(4,-bromophenyl)indolizine has been shown to result in carbon-carbon bond formation by substitution of the 7-chloro substituent.58 However, in the reaction of 7-chloro-4,6-dinitrobenzofuroxan the initial substitution is followed by intramolecular oxygen transfer from the N-oxide function and by rearrangement to give the zwitterionic spiro-adduct (15). An... 

The thermal rearrangement of spiro[naphthalene(naphthopyranofurazan)] oxides to spiro[naphthalene(phenalenofurazan)] oxides has been reported (Scheme 109) and an ionic mechanism proposed.160... 

Treatment of the 2-pyrrolyl allyl thioether (498) with acetic anhydride and quinoline at 170 °C (or in A jV-dimethylaniline at ca. 100 °C) results in a thio-Claisen rearrangement to give the 5-(3-allyl-2-pyrrolyl) thioacetate (499), whilst peracid oxidation of (498) produces the non-rearranged sulfone in low yield and Raney nickel reduction of (498) yields 3-propylpyrrole (78CJC221). The polyphosphoric acid-catalyzed cyclization of (2-pyrrolylthio) acetic acid (501 R = R = H) somewhat unexpectedly yields (502) via the Spiro intermediate, instead of forming the expected oxothiolane (500), which can be obtained by a Dieckmann cyclization of ethyl (3-ethoxycarbonyl-2-pyrrolylthio) acetate (501 R = Et, R = C02Et) (B-77MI30506). 

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