Formyl acetate

Pearlman, B.A. (1979) A Method for Effecting the Equivalent ofadeMayo Reaction with Formyl Acetic Ester. Journal of the American Chemical Society, 101, 6398-6404. 

ZOR2398). Thus, on heating this compound in glacial acetic acid or in formyl acetate in the presence of sodium formate, 2-benzyIidene-5-methoxynaphtho[frc]furan 50 has been obtained, whereas extended boiling of 49 in a mixture of acetic anhydride and triethylamine has led to C-acetyl derivative 51. 

Generally, there is no limitation in the 1,3-dicarbonyl compound used. However, several types of these substances are not stable, such as malone dialdehydes or formyl acetic acid. In such cases, l,l,l-trichloro-4-oxo-butanone 96 is an appropriate substitute, since the trichloromethylcarbonyl moiety can easily be transformed into a carboxylic acid ester after the reaction by treatment with an alcohol and a... 

Cycloadditions. This reagent serves as a formyl acetic ester equivalent in [2 + 2] cycloadditions with alkenes. The addition provides a new method for vicinal attachment of carboxaldehyde and acetic ester appendages to double bonds (e.g., 2->5). An intramolecular version of this reaction was used in a total synthesis of reserpine. ... 

O-Formylation Acetic-formic anhydride. Formic acid. Formylimidazole. p-ToluenesuIfonyl chloride-Dimethylformamide. 

Formic ester Acetic ester Formyl acetic ester... 

Me2N)3S][Me3Sip2], CH3CN, reflux, quant, or (Bu4N)(Ph3SiF2), CH3CN, reflux, 84% yield. Use of HF-pyridine resulted in formyl acetal formation by participation of an adjacent MOM ether. ... 

TIPSOCHjSEt, CuBrj, BU4NBL 4-A molecular sieves, CH2CI2,89-98% yield. This method can also be used to prepare a variety of other formyl acetals and esters. 

Condensation of Formyl Acetic Acid with Guanidine... 

Formyl acetic acid and guanidine undergo cyclization after condensation in the presence of fuming sulphuric acid with the loss of two moles of water. The cyclized product imdeigo keto-enol tautomerism, when the enoMorm, i.e., 4-hydroxy-2-amino pyrimidine is subsequently chlorinated with either phosphorus oxychloride (POCI3) or chlorosulfonic acid (CISO2OH) and finally reduced with zinc metal and ammonium hydroxide to obtain 2-amino-pyrimidine. 

Based on our experiences with the NHC-catalyzed synthesis of dihydropyra-nones, we thought it conceivable that ot,p-unsaturated enol ester 51a could be converted to the iridoid cyclopenta[c]pyran core (i.e., 52a) (Scheme 11). In turn, it was envisaged that the required unsaturated enol ester 51a could be prepared via acylation of methyl formyl acetate (53a) with enantioenriched acyl chloride 54. The NHC-catalyzed rearrangement would only prove viable if it proceeded with chemoselectivity, due to the presence of additional ester functionality in enol ester 51a, and stereoselectively, to provide the correct diastereomer of 52a for the natural product. Although it was unclear whether these selectivities could be achieved, or whether the reaction would proceed with substrates annulated about the a,p-unsaturation, it was envisaged that this study would, at the very least, allow the limitations of the NHC catalysis to be examined. From the iridoid core 52a, completion of the total synthesis would require the chemo- and stereoselective reduction of the lactone to the lactol, followed by glycosylation. 

Initial attempts at acylating formyl acetate 53b with acyl chloride 54 using pyridine in methylene chloride at 0 °C afforded the desired enol ester 51b, unfortunately as an inseparable mixture with Knoevenagel adduct 59 in a ratio of 84 16 (Table 1, entry 1). This would not be the last time that the reactivity of the formyl acetate increased the difficulty of seemingly simple transformations. Fortunately, under the same reactimis conditions, but in the presence of less nucleophilic bases, namely either triethylamine or Hiinig s base, formation of the byproduct was reduced to 96 4 and 99 1, respectively, with 51b isolated in up to 89% yield (Table 1, entries 2 and 3). Utilizing the optimized conditions, ethyl enol ester 51c was prepared in 91% yield (Table 1, entry 4). 

Having streamlined the synthesis of acyl chloride 54, the indirect preparation of methyl enol ester 51a was addressed. As previously discussed, attempts to synthesize 53a from formyl Meldrum s acid 58 had proven unsuccessful. However, Cossy and coworkers have reported the preparation of 53a via the ozonolysis of alkene 82 and subsequent use of the crude aldehyde in the total synthesis of octalactin. Thus, methyl vinyl acetate (82) was subjected to ozonolysis at —78 °C, followed by a reductive quench to provide formyl acetate 53a (Scheme 24). The crude methyl formyl acetate was acylated with acyl chloride 54, using the previously optimized conditions, to afford methyl enol ester 51a in 74% yield over two steps. This modification to the synthesis removes a further two reactions from the sequence with a formal synthesis of (—)-7-deoxyloganin (24) now achieved in 10 steps, a length more in keeping with the complexity of this target. 

Thus, as shown in Scheme 14.7, the reaction of ethyl formate with ethyl acetate in ether in the presence of sodium metal yielded ethyl sodium formyl acetate. Then, the addition product of ethyl bromide with thiourea was treated with aqueous base and the ethyl sodium formyl acetate was added so that, after standing for a number of hours, acidification with acetic acid yielded 2-ethylmercapto-6-oxypyrimidine. Treatment of the latter with phosphorus pentachloride yielded the corresponding 2-ethylmercapto-6-chloropyrimidine subsequent alcoholic ammonolysis generated 2-ethylmercapto-6-aminopyrimidine and boiling aqueous hydrobromic acid resulted in the production of 6-amino-2-oxypyrimidine (cytosine). 

The isomeric 2-amino-6-oxypyrimidine was prepared (Equation 14.2) by the reaction of ethyl sodium formyl acetate with guanidine. 

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