O-Formylation

In alkaline solution, the phenol 1 is deprotonated to the phenolate 4, which reacts at the ort/zo-position with dichlorocarbene 3. The initial addition reaction product 5 isomerizes to the aromatic o-dichloromethyl phenolate 6, which under the reaction conditions is hydrolyzed to the o-formyl phenolate." ... 

Mn(II) > Mg(II).270 It should be underlined that titanium and zirconium alkoxides are efficient catalysts for both stages of reaction. Lanthanide compounds such as 2,2/-bipyridyl, acetylacetonate, and o-formyl phenolate complexes of Eu(III), La(III), Sm(III), Er(III), and Tb(III) appear to be even more efficient than titanium alkoxides, Ca or Mn acetates, Sb203, and their mixtures.273 Moreover, PET produced with lanthanides has been reported to exhibit better thermal and hydrolytic stability as compared to PET synthesized with the conventional Ca acetate -Sb203 catalytic system.273... 

Acyl groups are common in bacterial polysaccharides. The parent acids are fatty acids, hydroxy acids, and amino acids. The simplest acid, formic acid, has only been found as the amide. The occurrence of O-formyl groups had been reported, but proved to be incorrect. A-Formyl groups have been found in different polysaccharides for example, in the 0-specific side-chains of the LPS from Yersinia enlerocolitica 0 9, which are composed of 4,6-dideoxy-4-formamido-D-mannopyranosyl residues. The formyl group can assume two main conformations, s-cis (41) and s-trans (42), which are... 

The first observation of a significant rate enhancement in the alkaline hydrolysis of an ester by a suitably positioned carbonyl group that was related to prior attack of hydroxide at the carbonyl group was made in 1955 (Djerassi and Lippman, 1955). However, in 1962, a more detailed mechanistic pathway was suggested which involved attack by hydroxide at an o-formyl or benzoyl group, followed by intramolecular nucleophilic attack on a benzoate ester (Newman and Hishida, 1962 Bender and Silver, 1962). 

A series of eighteen long chain, aliphatic a,a)-bis-isothiocyanates (297-314) and three a-isothiocyano-o-formyl analogues (315-317) was isolated from a Fijian species of Pseudaxinyssa [287]. The major constituents (297), (305) and (315) all have the same length of aliphatic chain (Cl8). Unlike terpenoid isothiocyanates, this series was not accompanied by the corresponding isocyanides or formamides. 

The greater hydrolytic lability of O-formyl than of O-benzoyl groups has been used in the preparation of ribonucleoside 2 -acetal 5 -esters.153 Acid-catalyzed reaction between 5,6-dihydro-4-methoxy-2//-pyran and N2-benzoyl-5 -0-benzoyl-3 -0-formylguanosine, followed by selective deformylation of the product with dilute methano-lic ammonia, gave N2-benzoyl-5 -0-benzoyl-2 -0-(4-methoxytetrahy-dropyran-4-yl)guanosine. 

Cyclizations of o-formyl or o-acylderivatives of (3-phenethylamine give 3,4-dihydroisoquinolines <88H(27)2403) (Scheme 24). 

On the basis of data obtained in the previous paragraphs, one can propose that formation of 5-oxoniachrysenes 67 (R2 = H) occurs via the primary O-formylation of 66 followed by cyclization of esters 70 (R2 = R3 = H), which is similar to the Pictet-Gams reaction (80T1279). Obviously, this mechanism can also be applied to the acylation of 66 with R2COOH (R2 does not equal H) in PPA in contrast to the scheme of formation of 2-benzopyrylium cations 30 from benzyl ketones 28 (Section II, C, 2). 

This methodology is valuable for similar derivatives in the D-manno [68], L-ara-bino [69] and 2-deoxy or 2,3-deoxy [70] series. Parallel work [71] on the O-formyl and O-acetyl phenyl P-D-glucopyranoside 70 and its a-anomer 71 yield compounds 72 and 73. The epimerization of 72 in acidic conditions leads to the more stable compound 73 by anomeric effect. Stereoelectronic effects can explain the twist-boat conformations of 69 and the chair conformation for the manno analog established by x-ray cristallography [72-73]. 

Another approach to a-ketoamide peptide mimetics was employed by Xu et al. [33] for the preparation of a human cytomegalovirus protease inhibitor library. In this case the oxidizable -OH group, protected as formate, belonged to the starting isocyanides. Thus, the reaction between N-acylated a-amino acids, amines, aldehydes, and isocyanides 42 afforded the a-hydroxyamides 43 in modest yields. Cleavage of the O-formyl bond was accomplished during the reaction by employing two... 

The hydroindole 548 was also converted to ( )-haemanthidine (382) and ( )-tazettine (397) (215). The transformation of 548 to 549 was achieved by sequential N- and O-formylation, selective hydrolysis of the formate ester, and then 0-acetylation. The elaboration of 549 to 551 was then effected via Bischler-... 

Ozonolysis of tri-O-acetyl-D-glucal (22) followed by work-up with Et3N-Ac20, led to the O-formylated derivative 23 of methyl-D-arabinonate in 77% yield.48... 

The overall process for this enzymatic resolution is compared with the conventional chemical process in Fig. 14. The enzymatic process can skip several tedious steps which are necessary in chemical resolution and this is a considerable practical advantage. There have been several reports on the application of enzymatic asymmetric hydrolysis to the optical resolution of pantolactone [141, 142], In these cases, esterified substrates, such as O-acetyl or O-formyl pantolactone, and lipases were used as the starting materials and catalysts, respectively. Since the lactonase of F. oxysporum hydrolyzes the intramolecular ester bond of pantolactone, it is not necessary to modify the substrate, pantolactone. This is one of the practical advantages of this enzyme. 

Carroll, J. D. Jones, P. R. Ball, R. G. Novel ring-chain tautomers derived from (o-formyl-phenyljethylamines./. Org. Chem. 1991, 56, 4208-4213. 

The Stille cross-coupling reactions of thienyl-3-carbamate 115 with o-formyl (trimethylstannyl)pyridines 118-120 (1994JHC1161) or acetal 121 (1992MI3, 1994JHC1161, 1994JOMC127) afford a series of isomeric thienonaphthyridines 122-125. The addition of CuO to the reaction mixture leads to an increase in rate (1993JOMC127). 

Taylor and coworkers have prepared o-fluoromethyl and o-difluoromethyl estrone sulfates82 and shown that these compounds are good substrates for steroid sulfatases.83 The phenol product of hydrolysis of o-fluoromethyl estrone sulfate undergoes heterolytic cleavage to form a quinone methide that inactivates the steroid sulfatase (Scheme 20C).83 The phenol product of hydrolysis of o-difluoromethyl estrone sulfate breaks down first to a quinone methide and then to the o-formyl estrone, which also inactivates the steroid sulfatase.83... 

Treatment of di-O-formyl-D-erythrose with methanolic hydrogen chloride has yielded a much higher proportion of the 0 isomer J. N. Baxter and A. S. Perlin, Chem. Inst. Canada, Abstracts 4th Western Conference, Sept. 4, 1958, p. 23. 

The mandelic acid formate ester obtained as a syrup as described above is stirred for 2 hours with 2.9 kg ( 1.75 I) of thionyl chloride at a temperature of about 70°C. The excess thionyl chloride is removed by evaporation and the residual green solution is vacuum distilled. The product, O-formyl mandeloyl chloride, distills over at 127°C to 130°C (15 mm) or at 108°C to 112°C (7 mm). 

To 13 I of ethyl acetate were added 85.1 g (2.59 mols) of 7-amino-3-(l-methyl-lH-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid and 1,361 g (10.37 mols) of monotrimethylsilyl acetamide, and the mixture was stirred at 50°C until a clear solution was obtained. The solution was cooled to 20°C and 514 g (2.59 mold of O-formyl mandeloyl chloride was added at a rate such that the temperature of the reaction solution was maintained between about 20°C to 25% with ice-cooling. 

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