Formyl ation

The well-known reaction of a-alkyl-/3-ketoaldehydes and hydroxyl-amine has been applied to the elucidation of the structure of formyl-ation products of ketones the conclusions are, however, open to question. Some workers attempted to overcome the ambiguity of the reaction of j8-ketoaldehydes and hydroxylamine, which results in a mixture of 3- and 5-monosubstituted isoxazoles and thus considerably lowers the preparative value of the method, by using various derivatives of yS-ketoaldehydes, especially those of their enolic forms (jS-substituted vinylketones) investigated by Kochetkov et al. The use of readily available /3-chlorovinylketones (12) in the reaction with hydroxylamine represents a rather useful preparative method to synthesize monoalkylisoxazoles but again gives rise to a mixture of 3- (13) and 5-alkylisoxazoles (14). This is due to the attack... 

Acetic formic anhydride has been prepared by the reaction of formic acid with acetic anhydride2 3 and ketene,4,5 and of acetyl chloride with sodium formate.6 The present procedure is essentially that of Muramatsu.6 It is simpler than others previously described and gives better yields. It is easily adapted to the preparation of large quantities, usually with an increase in yield. Acetic formic anhydride is a useful intermediate for the formyl-ation of amines,3,7 amino acids,8,9 and alcohols,2,10 for the synthesis of aldehydes from Grignard reagents,11 and for the preparation of formyl fluoride.12... 

Dimethoxyethane is preferred to dimethyl sulfoxide as solvent for the formyl-ation of ketones with carbon monoxide in the presence of an alkali metal alkoxide. This is due to the fact that DMSO is slightly protic in the presence of a strong base (potassium t-butoxide) and hence not inert. 

Formyl-tetreihydrofolate is more stable to atmospheric oxidadon them folic acid itself and is commonly used in pharmaceutical prepeu ations it is also known as folinic acid and the synthetic (racemic) compound as leucov-orin. Although the [6S, 6R] racemic mixture might be expected to have only 50% of the biologiceil activity of the naturally occurring 6S isomer, between 10% to 40% of the 6R isomer is biologically active (Baggott et al., 2001). 

From a synthetic point of view, the above studies have stimulated the synthesis of new types of /3-diketonato complexes. Thus, reactions at position 4 of the l-metalla-2,6-diox-acyclohexane rings, usually denominated the y-position (equation 2), such as halogen-ation , thiocyanogenation, chlorosulfenylation , arylsulfenylation, acylation, nitration, formylation , chloromethylation and dimethylaminomethylation (equation 2) ° have been performed as well as Suzuki coupling reactions (equation 3) , or an aldol reaction with p-nitrobenzaldehyde under Lewis acidic conditions (equation 4f. ... 

Compound (8), under Vilsmeier formylation and nitration (nitric acid-acetic anhydride) conditions, proceeded as might have been expected for electrophilic substitution reactions to give the 1-substituted products (142) and (143). Reduction of (143) gave predominantly the imidazopyridine (144) with a small amount of the tetrahydro derivative (145) (81JCS(P1)78). Heating (8) in D2O led to the 1-deutero derivative (78HCA1755) via deuter-ation-deprotonation or via the tautomeric 2-(diazomethyI)pyridine tautomer of (8). 

These substitutions are facilitated by electron release from the heteroatom pyrroles are more reactive than furans, which are in turn more reactive than thiophenes. Quantitative comparisons of the relative reactivities of the three heterocycles vary from electrophile to electrophile, but for trifluoroacetylation, for example, the pyrrole furan thiophene ratio is 5 x 10 1.5 x 10 I " in formylation, furan is 12 times more reactive than thiophene, and for acetylation, the value is 9.3. In hydrogen exchange (deuteriodeproton-ation), the partial rate factors for the a and p positions of A-methylpyrrole are 3.9 x 10 ° and 2.0 x 10 ° respectively for this same process, the values for furan are 1.6 x 10 and 3.2 x l(f and for thiophene, 3.9 X 10 and 1.0 x 10 respectively, and in a study of thiophene, a P ratios ranging from 100 1 to 1000 1 were found for different electrophiles. Relative substrate reactivity parallels positional selectivity i.e. the a P ratio decreases in the order furan > thiophene > pyrrole. ° Nice illustrations of these relative reactivities are found in acylations of compounds containing two different systems linked together. ... 

The amino alcohol 69 was selectively N-formylated to give the formamide 70, deoxygenation of which was achieved by bromin-ation with PBr followed by hydrogenation to yield 72. Removal of the protective group by acid treatment afforded (t)-dihydro-pinidine (73) (Fig. 12). 

This paper describes formylation, dichloromethylation, carboxyl-ation of phenol and its derivatives in high yields with high selectiv-ities by use of a small amount of CyD as catalyst. Selective formylation of indole is also reported. 

Prepa ation.—Dimethylsilyl enol ethers of aldehydes and ketones may be prepared by irradiating the carbonyl compounds in the presence of dodecamethyl-cyclohexasilane (MeaSije/ Highly stereoselective formylation of (Z)-enol silyl ethers has been achieved on treatment of acyclic ketones with ethyl tri-methylsilylacetate and tetrabutylammonium fluoride on the other hand lithiation of pentan-3-one with lithium 2,2,6,6-tetramethylpiperidide followed by chloro-trimethylsilane gave mainly (84%) the ( )-enol silyl ether... 

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