4-fluorophenyl groups

The T-conformation had two prevalent conformers 88 and 89 where the steric bulk of the 4-fluorophenyl group blocks the P-face of the oxonium ions (Scheme 7.27). Reduction occurs from the less hindered a-face on each conformer leading to the diastereomeric mixture of products. Since there was only a O kcalmoT1 energy difference in these lowest energy conformers 88 and 89, this nicely supported the observed product distribution of approximately 3 1 of 18 19 under the best reaction conditions. 

Since the introduction of fluoxetine (3) in 1987, a series of selective serotonin reuptake inhibitors (SSRIs) have been discovered that have seen broad application in many facets of mood disorders. These compounds include fluvoxamine (4) which contains a trifluoromethyl group and paroxetine (5) and citalopram (6) which contain 4-fluorophenyl groups [5,6]. 

Other non-covalent interactions such as C=0 F-C type, between a fluorine atom and the carbonyl of an amino acid, may take place for the stabilisation of enzyme-inhibitor supramolecular structures [28,30]. It is why the 4-fluorophenyl group is an important motif for binding pocket, as shown by the enhancement of one order of magnitude of the K by introducing one fluorine atom on thrombin inhibitor (Fig. 5) [30],... 

Moderate to good enantioselectivities were obtained for nearly all examples, but the products from 83a-c could be recrystallized to higher enantiomeric purity. Addition of iodine was critical for catalysis as was the use of a ligand with electron-poor para-fluorophenyl groups on the phosphorous atom. Substitution at the 3 position of the pyridine ring was described as being difficult for both the quinolines and pyridine systems. The resulting hydrazine derivatives could be easily converted to piperdines by reduction with Raney nickel or under Birch conditions. 

Protox herbicides. A number of Protox herbicides share a 2-fluorophenyl group. Initial investigations into an alternative synthesis of 2-fluoro-4-chlorophenyl triazolinones resulted in the very promising use of newer fluorinating reagents. The actual synthesis of carfentrazone-ethyl involved the use of 2-fluoroaniline as the starting material (Fig. 35) [150],... 

Recently the p-fluorophenyl group has been used as a label to study apparent symmetry of fragmentation processes (Bursey et al., 1968 Elwood et al., 1969). 

It has been concluded from pKa measurements and fluorine NMR data on pentafluoro-biphenyl derivatives, for example C6F5C6H4CO2H, C6F5C6H4F etc., that the penta-fluorophenyl group inductively withdraws electrons more strongly than phenyl but much less strongly than trifluoromethyl, whilst pentafluorophenyl and pentachlorophenyl have a similar capacity for electron withdrawal [40],... 

Electronic Properties. Ligands with the electron-poor penta-fluorophenyl groups have good jr-acceptor properties and electronically bridge the gap between phosphites and carbon monoxide. Other diols, with or without C2-symmetry, have been used as ligand backbones. Pentafluorophenyl can also be replaced by other aromatic electron-withdrawing groups. ... 

The concept may be extended by additional coordination of weakly binding peripheral donor functions to the metal centre, as exemplified by the yttrium complex displayed in Fig. 5. The 2-fluorophenyl groups provide an "active" ligand periphery which stabilizes the highly acidic Y-center [12],... 

Substitution of fluorine for hydrogen in the initiator molecule can sometimes be a useful method of labelling. PMMA formed with />-fluorobenzoyl peroxide showed two 19 F NMR signals 10 ppm apart, which corresponded to p-fluorobenzoyloxy and p-fluorophenyl groups.74 The ratio of the amounts of these groups were close to the corresponding ratio in the case of BPO (see Section 3.1.1). 

A related though simpler compound from Bristol-Meyers Squibb 216 is their anti-psychotic agent BMS 181100. It has two p-fluorophenyl groups joined through a C4-piperazine linker containing a chiral secondary alcohol. The compound is easily made58 by alkylation of an amine with the primary chloride 217. There are two opportunities from enzymatic resolution. 

---