Diketo compounds with (trifluoromethyl)trimethylsilane: Double nucleophilic trifluoromethylation reactions

Article abstract of DOI:10.1021/jo0057304

Reactions of various diketo compounds with (trifluoromethyl)trimethylsilane (Me₃SiCF₃) in the presence of catalytic amounts of cesium fluoride have been studied. γ-Ketoesters, CH₃COCH₂CH₂CO₂R (R = Et, Bu), were reacted with 2 equiv of Me₃SiCF₃ at room temperature to give CH₃C(OH)(CF₃)CH₂CH₂ COCF₃ in good yield after hydrolysis, α-Diketones, R₁COCOR₂ (R₁ = R₂ = Ph; R₁ = Ph, R₂ = Me; R₁ = R₂ = Me, R₂ = Me, R₂ = Et), when reacted with Me₃SiCF₃, formed 1:1 or 1:2 addition products depending on the reaction conditions and stoichiometry used. Reactions of diones CH₃COXCOCH₃ (X = -CH₂CH₂-, -C₆H₄C₆H₄-, -CH₂-) with Me₃SiCF₃ also led to the formation of the mono- or diaddition products depending on reaction conditions. With various kinds of substituted arylglyoxals, 2 equiv of Me₃SiCF₃ produced monoaddition products in 70-75% yield and diaddition products in 5-10% yield. One of the monoalcohols and two of the diols have been characterized by single-crystal X-ray analysis, and the presence of inter- and intramolecular hydrogen bonding has been confirmed.

Full text of DOI:10.1021/jo0057304

1436
J . Org. Chem. 2001, 66, 1436-1440
Dik eto Com p ou n d s w ith (Tr iflu or om eth yl)tr im eth ylsila n e: Dou ble
Nu cleop h ilic Tr iflu or om eth yla tion Rea ction s†
Rajendra P. Singh, J effry M. Leitch, Brendan Twamley, and J ean’ne M. Shreeve*
Department of Chemistry, University of Idaho, Moscow, Idaho 83844-2343
jshreeve@uidaho.edu
Received November 10, 2000
Reactions of various diketo compounds with (trifluoromethyl)trimethylsilane (Me3SiCF3) in the
presence of catalytic amounts of cesium fluoride have been studied. γ-Ketoesters, CH3COCH2CH2-
CO2R (R ) Et, Bu), were reacted with 2 equiv of Me3SiCF3 at room temperature to give
CH3C(OH)(CF3)CH2CH2COCF3 in good yield after hydrolysis. R-Diketones, R1COCOR2 (R1 ) R2 )
Ph; R1 ) Ph, R2 ) Me; R1 ) R2 ) Me; R1 ) Me, R2 ) Et), when reacted with Me3SiCF3, formed 1:1
or 1:2 addition products depending on the reaction conditions and stoichiometry used. Reactions of
diones CH3COXCOCH3 (X ) -CH2CH2-, -C6H4C6H4-, -CH2-) with Me3SiCF3 also led to the
formation of the mono- or diaddition products depending on reaction conditions. With various kinds
of substituted arylglyoxals, 2 equiv of Me3SiCF3 produced monoaddition products in 70-75% yield
and diaddition products in 5-10% yield. One of the monoalcohols and two of the diols have been
characterized by single-crystal X-ray analysis, and the presence of inter- and intramolecular
hydrogen bonding has been confirmed.
In tr od u ction
relatively small size (only 2.5 times the volume of a
methyl group) lead to significant changes in the chem-
istry of substituted compounds when compared with their
nonfluorinated analogues. The influence of the trifluoro-
methyl group in biologically active molecules is often
associated with increased lipophilicity6 that this sub-
stituent imparts giving active pharmaceutical and agro-
chemical compounds with improved transport character-
istics in vivo and facilitates lower doses rates. While a
wide variety of methods have been developed for intro-
ducing trifluoromethyl groups into organic compounds,7
the utilization of (trifluoromethyl)trimethylsilane (Me3-
SiCF3) as a nucleophilic trifluoromethylating reagent is
rapidly becoming the method of choice.8 Recently we and
others have reported the reactions of keto compounds
with Me3SiCF3 in the presence of fluoride ions.8,9 How-
ever, little effort has been devoted to diketo systems.10
We became interested in the double nucleophilic trifluo-
romethylation reactions of different kinds of dicarbonyl
The trifluoromethyl group is a highly important sub-
stituent in the field of organic chemistry. The introduc-
tion of a trifluoromethyl group into an organic compound
can bring about some remarkable changes in the physi-
cal, chemical, and biological properties that result in new
compounds/materials suitable for diverse applications in
the areas of materials science, agrochemistry, and
industry.1-5 Its powerful electron-withdrawing ability and
* To whom correspondence should be addressed. Tel: 208-885-6215.
Fax: 208-885-9146.
† Presented at the 16th International Symposium on Fluorine
Chemistry, Durham, England, J uly, 2000; Abstract No. IP-88.
(1) For the general applications of organofluorine compounds, see:
Organofluorine Chemistry: Principles and Commercial Applications;
Banks, R. E., Smart, B. E., Tatlow, J . C., Eds.; Plenum: New York,
1994.
(2) For the use of organofluorine compounds in medicinal and
biomedical chemistry, see: (a) Biomedical Frontiers of Fluorine
Chemistry; Ojima, I., McCarthy, J . R., Welch, J . T., Eds.; ACS
Symposium Series 639; American Chemical Society: Washington, DC,
1996. (b) Organic Chemistry in Medicinal Chemistry and Biomedical
Applications; Filler, R., Ed.; Elsevier: Amsterdam, 1993. (c) Welch, J .
T.; Eswaraksrishnan, S. Fluorine in Bioorganic Chemistry; J ohn Wiley
and Sons: New York, 1991. (d) Filler, R.; Kirk, K. Biological Properties
of Fluorinated Compounds. In Chemistry of Organic Fluorine Com-
pounds II: A Critical Review; Hudlicky, M., Pavlath, A. E., Eds.; ACS
Monograph 187; Americal Chemical Society: Washington, DC, 1995.
(e) Elliot, A. J . Fluorinated Pharmaceuticals. In Chemistry of Organic
Fluorine Compounds II; ACS Monograph 187; Americal Chemical
Society: Washington, DC, 1995. (f) Sholoshonok, V. A., Ed. Enantio-
controlled Synthesis of Organo-Fluorine Compounds: Stereochemical
Challenge and Biomedical Targets; J ohn Wiley and Sons: 1999.
(3) For the use of of organofluorine compounds in agrosciences,
see: (a) Cartwright, D. Recent Developments in Fluorine-Containing
Agrochemicals. In Organofluorine Chemistry: Principles and Com-
mercial Applications; Banks, R. E., Smart, B. E., Tatlow, J . C., Eds.;
Plenum: New York, 1994. (b) Lang, R. W. Fluorinated Agrochemicals.
In Chemistry of Organic Fluorine Compounds II; ACS Monograph 187;
American Chemical Society: Washington, DC, 1995.
(5) For recent discussions on the controversial topic of fluorine
hydrogen bonds, see: (a) O’Hagan, D. O.; Rzepa, H. S. J . Chem. Soc.,
Chem. Commun. 1997, 645. (b) Dunitz, J . D.; Taylor, R. Eur. Chem. J .
1997, 3, 89-92. (c) Howard, J . A. K.; Hoy, V. J .; O′Hagan, D. O.; Smith,
G. T. Tetrahedron 1996, 52, 12613-12622.
(6) (a) Organofluorine Chemicals and Their Industrial Applications;
Banks, R. E., Ed.; Ellis Harwood Ltd.: Chichester, 1979. (b) Welch, J .
T. Tetrahedron 1987, 43, 3123-3197.
(7) For general discussion on the synthesis of organofluorine com-
pounds, see: (a) Olah, G. A.; Prakash, G. K. S.; Chambers, R. D.
Synthetic Fluorine Chemistry; Wiley and Sons: New York, 1992. (b)
Furin, G. G. Synthetic Aspects of the Fluorination of Organic Com-
pounds; Harward Academic Publisher: London, 1991. McClinton, M.
A.; McClinton, D. A. Tetrahedron 1992, 48, 6555-6666.
(8) (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757-
786 and references therein. (b) Singh, R. P.; Shreeve, J . M. Tetrahedron
2000, 56, 7613-7633 and references therein.
(9) (a) Singh, R. P.; Kirchmeier, R. L.; Shreeve, J . M. Org. Lett. 1999,
1, 1047-1049. (b) Singh, R. P.; Shreeve, J . M. J . Org. Chem. 2000, 65,
3241-3243.
(10) (a) Quast, H.; Becker, C.; Witzel, M.; Peters, E.-M.; Peters, K.;
von Schnering; H. G. Leibigs Ann. 1996, 985-87. (b) Ramaiah, P.;
Prakash, G. K. S. Synlett. 1991, 643-45. (c) Singh, R. P.; Kirchmeier,
R. L.; Shreeve, J . M. J . Org. Chem. 1999, 64, 2579-2581.
(4) The ability of fluorine to change the properties of organic
molecules has been discussed extensively elsewhere. For example,
see: Smart, B. E. Characteristics of C-F systems. In Organofluorine
Chemistry: Principles and Commercial Applications; Banks, R. E.,
Smart, B. E., Tatlow, J . C., Eds.; Plenum: New York, 1994.
10.1021/jo0057304 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/18/2001

Double Nucleophilic Trifluoromethylation Reactions
J . Org. Chem., Vol. 66, No. 4, 2001 1437
Sch em e 1
Sch em e 2
compounds in order to examine the effect that substitu-
ents on the carbonyl moieties had on the formation of
mono and/or diaddition products. Here we report the
cesium fluoride catalyzed trifluoromethylation reactions
of various R, â and γ diketo compounds with (trifluorom-
ethyl)trimethylsilane.
Sch em e 3
Resu lts a n d Discu ssion
On the basis of a survey of the chemical literature, it
was obvious that the routes to compounds with at least
two methylene groups geminally substituted with tri-
fluoromethyl and hydroxy moieties are difficult or are
nonexistent. Little work has been done with nucleophilic
trifluoromethylations of dicarbonyl compounds with Me3-
SiCF3.10 The reactions of aldehydes and ketones with Me3-
SiCF3 are well explored in the literature.9,10b We and
others also reported conditions where esters can be
converted directly to the corresponding trifluoromethyl
ketones.11 Earlier studies examined the reactions of
different kinds of R-ketoesters10b and R-ketoamides10c
with Me3SiCF3 in the presence of tetrabutylammonium
fluoride or cesium fluoride as fluoride ion initiator. But,
in both cases, only the R-keto group was found to be
reactive even in the presence of excess Me3SiCF3.
With γ-keto esters (1a ,b) as substrates, the reaction
with two equivalents of Me3SiCF3 (TMSCF3) proceeded
smoothly in the presence of a catalytic amount of cesium
fluoride. The corresponding double addition disilyl ether
intermediates (2a ,b) were obtained in good yields and,
when hydrolyzed with aqueous HCl, gave the expected
product 3 with concomitant formation of Me3SiOR and
Me3SiOH. (Scheme 1).
The â and γ diones where the two keto groups are
separated by one or two methylene spacers or an aro-
matic moiety were also examined. Reaction of 9g with
3.25 equiv of Me3SiCF3 in the presence of a catalytic
amount of CsF in monoglyme at room temperature gave
10g as a minor and 11g as a major product, which upon
hydrolysis gave 12g and 13g (Scheme 3). Heating the
reaction mixture to 60 °C for several hours produced 11g
exclusively which, upon hydrolysis with aqueous HCl,
yielded 13g as a colorless solid in 78% yield (Scheme 3).
The crystal and molecular structure of 13g have been
determined by single-crystal X-ray analysis as discussed
below. Reaction with 9h was essentially analogous at 60
°C with excess Me3SiCF3 to produce mainly the diaddition
product (11h ) in 90% yield which upon hydrolysis af-
forded 13h as a colorless solid in 85% yield. Reaction of
acetylacetone (9i) was also tried with excess Me3SiCF3
at 60 °C which produced a mixture of the monoaddition
product (10i) as minor, the diaddition product (11i) as
the major and also the formation of some unidentified
products (based on GCMS) (Scheme 3). The use of excess
Me3SiCF3 is necessary due to the fact that the enol form
of acetylacetone also consumes Me3SiCF3 to form CF3H.
At 60 °C the initial formation of the monoaddition
product (10i) as the major one was confirmed by GCMS.
The concentration of 10i decreases because of conversion
into the diaddition product along with some decomposi-
tion products. The diaddition product (11i) was isolated
in 30% yield after thin-layer chromatography and char-
acterized by spectroscopic analyses. Hydrolysis of 11i
with 6 N HCl in THF at 55 °C gave a trace amount of
diol (13i) along with formation of some unidentified
product.
The reactions of diones with Me3SiCF3 are very de-
pendent on the nature of the substituents vicinal to the
keto functionalities. For example, the reaction of benzil
(4c) with 2.25 equivalents of Me3SiCF3, in the presence
of a catalytic amount of cesium fluoride, gave the corre-
sponding monoaddition silyl ether intermediate (5c) in
96% which upon hydrolysis produced the diphenyl keto
8a
alcohol (7c) in 94% yield (Scheme 2). Use of more than
3 equiv of Me3SiCF3 with concomitant heating (60 °C)
gave a complex mixture. Under similar reaction condi-
tions, 4d gave a mixture of monoaddition (5d ) and
diaddition (6d ) products which upon hydrolysis yielded
7d and 8d as the final products (Scheme 2). When the
reaction mixture was heated at 60 °C for 12 h (with 3.25
equiv of Me3SiCF3 in monoglyme), the diaddition product
6d (75%) was the main product, and after hydrolysis 8d
(78%). Similarly, 4e,f reacted with excess Me3SiCF3 at
60 °C to produce 5e,f (minor) and 6e,f (major) which upon
hydrolysis yielded 7e,f (minor) and 8e,f (major).
Arylglyoxal is a system where the two carbonyl groups
are vicinal but one is ketonic and one is aldehydic. The
reaction of 14j with 2 equiv of Me3SiCF3 in the presence
of a catalytic amount of cesium fluoride at room temper-
ature produced a mixture of monoaddition and diaddition
silyl ether intermediates which upon hydrolysis with
aqueous HCl, produced the corresponding monoalcohols
(15j, major) and dialcohol (16j, minor) (Scheme 4).
(11) (a) Wiedeman, J .; Heiner, T.; Mloston, G.; Prakash, G. K. S.;
Olah, G. A. Angew. Chem., Int. Ed. Engl. 1998, 37, 820-821. (b) Singh,
R. P.; Cao, G.; Kirchmeier, R. L.; Shreeve, J . M. J . Org. Chem. 1999,
64, 2873-2876.

1438 J . Org. Chem., Vol. 66, No. 4, 2001
Singh et al.
Sch em e 4
case of benzil only the monoaddition product was achieved
whereas when one phenyl group was replaced with
methyl (1-phenyl-1,2-propanedione), the diaddition prod-
uct was the major one when an excess of Me3SiCF3 was
utilized. This difference in products may arise from a
reduction in steric hindrance for the latter. With the
â-diketone, 2,4-pentanedione, in the presence of a large
excess of Me3SiCF3, conversion to the diaddition product
occurred. This reaction appears to occur stepwise with
the preference to react once with all of the starting
material before reaction begins at the second carbonyl.
In the γ-diketone system where the link between carbonyl
groups is either - CH2CH2- or -C6H4C6H4-, the diad-
dition product is the major product for the former and
the sole product for the latter. Reactions of various
arylglyoxals with 2.5 equiv of Me3SiCF3 gave monoad-
dition at the aldehyde as the major product. Attempts to
react the arylglyoxals with a large excess of Me3SiCF3
at 60 °C in order to achieve diaddition as the major
product resulted only in a complex mixture.
Essentially similar reactivity was also observed with
14k -n . With 2 equiv of Me3SiCF3, the reactions of
14k -n yielded the corresponding silyl ether intermedi-
ates which gave 15k -n (major) and 16k -n (minor) after
hydrolysis.
X-r a y Cr ysta l Str u ctu r es of 13g, 15j, a n d 16j.
Compounds 13g, 15j, and 16j crystallized from a mixture
of pentane and ether, and their structures were con-
firmed by single-crystal X-ray analyses. Compounds 13g,
15j, and 16j crystallize in the following respective mono-
clinic space groups: P2(1)/n, P2(1)/c, and C2/c. All com-
pounds form discrete molecular units; however, in the
solid state, hydrogen bonding and weak H‚‚‚F bonding
are evident. Compound 13g is centrosymmetric with two-
half molecules in the asymmetric unit. It is a complex
three-dimensional network of hexanediol units cross-
linked via hydrogen bonding. Both hydroxyl groups of the
diol are involved in intermolecular hydrogen bonding
resulting in a “square” of O-H..O interactions (2.7578-
(19) and 2.7086(18) Å) related by symmetry. These
hydrogen-bonded units extend along the b-axis with the
staggered squares parallel to the c-axis. 15j possesses an
extended two-dimensional structure linked via one weak
intermolecular hydrogen bond (3.4465(19) Å) and a weak
F‚‚‚F close contact (2.84(2) Å) with a different molecule.
This gives rise to an “S” shaped moiety, which extends
along the b-axis. The “S”-shaped extensions interweave
but are not connected by close contacts or hydrogen
bonding. Compound 16j shows a greater range of hydro-
gen-bonding interactions, both inter- and intramolecular.
In both 15j and 16j molecules an aromatic hydrogen from
the piperonal moiety is in close proximity (2.753(7), 2.686-
(5) Å) to the oxygen of the first alcohol group. Each
molecule also forms hydrogen bonds with two other
molecules (2.978(7), 2.687(10), and 2.755(9) Å) to form a
twisted “stack” which extends along the c-axis with the
aromatic units of the piperonal moiety parallel to the
b-axis. Every fourth repeat of this stack is hydrogen
bonded through one of the methylene hydrogens of the
piperonal to the adjacent oxygen on another molecule
(3.024(10) Å), which causes the solid-state structure to
be three-dimensional.
Exp er im en ta l Section
Gen er a l Meth od s. All the reactions were performed under
dry nitrogen. (Trifluoromethyl)trimethylsilane was prepared
by published procedures.12 Cesium fluoride was placed in an
oven at 200 °C and repeatedly ground until it remained as a
finely divided powder. Once this stage is reached, it may be
used in the reactions. Storing in an oven at 200 °C retains
the compound in its finely divided state indefinitely. The
arylglyoxals were purchased from SynChem and all of the
other diketo compounds were obtained from Aldrich and were
used as received. Ethylene glycol dimethyl ether (monoglyme)
of high purity (Aldrich) was used as solvent. H, 19F, and 13C
1
NMR spectra were recorded in CDCl3 on a spectrometer
operating at 200, 188, and 50 MHz, respectively. Chemical
shifts are reported in ppm relative to the appropriate standard,
1
CFCl3 for 19F and TMS for H and 13C NMR spectra. IR spectra
were recorded using NaCl plates for neat liquids and KBr
pellets for solids. Mass spectra were measured on an electron
impact 70 ev spectrometer and high-resolution mass spectra
(HRMS) were obtained using a suitable mass spectrometer.
Elemental analyses were performed by Desert Analytics
Laboratory, Tucson, AZ.
X-r a y Cr ysta llogr a p h ic Stu d ies. The crystals were re-
moved from the flask and covered with a layer of hydrocarbon
oil. A suitable crystal was selected, attached to a glass fiber
and placed in the low-temperature nitrogen stream.13 Data for
13g, 15j, and 16j were collected near 203 K using a Siemens
SMART 1000 instrument (Mo R radiation, R ) 0.717 03 Å)
equipped with a Siemens LT-2A low-temperature device. The
SHELXTL v. 5.10 program package was used for structure
solution and refinement.14 An absorption correction was ap-
plied to 13g and 15j using SADABS.15 The structures were
solved by direct methods and refined by full matrix least
squares procedures. All non-hydrogen atoms were refined
anisotropically. The data were restricted to 2R ) 45° for 15j
as there was little high angle data. Some details of the data
collection and refinement are given in the Experimental
Sections. Further details are provided in the Supporting
Information.
Tr iflu or om eth yla tion of γ-Keto Ester s. In a typical
experiment, γ-keto esters (5 mmol) (1a ,b) were dissolved in
In summary, in an effort to synthesize both mono-
(trifluoromethyl)alcohols and bis(trifluoromethyl) diols,
we have studied the reactions of R, â, and γ dicarbonyl
compounds with Me3SiCF3. Not unexpectedly γ-ke-
toesters and γ-diketones are excellent precursors to both
mono(trifluoromethyl)alcohols and, for the latter, bis-
(trifluoromethyl)diols in much larger yields. With R-ke-
todiones, varying products were found apparently as a
function of the substitutent groups. For example, in the
(12) (a) Nelson, D. W.; O’Reilly, N. J .; Speier, J .; Gassman, P. G. J .
Org. Chem. 1994, 59, 8157-8171. (b) Ramaiah, P.; Krishnamurty, R.;
Prakash, G. K. S. Organic Syntheses; Wiley: New York, 1998; Collect
Vol. IX, pp 711-715.
(13) Hope, H. Prog. Inorg. Chem. 1995, 41, 1-3.
(14) SHELXTL Ver. 5.10 PCNT Bruker AXS, Madison, WI, 1998.
(15) SADABS (Siemens Area Detector ABSorption correction pro-
gram), an empirical absorption program by G. M. Sheldrick using the
method described by Blessing: Blessing, R. H. Acta Crystallogr. 1995,
A51, 33.

Double Nucleophilic Trifluoromethylation Reactions
J . Org. Chem., Vol. 66, No. 4, 2001 1439
1
monoglyme (5 mL) and cooled to 0 °C. Me3SiCF3 (5.25 mmol)
and a catalytic amount of cesium fluoride (0.1 mmol) were
added sequentially. The bath temperature was allowed to rise
to room temperature and the reaction solution was stirred for
6 h. Glyme and excess Me3SiCF3 were removed at reduced
pressure and THF (2 mL) was added to the residue. It was
cooled to 0 °C and 6 N HCl (8 mL) was added dropwise. The
solution was stirred at room temperature for 3 h. Volatile
materials were removed at reduced pressure and the product
was extracted with diethyl ether (40 mL). Purification was
accomplished via column chromatography using an ether/
pentane mixture to yield 3 in 60% yield.
10i: H NMR (CDCl3) δ 0.13 (s, 9H), 1.49 (s, 3H), 1.53 (s,
3H), 2.20 (s, 1H); 19F NMR (CDCl3) δ -83.07 (s, 3F); MS (EI)
m/z (species, rel int) 243 (M + H, 1), 32], 185 (M+
-
CH3COCH2, 7), 173 [M+ - CF3, 115 [M+ - (CF3 + CH3 + CH3-
CO), 86], 69 (CF3, 8), 43 (CH3CO+, 100).
1
11g: yield 81%; liquid; IR (film) 2960; H NMR (CDCl3) δ
0.13 (s, 18H), 1.34(s, 6H), 1.72 (t, 3H, J ) 5 Hz), 1.89 (t, 2H,
J ) 5 Hz); 19F NMR (CDCl3) δ -83.05 (s, 3F), 83.57 (s, 3F);
MS (EI) m/z (species, rel int) 398 (M+, 1), 363 [M+- (HF + CH3),
1], 329 (M+ - CF3, 1), 185 (CH3C(OSiMe3), 20], 73 (SiMe3, 94),
43 (CH3CO+, 100).
11h : yield 90%; colorless viscous liquid; IR (film) 2960, 1668,
1498, 1462, 1380, 1296, 1255, 1169, 995 cm-1; 1H NMR (CDCl3)
δ 0.13 (s, 18H), 1.85 (s, 6H), 7.2-7.6 (m, 8H); 19F NMR (CDCl3)
δ -83.68 (s, 6F); 13C NMR (CDCl3) δ 2.00, 22.73, 76.53 (q,
J C-C-F ) 31 Hz); 125.30 (q, J C-F ) 280.5 Hz), 126.66, 127.01,
127.31, 139.32, 140.42; MS (EI) m/z (species, rel int) 522 (M+,
8), 453 (M+ - CF3, 100), 73 (SiMe3, 84).
2a : yield 90%; liquid; IR (film) 1632, 1428, 1255, 970 cm-1
;
1H NMR (CDCl3) δ 0.13 (s, 9H), 0.15 (s, 9H), 1.15 (t, 3H, J )
7 Hz), 1.34 (s, 3H), 1.81 (m, 2H), 3.57 (q, 2H, J ) 7 Hz); 19F
NMR (CDCl3) δ -80.26 (s, 3F), -81.69 (s, 3F); 13C NMR (CDCl3)
δ 1.40, 1.86, 15.25, 21.36, 29.85, 31.96, 60.49, 75.56 (q, J C-C-F
) 28 Hz) 98.10 (q, J C-C-F ) 29 Hz), 121.87 (q, J C-F ) 143 Hz),
127.61 (q, J C-F ) 138 Hz); MS (EI) m/z (species, rel int) 429
(M+ + H, 8), 413 (M+ - CH3, 5), 359 (M+ - CF3, 46), 271 [M+
- CF3, + SiMe3 + CH3), 42), 215 [C(OSiMe3)(CF3)O2C2H5+, 81],
143 (CH3COCH2CHCO2C2H5+, 37), 73 (Me3Si+, 100).
1
11i: yield 30%; colorless liquid; H NMR (CDCl3) δ 0.02 (s,
18H), 1.40 (s, 6H), 2.10 (s, 2H); 19F NMR (CDCl3) δ -78.80 (s,
3F); MS (EI) m/z (species, rel int) 385 (M+ + H, 1), 369 [M+
-
CH3, 1], 315 (M+ - CF3, 1), 185 (CH3C(CF3)(OSiMe3, 15), 69
(CF3, 4), 43 (CH3CO+, 100); HRMS calcd for C13H26F6O2Si2
384.1375, found 384.1369.
3: yield 60%; liquid; IR (film) 3250, 1762, 1250, 972 cm-1
;
1H NMR (CDCl3) δ 1.32 (s, 3H), t (2.40, t, 2H, J ) 6.5 Hz),
2.65 (t, 2H, J ) 6.5 Hz); 19F NMR (CDCl3) δ -78.5, -82.2; MS
(EI) m/z (species, rel int) 238 (M+, 11), 221 (M+ - OH, 62),
13g: yield 72%; colorless solid; mp 89-90 °C; IR (KBr) 3425,
1660, 1505, 1450, 1245, 1160, 1090, 920; cm-1 1H NMR
;
169 (M+ - CF3, 55), 148 [M+ - (HF + CF3H), 70), 116 [M+
(HF + CH3 + CF3 + H2O), 100), 69 (CF3, 21).
-
(CDCl3) δ 1.38 (s, 3H), 1.40 (s, 3H), 1.81 (t, 2H), 1.98 (t, 2H),
2.35 (broad, s, 1H), 2.53 (broad, s, 1H); 19F NMR (CDCl3) δ
-83.05 (s, 3F); 13CNMR (CDCl3) δ 20.46, 21.03, 27.66, 28.29,
73.30 (J C-C-F ) 28 Hz), 73.70 (J C-C-F ) 28 Hz), 124.30 (J C-F
Gen er a l Tr iflu or om eth yla tion of r, â a n d γ Dik eton es.
Diketones (5 mmol) were dissolved in monoglyme (5 mL) and
cooled to 0 °C. The required amount of Me3SiCF3 and a
catalytic amount of cesium fluoride (0.1 mmol) were added
sequentially. The bath temperature was allowed to rise to room
temperature, and the reaction solution was heated to 60 °C
with stirring until all the diketones were consumed. Reactions
were monitored by GCMS. Glyme was removed at reduced
pressure, and THF (2 mL) was added to the residue. It was
cooled to 0 °C, and 6 N HCl (8 mL) was added dropwise. The
solution was stirred at room temperature for 3 h. Volatile
materials were removed at reduced pressure, and the product
was extracted with diethyl ether. Purification was accom-
plished via column chromatography using an ether/pentane
mixture to yield the pure products.
) 282 Hz), 129.0 (J C
) 282 Hz); MS (EI) m/z (species, rel
-F
int) 254 (M+, 1), 201 [M+ - (2 × OH + F), 6], 185 (M+ - CF3,
7), 167 [M+ - (H2O + CF3), 4], 113 (CH3C(OH)CF3+, 8), 69
(CF3, 5), 43 (CH3CO+, 100). Anal. Calcd for C8H12F6O2: C,
37.78; H, 4.76. Found: C, 38.02; H, 4.99. X-ray crystallographic
data: crystal system, monoclinic; space group, C2/c; unit cell
diamensions, a ) 18.022(2) Å, b ) 12.0302(14) Å, c ) 10.4922-
(12) Å, R ) 90°, â ) 106.675(2)°, λ ) 90°; Z ) 8; F(000) ) 1040;
crystal size ) 0.43 × 0.30 × 0.30 mm3; R1 ) 0.0483, wR2 )
0.1379.
13h : yield 89%; colorless solid; mp 118 °C; IR (film) 3410,
2946, 1650, 1462, 1385, 1273, 1157, 1071, 930, 818 cm-1; H
1
NMR (CDCl3) δ 1.80 (s, 6H), 2.47 (s, 2H), 7.2-7.6 (m, 8H); 19
F
5c: yield 96%; viscous liquid; IR (film) 1780, 1598, 1492,
NMR (CDCl3) δ -81.34 (s, 6F); 13C NMR (CDCl3) δ 23.90,
74.77, 29 (q, J C-C-F ) 31 Hz), 125.53 (q, J C-F ) 283 Hz), 126.56,
127.01, 137.65, 140.60; MS (EI) m/z (species, rel int) 378 (M+,
21), 309 (M+ - CF3, 46), 240 (M+ - 2 × CF3), 43 (CH3CO, 100).
Anal. Calcd for C18H16F6O2: C, 57.13; H, 4.26. Found: C, 56.92;
H, 4.16.
1208, 1090, 988, 750 cm-1 1H NMR (CDCl3) δ 0.04 (s, 9H),
;
7.0-8.0 (m, 10H); 19F NMR (CDCl3) δ -74.18 (s, 3F); 13C NMR
(CDCl3) δ 0.97, 83.73 (q, J C-C-F ) 31 Hz), 123.50 (q, J C-F
)
286 Hz), 126.29, 128.03, 128.51, 129.24, 130.86, 133.25, 135.18,
193.43; MS (EI) m/z (species, rel int) 352 (M+, 6), 275 (M+
Ph, 38), 247 (M+ - PhCO, 70), 105 (PhCO+ 100), 69 (CF3
35), 73 (Me3Si+, 42).
-
+
1
,
13i: H NMR (CDCl3) δ 1.50 (s, 6H), 2.03 (s, 2H), 2.95 (s,
2H); 13C NMR (CDCl3) δ 26.20, 62.82, 74.09 (q, J C-C-F ) 28.3
Hz), 125.75 (q, J C-F ) 285 Hz); 19F NMR (CDCl3) δ -83.81 (s,
6d : yield 77%; viscous liquid; IR (film) 2962, 1494, 1456,
1
1251, 1201, 1013, 976, 849 cm-1; H NMR (CDCl3) δ 0.16 (s,
6F); MS (EI) m/z (species, rel int) 241 (M+ + H, 1), 225 (M+
-
9H), 0.28(s, 9H), 1.73 (s, 1H), 7.37 (m, 3H), 7.64 (m, 2H); 19F
NMR (CDCl3) δ -66.32 (s, 3F), -73.64 (s, 3F); 13C NMR
(CDCl3) δ 1.68, 19.28, 81.06 (q, J C-C-F ) 26 Hz), 83.21 (q,
CH3, 1), 207 [M+ - (CH3 + H2O), 1], 187 [M+ - (CH3 + H2O
+ HF), 4], 171 (M+ - CF3, 6), 113, 69 (CF3+, 4), 43 (CH3CO+,
100).
J C-C-F ) 26 Hz), 125.10 (q, J C-F ) 288 Hz), 125.50 (q, J C-F
)
Tr iflu or om eth yla tion of Ar ylglyoxa l. Arylglyoxal (5
mmol) and TMSCF3 (10.25 mmol) were dissolved in monogly-
me (50 mL), and the mixture was cooled with water/ice (about
0 °C). To the stirred solution was added powdered cesium
fluoride (0.1 mmol). Heat was generated as the reaction began.
After 1 h, the water bath was removed, and the reaction
mixture was stirred for additional 5 h. Volatile materials were
removed. THF (5 mL) was added followed by the addition of 6
N HCl (10 mL), and the solution was stirred for 3 h at room
temperature. Products were extracted with diethyl ether and
dried over anhydrous MgSO4. Removal of solvent left the
products which were purified by column chromatography.
15j: yield 80%; mp 122 °C; IR (KBr) 3419, 1664, 1595, 1500,
1452, 1244, 1152, 1091, 1031, 991, 927 cm-1; 1H NMR (CDCl3)
δ 4.26 (d, 1H, J ) 8 Hz), 5.28 (m, 1H), 6.08 (s, 2H), 6.89 (d,
1H, J ) 8.2 Hz), 7.42 (s, 1H), 7.55 (d, 1H, J ) 8.2 Hz); 19F
NMR (CDCl3) δ -74.28 (d, 3F, 6.8 Hz); 13C NMR (CDCl3) δ
70.27 (q, J C-C-F ) 31 Hz), 102.39, 108.26, 108.68, 122.33 (q,
J C-F ) 282.5 Hz), 126.81, 127.87, 148.62, 153.81, 190.55; MS
288 Hz), 126.81, 128.23, 133.60, 135.81; MS (EI) m/z (species,
rel int) 417 (M+ - CH3, 2), 363 (M+ - CF3, 2), 247 [PhC-
(OSiMe3)(CF3)C+, 40], 185 [MeC(OSiMe3)(CF3)C+, 30], 105
(PhCO+, 65), 69 (CF3+, 1), 73 (SiMe3+, 100); HRMS calcd for
C
17H26F6O2Si2 432.1375, found 432.1370.
7c: yield 94%; IR (film) 3268, 1560, 1450, 1270, 991 cm-1
;
1H NMR (CDCl3) δ 4.8 (broad, s, 1H), 7.0-8.0 (m, 10H); 19F
NMR (CDCl3) δ -73.47 (s, 3F); MS (EI) m/z (species, rel int)
280 (M+, 5), 263 (M+ - OH, 6), 175 (M+ - PhCO, 28), 105
(PhCO+ 100), 77 (Ph+, 24), 69 (CF3+, 18); HRMS calcd for
C
15H11F3O2 280.0711, found 280.0704.
8d : yield 68%; IR (KBr) 3422, 1658, 1500, 1458, 1246, 1168,
1
1089, 930 cm-1; H NMR (CDCl3) δ 2.01 (s, 3H), 3.17 (s, 1H),
3.70 (s, 1H), 7.0-7.6), m, 5H); 19F NMR (CDCl3) δ -70.30 (q,
J ) 9 Hz), -75.40 (q, J ) 9 Hz); MS (EI) m/z (species, rel int)
268 (M+ - HF, 5), 175 (Ph(CF3)(OH)C+, 76), 105 (PhCO+, 100),
77 (Ph+, 35), 69 (CF3+, 9), 43 (CH3CO+, 32); HRMS calcd for
C
11H9F5O2 (M+ - HF) 268.0523, found 268.0521.

1440 J . Org. Chem., Vol. 66, No. 4, 2001
Singh et al.
(EI) m/z (species, rel int) 248 (M+, 8), 179 (M+ - CF3, 1), 149
(M+ - CH(OH)CF3, 100), 121 (M+ - COCH(OH)CF3, 32). Anal.
Calcd for C10H7F3O4: C, 48.38; H, 2.84. Found: C, 48.07; H,
2.80. X-ray crystallographic data: crystal system, monoclinic;
space group, P2(1)/n; unit cell diamensions, a ) 11.22160(10)
Å, b ) 5.33550(10) Å, c ) 16.2074(3) Å, R ) 90°, â ) 98.2470-
(10)°, λ ) 90°; Z ) 4; F(000) ) 500; crystal size ) 0.50 × 0.25
× 0.13 mm3; R1 ) 0.0495, wR2 ) 0.1060.
833 cm-1; 1H NMR (CDCl3) δ 3.79 (s, 3H), 4.35 (d, 1H, J ) 8.1
Hz), 5.31 (m, 1H), 6.97 (d, 2H, J ) 8 Hz), 7.94 (d, 2H, J ) 8
Hz); 19F NMR (CDCl3) δ -74.32 (d, 3F, J ) 6.7 Hz); 13C NMR
(CDCl3) δ 21.84, 70.74 (q, J C-C-F ) 31.0 Hz), 122.36 (q, J C-F
)
282.3 Hz), 129.03, 129.66, 130.80, 192.34; MS (EI) m/z (species,
rel int) 234 (M+, 3), 165 (M+ - CF3, 1), 135 (M+ - CF3CHOH,
100), 107 (M+ - COCF3CHOH, 15), 92 [M+ - (COCF3CHOH
+ CH3], 14). Anal. Calcd for C10H9F3O3: C, 51.27; H, 3.88.
Found: C, 51.24; H, 3.88.
15k : yield 82%; mp 128 °C; IR (KBr) 3379, 1683, 1600, 1402,
1313, 1224, 1182, 1122, 972, 854, 829 cm-1; 1H NMR (CDCl3)
δ 4.28 (d, 1H, J ) 8 Hz), 5.42 (m, 1H), 7.20-7.67 (m, 5H),
7.73 (d, 1H, J ) 6.4 Hz), 8.04 (d, 1H, J ) 8.4 Hz); 19F NMR
(CDCl3) δ -74.01 (d, 3F, 6.7 Hz); MS (EI) m/z (species, rel int)
204 (M+, 5), 107 (M+ - COCOCF3, 71), 105 [M+ - CH(OH)-
CF3, 100], 78 [M+ - COC(OH)CF3, 40], 77 (M+ - COC(OH)-
CF3, 71), 76 (C6H4+, 13), 69 (CF3+, 1), Anal. Calcd for
C9H7F3O2: C, 64.27; H, 3.96. Found: C, 64.00; H, 4.01.
15l: yield 78%; mp 125 °C; IR (KBr) 3383, 1659, 1516, 1415,
1325, 1228, 1178, 1126, 869, 812 cm-1; 1H NMR (CDCl3) δ 4.15
(broad, d, 1H), 5.18 (m, 1H), 7.21 (m, 1H), 7.84 (m, 2H); 19F
NMR (CDCl3) δ -74.73 (d, 3F); 13C NMR (CDCl3) δ 71.91 (q,
J C-C-F ) 31.5 Hz), 122.22 (q, J C-F ) 282.2 Hz), 128.83, 135.46,
137.43, 139.53, 184.56; MS (EI) m/z (species, rel int) 210 (M+,
2), 141 (M+ - CF3, 1), 111 (M+ - CF3CHOH, 100), 83 (S -
C4H3+, 11), 69 (CF3, 4). Anal. Calcd for C7H5F3O2S: C, 40.00;
H, 2.40. Found: C, 39.70; H, 2.35.
16j: yield 10%; mp 123 °C; IR (KBr) 3300, 1618, 1450, 1348,
1
1126, 919 cm-1; H NMR (CDCl3) δ 4.58 (broad, s, 2H), 5.24
(m, 1H), 6.01 (s, 2H), 6.78 (d, 1H, J ) 8 Hz), 7.00 (d, 1H, J )
8 Hz), 7.18 (s, 1H); 19F NMR (CDCl3) δ -73.40 (m, 3F), 76.10
(m, 3F); MS (EI) m/z (species, rel int) 318 (M+, 20), 248 (M+
-
CF3H, 2), 219 (M+ - CH(OH)CF3, 82), 149 [M+ - (CF3H +
CH(OH)CF3), 100], 99 (CH(OH)CF3, 90), 69 (CF3, 11). X-ray
crystallographic data: crystal system, monoclinic; space group,
P2(1)/c; unit cell dimensions, a ) 11.7029(7) Å, b ) 19.1585-
(12) Å, c ) 10.7623(7) Å, R ) 90°, â ) 96.669(2)°, λ ) 90°; Z )
8; F(000) ) 1280; crystal size ) 0.35 × 0.08 × 0.05 mm3; R1
) 0.1514, wR2 ) 0.1759.
Ack n ow led gm en t. This work was supported by the
National Science Foundation (Grant No. CHE-9720365)
and by the Petroleum Research Fund, administered by
the ACS. We are thankful to Dr. G. Knerr for obtaining
high-resolution mass spectra. J .M.L. was an NSF-
EPSCOR REU and Renfrew Summer Fellow.
15m : yield 72%; mp 97-98 °C; IR (KBr) 3442, 1678, 104,
1300, 1247, 1226, 1175, 1126, 968, 864 cm-1; 1H NMR (CDCl3)
δ 2.43 (s, 3H), 4.29 (d, 1H, J ) 8.2 Hz), 5.36 (m, 1H), 7.30 (d,
2H, J ) 8.2 Hz), 7.86 (d, 2H, J ) 8.2 Hz); 19F NMR (CDCl3) δ
-74.16 (d, 3F, J ) 6.7 Hz); 13C NMR (CDCl3) δ 21.84, 70.74
(q, J C-C-F ) 31.0 Hz), 122.36 (q, J C-F ) 282.3 Hz), 129.03,
129.66, 130.80, 192.34; MS (EI) m/z (species, rel int) 218 (M+,
1), 149 (M+ - CF3, 1), 119 (M+ - CF3CHOH, 100), 91
(CH3C6H4+, 64), 69, CF3, 1). Anal. Calcd for C10H9F3O2: C,
55.03; H, 4.16. Found: C, 55.02; H, 4.16.
Su p p or t in g In for m a t ion Ava ila b le: Crystal data and
structure refinement, atomic coordinates, bond lengths and
bond angles, anisotropic displacement parameters, hydrogen
coordinates, ORTEP drawings, and crystal packing diagrams
for 13g, 15j, and 16j. This material is available free of charge
via the Internet at http://pubs.acs.org.
15n : yield 70%; viscous liquid; IR (KBr) 3437, 2950, 1677,
1602, 1572, 1514, 1463, 1421, 1249, 1180, 1130, 1028, 974, 867,
J O0057304