Oxidants trimethyl orthoformate

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

Triethylamine, 61,83,87,88,94,99,100,112 Triethylamine N-oxide, 84 Triethylbenzylammonium chloride, 49 Triethylsilane, 104,127.128 Trifluoroacetic acid, 59 Trimethyi-m-dimethylaminophenylsilane, 40 Trimethyl orthoformate, 109... 

Methyl cc-D-glucofuranosidurono-6,3-lactone (26) may be obtained exclusively by reaction of 4 with trimethyl orthoformate in the presence of boron trifluoride etherate.28 Its 2,5-dimethyl ether (27) is formed by methyl iodide-silver oxide methylation29,30 (Purdie-Ir-... 

The anodic chlorination in some cases allows one to achieve better regioselec-tivities than chemical alternatives (p/o ratio of chlorotoluene in chlorination of toluene anodic 2.2, chemical alternative 0.5-1.0) [215]. Anodic oxidation of iodine in trimethyl orthoformate afforded a positive iodine species, which led to a more selective aromatic iodination than known methods ]216]. Aryliodination is achieved in good yield, when an aryhodide is oxidized in HOAc, 25% AC2O, 5% H2SO4 in the presence of an arene ]217, 218]. Alkyl nitroaromatic compounds, nitroaromatic ketones, and nitroanihnes are prepared in good yields and regioselectivity by addition of the corresponding nucleophile to a nitroarene and subsequent anodic oxidation of the a-complex (Table 13, number 11) ]219, 220]. 

Electrochemical oxidation of easily accessible alkyl aryl ketones (58) in trimethyl orthoformate containing a small amount of iodine or organo-iodo compounds gave methyl a-alkylalkanoates (59) in high yields (Scheme 22) [92]. The products (59) are precursors for drugs possessing antiinflammatory and analgesic activities. 

Methyla-arylacetates. These esters have been obtained by oxidative rearrangement of alkyl aryl ketones with thallium(III) nitrate in acidic methanol or trimethyl orthoformate (4,496 5, 656 7, 362). A new method, which avoids the toxic TTN, is based on the Woodward version of the Prevost reaction. Thus, treatment of the ketone with iodine (or bromine) and silver nitrate (2 equiv.) in refluxing methanol containing trimethyl orthoformate results in methyl a-arylacetates in 90% yield from simple substrates. Yields are lowered by electron-withdrawing substituents on the aromatic group and by a-branching in the alkyl group.2... 

Oxidative rearrangement of aryl methyl ketonesThese ketones have been converted into methyl a-methoxyarylacetates on reaction with T1(N03)2 in trimethyl orthoformate (7, 362). This oxidative rearrangement can also be effected with C6H5I(OAc)2 (2 equiv.) in trimethyl orthoformate in equally good yield. 

Anodic oxidation of iodine or Mel in trimethyl orthoformate (TMOF) gives a new positive iodine active species ( I /TMOF), which makes possible a unique rearrangement of aryl alkyl ketones (28) to methyl arylalkanoates (29 equation 72). ... 

The best results are obtained with the above-named oxidants in a mixed solvent of methanol and trimethyl orthoformate in the presence of a strong acid these conditions presumably oisure rq>id acetaliza-tion of the carbonyl to prevent a-oxidation. This side reaction is more smous when is alkyl and the orthoformate is omitted, or if ethyl carbonate or acetonitrile is used as solvent. Prefenol ethers and enamines give the desired oxidative rearrangement in hig yield. 

The nitrile group of (172) reacts with hydroxylamine to give the hydroxyamidine (173). Reduction of the nitro to an amino group and then treatment with trimethyl orthoformate gives the aminopyrazolopyrimidine (V-oxide (174) which, with care, can be hydrolyzed to the cyclic hydroxamic acid (175 Scheme 54) (70JHC863). 

Sulfonic esters are most frequently prepared by treatment of the corresponding sulfonyl halides with alcohols in the presence of a base. This procedure is the most common method for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (16-61). Propylenediamines have also been used to facilitate tosylation of an alcohol. Silver oxide has been used, in conjunction with KI. Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to A,A-disubstituted sulfonamides that is, R— may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually RO . However, R may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate, HC(OR)3, without catalyst or solvent and with a trialkyl phosphite, P(OR)3. ... 

Trimethylamine, 87 Trimethylamine oxide, 114, 309-310 Tiimethyl borate, 296, 310 Trimethylchlorosilane, 310-312, 316 1,1,1O-Trimethyl-rrans-2-decalone, 179 Trimethylenemethane, 101 Trimethylironlithium, 312-313 Trimethylmanganeselithium, 112 Trimethylolpropane, 144 Trimethyl orthoformate, 103, 313... 

The examples given in the table are based on chemical oxidation. By contrast, anodic oxidation of iodine in trimethyl orthoformate provides the iodonium ion which is effective for the iodination of appropriate substituted benzenoid compounds (ref.37) and has been considered superior to the iodonium ion developed in acetonitrile solution. Thus the additbn of the anolyte (4 moles) from trimethyl orthoformate (TMOF), elemental iodine and lithium perchlorate trihydrate, by anodic oxidation at ambient temperature in a divided electrolytic cell equipped with a ceramic diaphragm and platinum electrodes, to anisole (1 mole) in TMOF afforded iodoanisoles in 69% yield, in the proportions, 4-iodomethoxybenzene (87%), and the 2-iodo isomer (13%) with none of the 3-isomer. 

Inhibitors of the enzyme aldose reductase (which has a role in the development of cataract) have been synthesized from chromanones. Spirohydantoins and spiro-oxazolidines derived from chromanone are of interest, especially the (4S)(-)-enantiomer ( 102).106 107 Oxidation of chromanones in methanol-perchloric acid or trimethyl orthoformate has given moderately good yields of chromones together with minor amounts of 3-methoxychromanones.108 The 13C n.m.r spectrum of the benzochromanone fonsecin (103) has been analysed and its biosynthesis from a new type of polyketide chain folding demonstrated.109... 

The interesting conversion of nornarceine (181) into the rhoeadine analogues (187) and (188) has been carried out as shown in Scheme 9. Nornarceine (181), obtained from (— )-a-narcotine, was heated in base to afford the enamine (182) which readily cyclized in dilute acetic acid to the y-lactone (183). Upon standing, (183) was oxidized to the ketone (184). Lithium borohydride reduction led to the c/.s-acid (185). The derived ds-fused lactone (186) was then reduced to the hemi-acetal (187) which upon O-methylation with trimethyl orthoformate gave (188). The structure of the methiodide salt of (187) was confirmed by an X-ray analysis. The phthalideisoquinoline alkaloid (— )-bicuculline (189) was then converted into naturally occurring (+ )-rhoeadine (190) by an analogous route. Since (— )-bicuculline was obtained from (—)-)3-hydrastine, whose synthesis had been reported in 1950, this transformation represents the first total synthesis of a rhoeadine alkaloid. ... 

On treatment of both quinoline and pyridine /V-oxides with bromine and thallium(iil) acetate, y-bromo-derivatives are formed pyridine JV-oxides are the less reactive substrates/ The reaction of 8-methoxyquinoline iV-oxide with acetic anhydride and methanol yields 84% of 2,8-dimethoxyquinoline. Similarly, the reaction of the 6-methoxy-iV-oxide and ethanol and acetic anhydride gives 2-ethoxy-6-methoxyquinoline, but, under the same conditions, the 7-methoxy-N-oxide is unchanged/ The Reissert compounds (149) derived from substituted quinolines, on treatment with thallium(lll) nitrate and trimethyl orthoformate, undergo either smooth ring-contraction or oxidative debenzoyl-ation, depending on the substitution pattern in the aromatic ring (Scheme 61)/ ... 

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