Formylation, rearrangements with

Formylation of isobutane with carbon monoxide in the presence of an excess of A1C13 was first reported by Nenitzescu to yield, among others, methyl isopropyl ketone (31%).168 A new highly efficient superelectrophilic formylation-rearrange-ment of isoalkanes by Olah and coworkers has been described.282 Selective formation of branched ketone in high yield with no detectable branched acids, that is, the Koch products, was achieved. A particularly suitable acid is HF—BF3, which transforms, for example, isobutane to methyl isopropyl ketone in 91% yield. The... 

Drewes et al. have investigated the reaction of formyl imidazole with a-hydroxyaryl derivatives of methyl acrylate in the both the presence and absence of DABCO, with THF and methanol as solvent, respectively, to afford novel synthetic intermediates. By such control of the reaction conditions, either allylic substitution products 285 (THF, DABCO) or rearrangement (MeOH, no DABCO) products 286 could be obtained (Scheme 3.112). " ... 

SchifT bases from amines and 4-formylpyridine or 4-formyl-l-methyl-pyridinium benzenesulphonate undergo prototropic rearrangement with DBU, affording carbonyl products on acidic hydrolysis [equation (1)]. 

The reaction of trivalent carbocations with carbon monoxide giving acyl cations is the key step in the well-known and industrially used Koch-Haaf reaction of preparing branched carboxylic acids from al-kenes or alcohols. For example, in this way, isobutylene or tert-hutyi alcohol is converted into pivalic acid. In contrast, based on the superacidic activation of electrophiles leading the superelectrophiles (see Chapter 12), we found it possible to formylate isoalkanes to aldehydes, which subsequently rearrange to their corresponding branched ketones. 

An early attempt to hydroformylate butenediol using a cobalt carbonyl catalyst gave tetrahydro-2-furanmethanol (95), presumably by aHybc rearrangement to 3-butene-l,2-diol before hydroformylation. Later, hydroformylation of butenediol diacetate with a rhodium complex as catalyst gave the acetate of 3-formyl-3-buten-l-ol (96). Hydrogenation in such a system gave 2-methyl-1,4-butanediol (97). 

Thiophene, 3-pentadeuterophenyl-chemical shifts, 4, 730 Thiophene, 2-phenyl-oxidation, 4, 800 phototranspositions, 4, 743 rearrangement, 4, 42 reduction, 4, 775 synthesis, 4, 865, 914 UV spectrum, 4, 735 Thiophene, 3-phenyl-photochemical rearrangements, 4, 735 phototranspositions, 4, 743 lsmeier formylation, 4, 759 Thiophene, 2-pivaloyl-Birch reduction, 4, 775 Thiophene, polybromo-reactivity, 4, 829 Thiophene, polylithio-synthesis, 4, 831 Thiophene, (propargylthio)-rearrangement, 4, 746 Thiophene, 2-(3-pyridinyl)-synthesis, 4, 781 Thiophene, 2-(5-pyrimidinyl)-synthesis, 4, 781 Thiophene, 3-pyrrolidinyl-cycloaddition reactions, 4, 68 with dimethyl acetylenedicarboxylate, 4, 788-789... 

Apparently the role of methanol is to intercept unstable species which otherwise tend to polymerize or rearrange. The methoxy peroxide (72) can be isolated in crystalline form if desired, but it is preferable to treat the methylene dichloride solution at 0° with zinc dust and acetic acid until the mixture shows a negative potassium iodide test. The resulting crude seco-aldehyde (73) is then cyclized to (74) by stirring with neutral alumina in benzene at room temperature for 3 hr. ° Wechter has recently reported a number of transformations of a 5yS-hydroxy-6yS-formyl-B-norpregnane prepared in 8% yield by photolysis and hydrolysis of a 5a-hydroxy-6 -azidopregnane. 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

A second convergent synthesis of haliclamine A (64) was achieved in a stepwise sequence from cyclopropyl(thiophen-2-yl)methanone (76) (Scheme 7) [37]. The protected thiophene 77 was condensed with formyl-piperidine to give 78, suitable for a Wittig olefination with 79. After desulfurization of the product 80, the deprotected alcohol 82 was subjected to homoallylic rearrangement using MesSiBr in the presence of ZnBr2. The re-... 

Nowhere, perhaps, is this phenomenon better illustrated than in the phenothiazine class. The earlier volume devoted a full chapter to the discussion of this important structural class, which was represented by both major tranquilizers and antihistamines. The lone phenothiazine below, flutiazin (130), in fact fails to show the activities characteristic of its class. Instead, the ring system is used as the aromatic nucleus for a nonsteroidal antiinflammatory agent. Preparation of 130 starts with formylation of the rather complex aniline 123. Reaction with alcoholic sodium hydroxide results in net overall transformation to the phenothiazine by the Smiles rearrangement. The sequence begins with formation of the anion on the amide nitrogen addition to the carbon bearing sulfur affords the corresponding transient spiro intermediate 126. Rearomatization... 

Phenylthio-l-trimethylsilylalkanes are easily prepared by the alkylation of (phenylthioXtrimethylsilyl)mcthane as shown in Scheme 10 [40], The treatment of (phenylthio)(trimethylsilyl)methane with butyllithium/tetramethylethylene-diamine (TMEDA) in hexane followed by the addition of alkyl halides or epoxides produces alkylation products which can be oxidized electrochemically to yield the acetals. Since acetals are readily hydrolyzed to aldehydes, (phenylthioXtrimethylsilyl)methane provides a synthon of the formyl anion. This is an alternative to the oxidative transformation of a-thiosilanes to aldehydes via Sila-Pummerer rearrangement under application of MCPBA as oxidant [40, 41]. 

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