Oxidative rearrangements bonds

The pseudobenzylisoquinoline alkaloids are fairly widespread in nature, being found among members of Berberidaceae, Annonaceae, Fumariaceae, and Ranunculaceae. The biogenesis of the pseudobenzylisoquinoline alkaloids assumes their formation from protoberberinium salts by C-8—C-8a bond scission in a Baeyer-Villiger-type oxidative rearrangement to produce the enamides of type 73 and 74. These amides may be further biotransformed either to rugosinone (76) type alkaloids by hydrolytic N-deformylation followed by oxidation or to ledecorine (75) by enzymatic reduction. These transformations were corroborated by in vitro studies (80-82). It is suggested that enamide seco alkaloids may be precursors of aporphine alkaloids (80), on one hand, and of cularine alkaloids (77), on the other. 

A double oxidation at the 5,6-carbon-carbon double bond and N-9 by 2equiv of OT-chloroperbenzoic acid (MCPBA) was postulated as the mechanism for the oxidative rearrangement of 8-dialkylaminoxanthines to novel l-oxo-2,4,7,9-tetraazaspiro[4,5]dec-2-ene-6,8,10-triones <1999EJ02419>. The presence of an electron-donating 8-amino substituent was essential for this reaction to occur. Further oxidation of the products gave 1,3-dimethylpara-benic acid 45, which was also produced directly when selenium dioxide or hydrogen peroxide were used (Scheme 11). 

The vincadifformine-tabersonine group of alkaloids provide a rich field for the study of oxidative rearrangements. New work reported recently101" includes a study of the oxidation of 3-oxovincadifformine (189) with m-chloroper oxy benzoic acid (Scheme 27). The products were 3-oxovincamine (190), 3-oxo-16-ep/-vincamine (191), and a dilactam (192), which is simply the result of oxidative fission of the 2,16 bond. Under carefully controlled conditions, the hydroxy-indolenine (193) was isolated, and it was subsequently shown to be an intermediate (as expected) in the formation of (190)—(192). Photochemical oxidative rearrangement gave similar results. 

However, the conversion to the transposed a,p-unsaturated carbtxiyl compound is by far the more useful reaction. The fiill sequence serves both to form carbon-carbon bonds as well as to adjust the functional group array in tlw synthetic intermediate. Thus, starting with the enone (15), organometallic addition generates a tertiary allylic alcohol (16) and oxidative rearrangement yields a P-a]kyl-a,p-enone... 

Into this group fall the named oxidation rearrangement reactions which proceed with carbon-carbon bond cleavage and 1,2-transfer of an alkyl group to a heteroatom, such as the Baeyer-Villiger reaction (discussed in Chapter 5.1, this volume) and the Beckmann reaction (found in Chapter 5.2, this volume) of ketones, as well as the Hofmann reaction/Schmidt reaction/Curtius reanangement of carboxylic acid derivatives. The two examples discussed here involve related reactions of alcohols. 

In contrast to lead tetraacetate, simple addition to the double bond does not occur as a side re-action. While allylic rearrangement is common and mixtures of products are frequently obtained, the reaction often proceeds in very high yield and is simple to carry out the alkene is simply heated in an appropriate solvent with mercury(II) acetate until reaction is complete. Mercury(II) acetate has also been us for dehydrogenation, particularly in the steroid field. One interesting example incorporating simultaneous dehydrogenation and allylic oxidative rearrangement is seen in the reaction of abietic acid (37 equation 16). ... 

Treatment of bicyclo[4.1.0]heptan-2-ols with perchloric acid in acetic acid caused very clean rearrangement with formation of cyclohept-3-enyl acetates (Table 1). Only in the case of cxo-7-methylbicyclo[4.1.0]heptan-2-ol was the cyclohex-2-enyl acetate the major product probably because the 7-methyl group conferred additional stabilization on the carbocation formed by j0-scission of the outer cyclopropane bond. The same type of reactant could be oxidatively rearranged using pyridinium chlorochromate to afford cyclohepten-4-ones, together with (chloromethyl)cyclohexenes. However, if the chloride in the reagent was replaced with tetrafluoroborate, or if pyridinium chlorochromate was used with silver(I) nitrate, formation of the substituted cyclohexenes was completely suppressed, e.g. formation of 7 from 6, although the reported yields were low. ... 

The photochemical cycloaddition of 4-methyl-l,2,4-triazoline-3,5-dione to the dibenzo-cyclooctatetraene 289 yields 3.5% of the cycloadduct 290, together with 36% of 291, the product of a di-jr-methane rearrangement (equation 153. Anthrasteroids 293 (R = H, Ac or COPh) are produced in an oxidative rearrangement when the phenyltriazoline-dione adduct of 292 is treated with boron trifluoride etherate. The 5,7-diene system of ergosteryl acetate 294 can be protected by cycloadduct formation, allowing selective hydrogenation of the 22,23-double bond " ... 

JV-Oxide rearrangements in heteroaromatic compounds are frequently induced by either photochemical or acid anhydride initiated processes, and usually involve formation of a C—O bond at the carbon a to the original N-oxide. 60 One of the few -rearrangements is observed by treating 1,3-dimethylpyrido[2,3-r/Jpyrimidine-2,4(l //,3//)-dione 8-oxide (1 see Section 7.2.2.1.1.5.1.) with acetic acid/acetic anhydride at 90 CC, which gives 6-acetoxy-l,3-dimethylpyrido[2,3-t/]pyrimidine-2,4(l//,3//)-dione (2). When the reaction is run at reflux temperature in trifluoroacctic anhydride/trifluoroacetic acid, a 46% yield each of the a- and -product, 3 and 4, respectively, is obtained.310... 

Reactions of (8) (X = Cl, Ph) with NaOR (R = Me, Ph) afford mono- and disubstituted products with the oxide ligand(s) attached to P. Compound (10) (R = Ph) reacts with NaOR (R = Me, Et, Pr, Ph) to afford products with the oxide ligands bonded to P and/or C. They readily rearrange to products with phosphazane character ... 

To execute this proposal (route A) by chemical transformation, synthesis of a hypothetical intermediate 159 and its oxidative rearrangement to the oxindole derivative have been examined. The C-21 aldehyde carbon in ajmaline (14) was removed by C-20,21 bond cleavage in the glycol derivative 162, which was prepared from 14 by a six-step operation (Scheme 24). 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

---