Cyclopropanol oxidation

An approach to a prostaglandin intermediate employed a cyclopropanol oxidation with a mixed chro-mate/cerate reagent shown in equation (26), but the yield was unacceptably low. Although no information on the selectivity is available, the trans stereochemistry of oxidative cleavage in the reported product is of note. In these more complex substrates, side reactions and low yields plague the reaction, which will see only limited use in synthesis unless a better reagent system is developed. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

A similar ring expansion has been reported in the oxidation of cyclopropanol 225 with manganese(III) tris(2-pyridinecarboxylate) to generate the / -keto radical, which is allowed to add to the silyl enol ether 226 [124], The... 

Another example is the asymmetric synthesis of ( )-pinidine 208 and its isomers. These syntheses are achieved via asymmetric enolization, stereoselective cyclopropanation, and oxidative ring cleavage of the resulting cyclopropanol system (Scheme 5-68).123... 

In the hydroxycyclopropanation of alkenes, esters may be more reactive than N,N-dialkylcarboxamides, as is illustrated by the exclusive formation of the disubstituted cyclopropanol 75 from the succinic acid monoester monoamide 73 (Scheme 11.21) [91]. However, the reactivities of both ester- as well as amide-carbonyl groups can be significantly influenced by the steric bulk around them [81,91]. Thus, in intermolecular competitions for reaction with the titanacydopropane intermediate derived from an alkylmagnesium halide and titanium tetraisopropoxide or methyltitanium triisoprop-oxide, between N,N-dibenzylformamide (48) and tert-butyl acetate (76) as well as between N,N-dibenzylacetamide (78) and tert-butyl acetate (76), the amide won in both cases and only the corresponding cyclopropylamines 77 and 79, respectively, were obtained (Scheme 11.21) [62,119]. 

Cyclopropanes have been used to test the reactivity of oxidizing enzymes. Thus, while the monooxygenase enzyme from Methylococcus capsulatus oxidizes cyclopropane 3 to cyclopropanol 4, on the other hand methylcyclopropane 1 a is oxidized to cyclopropylmethanol 5, also without ring opening, Eq. (2) [6]. 

Pyrroloquinoline quinone (PQQ) (or methoxatin) 6 is a coenzyme, responsible for the oxidation of methanol [7]. It has been found that cyclopropanol 4 inactivates the enzyme from M. methanica [8], the dimeric methanol dehydrogenase and the monomeric enzyme from a Pseudomonas PQQ-dependent methanol dehydrogenase [9] by forming adducts such as 7, through a one-electron oxidation process and the ready ring opening of a cyclopropyloxonium radical, Eq. (3) [8,9]. 

A flavoprotein oxidase, which is also a methanol oxidizing enzyme, was inhibited by cyclopropanol 4 through the formation of a N-5 flavin adduct with a ring opened cyclopropyloxy radical [10]. 

Oxidative addition of the carbon-carbon bond of cyclopropanes to zero-valent cobalt species is not in general a facile process. It is assumed that in this reaction the alkynyl part of the molecule works as an anchor for the cobalt carbonyl, which enables an efficient insertion of the cobalt moiety into the proximal carbon-carbon bond of the cyclopropane to proceed. It therefore became a matter of interest to see whether direct connection of the alkynyl part with the cyclopropanol is essential or not for this type of reaction. 

Alkyl substituted cyclopropanols and cyclopropanone hemiacetals 115,116a) aiso undergo oxidative cleavage when exposed to air or peroxides the initial products are hydroperoxides such as 148. In the case of l-methoxy-2,2-dimethylcyclopropanol, the reaction can be followed by observing the emission peaks in the NMR spectrum, and these CIDNP effects have enabled identification of radical intermediates.1154) With di-f-butylperoxylate (TBPO), the isomeric radicals 143 and 144 are formed and these may undergo a diverse number of further reactions as indicated by the complex product mixture given in Table 20. 

Bridgehead bicyclic cyclopropanols or cyclopropyl silyl ethers 103 (R=H) cleaved to ring-expanded mixtures of cyclic (1-hydroxy ketones 105 and (1-diketones 106 in good overall yields catalyzed by 10 mol% of VO(acac)2 in the presence of oxygen (Fig. 32) [191, 192]. With 3-substituted substrates 103 (R=Me), mixtures of bicyclic endoperoxide hemiketals 104B and (1-hydroxy ketones 105 arose. In separate experiments it was shown that 105 is not oxidized to 106 under the reaction conditions, and thus the products most likely form from... 

Fig. 32 Vanadyl acetylacetonate-catalyzed oxidative ring expansion of bicyclic cyclopropanols...

The oxidative radical ring opening of cyclopropanols 191 mediated by Mn(pic)3 was developed by Narasaka and coworkers. Their efforts culminated recently in the development of a silver-catalyzed method (see Part 3, Sect. 6.2). Kulinkovich et al. based a manganese-catalyzed process on it. Manganese abietate 192 (1—1.5 mol%) was used as the catalyst and oxygen as the terminal oxidant (Fig. 54) [289]. 

---