Introduction of fluorine into a certain position of bioactive compound such as a pharmaceutical and an agricultural chemical may remarkably reduce the toxicity of the compound, or improve the efficiency of medicine. This is due to the mimic and blocking effect characterized by fluorine. Many compounds, such as 5-fluorouracil, have been reported as success case.
Attempts to efficiently synthesize fluorine-containing compounds are performed in many fields. Methods to introduce fluorine into a certain position through the use of fluorinating agents or the use of fluorine-containing building blocks have been reported.

Recently, triethyl 2-fluoro-2-phosphonoacetate has increasingly been utilized as a useful bifunctional fluorine-containing intermediate. This compound is very useful in the generation of physiologically active compounds because it can generate α-fluoro-α,β-unsaturated ester from the reaction with carbonyl compounds in the presence of a base. A subsequent reduction of the above ester leads to the corresponding aldehyde or alcohol. As examples, vitamin A derivatives¹⁾, pheromone of insect origin, synthesis of Pyrethroide having insecticidal efficacy, etc., can be given.

Electrophilic Fluorinating Reagents

Nucleophilic Fluorinating Reagents

Fits Reagents

Fluorinated Building Blocks

Fluorinated Bioactive Compounds

Electrophilic Fluorinating Reagents

D3812	F0346	F0328
F0344	F0334	F0343
F0327	F0342	F0358
F0335

Nucleophilic Fluorinating Reagents

D1868	D2831	B2440
M1573	T1295	T1909
T1592	T1635	T1037
T1125	T1338	T1339
T2027	T2026	T2022

Fits Reagents

P1081	P1080	P1659
P1082

Fluorinated Building Blocks

Aliphatic Compounds

F0518	D2525	D2524
T1570	T2638	T2547
T0435	M1193	T1516
T1604	T1512	B1801
B3498	C2381	C0990
C1503	F0283	D2523
D1423	E0663	D2782
E0547	T0810	B1463
B1673	C1458	C1467
D2530	D2498	F0030
T0432	F0341	H0598
T1245	C1586	F0311
C0991	F0340	T0791
T0433

F0518	(1-Fluorovinyl)methyldiphenylsilane
D2525	(R)-N-(2,2-Difluoroethylidene)-1-phenylethylamine
D2524	(S)-N-(2,2-Difluoroethylidene)-1-phenylethylamine
T1570	(Trifluoromethyl)trimethylsilane [Trifluoromethylating Reagent]
T2638	2,2,2-Trifluoro-N-(4-methoxyphenyl)acetimidoyl Chloride
T2547	2,2,2-Trifluoro-N-phenylacetimidoyl Chloride
T0435	2,2,2-Trifluoroethanol
M1193	2,2,2-Trifluoroethyl Methanesulfonate
T1516	2,2,2-Trifluoroethyl p-Toluenesulfonate
T1604	2,2,2-Trifluoroethyl Trifluoromethanesulfonate
T1512	2-(Trifluoromethyl)acrylic Acid
B1801	2-Bromo-3,3,3-trifluoro-1-propene (stabilized with Copper chip)
B3498	2-Bromo-4-fluorobenzaldehyde
C2381	2-Chloro-5-fluorobenzaldehyde
C0990	Chlorodifluoroacetic Acid
C1503	Chlorodifluoroacetic Anhydride
F0283	Diethyl Fluoromalonate
D2523	Difluoroacetaldehyde Ethyl Hemiacetal
D1423	Difluoroacetic Acid
E0663	Ethyl 2-Fluoropropionate
D2782	Ethyl 3-(Dimethylamino)-3-ethoxy-2,2-difluoropropionate
E0547	Ethyl 3-Ethoxy-2,2-difluoro-3-hydroxypropionate
T0810	Ethyl 4,4,4-Trifluoroacetoacetate
B1463	Ethyl Bromodifluoroacetate
B1673	Ethyl Bromofluoroacetate
C1458	Ethyl Chlorodifluoroacetate
C1467	Ethyl Chlorofluoroacetate
D2530	Ethyl Dibromofluoroacetate
D2498	Ethyl Difluoroacetate
F0030	Ethyl Fluoroacetate
T0432	Ethyl Trifluoroacetate
F0341	Fluoromethyl Phenyl Sulfone
H0598	Ishikawa's Reagent [Fluorinating Reagent]
T1245	Methyl 4,4,4-Trifluoroacetoacetate
C1586	Methyl Chlorodifluoroacetate
F0311	Methyl Fluorosulfonyldifluoroacetate
C0991	Sodium Chlorodifluoroacetate
F0340	Triethyl 2-Fluoro-2-phosphonoacetate
T0791	Trifluoroacetaldehyde Ethyl Hemiacetal (contains ca. 10% Ethanol)
T0433	Trifluoroacetic Anhydride

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Heterocyclic Compounds

B3177	B3178	D3614
D3615	D3642	T1778
D3374	D2610	D1741
A1664	A1993	B2799
C2270	E0684	F0533
F0579	F0523	F0647
F0656	F0180	F0693
F0575	F0217	T2342
T2061	D3317	B3244
C1549	F0207	A1546
A2125	F0556	F0628
B2705	C2113	C1666
F0547	F0316	F0420
F0038	F0534	F0369
F0589	F0382	C2221
F0300	F0520	F0581
F0352	F0519	F0555
F0551

B3177	(2S,4R)-1-(tert-Butoxycarbonyl)-4-fluoro-2-pyrrolidinecarboxylic Acid
B3178	(2S,4S)-1-(tert-Butoxycarbonyl)-4-fluoro-2-pyrrolidinecarboxylic Acid
D3614	2'-Deoxy-2'-fluorocytidine Hydrate
D3615	2'-Deoxy-2'-fluorouridine
D3642	2'-Deoxy-5-fluorocytidine
T1778	2,3,5,6-Tetrafluoropyridine
D3374	2,4-Dichloro-5-fluoropyrimidine
D2610	2,6-Dichloro-5-fluoronicotinic Acid
D1741	2,6-Difluoropyridine
A1664	2-Amino-5-fluoropyridine
A1993	2-Amino-6-fluorobenzothiazole
B2799	2-Bromo-5-fluoropyridine
C2270	2-Chloro-5-fluoropyridine
E0684	2-Ethoxy-5-fluoro-4-pyrimidinone
F0533	2-Fluoro-3-picoline
F0579	2-Fluoro-4-picoline
F0523	2-Fluoro-5-iodopyridine
F0647	2-Fluoroadenine
F0656	2-Fluoroadenosine
F0180	2-Fluorobenzothiazole
F0693	2-Fluoroisonicotinic Acid
F0575	2-Fluoronicotinic Acid
F0217	2-Fluoropyridine
T2342	3,3,4,4-Tetrafluoropyrrolidine Hydrochloride
T2061	3,5,6-Trifluoro-2-hydroxypyridine
D3317	3,5-Dichloro-2-fluoropyridine
B3244	3-Bromo-5-fluoropyridine
C1549	3-Chloro-2,4,5,6-tetrafluoropyridine
F0207	3-Fluoropyridine
A1546	4-Amino-2,3,5,6-tetrafluoropyridine
A2125	4-Amino-5-fluoro-2-methoxypyrimidine
F0556	4-Fluoroindole
F0628	4-Fluoropyridine Hydrochloride
B2705	5-Bromo-2-fluoropyridine
C2113	5-Chloro-2,3-difluoropyridine
C1666	5-Chloro-2,4,6-trifluoropyrimidine
F0547	5-Fluoro-2-methoxy-4-pyrimidinone
F0316	5-Fluoro-2-methylbenzothiazole
F0420	5-Fluoro-2-methylbenzoxazole
F0038	5-Fluoro-8-quinolinol
F0534	5-Fluorocytidine
F0369	5-Fluoroindole
F0589	5-Fluoroisatin
F0382	5-Fluoroorotic Acid Monohydrate
C2221	6-Chloro-2-fluoropurine
F0300	6-Fluoro-2-methylquinoline
F0520	6-Fluoro-2-picoline
F0581	6-Fluoro-3-picoline
F0352	6-Fluoroindole
F0519	7-Fluoro-2-methylquinoline
F0555	7-Fluoroindole
F0551	7-Fluoroisatin

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Fluorinated Bioactive Compounds

D3773	D2235	D3579
F0635	F0321	F0151
F0636	B1837	B3165
C2227	D1961	E0762
E0786	F0646	F0437
F0691	F0371	F0525
L0193	L0216	T2506
T2303	T2511

D3773	1,1-Dimethyl-3-[3-(trifluoromethyl)phenyl]urea
D2235	2'-Deoxy-5-fluorouridine
D3579	5'-Deoxy-5-fluorouridine
F0635	5-Fluoro-1-(tetrahydro-2-furfuryl)uracil
F0321	5-Fluorocytosine
F0151	5-Fluorouracil
F0636	5-Fluorouridine
B1837	Betamethasone
B3165	Betamethasone 21-Acetate
C2227	Ciprofloxacin Hydrochloride Monohydrate
D1961	Dexamethasone
E0762	Enoxacin Sesquihydrate
E0786	Enrofloxacin
F0646	Fleroxacin
F0437	Flunisolide
F0691	Fluoromethyl 1,1,1,3,3,3-Hexafluoroisopropyl Ether
F0371	Flurbiprofen
F0525	Fluticasone Propionate
L0193	Levofloxacin
L0216	Lomefloxacin Hydrochloride
T2506	Tosufloxacin p-Toluenesulfonate Hydrate
T2303	Triamcinolone
T2511	Trifluorothymidine

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Literature

1) Synthesis of fluorinated retinoic acids and their analogs
R. S. H. Liu, H. Matsumoto, A. E. Asato, M. Denny, Y. Shichida, T. Yoshizawa, F. W. Dahlquist, J. Am. Chem. Soc., 1981, 103, 7195 [DOI]; A. J. Lovey, B. A. Pawson, J. Med. Chem., 1982, 25, 71 [DOI].
2) Triethyl 2-Fluoro-2-phosphonoacetate
M. Kikuchi, T. Onozawa, Yuki Gosei Kagaku Kyokaishi (J. Synth. Org. Chem., Jpn), 1997, 55, 88.