2-fluoroacetaldehyde

Figure 1.2 Fluoroacetaldehydes length of C=0 bond and electronic repartition.

Molecular orbital calculations on fluorinated butadienes and hexatrienes were used to model the effects of fluorination on the properties of poly(acetylene). Like poly(acetylene), "head-to-head" poly(fluoro- acetylene), (-CH=CF-CF=CH-), is predicted to adopt a planar, all trans structure, but poly(difluoro-acetylene) favors a non-planar skewed chain conformation. "Head-to-tail" poly(fluoroacetylene), (-CH=CF-CH=CF-) is predicted to favor a nearly planar cis structure stabilized by intramolecular CF-HC hydrogen binding. Calculations on 2-fluoroethanol and on both 2-fluoroacetaldehyde enol and its alkali metal (Li, Na, K) enolates reveal moderately strong intramolecular CF—HO hydrogen bonds(1.9 and 3.2 kcal/mol, respectively) and even stronger intramolecular coordination of CF to alkali metal cations (9-12 kcal/mol). 

The nature of the hydrogen bond in 2-fluoroacetaldehyde enol is quite different from that in the alcohol. Among the four structures shown below, the cis-syn structure is the most stable (Table V). The difference in energies of the cis-syn and cis-anti structures gives an estimate of the hydrogen bond energy. At the MP-2 level, this is 3.53 kcal/mol and corrections for zero-point effects yield a value of 3.21 kcal/mol. (The... 

Table V. Relative Energies (kcal/mol) of 2-Fluoroacetaldehyde Enol Structures...

Table VI. Relative Energies and Bond Lengths of 2-Fluoroacetaldehyde Enolate Isomers...

The reaction between F.E.A. and manganese dioxide and sulphuric acid was investigated initially with a view to preparingthe corresponding fluorinated acetal. It soon became apparent that the isolation of the hitherto undescribed fluoroacetaldehyde might be possible in this experiment, and accordingly attention was directed to that end. 

By analogy with chloral and monochloroacetaldehyde it is to be expected that fluoroacetaldehyde might readily form a hydrate, and it was in this form that the fluoroacetaldehyde was obtained in small yields by the above-mentioned oxidation of F.E.A. 

Class B Fluoroacetic acid and salts, e.g. sodium fluoroacetate, triethyl-lead fluoroacetate all simple esters of fluoroacetic acid fluoroacetamide and substituted amides fluoroacetamidine hydrochloride fluoroacetyl chloride and fluoride fluoro-ethanol and its simple esters fluoroacetaldehyde. 

The product of the PNP enzyme, FDRP 9 has been purified and characterised. The evidence suggests that FDRP 9 is then isomerised to 5-fluoro-5-deoxyribulose-1-phosphate 10, acted upon by an isomerase (Scheme 7). Such ribulose phosphates are well-known products of aldolases and a reverse aldol reaction will clearly generate fluoroacetaldehyde 11. Fluoroacetaldehyde 11 is then converted after oxidation to FAc 1. We have also shown that there is a pyridoxal phosphate (PLP)-dependent enzyme which converts fluoroacetaldehyde 11 and L-threonine 12 to 4-FT 2 and acetaldehyde in a transaldol reaction as shown in Scheme 8. Thus, all of the biosynthetic steps from fluoride ion to FAc 1 and 4-FT 2 can be rationalised as illustrated in Scheme 7. 

Scheme 8. The conversion of L-threonine 12 and fluoroacetaldehyde 11 to 4-FT 2 and acetaldehyde catalysed by the PLP enzyme threonine transaldolase from Streptomyces cattleya [18].

C. Schaffrath, C.D. Murphy, J.T.G. Hamilton, D. O Hagan, Biosynthesis of fluoroace-tate and 4-fluorothreonine in Streptomyces cattleya. Incorporation of oxygen-18 from [2- H,2- 0]-glycerol and the role of serine metabolites in fluoroacetaldehyde biosynthesis, J. Chem. Soc. Perkin Trans. 1 (2001) 3100-3105. 

The first step in this pathway involves SN2 displacement by fluoride on S-adenosine-L-methionine (SAM) catalyzed by the newly discovered enzyme fluor-inase (905-910), which also can function as a chlorinase (912). Fluorinase has been isolated and characterized, and the gene has been cloned (916). Both 5 -fluoro-5 -deoxyadenosine (847) and 5 -fluoro-5 -deoxy-D-ribose-l-phosphate (848) have been identified as intermediates (905-908). Fluoroacetaldehyde (850) is the immediate precursor, presumably via fluororibulose-1-phosphate (849) (915), to both fluoroacetate and 4-fluorothreonine (837) (901). The requisite enzymes fluoroacetaldehyde dehydrogenase (902) and L-threonine transaldolase-PLP (903) have been isolated and purified. The steps from 848 to 850 remain to be established but are based on known biochemistry. The pronounced toxicity of fluoroacetic acid... 

Moss SJ, Murphy CD, Hamilton JTG, McRoberts WC, O Hagan D, Schaffrath C, Harper DB (2000) Fluoroacetaldehyde A Precursor of Both Fluoroacetate and 4-Fluorothreonine in Streptomyces cattleya. Chem Commun 2281... 

Murphy CD, Moss SJ, O Hagan D (2001) Isolation of an Aldehyde Dehydrogenase Involved in the Oxidation of Fluoroacetaldehyde to Fluoroacetate in Streptomyces cattleya. Appl Environ Microbiol 67 4919... 

Zinc(II) chloride is also the best Lewis acid for the cycloaddition of hemiacetal 3. a di-fluoroacetaldehyde equivalent, with siloxydienes. Only one regioisomer 4 is obtained, in agreement with the prediction from orbital coelTicients. ... 

Stabilization of the lithium enolate by intramolecular chelation with fluorine of the C—F bond has been demonstrated by calculation. The (Z)-enolate (49) of fluoroacetaldehyde is more stable than the (E)-enolate (50) [24]. Likewise, the double fluorine-chelated (Z)-enolate (51) of 4,4,4-trifluorobutanal is the most stable among the lithium enolates (51-54) [25] (see Table 3.4). 

Lower levels of asymmetric induction are typically seen in the cycloadditions of ketenes with imines bearing chiral substituents on the nitrogen, although in exceptional cases excellent results are obtained. Cycloaddition of imine 23 (X = F), obtained from fluoroacetaldehyde and 1-phenylethylamine with phthalimidoketene, gives a 59% yield of m-/Mactam 24 in 81 19 d.r.68. Imine 23 (X = Cl) gives a 74% yield of cw-/f-lactam 24 in 90 10 d.r.69. 

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