Synthesis of O-phosphorylated 1-substituted 2,2,2-trifluoroethanols, serine hydrolase inhibitors

Article abstract of DOI:10.1007/s11172-010-0050-2

Reactivity of trifluoromethyl carbonyl compounds in a two-step reaction with dialkyl phosphites (the Abramov reaction and phosphonate-phosphate rearrangement) has been studied and the scope of this reaction for the preparation of O-phosphorylated 1-substi

Full text of DOI:10.1007/s11172-010-0050-2

Russian Chemical Bulletin, International Edition, Vol. 59, No. 1, pp. 102—106, January, 2010
102
Synthesis of Oꢀphosphorylated 1ꢀsubstituted 2,2,2ꢀtrifluoroethanols,
serine hydrolase inhibitors
A. Yu. Aksinenko, V. B. Sokolov, T. V. Goreva, and G. F. Makhaeva
Institute of Physiologically Active Compounds, Russian Academy of Sciences,
1 Severnyi proezd, 142432 Chernogolovka, Moscow Region, Russian Federation.
Fax: +7 (496) 524 9508. Eꢀmail: alaks@ipac.ac.ru
Reactivity of trifluoromethyl carbonyl compounds in a twoꢀstep reaction with dialkyl phosꢀ
phites (the Abramov reaction and phosphonate—phosphate rearrangement) has been studied and
the scope of this reaction for the preparation of Oꢀphosphorylated 1ꢀsubstituted 2,2,2ꢀtrifluoroꢀ
ethanols, serine hydrolase inhibitors, has been determined.
Key words: dialkyl phosphites, trifluoroacetone, trifluoroacetophenone, hexafluoroacetone,
methyl 3,3,3ꢀtrifluoropyruvate, 1ꢀhydroxyphosphonates, O,OꢀdialkylꢀOꢀ(2,2,2ꢀtrifluoroꢀ1ꢀpheꢀ
nylethyl) phosphates, methyl 2ꢀ(dialkoxyphosphoryl)oxyꢀ3,3,3ꢀtrifluoropropionates, the Abraꢀ
mov reaction, phosphonateꢀphosphate rearrangement.
OꢀPhosphorylated phenols and alcohols containing
We studied the reactions of dialkyl phosphites 1a—j
with trifluoroacetone 2a, trifluoroacetophenone 2b, hexafluoꢀ
roacetone 2c, and methyl trifluoropyruvate 2d (Scheme 1).
electronꢀwithdrawing substituents in the aryl and alkoxy
parts of the molecule are of undoubted interest for the
practical use in agrochemistry and medicine. Parathion,
mercaptophos,1 dichlophos,2 armin3 can serve as examꢀ
ples. Physiological effect of this type of compounds is first
of all determined by their ability to inhibit serine esterases
and considerably depends on the structure of alkoxy leavꢀ
ing group. Thus, it is obvious that a general approach to
the molecular design of this type of esterase inhibitors conꢀ
sists in the variations of substituents in the leaving group.
Earlier, we have obtained the data on selective inhibiꢀ
tory activity of methyl 2ꢀ(dialkoxyphosphoryl)oxyꢀ3,3,3ꢀ
trifluoropropionates4 (their synthesis has not been deꢀ
scribed so far) and O,Oꢀdialkyl Oꢀ(1ꢀtrifluoromethylꢀ
2,2,2ꢀtrifluoroethyl) phosphates,5 possessing low acute
toxicity with respect to four serine esterases, viz., acetylꢀ
cholinesterase, butyrylcholinesterase, carboxylesterase,
and neurotoxic esterase.
The purpose of this research is the development of
a convenient preparative method for the synthesis of
Oꢀphosphorylated 1ꢀsubstituted 2,2,2ꢀtrifluoroethanols,
serine hydrolase inhibitors, based on the Abramov reacꢀ
tion of dialkyl phosphites with trifluoromethyl carbonyl
compounds and phosphonateꢀphosphate rearrangement,
as well as the study of the scope of the latter reaction.
Synthesis of some representatives of polyfluoroalkyl phosꢀ
phates by the reaction of dialkyl phosphorochloridates with
fluorinated alcohols6,7 and by the reaction of dialkyl phosꢀ
phites and polyhalogeno ketones with subsequent phosꢀ
phonate—phosphate rearrangement is documented.6,8,9
Under mild conditions,8,9 the latter reaction led to a mixꢀ
ture of phosphonates and phosphates.
Scheme 1
1: R = Me (a), Et (b), Pr (c), Pri (d), Bu (e), Bui (f), Bus (g),
nꢀC5H11 (h), iꢀC5H11 (i), nꢀC6H13 (j);
2: R´ = Me (a), Ph (b), CF3 (c), C(O)OMe (d);
3: R = Me; R´ = Me (a), Ph (b), CF3 (c), C(O)OMe (d);
4: R´ = Ph; R = Me (a), Et (b), Pr (c), Pri (d), Bu (e), Bui (f),
Bus (g), nꢀC5H11 (h), iꢀC5H11 (i), nꢀC6H13 (j);
5: R´ = CF3; R = Me (a), Et (b);
6: R´ = C(O)COMe; R = Me (a), Et (b), Pr (c), Pri (d), Bu (e),
Bui (f), Bus (g), nꢀC5H11 (h), iꢀC5H11 (i), nꢀC6H13 (j)
Compounds studied as the trifluoromethyl carbonꢀ
yl components in the transformations under considerꢀ
ation differ in their electrophilic properties, which deꢀ
termined their behavior in the reactions with dialkyl
phosphites.
The less electrophilic of trifluoromethyl ketones studꢀ
ied, trifluoroacetone (2a) and trifluoroacetophenone (2b),
are phosphorylated with dimethyl phosphite only in the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 103—106, January, 2010.
1066ꢀ5285/10/5901ꢀ0102 © 2010 Springer Science+Business Media, Inc.

Phosphorylated trifluoroethanols
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
103
presence of Et3N as a catalyst, which leads to phosphoꢀ
nates 3a and 3b (it should be noted that, according to
the 31P NMR spectral data of the reaction mixture, no
Cꢀphosphorylated products are formed upon prolonged
(20 h) reflux of an equimolar mixture of reactants in toluꢀ
ene if the base is absent). A possibility of the phosphonateꢀ
phosphate rearrangement is determined by electronꢀwithꢀ
drawing properties of a substituent on the carbon atom in
the αꢀposition. Thus no phosphonate—phosphate rearꢀ
rangement product 3a, i.e., the corresponding phosphate,
has been detected by us after prolonged (10 h) reflux
of phosphonate 3a either in toluene with Et3N or in DMF
in the presence of CsF. Unlike 3a, the Cꢀphosphorylaꢀ
tion product of trifluoroacetophenone 3b upon reflux
for 3 h in toluene in the presence of Et3N in catalytic
amounts was converted to phosphate 4a, which was isoꢀ
lated in 69% yield (isolation by chromatography yielded
88% of 4a).8
In contrast to trifluoroacetone (2a) and trifluoroaceꢀ
tophenone (2b), hexafluoroacetone (2c) and methyl trifluꢀ
oropyruvate (2d) react exothermically with dimethyl phosꢀ
phite (1a) in the absence of basic catalysis to form a mixꢀ
ture of phosphonate 3c and phosphate 5a (1 : 4) (in Ref. 9,
this ratio was found to be 6 : 94) and phosphonate 3d and
phosphate 6a (1 : 3), respectively. The ratio of products
was determined based on the 31P NMR spectra of the
reaction mixtures. The signals in the 31P NMR spectra of
compounds studied (the Abramov reaction and subsequent
phosphonate—phosphate rearrangement) allowed broadꢀ
ening the synthetic scope of the method under considerꢀ
ation for the preparation of Oꢀphosphorylated 1ꢀsubstiꢀ
tuted 2,2ꢀtrifluoroethanols, which is determined by elecꢀ
tronꢀwithdrawing properties of the αꢀsubstituent in
the trifluoromethyl carbonyl component and, first of all,
by the possibility of the phosphonate—phosphate rearranꢀ
gement of the Abramov reaction product, i.e., phosꢀ
phonate. The presence of an electronꢀwithdrawing subꢀ
stituent on the αꢀC atom of trifluoromethyl ketones is
a decisive prerequisite for the phosphonate—phosphate reꢀ
arrangement.
Experimental
1
H, 19F, 13C, and 31P NMR spectra were recorded on
a Bruker DXP 200 spectrometer (200.13, 188.29, 50.32, and
81.01 MHz, respectively) with tetramethylsilane as an internal
standard, and CF3COOH and 85% aqueous H3PO4 as external
standards.
O,OꢀDimethyl 2,2,2ꢀtrifluoroꢀ1ꢀhydroxyꢀ1ꢀmethylethylꢀ
phosphonate (3a). A solution of trifluoroacetone (2a) (5.0 g,
44.6 mmol), dimethyl phosphite (1a) (4.5 g, 40.9 mmol), and
triethylamine (0.2 g) in benzene (20 mL) was kept for 1 day in
a sealed tube at room temperature, benzene was evaporated, and
the residue was fractionally distilled to yield phosphonate 3a
(4.2 g, 45%), b.p. 90—93 °C (3 Torr), m.p. 47—49 °C.
O,OꢀDimethyl 2,2,2ꢀtrifluoroꢀ1ꢀhydroxyꢀ1ꢀphenylethylphosꢀ
phonate (3b). A solution of trifluoroacetophenone (2b) (1.0 g,
6.2 mmol), dimethyl phosphite (1a) (0.68 g, 6.2 mmol), and
triethylamine (0.2 g) in benzene (10 mL) was kept for 1 day at
room temperature, benzene was evaporated, and the residue was
recrystallized from hexane to yield phosphonate 3b (0.5 g, 30%),
m.p. 138—140 °C.
3c (δ 15.34 sept, JP,F = 3.3 Hz) and 3d (δ 16.23 q, JP,F
=
= 3.4 Hz) are in the region characteristic of phosphonates
with the corresponding spinꢀspin coupling constants
JP,F = 3.3 Hz, the signals in the spectra of 5a (δ 1.03 s) and
6a (δ 1.02 s) indicate their phosphate structure. In the
presence of Et3N, the reaction of 1a with 2c and methyl
trifluoropyruvate 2d leads (according to the 31P NMR
spectra of the reaction mixtures) to phosphates 5a and 6a
in virtually quantitative yields. Phosphates 5b and 6b—j
were obtained similarly.
Phosphates 4—6, obtained in 58—90% yields, are colꢀ
orless light liquids, their composition and structures are
established based on data from elemental analysis and 1H,
19F, and 31P NMR spectra. Thus the 31P NMR spectra
exhibit signals in the region δ from –3 to 2, which confirm
the phosphate nature of compounds 4—6.
The inhibitory activity of phosphates 4—6 with respect
to serine esterases enhances with the increase in the elecꢀ
tronꢀwithdrawing properties of αꢀsubstituents in trifluoroꢀ
ethoxy leaving group in the order 4 < 5 < 6; these data will
be published elsewhere. The data from biochemical studꢀ
ies of phosphates 4—6 are in good enough agreement with
the known concepts,10 including those published by us
earlier4,5,11,12 on the optimization of the leaving group
structure in the molecules of organophosphorus serine esꢀ
terase inhibitors.
The yields, boiling points, and spectral characteristics of
phosphonates 3a,b are given in Tables 1 and 2.
O,OꢀDimethyl Oꢀ(2,2,2ꢀtrifluoroꢀ1ꢀphenylethyl) phosphate
(4a). A solution of trifluoroacetophenone (2b) (2 g, 11.5 mmol),
dimethyl phosphite (1a) (1.3 g, 11.8 mmol), and triethylamine
(0.2 g) in toluene (10 mL) was refluxed for 3 h, toluene was
evaporated, the residue was fractionally distilled to yield phosꢀ
phate 4a (2.3 g, 69%). 13C NMR (CDCl3), δ: 55.00 (d, MeO,
JC,P = 5.8 Hz); 55.79 (d, MeO, JC,P = 5.8 Hz); 76.68 (dq, CCF3,
JC,P = 4.3 Hz, JC,F = 33.9 Hz), 123.31 (dq, CF3, JC,F = 280.6 Hz,
JC,P = 9.7 Hz); 128.27 (q, oꢀPh, JC,F = 1.0 Hz); 129.11 (s, mꢀPh);
130.63 (s, pꢀPh); 131.55 (m, ipsoꢀPh).
O,OꢀDialkyl Oꢀ(2,2,2ꢀtrifluoroꢀ1ꢀphenylethyl) phosphaꢀ
tes (4b—j) were obtained similarly to phosphate 4a from dialꢀ
kyl phosphites 1b—j (10.5 mmol), trifluoroacetophenone 2b
(10.5 mmol), and Et3N (0.2 g). The yields, boiling points,
and spectral characteristics of phosphates 4a—j are given in Taꢀ
bles 1 and 2.
O,OꢀDimethyl Oꢀ(1,1,1,3,3,3ꢀhexafluoropropanꢀ2ꢀyl) phosꢀ
phate (5a). A solution of dimethyl phosphite (1a) (3.0 g, 27.3 mmol),
hexafluoroacetone (2c) (5.5 g, 33.1 mmol), and Et3N (0.2 g) in
THF (10 mL) was kept for 1 day in a sealed tube at room temperꢀ
ature, the solvent was evaporated, and the residue was fractionꢀ
ally distilled to obtain phosphate 5a (6.0 g, 80%).
In conclusion, the synthetic potential of the twoꢀstep
reaction of phosphites with αꢀtrifluoromethyl carbonyl

104
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
Aksinenko et al.
Table 1. Yields, boiling points, and elemental analysis data of compounds 3a,b, 4a—j, 5a,b, and 6a—j
Comꢀ Yield
B.p./°C
(p/Torr)
Found
Calculated
Molecular
formula
Comꢀ Yield
B.p./°C
(p/Torr)
Found
Calculated
Molecular
formula
(%)
P
(%)
P
poꢀ
und
(%)
poꢀ
und
(%)
C
H
C
H
3a
3b
4a
4b
4c
4d
4e
4f
45 090—92 (3)
092 (3)
30 00000—
27.07 4.79 13.97 C5H10F3O4P
27.04 4.54 13.95
42.43 4.33 11.06 C10H12F3O4P
42.27 4.26 10.90
42.34 4.23 11.19 C10H12F3O4P
42.27 4.26 10.90
5a
5b
6a
6b
6c
6d
6e
6f
80 053—54 (3)
21.63 2.59 10.92 C5H7F6O4P
27.61 3.87 10.25 C7H11F6O4P
059—60 (8)6 21.75 2.56 11.22
88 063—65 (5)
65 077—78 (1)
82 088—89 (1)
77 090—91 (1)
79 088—90 (1)
071—72 (10)6 27.65 3.65 10.18
69 097—98 (3)
27.23 4.59 11.42 C6H10F3O6P
27.08 3.79 11.64
32.44 4.89 9.71 C8H14F3O6P
32.66 4.80 9.83
37.38 5.74 9.78 C10H18F3O6P
37.28 5.63 9.61
37.48 5.81 9.52 C10H18F3O6P
37.28 5.63 9.61
62 105—107 (3) 50.12 5.02 9.49 C12H16F3O4P
49.86 5.17 9.92
58 122—124 (3) 49.69 5.55 9.32 C14H20F3O4P
49.67 5.52 9.10
88 103—106 (3) 52.30 5.56 9.42 C14H20F3O4P
52.17 5.92 9.10
90 123—125 (4) 45.83 6.56 8.45 C16H24F3O4P
81 120—122 (1) 41.19 6.51 8.55 C12H22F3O6P
41.15 6.33 8.84
76 120—122 (1) 41.31 6.57 8.65 C12H22F3O6P
41.15 6.33 8.84
(95)8
45.87 6.67 8.49
89 124—126 (5) 45.77 6.46 8.35 C16H24F3O4P
45.87 6.67 8.49
4g
4h
4i
89 124—128 (5) 46.02 6.51 8.73 C16H24F3O4P
45.87 6.67 8.49
64 152—155 (6) 54.42 7.32 7.73 C18H28F3O4P
54.54 7.12 7.81
59 152—153 (3) 54.32 7.41 7.86 C18H28F3O4P
54.54 7.12 7.81
6g
6h
6i
82 124—126 (1) 41.28 6.17 8.96 C12H22F3O6P
41.15 6.33 8.84
85 135—140 (1) 44.41 6.83 8.12 C14H26F3O6P
44.45 6.93 8.19
78 120—126 (1) 44.23 6.74 8.02 C14H26F3O6P
44.45 6.93 8.19
4j
50 150—154 (5) 56.93 4.88 8.14 C20H32F3O4P
56.80 4.77 8.28
6j
71 148—149 (1) 47.54 7.83 7.41 C16H30F3O6P
47.29 7.44 7.62
Table 2. 1H, 19F, and 31P NMR spectra of compounds 3a,b, 4a—j, 5a,b, and 6a—j in DMSOꢀd6
Comꢀ
pound
NMR, δ (J/Hz)
1H
19F
{
31P}
3a
3b
4a
4b
4c
1.64 (d, 3 H, MeC, JH,P = 14.7); 3.87 (d, 3 H, MeO, JH,P = 5.7);
3.93 (d, 3 H, MeO, JH,P = 5.7); 5.39 (s, 1 H, OH)
0.41 (d,
JF,P = 3.3)
18.15 (q,
JP,F = 3.4)
3.59 (d, 3 H, MeO, JH,P = 10.5); 3.80 (d, 3 H, MeO, JH,P = 10.5);
5.28 (d,
JF,P = 3.7)
17.44 (q,
JP,F = 3.9)
7.38 (m, 3 H, CHAr); 7.77 (m, 2 H, CHAr
3.60 (d, 3 H, MeO, JH,P = 11.4); 3.82 (d, 3 H, MeO, JH,P = 11.4);
5.64 (dq, 1 H, JH,F = 6.3, JH,P = 10.0); 7.40—7.60 (m, 5 H, CHAr
1.17 (t, 3 H, Me, JH,H = 7.0); 1.34 (t, 3 H, Me, JH,H = 7.0); 3.94 (m, 2 H, CH2);
4.16 (m, 2 H, CH2); 5.63 (m, 1 H, CHO); 7.40—7.60 (m, 5 H, CHAr
)
0.45 (d,
JF,H = 6.7)
1.59 s
)
0.51 (d,
JF,H = 6.7)
–0.88 s
–0.56 s
)
0.82 (t, 3 H, JH,H = 7.0); 0.96 (t, 3 H, JH,H = 7.0); 1.54 (m, 2 H, CH2);
0.52 (d,
1.71 (m, 2 H, CH2); 3.82 (m, 2 H, CH2O); 4.06 (m, 2 H, CH2O);
JF,H = 6.7)
5.63 (m, 1 H, CHO); 7.40—7.60 (m, 5 H, CHAr
)
4d
4e
4f
1.07, 1.18 (both d, 3 H each, Me, JH,H = 6.5);
1.30, 1.37 (both d, 3 H each, Me, JH,H = 6.0); 4.36 (m, 1 H, CHCO);
4.62 (m, 1 H, CHCO); 5.73 (m, 1 H, CHO); 7.40—7.60 (m, 5 H, CHAr);
0.89 (d,
JF,H = 6.2)
–0.54 s
–0.54 s
0.85, 0.95 (both t, 3 H each, Me, JH,H = 7.0); 1.25, 1.66 (both m, 2 H each, СН2);
1.46 (m, 4 H, СН2); 3.86, 4.10 (both m, 2 H each, CH2O); 5.63 (m, 1 H, CHO);
0.53 (d,
JF,H = 6.7)
7.40—7.60 (m, 5 H, CHAr
)
0.82, 0.98 (both dm, 6 H each, Me, JH,H = 6.7); 1.75, 1.97 (both m, 1 H each, CH);
0.89 (d,
–0.54 s
3.56, 3.81 (both m, 2 H each, CH2O); 5.75 (m, 1 H, CHO), 7.40—7.60 (m, 5 H, CHAr
)
JF,H = 7.2)
(to be continued)

Phosphorylated trifluoroethanols
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
105
Table 2 (contunued)
Comꢀ
pound
NMR, δ (J/Hz)
1H
19F
{
31P}
4g
0.76, 0.97 (both t, 1.5 H each, Me); 1.09 (m, 6 H, CH2);
1.26 (m, 2 H, CH2); 1.41 (m, 4 H, CH); 1.72 (m, 2 H);
4.23, 4.49 (both m, 1 H each, CHOBu);
0.91 (d,
JF,H = 7.2);
0.97 (d,
–1.58;
–1.43;
–1.37;
5.79 (m, 1 H, CHO), 7.40—7.60 (m, 5 H, CHAr
)
JF,H = 6.5)
–1.19 all s
4h
4i
0.82, 0.93 (both t, 3 H each, Me, JH,H = 7.0); 1.24, 1.37 (both m, 4 H each, CH2);
1.51 (m, 2 H, CH2); 1.68 (m, 2 H, CH2); 3.86, 4.09 (both m, 2 H each, CH2O);
0.54 (d,
JF,H = 6.7)
–0.56 s
5.63 (m, 1 H, CHO); 7.40—7.60 (m, 5 H, CHAr
)
0.84, 0.98 (both d, 3 H each, Me, JH,H = 6.4); 1.37 (m, 2 H, CH2); 1.57 (m, 3 H);
0.87 (d,
–0.36 s
1.77 (m, 1 H); 3.82, 4.07 (both m, 2 H each, CH2O);
JF,H = 6.7)
5.77 (m, 1 H, CHO); 7.40—7.60 (m, 5 H, CHAr
)
4j
0.93 (m, 6 H); 1.10—1.5 (m, 16 H); 1.66 (m, 2 H); 3.78, 4.02 (both m,
0.89 (d,
JF,H = 6.7)
–0.42 s
1.03 s
2 H each, CH2O); 5.75 (m, 1 H, CHO); 7.40—7.60 (m, 5 H, CHAr
)
5aa
5ba
6ab
6ba
6cb
6db
6e
3.88 (d, 6 H, MeO, JH,P = 11.6);
5.20 (dsept, 1 H, OH, JH,P = JH,F = 6.0)
3.68 (d,
JF,H = 6.0)
1.40 (t, 6 H, Me, JH,H = 7.2); 4.22 (m, 4 H, CH2O);
5.20 (dsept, 1 H, OH, JH,P = JH,F = 6.0)
3.70 (d,
JF,H = 6.0)
–1.23 s
1.02 s
3.93, 3.96 (both d, 3 H each, MeOP, J = 7.0);
3.98 (s, 3 H, MeOC(O)); 5.41 (m, 1 H, OH)
3.56 (d,
JF,H = 6.9)
1.42 (m, 6 H, Me); 3.92 c (s, 3 H, MeOC(O));
4.24 (m, 4 H, CH2O); 5.27 (m, 1 H, CHO)
2.68 (d,
JF,H = 6.9)
–2.05 s
–2.48 s
–2.89 s
–1.4 s
0.96 (t, 6 H, Me, JH,H = 7.0); 1.42 (m, 4 H, CH3CH2);
3.92 c (s, 3 H, MeOC(O)); 4.76 (m, 4 H, CH2O); 5.34 (m, 1 H, CHO)
3.65 (d,
JF,H = 6.9)
1.36 (m, 12 H, Me + CH2); 3.93 c (s, 3 H, MeOC(O));
4.76 (m, 2 H, CH2O); 5.38 (m, 1 H, CHO)
3.45 (d,
JF,H = 6.9)
0.96 (m, 6 H, Me); 1.42 (m, 4 H, CH2); 1.70 (m, 4 H, CH2);
4.02 (d,
3.90 (s, 3 H, MeOC(O)); 4.14 (m, 4 H, CH2O); 5.74 (m, 1 H, CHO)
JF,H = 6.8)
6fa
6ga
6hb
6ia
6ja
0.98 (m, 12 H, Me + CH2); 1.98 (m, 2 H, CH); 3.90 (s, 3 H, MeOC(O));
4.04 (m, 4 H, CH2O); 5.28 (m, 1 H, CHO)
2.96 (d,
JF,H = 6.9)
–2.76 s
–2.05 s
–1.05 s
–2.81 s
–1.81 s
0.96 (m, 6 H, CH3CH2); 1.28—1.48 (m, 6 H, CH3CH); 1.56—1.88 (m, 4 H, CH2);
3.96 (s, 3 H, MeOC(O)); 4.60 (m, 2 H, CH3CH); 5.38 (m, 1 H, CHO)
3.46 (d,
JF,H = 6.9)
0.96 (m, 6 H, Me); 1.44 (m, 8 H, CH2); 1.74 (m, 4 H, CH2);
3.94 (s, 3 H, MeOC(O)); 4.24 (m, 4 H, CH2O); 5.44 (m, 1 H, CHO)
3.53 (d,
JF,H = 6.9)
1.21 (m, 12 H, Me + CH2); 1.88 (m, 4 H, CH2); 2.02 (m, 2 H, CH);
4.12 (s, 3 H, MeOC(O)); 4.14 (m, 4 H, CH2); 5.42 (m, 1 H, CHO)
2.91 (d,
JF,H = 6.9)
0.96 (m, 6 H, Me); 1.44 (m, 12 H, CH2); 1.74 (m, 4 H, CH2);
2.61 (d,
3.94 (s, 3 H, MeOC(O)); 4.24 (m, 4 H, CH2O); 5.44 (m, 1 H, CHO)
JF,H = 6.9)
a In CDCl3.
b In CD3CN.
O,OꢀDiethyl Oꢀ(1,1,1,3,3,3ꢀhexafluoropropanꢀ2ꢀyl) phosꢀ
References
phate (5b) was obtained similarly to phosphate 5a from diethyl
phosphite (1b) (3.0 g, 21.7 mmol) and hexafluoroacetone (2c)
(5.5 g, 33.1 mmol) in the presence of Et3N (0.2 g).
Methyl 2ꢀ(dialkoxyphosphoryl)oxyꢀ3,3,3ꢀtrifluoropropionates
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fractionally distilled. The yields, boiling points, and spectral charꢀ
acteristics of compounds 6a—j are given in Tables 1 and 2.
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Received December 3, 2008;
in revised form June 19, 2009