4- Fluorobenzaldehyde

There were two potential starting materials for Trost s Mo chemistry (Scheme 2.7). The first approach utilized the commercially available 3-fluorocinnamic acid (4). However, reduction of 4 did not proceed well with various reducing agents and provided the desired allylic alcohol 28 in only mediocre yield. Alternatively, 3-fluorobenzaldehyde (29) was used as the starting material. Vinyl Grignard addi-... 

Toluene (60 L) and 3-fluorobenzaldehyde (31.2 mole) were mixed, cooled to —5°C and 1.6 M vinylmagnesium bromide (32.8 mol) added over 90 minutes while maintaining the temperature below 0°C. The reaction was stirred one hour and methyl chloroformate (35.4 mol) added over 30 minutes while keeping the temperature below 0 °C. After 1 hour 40 L 0.5 M HCl was added at such a rate the temperature exceeded 20 °C, the organic layer separated, filtered through silica gel, concentrated, to obtain 56.7% of the product. H-NMR data supplied. 

Acetic anhydride is added to 3-fluorobenzaldehyde, N-acetyl glycine, and anhydrous sodium acetate in ethyl acetate. The reaction mixture is heated to 80 °C. After completion of the reaction, the mixture is cooled, water is added, and the resultant precipitate is filtered and washed. The crude azlactone intermediate is then treated with aqueous sodium hydroxide followed by acidification. The resultant precipitate is filtered, washed, and dried to provide the N-acetyl dehydro-3-fluorophenylalanine in 70% yield from the aldehyde on a 50 kg scale. 

The McMurry35 uses low-valent titanium to couple two carbonyl groups together and works very well when the two compounds are the same the symmetrical stilbene -174 can be made in 95% yield and in almost perfect (99.92 0.04 E Z) -selectivity from 3-fluorobenzaldehyde 173. The low-valent titanium is produced by reduction of Ti(III) with lithium metal.36... 

The highly stereospecific inter-proton /(H3,CHO) coupling in benzaldehyde derivatives was found to be perturbed by the intramolecular hydrogen bond in salicylaldehyde, reducing such couphng about 25%. Similarly, the fluorine-proton coupling J(F3,CHO) in 3-fluorosalicylaldehyde is decreased about 50% from the corresponding value in 3-fluorobenzaldehyde. ... 

Fluorobenzaldehyde 4-Fluorobenzaldehyde Fluorobenzene 4-Fluorobenzeneaceticacid 2-Fluorobenzeneacetonitrile 4-Fluorobenzeneacetonitrile 4-Fluorobenzenemeihanamine 4-Fluorobenzenemelhanol 4-Fluorobenzenesulfonyl chloride 2-Fluorobenzoicacid... 

---