Methylenation of perfluoroalkyl ketones using a Peterson olefination approach

Article abstract of DOI:10.1021/jo402577n

An operationally simple, inexpensive, and rapid route for the olefination of a wide array of trifluoromethyl ketones to yield 3,3,3- trifluoromethylpropenes is reported. Using a Peterson olefination approach, the reaction gives good to excellent yields of the alkene products and can be performed without purification of the β-hydroxysilyl intermediate. The reaction can be extended to other perfluoroalkyl substituents and is easily scaled up. The alkenes prepared can be readily transformed into a variety of other perfluoroalkyl-containing compounds.

Full text of DOI:10.1021/jo402577n

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Article
Methylenation of Perfluoroalkyl Ketones
using a Peterson Olefination Approach
Trevor A. Hamlin, Christopher Brian Kelly, Robin M. Cywar, and Nicholas E. Leadbeater
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo402577n • Publication Date (Web): 10 Jan 2014
Downloaded from http://pubs.acs.org on January 19, 2014
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The Journal of Organic Chemistry
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Methylenation of Perfluoroalkyl Ketones using a Peterson
Olefination Approach
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Trevor A. Hamlin1, Christopher B. Kelly1, Robin M. Cywar1,
and Nicholas E. Leadbeater1,2,*
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1. Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs,
Connecticut, 06269-3060, USA
2. Department of Community Medicine & Health Care, University of Connecticut Health Center,
The Exchange, 263 Farmington Ave, Farmington, CT 06030, USA
email: nicholas.leadbeater@uconn.edu
TABLE OF CONTENTS GRAPHIC
Abstract
An operationally simple, inexpensive, rapid route for the olefination of a wide array of
trifluoromethyl ketones to yield 3,3,3ꢀtrifluoromethylpropenes is reported. Using a Peterson
olefination approach, the reaction gives good to excellent yield of the alkene products and can be
performed without purification of the βꢀhydroxysilyl intermediate. The reaction can be extended
to other perfluoroalkyl substituents and is easily scaled up. The alkenes prepared can be readily
transformed into a variety of other perfluoroalkylꢀcontaining compounds.
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Introduction
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The incorporation of the trifluoromethyl group (ꢀCF3) into organic molecules has
garnered much attention because of its ability to enhance the metabolic stability and membrane
permeability of the parent molecule while also serving as a bioisostere for several
functionalities.1 In addition to these properties, its strongly electronꢀwithdrawing nature allows it
to impart significant changes to the reactivity of the functional groups to which it is attached. As
such, many medicinallyꢀrelevant molecules not only feature this moiety, but capitalize on the
unique chemistry of trifluoromethylꢀbearing compounds in synthetic strategies.
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One class of compounds that greatly benefits from CF3 substitution are alkenes. Of
particular interest is the 3,3,3ꢀtrifluoropropenyl (CF3CR=CRꢀ) moiety, which is attractive to
medicinal chemistry as an isostere to certain amino acid groups,2 and to agrochemistry3 as key
intermediates in the synthesis of potent insecticides (or, in some cases, insecticides themselves).
Macrocycles containing this moiety, such as 26ꢀtrifluoroꢀ(E)ꢀ9,10ꢀdehydroepothilone,4 are
promising antiꢀcancer compounds, while conjugating the 3,3,3ꢀtrifluoropropenyl group into
higher order πꢀsystems yields potential organic lightꢀemitting diodes (OLEDs).5
The synthetic approach taken to prepare trifluoromethylꢀfunctionalized alkenes is highly
dependent on the location of the CF3 group on the alkene. In the case of βꢀCF3 alkenes, such as
βꢀtrifluoromethylstyrene derivatives, several strategies have been reported.3a,6 Of note are two
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recent reports by Buchwald6 and Prakash,6b which contrast two distinct approaches to CF3 alkene
construction: via direct trifluoromethylation of activated alkenes, or by transition metalꢀmediated
cross coupling using simple CF3 alkenyl building blocks, respectively.
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αꢀCF3 alkenes can be accessed by the methylenation of trifluoromethyl ketones (TFMKs)
or by transition metal coupling (Figure 1). In the case of the former, classical approaches
employing Wittig7 chemistry or a modified Julia approach8 have been utilized. A protocol using
Wilkinson’s catalyst, ClRh(PPh3)3, has also been developed.9 However, excess PPh3 and
trimethylsilyldiazomethane are required, limiting scalability. Alternatively, arenes can be
coupled with 2ꢀbromoꢀ3,3,3ꢀtrifluoropropꢀ1ꢀene using Suzuki,10 Negishi11 or Kumada12,13
coupling reactions. While useful, these methods are limited to preparing αꢀCF3 styryl derivatives.
Another metalꢀmediated methodology involves conversion of (trifluoromethyl)trimethylsilane
into CuCF3 and then using this for trifluoromethylation of activated and nonꢀactivated alkenyl
halides in 1,3ꢀdimethylꢀ3,4,5,6ꢀtetrahydroꢀ2(1H)ꢀpyrimidinone (DMPU) as a chelating solvent.14
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Building on our successes in developing methods to access various TFMKs,15 we
envisioned that constructing αꢀperfluoroalkyl alkenes by dehydrative desilylation in a Peterson16
manner might offer an attractive alternative to the established protocols. To the best of our
knowledge, no such approach had been reported previously. Such a methodology has several
advantages over current approaches: 1) it would be metalꢀ and phosphineꢀfree; 2) it would avoid
the use of highly toxic trimethylsilyldiazomethane; 3) the process would be scalable; and 4) the
reaction conditions would be mild. We therefore decided to pursue this potential methodology
and report our findings here.
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Established Routes to Access -CF3 Alkenes
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Wittig
I
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O
Ph3P CH3
CF3
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KOtBu, THF
- 78 oC to rt
Ph
Ph
CF3
O
S Cl
Modified-Julia
CF3
O
O
Ph
KF, 18-crown-6
DMF, 110 oC, 5 h
Ph
CF3
Transition-metal coupling
CF3
Pd or Ni catalyst
Ar
Br
CF3
Ar-B(OH)2 or ArMgBr
Rhodium(I)-mediated
Me3SiCHN2
ClRhPPh3 (cat.)
O
CF3
Ph
CF3
Ph
i-PrOH, PPh3
THF, rt
Trifluoromethylation
TMS-CF3
CuI, KF
CF3
R
X
R
O
DMPU
80 oC, 16 h
This work
1.Me3SiCH2MgCl
Et2O, rt 12 h
CF3
Ph
CF3
Ph
2. TMSOTf, DCM.
45 oC, 4 h
Figure 1. Strategies to access αꢀCF3 alkenes from TFMKs
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Results and Discussion
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We began our investigation by first constructing a representative αꢀtrifluoromethylꢀβꢀ
hydroxysilyl alcohol, 2a. With this alcohol in hand, we then explored a variety of acid catalysts
to promote dehydrative desilylation to yield the desired alkene 3a (Table 1). Initially, we hoped
to use the crude ethereal mixture of 2a obtained after workup and treat it with hydrochloric acid
to facilitate elimination (Table 1, entry 1). However, we did not observe any elimination in this
case. We then opted to use pure carbinol for our remaining trials. We screened a variety of protic
and aprotic Lewis acids to evaluate the propensity for dehydrative desilylation. Surprisingly, 2a
proved remarkably resilient to this transformation with nearly all traditional Lewis acids giving
little to no 3a (Entries 2ꢀ9). This is in stark contrast to traditional Peterson olefination reactions
which proceed easily using HCl or other standard Lewis acids.14 The combined effect of
diminished oxygen nucleophilicity and high activation barrier for E2ꢀlike elimination makes the
oleifination process too energetically unfavorable (Figure 2).14 To circumvent this, we therefore
turned to a more powerful catalyst, TMSOTf, and encountered success, albeit with low
conversion. Solvent had a significant role, with dichloromethane being superior to the more
Lewis basic diethyl ether and acetonitrile. To expedite elimination, we chose to heat the reaction
to reflux and slightly increase the loading of TMSOTf from 0.10 to 0.15 equiv allowing
complete conversion to the desired alkene in 4 h.
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Table 1. Catalyst Screen for Dehydrative Desilylationa
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entry
1c
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solv.
Et2O
Lewis acid cat. temp. (°C) time (h) conv. (%)b
2M HCl
Sc(OTf)3
Gd(OTf)3
Mg(OTf)2
TFA
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1.0
0.5
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0.5
1.0
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0.5
1.0
4.0
0
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0
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
Et2O
MeCN
DCE
DCM
DCM
DCM
DCM
pꢀTSA
SnCl4
BF3
●
OEt2
9
TfOH
Trace
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15d
16d
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
TMSOTf
0
0
9
16
30
55
100 (74)e
aReaction conditions unless otherwise noted: 2a (0.3 mmol, 1 equiv), catalyst (0.03 mmol, 0.1
b
1
c
d
equiv), solvent (1.5 mL). Conversion determined by H NMR. 0.5 equiv catayst used. 0.15
equiv catalyst used. eNumber in parentheses indicates isolated yield of 3a.
Figure 2. Possible explaination for resistance to dehydrative desilylation
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With the optimized reaction conditions in hand, we next explored the scope of this
process. We were pleased to find that our protocol could be extended to a range of
functionalities. Electronꢀrich (Table 2, entries 1ꢀ3, 5) and electronꢀpoor arenes (entry 4) were
both tolerated under our reaction conditions, though with a significant disparity in reactivity.
Electronꢀrich and electronꢀneutral arenes underwent elimination in as little as 15 min at room
temperature while electronꢀpoor arenes required our original optimized conditions. An exception
to this trend is 2d (entry 3). This substrate behaved much like an electronꢀpoor arene, requiring a
significantly higher reaction temperature and catalyst loading to reach completion. This reversal
of reactivity can likely be attributed to protonation of the dimethylamino group during the course
of the reaction, thereby preventing electron donation into the ring system. Heteroarenes (Table 1,
entries 7 and 8) showed a similar, more pronounced disparity in reactivity based on the
electronics of the ring system. We attribute the failure of the pyridyl system (entry 7) to a similar
rationale to the dimethylaniline case. The protonation (or silylation) of the nitrogen combined
with the inherent deactivation of the pyridyl ring prohibited dehydrative desilylation.
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We next explored aliphatic carbinols finding that unbranched and branched examples
were amenable to dehydrative desilylation (entries 9ꢀ11). A representative furyl system (entry
12) was also screened in these trials. However, extensive polymerization occurred when
attempting dehydrative desilylation of this substrate, even at lower temperatures and catalyst
loadings. We next turned our attention to different perfluoroalkyl groups (entries 13ꢀ15). As one
might expect, the more destabilizing αꢀCF2CF3 group required higher temperatures to facilitate
elimination; hence, dichloroethane (DCE) was employed as the solvent. Likewise, the less
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destabilized αꢀCF2H and αꢀCFH2 carbinols underwent dehydrative desilylation more rapidly
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than their trifluoromethyl congeners.
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Table 2. Scope of Methylenation of Various TMFKsa
temp. (°C) time (min) yield (%)b
entry
1
R
RF
CF3
25
15
86
2
3d,e
4
CF3
CF3
CF3
25
90
45
15
80 (88)c
95
270
240
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CF3
25
15
85
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CF3
CF3
25
90
15
91
ꢀf
7d
270
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9
CF3
CF3
CF3
25
45
45
15
86
88
65
240
240
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3j
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CF3
CF3
45
ꢀ78
90
240
60
84
ꢀg
CF2CF3
240
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14d
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CF2H
CFH2
CF3
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92
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86
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CF3
18
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CF3
CF3
25
25
60
30
85
ꢀg
aReaction conditions unless otherwise noted: alcohol (1 equiv), TMSOTf (0.15 equiv), CH2Cl2
(0.2 M in alcohol). bIsolated yields. cValues in parentheses indicates isolated yield of alkene on
57 mmol scale. dPerformed in DCE. e0.3 equiv of TMSOTf was used. fNo reaction even at 2
equiv TMSOTf loading. gExtensive polymerization.
We also investigated whether conjugated dienes could be accessed via this methodology
and we met mixed success. While cinnamylꢀderived and straight chain dienes (entries 16ꢀ18)
could be prepared in good yield, the furylꢀsubstituted alkene (entry 19) gave the same result as
its saturated counterpart (entry 12); namely polymerization. Finally, it should be noted that in
nearly all cases, the intermidate carbinol can be carried directly to the dehydrative desilylation
reaction without need for further purification. Additionally, this process can be scaled up
substantially (entry 2, 57 mmol scale) without compromising yield.
Representative Reactions Utilizing CF3 Alkenes
To probe the utility of the alkene products prepared in this study, we conducted several
derivatization reactions using 3c as a representative alkene (Scheme 1). We selected reactions
that would either provide potentially valuable synthons for further elaboration or that
demonstrate key functionalizations that capitalize on the unique electronic nature of the 3,3,3ꢀ
trifluoropropenyl system. We first explored difluoromethylcyclopropanation using the conditions
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recently disclosed by Hu and Prakash.17 We were pleased to find we could obtain the highlyꢀ
fluorinated cyclopropane 4c in excellent yield. Next, we sought to convert our representative
alkene into a potential partner for crossꢀcoupling processes. We successfully prepared the vinyl
bromide 5c in similarly good yield using a modified literature protocol.18 Next, based on reports
by Bégué and BonnetꢀDelpon,19 we sought to access functionalized gemꢀdifluoroalkenes by
treatment of 3c with the appropriate organolithium species. While we were unable to react
phenyllithium successfully with 3c, treatment with lithiated piperidine successfully led to
amination and the generation of difluoroalkene 6c in good yield. Finally, we subjected 3c to
dihydroxylation using traditional Upjohn conditions.20 This too was successful, giving the diol 7c
in 85% yield.
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Scheme 1. Applications of αꢀCF3ꢀSubstituted Alkenes
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Conclusions
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In summary, we have disclosed an effective, userꢀfriendly methodology for the
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preparation of αꢀperfluoroalkylꢀfunctionalized alkenes by the dehydrative desilylation of αꢀ
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trifluoromethylꢀβꢀhydroxysilyl carbinol using TMSOTf. The reaction is compatible with a range
of functionalities and the alkene products can be obtained in good to excellent yields. The
reaction is scalable and minimal product purification is required. Finally, these alkenes can be
used to access other valuable fluorinated products.
Experimental Section
General:
All chemical transformations requiring inert atmospheric conditions or vacuum distillation
utilized Schlenk line techniques with a 3ꢀ or 4ꢀport dualꢀbank manifold. Nitrogen was used to
1
provide such an atmosphere. NMR Spectra (1H, 13C, 19F) were obtained at 298 K. HꢀNMR
Spectra obtained in CDCl3 were referenced to residual nonꢀdeuterated chloroform (7.26 ppm) in
the deuterated solvent. 13CꢀNMR Spectra obtained in CDCl3 were referenced to chloroform (77.3
19
ppm). FꢀNMR spectra were referenced to hexafluorobenzene (–164.9 ppm)21. Reactions were
monitored by a gas chromatograph attached to a mass spectrometer, 1HꢀNMR, and/or by TLC on
silica gel plates (60Å porosity, 250 ꢁm thickness). Highꢀresolution mass spectra were performed
on either a TOFꢀDART instrument in positive direct analysis in real time (DART) ionization
method, using PEG as the internal standard or using an ESI Ionization source. IR spectra were
obtained using an ATR accessory. TLC analysis was performed using Hex/EtOAc as the eluent
and visualized using permanganate stain, pꢀanisaldehyde stain, Seebach’s Stain, and/or UV light.
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Flash chromatography and silica plugs utilized flash silica gel (60Å porosity, 32ꢀ63 ꢂm) or an
automated flash chromatography unit.
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Chemicals:
Deuterated NMR solvents (CDCl3) were stored over 4Å molecular sieves and K2CO3. Unless
otherwise specified, all aldehydes were purchased from commercial sources and used without
further purification. 2ꢀ(Benzyloxy)benzaldehyde22 and benzofuranꢀ2ꢀcarbaldehyde23 were
prepared according to literature protocols. Trifluoromethyl ketone (TFMK) substrates 1a-c, 1g,
1k, and 1s were prepared as in our previously published protocol.15b TFMK substrates 1e, 1f, 1h-
j, 1l-n, 1q, 1r, 1t were prepared as in our previously published protocol.15a,c To prepare the
requisite trifluoromethyl carbinols for the latter TFMK synthesis, aldehydes were treated with
Me3SiꢀCF3 using our outlined protocol, which is a modification of the procedure outlined by
Prakash.15a,24 The oxoammonium salt 4ꢀacetamidoꢀ2,2,6,6ꢀtetramethylꢀ1ꢀoxopiperidinꢀ1ꢀium
tetrafluoroborate required for the latter oxidation route was prepared according to our recently
published protocol.25 1ꢀ(4ꢀ(Dimethylamino)phenyl)ꢀ2,2,2ꢀtrifluoroethanone26 (1d) 1,1ꢀdifluoroꢀ
4ꢀphenylbutanꢀ2ꢀone27 (1o) and 1ꢀfluoroꢀ4ꢀphenylbutanꢀ2ꢀone28 (1n) substrates were prepared
according to literature protocols.
General Procedure for the Grignard reaction of Perfluoroalkyl Ketones using
trimethylsilyl-methylmagnesium chloride
1,1,1-trifluoro-4-phenyl-2-((trimethylsilyl)methyl)butan-2-ol (2a) The following is a
modification of the procedure outlined by O'Doherty.29 To a 100 mL round bottom flask was
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added crushed magnesium turnings (0.6807 g, 28 mmol, 1.4 equiv) and a stirbar. The flask was
sealed with a rubber septum, the atmosphere was evacuated from the flask via an inlet needle,
and the flask flamed dried under vacuum.30 The flask was flushed with nitrogen and placed in a
room temperature oil bath. Chloromethyltrimethylsilane (2.9125 g, 24 mmol, 1.2 equiv)
dissolved in anhydrous Et2O (14 mL) was added to the flask dropwise31 via an addition funnel
atop a reflux condenser. The reaction mixture was heated to reflux for 1.5 h while under a N2
atmosphere. The reaction mixture gradually became cloudy then dark grey. After this time the
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flask was cooled to 0 C in an ice bath for ten minutes. Subsequently the 1,1,1ꢀtrifluoroꢀ4ꢀ
phenylbutanꢀ2ꢀone, 1a (4.00 g, 20 mmol, 1 equiv) dissolved in anhydrous Et2O was added to the
flask dropwise. Ten minutes after completion of this addition, the ice bath was removed and the
solution was stirred at rt for 12 h. After this time, the solution was was quenched with 0.5 M
aqueous HCl (20 mL) and transferred to a separatory funnel. The phases were separated and the
aqueous layer was extracted with Et2O (3 x 100 mL). The combined organic layers were washed
with sat. NaHCO3 (≈150 mL), brine (≈150 mL), and dried with Na2SO4. The solvent was
removed in vacuo by rotary evaporation to give the pure carbinol 2a (3.552 g, 61 %) as a clear,
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colorless liquid. H NMR (CDCl3, 400 MHz) δ ppm 0.16 (s, 9 H) 1.16 (d, J = 15.16 Hz, 1 H)
1.27 (d, J = 15.16 Hz, 1 H) 1.90 (s, 1 H) 1.99 ꢀ 2.08 (m, 2 H) 2.72 ꢀ 2.81 (m, 2 H) 7.19 ꢀ 7.26 (m,
3 H) 7.28 ꢀ 7.36 (m, 2 H); 13C NMR (CDCl3, 100 MHz) δ ppm 0.5 (CH3) 23.6 (CH2) 29.9 (CH2)
38.8 (CH2) 76.4 (q, JCꢀCꢀF = 27.90 Hz, C) 126.5 (CH) 127.0 (q, JCꢀF = 286.1 Hz, CF3) 128.6 (CH)
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128.9 (CH) 141.5 (C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ84.13; GCꢀMS (EI) 290 ([M]+, 2%)
200 (10%) 161 (39%) 146 (6%) 129 (7%) 91 (100%) 77 (15%) 73 (27%); HRMS (DART), calcd
for C14H21F3OSi [M + NH4]+: 308.1658, found 308.1665.
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4-(4-(tert-butyl)phenyl)-1,1,1-trifluoro-2-((trimethylsilyl)methyl)butan-2-ol (2b) (1.491 g,
76%) was prepared according to the representative procedure for the synthesis of 2a from 1ꢀ(4ꢀ
(tertꢀbutyl)phenyl)ꢀ2,2,2ꢀtrifluoroethanone, 1b (1.42 g, 6.17 mmol) affording the pure αꢀ
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perfluoroalkylꢀβꢀtrimethylsilylꢀ carbinol as a clear, orange oil. H NMR (CDCl3, 500 MHz) δ
ppm ꢀ0.17 (s, 9 H) 1.34 (s, 9 H) 1.47 (d, J = 14.82 Hz, 1 H) 1.65 (d, J = 14.98 Hz, 1 H) 2.33 (s, 1
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H) 7.40 (d, J = 8.20 Hz, 2 H) 7.48 (d, J = 8.20 Hz, 2 H); C NMR (CDCl3, 125 MHz) δ ppm
0.01 (CH3) 25.3 (CH2) 31.6 (CH3) 34.77 (C) 77.6 (q, JCꢀCꢀF = 28.8 Hz, C) 125.3 (CH) 126.1 (CH)
126.3 (q, JCꢀF = 285.7 Hz, CF3) 135.4 (C) 151.6 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ85.06;
GCꢀMS (EI) 228 ([M]+, 20%) 213 (100%) 185 (45%) 164 (4%) 151 (4%) 129 (5%) 128 (8%)
115 (11%) 69 (2%) 41 (6%); HRMS (DART), calcd for C16H25F3OSi [M + NH4]+: 336.1970,
found: 336.1955.
1,1,1-trifluoro-2-(4-methoxyphenyl)-3-(trimethylsilyl)propan-2-ol (2c) (3.683 g, 85%) was
prepared according to the representative procedure for the synthesis of 2a from 2,2,2ꢀtrifluoroꢀ1ꢀ
(4ꢀmethoxyphenyl)ethanone, 1c (3.023 g, 14.8 mmol) affording the pure carbinol as a pale
yellow solid (m.p. 63ꢀ65 C). 1H NMR (CDCl3, 300 MHz) δ ppm ꢀ0.16 (s, 9 H) 1.38 ꢀ 1.48 (m, 1
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H) 1.63 (d, J = 15.17 Hz, 1 H) 2.26 (s, 1 H) 3.82 (s, 3 H) 6.86 ꢀ 6.94 (m, 2 H) 7.46 (d, J = 9.22
Hz, 2 H); 13C NMR (CDCl3, 125 MHz) δ ppm 0.1 (CH3) 25.1 (CH2) 55.5 (CH3) 77.4 (q, JCꢀCꢀF
=
28.8 Hz, C) 113.7 (CH) 126.2 (q, JCꢀF = 284.8 Hz, CF3) 127.8 (CH) 130.4 (C) 159.8 (C); 19F
NMR (CDCl3, 377 MHz) δ ppm ꢀ85.47; GCꢀMS (EI) 202 ([M]+, 98%) 186 (5%) 159 (7%) 133
(100%) 118 (13%) 109 (30%) 103 (11%) 89 (16%) 69 (5%) 63 (13%); HRMS (DART), calcd
for C13H19F3O2Si [M ꢀ OH]+: 275.1079, found: 275.1080.
2-(4-(dimethylamino)phenyl)-1,1,1-trifluoro-3-(trimethylsilyl)propan-2-ol (2d) (4.463 g,
91%) was prepared according to the representative procedure for the synthesis of 2a from 1ꢀ(4ꢀ
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(dimethylamino)phenyl)ꢀ2,2,2ꢀtrifluoroethanone, 1d (3.475 g, 16 mmol) affording the pure
carbinol as clear, orange oil. 1H NMR (CDCl3, 400 MHz) δ ppm ꢀ0.16 (s, 9 H) 1.47 (d, J = 14.92
Hz, 1 H) 1.67 (d, J = 15.16 Hz, 1 H) 2.41 (s, 1 H) 2.94 ꢀ 3.04 (m, 6 H) 6.75 (d, J = 9.05 Hz, 2 H
7.41 (d, J = 8.80 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ ppm 0.2 (CH3) 24.8 (CH2) 40.6 (CH3)
77.3 (q, JCꢀCꢀF = 28.6 Hz, C) 112.1 (CH) 126.4 (q, JCꢀF = 286.1 Hz, CF3) 125.8 (CH) 127.3 (C)
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150.6 (C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ85.24; GCꢀMS (EI) 305 ([M]+, 18%) 287 (4%)
236 (40%) 220 (20%) 214 (22%) 196 (12%) 178 (9%) 146 (100%) 75 (12%) 73 (10%); HRMS
(ESI+), calcd for C14H22F3NOSi [M + H]+: 306.1501, found: 306.1479.
1,1,1-trifluoro-2-(4-(trifluoromethyl)phenyl)-3-(trimethylsilyl)propan-2-ol (2e) (1.978 g,
91%) was prepared according to the representative procedure for the synthesis of 2a from 2,2,2ꢀ
trifluoroꢀ1ꢀ(4ꢀ(trifluoromethyl)phenyl)ethanone, 1e (1.600 g, 6.6 mmol) affording the pure
carbinol as a clear, pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm ꢀ0.17 (s, 9 H) 1.46 ꢀ 1.53
(m, 1 H) 1.63 ꢀ 1.71 (m, 1 H) 2.40 (s, 1 H) 7.66 (d, J = 8.80 Hz, 2 H) 7.72 (d, J = 8.31 Hz, 2 H);
13C NMR (CDCl3, 100 MHz) δ ppm 0.01 (CH3) 25.3 (CH2) 77.6 (q, JCꢀCꢀF = 29.3 Hz, C) 124.3
(q, JCꢀF = 272.2 Hz, CF3) 125.8 (q, JCꢀF = 286.8 Hz, CF3) 125.4 (q, JCꢀCꢀF =3.7 Hz, CH) 127.2 (d,
JCꢀCꢀCꢀCꢀF = 1.5 Hz, CH) 131.0 (q, JCꢀCꢀF = 33.0 Hz, C) 142.3 (C); 19F NMR (CDCl3, 377 MHz) δ
ppm ꢀ84.90 (s, 3 F) ꢀ65.72 (s, 3 F); GCꢀMS (EI) 240 ([M]+, 86%) 221 (40%) 201 (4%) 171
(100%) 169 (14 %) 151 (95%) 145 (12%) 102 (15%) 75 (12%) 69 (12%) 50 (5%); HRMS
(DART), calcd for C13H16F6OSi [M + HF]+: 350.0937, found: 350.0978 FTIR (cm‐1, neat, ATR)
= 3622, 2958, 2362, 1622, 1327, 1168, 1129, 841.
2-(2-(benzyloxy)phenyl)-1,1,1-trifluoro-3-(trimethylsilyl)propan-2-ol (2f) (3.250 g, 79%) was
prepared according to the representative procedure for the synthesis of 2a from 1ꢀ(2ꢀ
(benzyloxy)phenyl)ꢀ2,2,2ꢀtrifluoroethanone, 1f (3.097 g, 11.13 mmol) affording the pure
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carbinol as a cloudy, pale yellow oil. 1H NMR (CDCl3, 500 MHz) δ ppm ꢀ0.07 (s, 9 H) 1.52 (d, J
= 14.98 Hz, 1 H) 1.68 (dd, J = 14.82, 2.84 Hz, 1 H) 5.18 (d, J = 2.36 Hz, 2 H) 6.23 ꢀ 6.40 (m, 1
H) 7.02 ꢀ 7.11 (m, 2 H) 7.32 ꢀ 7.41 (m, 3 H) 7.41 ꢀ 7.49 (m, 4 H); 13C NMR (CDCl3, 125 MHz) δ
ppm 0.5 (CH3) 23.2 (CH2) 72.2 (CH2) 79.6 (q, JCꢀCꢀF = 29.7 Hz, C) 114.3 (CH) 121.8 (CH) 126.5
(q, JCꢀF = 287.4 Hz, CF3) 126.1 (CH) 128.0 (CH) 128.9 (CH) 129.2 (CH) 130.4 (CH) 130.8 (C)
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135.8 (C) 157.9 (C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ85.44; GCꢀMS (EI) 368 ([M]+, 10%)
260 (16%) 175 (12%) 149 (23%) 91 (100%) 75 (10%) 65 (9%); HRMS (DART), calcd for
C19H23F3O2Si [M ꢀ OH]+: 351.1392, found: 351.1438.
1,1,1-trifluoro-2-(naphthalen-1-yl)-3-(trimethylsilyl)propan-2-ol (2g) (2.618 g, 79%) was
prepared according to the representative procedure for the synthesis of 2a from 2,2,2ꢀtrifluoroꢀ1ꢀ
(naphthalenꢀ1ꢀyl)ethanone, 1g (2.386 g, 10.64 mmol) affording the pure carbinol as a cloudy,
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pale yellow oil. H NMR (CDCl3, 400 MHz) δ ppm ꢀ0.16 (s, 9 H) 1.69 (d, J = 15.41 Hz, 1 H)
2.23 (d, J = 15.41 Hz, 1 H) 2.60 (s, 1 H) 7.43 ꢀ 7.58 (m, 3 H) 7.74 ꢀ 7.84 (m, 1 H) 7.89 (d, J =
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7.82 Hz, 2 H) 8.73 ꢀ 8.95 (m, 1 H); C NMR (CDCl3, 100 MHz) δ ppm 0.2 (CH3) 26.7 (CH2)
80.5 (q, JCꢀCꢀF = 29.3 Hz, C) 126.6 (q, JCꢀF = 286.8 Hz, CF3) 124.6 (CH) 125.6 (CH) 126.1 (CH)
127.0 (q, JCꢀCꢀCꢀF = 1.5 Hz, C) 127.4 (br. s., CH) 129.4 (CH) 130.7 (CH) 131.9 (C) 133.9 (C)
135.2 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ82.01; GCꢀMS (EI) 312 ([M]+, 13%) 243 (26%)
227 (12%) 201 (8%) 183 (30%) 153 (100%) 127 (10%) 115 (5%) 73 (13%); HRMS (DART),
calcd for C16H19F3OSi [M]+: 312.1157, found: 312.1183.
1,1,1-trifluoro-2-(pyridin-2-yl)-3-(trimethylsilyl)propan-2-ol (2h) (1.266 g, 23%) was
prepared according to the representative procedure for the synthesis of 2a from 2,2,2ꢀtrifluoroꢀ1ꢀ
(pyridinꢀ2ꢀyl)ethanone, 1h (3.600 g, 21 mmol)32 affording the pure carbinol as a clear, brown oil.
1H NMR (CDCl3, 400 MHz) δ ppm ꢀ0.23 (s, 9 H) 1.43 (d, J = 14.92 Hz, 1 H) 1.71 (d, J = 14.67
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1.59 Hz, 1 H) 8.57 (dq, J = 4.89, 0.82 Hz, 1 H); C NMR (CDCl3, 100 MHz) δ ppm ꢀ0.1 (CH3)
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Hz, CH) 124.0 (CH) 137.6 (CH) 147.4 (CH) 155.9 (C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ
84.71; GCꢀMS (EI) 263 ([M]+, 15%) 248 (24%) 242 (17%) 194 (26%) 190 (12%) 178 (35%) 154
(100%) 150 (13%) 134 (42%) 104 (62%) 78 (30%) 73 (30%) 45 (11%); HRMS (ESI+), calcd for
C11H16F3NOSi [M + H]+: 264.1032, found: 264.1056.
2-(benzofuran-2-yl)-1,1,1-trifluoro-3-(trimethylsilyl)propan-2-ol (2i) (1.9367 g, 94%) was
prepared according to the representative procedure for the synthesis of 2a from 1ꢀ(benzofuranꢀ2ꢀ
yl)ꢀ2,2,2ꢀtrifluoroethanone, 1i (1.450 g, 6.8 mmol) affording the pure carbinol as a clear, pale
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yellow oil. H NMR (CDCl3, 500 MHz) δ ppm ꢀ0.09 (s, 9 H) 1.48 ꢀ 1.57 (m, 1 H) 1.63 (s, 1 H)
2.89 (s, 1 H) 6.82 (d, J = 0.73 Hz, 1 H) 7.23 ꢀ 7.36 (m, 2 H) 7.48 ꢀ 7.53 (m, 1 H) 7.57 ꢀ 7.61 (m,
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1 H); C NMR (CDCl3, 125 MHz) δ ppm ꢀ0.2 (CH3) 22.5 (CH) 75.5 (q, JCꢀCꢀF = 30.8 Hz, C)
105.6 (CH) 111.7 (CH) 125.2 (q, JCꢀF = 286.1 Hz, CF3) 121.7 (CH) 123.5 (CH) 125.2 (CH) 128.1
(C) 153.9 (C) 155.0 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ85.44; GCꢀMS (EI) 302 ([M]+,
16%) 233 (36%) 212 (28%) 193 (41%) 165 (4%) 143 (100%) 131 (7%) 115 (25%) 73 (19%);
HRMS (DART), calcd for C14H17F3O2Si [M ꢀ CF3]+: 233.0993, found: 233.1025.
1,1,1-trifluoro-2-((trimethylsilyl)methyl)tridecan-2-ol (2j) (3.416 g, 90%) was prepared
according to the representative procedure for the synthesis of 2a from 1,1,1ꢀtrifluorotridecanꢀ2ꢀ
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one, 1j (2.800 g, 11.1 mmol) affording the pure carbinol as clear, pale yellow oil. H NMR
(CDCl3, 500 MHz) δ ppm 0.06 (s, 9 H) 0.85 ꢀ 0.91 (m, 3 H) 1.06 (d, J = 15.13 Hz, 1 H) 1.15 (d, J
= 15.13 Hz, 1 H) 1.23 ꢀ 1.34 (m, 16 H) 1.35 ꢀ 1.45 (m, 2 H) 1.60 ꢀ 1.74 (m, 2 H) 1.76 ꢀ 2.01 (m, 1
H); 13C NMR (CDCl3, 125 MHz) δ ppm 0.4 (CH3) 14.4 (CH3) 23.0 (CH2) 23.3 (CH2) 23.5 (CH2)
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29.6 (CH2) 29.8 (CH2) 29.9 (2 x CH2) 29.9 (CH2) 30.3 (CH2) 32.2 (CH2) 37.0 (CH2) 76.5 (q, JCꢀ
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= 28.0 Hz, C) 127.1 (q, JCꢀF = 285.7 Hz, CF3); F NMR (CDCl3, 377 MHz) δ ppm ꢀ84.31;
CꢀF
GCꢀMS (EI) 340 ([M]+, 2%) 222 (3%) 193 (5%) 180 (5%) 165 (7%) 151 (7%) 140 (5%) 131
(7%) 125 (6%) 111 (30%) 103 (10%) 97 (49%) 89 (12%) 83 (48%) 70 (65%) 57 (91%) 43
(100%); HRMS (DART), calcd for C17H35F3OSi [M + NH4]+: 358.2753, found: 358.2759.
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4-(4-(tert-butyl)phenyl)-1,1,1-trifluoro-2-((trimethylsilyl)methyl)butan-2-ol (2k) (2.728 g,
89%) was prepared according to the representative procedure for the synthesis of 2a from 3ꢀ
cyclohexylꢀ1,1,1ꢀtrifluoropropanꢀ2ꢀone, 1k (2.100 g, 10.8 mmol) affording the pure carbinol as a
clear, pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm 0.10 (s, 9 H) 0.91 ꢀ 1.36 (m, 8 H) 1.52
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ꢀ 1.60 (m, 2 H) 1.60 ꢀ 1.74 (m, 4 H) 1.76 (s, 1 H) 1.83 ꢀ 1.93 (m, 1 H); C NMR (CDCl3, 100
MHz) δ ppm 0.4 (CH3) 24.4 (CH2) 26.4 (CH2) 26.6 (CH2) 26.7 (CH2) 33.3 (CH) 35.2 (CH2) 35.6
(CH2) 43.7 (CH2) 77.0 (q, JCꢀCꢀF = 27.9 Hz, C) 127.0 (q, JCꢀF = 286.1 Hz, CF3); 19F NMR (CDCl3,
377 MHz) δ ppm ꢀ84.53; GCꢀMS (EI) 282 ([M]+, 2%) 213 (3%) 153 (10%) 133 (26%) 131
(11%) 125 (8%) 111 (13%) 83 (100%) 73 (77%); HRMS (DART), calcd for C13H25F3OSi [M +
H]+: 283.1705, found: 283.1701.
1,1,1-trifluoro-3-methyl-4-phenyl-2-((trimethylsilyl)methyl)butan-2-ol (2l) (1.9725 g, 88%)
was prepared according to the representative procedure for the synthesis of 2a from 1,1,1ꢀ
trifluoroꢀ3ꢀmethylꢀ4ꢀphenylbutanꢀ2ꢀone, 1l (1.600 g, 7.9 mmol) affording the pure carbinol as a
clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm 0.20 (apparent doublet, J = 5.38 Hz, 9 H)
0.94 (t, J = 7.58 Hz, 3 H) 1.09 ꢀ 1.27 (m, 2 H) 2.05 (br. s., 1 H) 2.10 ꢀ 2.34 (m, 2 H) 3.23 (t, J =
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11.70 Hz, 1 H) 7.18 ꢀ 7.28 (m, 3 H) 7.30 ꢀ 7.37 (m, 2 H); C NMR (CDCl3, 100 MHz) δ ppm
0.5 (CH3) 0.5 (CH3) 13.9 (q, JCꢀCꢀCꢀCꢀF = 2.2 Hz, CH3) 14.0 (d, JCꢀCꢀCꢀCꢀF = 1.5 Hz, CH3) 20.1
(CH2) 21.8 (CH2) 37.4 (d, JCꢀCꢀCꢀF = 1.5 Hz, CH) 37.6 (d, JCꢀCꢀCꢀF = 2.2 Hz, CH) 42.7 (CH2) 43.1
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(CH2) 78.7 (q, JCꢀCꢀF = 26.4 Hz, C) 79.0 (q, JCꢀCꢀF = 26.4 Hz, C) 127.3 (q, JCꢀF = 287.6 Hz, CF3)
127.4 (q, JCꢀF = 287.6 Hz, CF3) 141.0 (C) 141.3 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ79.49
(s, 3 F) ꢀ78.92 (s, 3 F); GCꢀMS (EI) 304 ([M]+, 4%) 214 (4%) 194 (6%) 175 (16%) 147 (4%)
117 (6%) 91 (100%) 73 (24%); HRMS (DART), calcd for C15H23F3OSi [M + NH4]+: 322.1814,
found: 322.1849.
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1,1,1-trifluoro-4-(furan-2-yl)-2-((trimethylsilyl)methyl)butan-2-ol (2m) (5.280 g, 73%) was
prepared according to the representative procedure for the synthesis of 2a from 1,1,1ꢀtrifluoroꢀ4ꢀ
(furanꢀ2ꢀyl)butanꢀ2ꢀone, 1m (4.9956 g, 26 mmol) affording the pure carbinol as a clear, brown
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oil. H NMR (CDCl3, 400 MHz) δ ppm 0.12 (s, 9 H) 1.06 ꢀ 1.15 (m, 1 H) 1.16 ꢀ 1.24 (m, 1 H)
1.92 (s, 1 H) 2.02 ꢀ 2.12 (m, 2 H) 2.79 (dd, J = 10.39, 6.48 Hz, 2 H) 6.02 (d, J = 3.18 Hz, 1 H)
6.29 (dd, J = 3.18, 1.96 Hz, 1 H) 7.32 (d, J = 1.22 Hz, 1 H); 13C NMR (CDCl3, 100 MHz) δ ppm
0.3 (CH3) 22.4 (CH2) 23.5 (CH2) 34.9 (CH2) 76.1 (q, J = 28.6 Hz, C) 105.4 (CH) 110.5 (CH)
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126.9 (q, J = 286.1 Hz, CF3) 141.5 (CH) 155.1 (C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ84.07;
GCꢀMS (EI) 280 ([M]+, 5%) 262 (8%) 170 (21%) 151 (9%) 141 (4%) 123 (11%) 103 (9%) 94
(14%) 81 (100%) 73 (44%) 53 (17%) 45 (10%); HRMS (DART), calcd for C12H19F3O2Si [M +
H]+: 281.1185, found: 281.1179.
1,1,1,2,2-pentafluoro-5-phenyl-3-((trimethylsilyl)methyl)pentan-3-ol (2n) (1.508 g, 93%) was
prepared according to the representative procedure for the synthesis of 2a from 1,1,1,2,2ꢀ
pentafluoroꢀ5ꢀphenylpentanꢀ3ꢀone, 1n (1.200 g, 4.76 mmol) affording the pure carbinol as a
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clear, yellow oil. H NMR (CDCl3, 400 MHz) δ ppm 0.19 (s, 8 H) 1.19 ꢀ 1.27 (m, 1 H) 1.33 ꢀ
1.41 (m, 1 H) 2.03 (s, 1 H) 2.10 (dd, J = 11.25, 6.11 Hz, 2 H) 2.72 ꢀ 2.83 (m, 2 H) 7.19 ꢀ 7.25 (m,
3 H) 7.30 ꢀ 7.37 (m, 2 H); 13C NMR (CDCl3, 100 MHz) δ ppm 0.7 (CH3) 23.5 (CH2) 30.0 (br. s,
CH2) 39.2 (CH2) 77.3 (t, JCꢀCꢀF = 22.70 Hz, C) 115.9 (tq, JCꢀF = 261.2, 34.5 Hz, CF2) 119.9 (qt,
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JCꢀF = 288.3, 37.4 Hz, CF3) 126.5 (CH) 128.6 (CH) 128.9 (CH) 141.4 (C); 19F NMR (CDCl3, 377
MHz) δ ppm ꢀ125.31 ꢀ ꢀ123.20 (m, 2 F) ꢀ80.98 (s, 3 F); GCꢀMS (EI) 340 ([M]+, 4%) 250 (11%)
231 (9%) 211 (8%) 191 (5%) 161 (9%) 129 (7%) 119 (3%) 105 (8%) 91 (100%) 73 (28%);
HRMS (DART), calcd for C15H21F5OSi [M + NH4]+: 358.1626, found: 358.1640.
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1,1-difluoro-4-phenyl-2-((trimethylsilyl)methyl)butan-2-ol (2o) (4.7627 g, 92%) was prepared
according to the representative procedure for the synthesis of 2a from 1,1ꢀdifluoroꢀ4ꢀ
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phenylbutanꢀ2ꢀone, 1o (3.500 g, 19 mmol) affording the pure carbinol as a clear, orange oil. H
NMR (CDCl3, 400 MHz) δ ppm 0.14 (s, 9 H) 1.09 (d, J = 11.74 Hz, 2 H) 1.75 (s, 1 H) 1.89 ꢀ 1.98
(m, 2 H) 2.69 ꢀ 2.80 (m, 2 H) 5.62 (t, J = 57.00 Hz, 1 H) 7.17 ꢀ 7.24 (m, 3 H) 7.27 ꢀ 7.34 (m, 2
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H); C NMR (CDCl3, 100 MHz) δ ppm 0.7 (CH3) 23.3 (CH2) 29.6 (CH2) 38.7 (t, JCꢀCꢀCꢀF = 1.8
Hz, CH2) 75.5 (t, JCꢀCꢀF = 21.3 Hz, C) 117.9 (t, JCꢀF = 248.7 Hz, CF2H) 126.3 (CH) 128.6 (CH)
128.8 (CH) 142.0 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ134.72 (dd, J = 276.56, 55.86 Hz, 1
F) ꢀ133.29 (dd, J = 276.57, 57.22 Hz, 1 F); GCꢀMS (EI) 272 ([M]+, 3%) 254 (2%) 221 (6%) 182
(8%) 162 (10%) 143 (45%) 128 (16%) 104 (11%) 91 (100%) 73 (31%) 65 (8%) 47 (7%); HRMS
(DART), calcd for C14H22F2OSi [M + NH4]+: 290.1752, found: 290.1770.
1-fluoro-4-phenyl-2-((trimethylsilyl)methyl)butan-2-ol (2p) (1.98 g, 52%) was prepared
according to the representative procedure for the synthesis of 2a from 1ꢀfluoroꢀ4ꢀphenylbutanꢀ2ꢀ
one, 1p (2.49 g, 15 mmol) with the following modifications: (a) Further purification was
accomplished by FCC (gradient Hex to 95:5 Hex: EtOAc to 9:1 Hex:EtOAc). The pure carbinol
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was obtained as an off white semiꢀsolid. H NMR (CDCl3, 400 MHz) δ ppm 0.20 (s, 9 H) 1.07
(apparent quartet of doublets, J = 12.00, 2.00 Hz, 2 H) 1.95 (dd, J = 11.25, 6.11 Hz, 2 H) 2.04
(s, 1 H) 2.77 (apparent doublet of doublets, J = 10.88, 5.80 Hz, 2 H) 4.33 (dq, J = 47.80, 8.60
Hz, 2 H) 7.27 (m, 3 H) 7.36 (apparent triplet, J = 7.20 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ
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ppm 0.7 (CH3) 25.3 (d, JCꢀCꢀCꢀF = 3.1 Hz, CH2) 30.5 (CH2) 40.9 (d, JCꢀCꢀCꢀF = 3.3 Hz, CH2) 74.7
(d, JCꢀCꢀF = 17.6 Hz, C) 89.3 (d, JCꢀF = 174.1 Hz, CFH2) 126.2 (CH) 128.5 (CH) 128.7 (CH) 142.2
(C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ227.55 (t, J = 47.70 Hz); GCꢀMS (EI) 254 ([M]+, 1%)
236 (2%) 221 (8%) 164 (4%) 149 (10%) 145 (18%) 129 (29%) 117 (19%) 104 (12%) 91 (100%)
75 (29%) 65 (11%) 57 (15%) 45 (9%); HRMS (DART), calcd for C14H23FOSi [M + NH4]+:
272.1846, found: 272.1842.
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(E)-1,1,1-trifluoro-4-phenyl-2-((trimethylsilyl)methyl)but-3-en-2-ol (2q) (3.514 g, 81%) was
prepared according to the representative procedure for the synthesis of 2a from (E)ꢀ1,1,1ꢀ
trifluoroꢀ4ꢀphenylbutꢀ3ꢀenꢀ2ꢀone, 1q (2.900 g, 15 mmol) with the following modification: (a) A
gradient was used (pentane to 95:5 pentane:EtOAc) when eluting the off the silica gel plug.33
The pure carbinol was obtained as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm 0.04 (s,
9 H) 1.23 ꢀ 1.41 (m, 2 H) 2.16 (s, 1 H) 6.21 (d, J = 16.14 Hz, 1 H) 6.85 (d, J = 16.14 Hz, 1 H)
7.26 ꢀ 7.48 (m, 5 H); 13C NMR (CDCl3, 100 MHz) δ ppm 0.5 (CH3) 24.1 (CH2) 76.8 (q, JCꢀCꢀF
=
29.3 Hz, C) 125.9 (q, JCꢀF = 286.1 Hz, CF3) 127.0 (CH) 128.5 (CH) 129.0 (CH) 131.8 (CH 136.1
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(C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ86.05; GCꢀMS (EI) 288 ([M]+, 3%) 219 (53%) 203
(10%) 177 (12%) 159 (45%) 129 (100%) 115 (9%) 73 (22%) 69 (1%); HRMS (DART), calcd
for C14H19F3OSi [M ꢀ CF3]+: 219.1205, found: 219.1198.
(E)-1,1,1-trifluoro-3-methyl-4-phenyl-2-((trimethylsilyl)methyl)but-3-en-2-ol (2r) (3.150 g,
87%) was prepared according to the representative procedure for the synthesis of 2a from (E)ꢀ
1,1,1ꢀtrifluoroꢀ3ꢀmethylꢀ4ꢀphenylbutꢀ3ꢀenꢀ2ꢀone, 1r (2.570 g, 12 mmol) affording the pure
carbinol as a clear, pale yellow oil. 1H NMR (CDCl3, 500 MHz) δ ppm 0.15 (s, 9 H) 1.33 (d, J =
14.98 Hz, 1 H) 1.53 (d, J = 15.13 Hz, 1 H) 1.95 (s, 3 H) 2.21 (s, 1 H) 6.93 (s, 1 H) 7.30 (d, J =
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7.09 Hz, 3 H) 7.37 ꢀ 7.44 (m, 2 H); C NMR (CDCl3, 125 MHz) δ ppm 0.3 (CH3) 15.2 (CH3)
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22.6 (CH2) 79.0 (q, JCꢀCꢀF = 28.0 Hz, C) 126.3 (q, JCꢀF = 287.4 Hz, CF3) 127.1 (CH) 128.5 (CH)
128.8 (CH) 129.3 (CH) 135.2 (C) 137.6 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ83.65; GCꢀMS
(EI) 302 ([M]+, 9%) 233 (99%) 217 (11%) 197 (14%) 177 (19%) 173 (35%) 143 (100%) 128
(78%) 115 (39%) 91 (16%) 73 (40%) 69 (2%); HRMS (DART), calcd for C15H21F3OSi [M ꢀ
OH]+: 285.1286, found: 285.1277.
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(E)-1,1,1-trifluoro-2-((trimethylsilyl)methyl)dodec-3-en-2-ol (2s) (2.339 g, 92%) was
prepared according to the representative procedure for the synthesis of 2a from (E)ꢀ1,1,1ꢀ
trifluorododecꢀ3ꢀenꢀ2ꢀone, 1s (1.820 g, 8.19 mmol) affording the pure carbinol as a clear,
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colorless oil. H NMR (CDCl3, 400 MHz) δ ppm 0.07 ꢀ 0.11 (m, 9 H) 0.87 ꢀ 0.96 (m, 3 H) 1.13
(d, J = 14.92 Hz, 1 H) 1.26 (d, J = 14.92 Hz, 1 H) 1.32 (s, 8 H) 1.39 ꢀ 1.51 (m, 2 H) 2.05 ꢀ 2.09
(m, 1 H) 2.12 (d, J = 7.09 Hz, 2 H) 5.51 (d, J = 15.65 Hz, 1 H) 5.92 (d, J = 15.65 Hz, 1 H); 13C
NMR (CDCl3, 100 MHz) δ ppm 0.5 (CH3) 14.3 (CH3) 22.9 (CH2) 23.7 (CH2) 29.1 (CH2) 29.4
(CH2) 29.5 (CH2) 32.1 (CH2) 32.4 (CH2) 76.3 (q, JCꢀCꢀF = 28.6 Hz, C) 126.0 (q, JCꢀF = 285.4 Hz,
CF3) 128.0 (CH) 133.3 (CH); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ86.47; GCꢀMS (EI) 324
([M]+, 2%) 251 (8%) 224 (3%) 177 (4%) 139 (11%) 115 (11%) 97 (16%) 84 (32%) 73 (15%) 69
(71%) 56 (81%) 43 (100%); HRMS (DART), calcd for C16H31F3OSi [M ꢀ H]+: 323.2018, found:
323.2014.
(E)-1,1,1-trifluoro-4-(furan-2-yl)-2-((trimethylsilyl)methyl)but-3-en-2-ol (2t) (1.627 g, 61%)
was prepared according to the representative procedure for the synthesis of 2a from (E)ꢀ1,1,1ꢀ
trifluoroꢀ4ꢀ(furanꢀ2ꢀyl)butꢀ3ꢀenꢀ2ꢀone, 1t (1.82 g, 9.47 mmol) with the following modification:
(a) A gradient was used (pentane to 95:5 pentane:EtOAc) when eluting the off the silica gel
plug.33 The pure carbinol was obtained as a clear, brown oil. 1H NMR (CDCl3, 400 MHz) δ ppm
0.04 ꢀ 0.12 (m, 9 H) 1.25 (d, J = 14.92 Hz, 1 H) 1.32 (d, J = 14.67 Hz, 1 H) 2.18 (br. s., 1 H) 6.16
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(d, J = 15.89 Hz, 1 H) 6.33 (d, J = 3.18 Hz, 1 H) 6.40 (dd, J = 3.30, 1.83 Hz, 1 H) 6.66 (d, J =
15.89 Hz, 1 H) 7.38 (d, J = 1.47 Hz, 1 H); 13C NMR (CDCl3, 100 MHz) δ ppm 0.4 (CH3) 24.3
(CH2) 76.6 (q, JCꢀCꢀF = 29.3 Hz, C) 109.7 (CH) 111.7 (CH) 120.3 (CH) 125.9 (q, JCꢀF = 285.4 Hz,
CF3) 125.5 (CH) 143.0 (CH) 152.0 (C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ85.93; GCꢀMS (EI)
278 ([M]+, 29%) 209 (83%) 193 (19%) 188 (10%) 170 (12%) 159 (11%) 149 (14%) 141 (7%)
119 (100%) 109 (10%) 91 (69%) 81 (10%) 77 (26%) 73 (68%) 65 (15%) 55 (21%); HRMS
(DART), calcd for C12H17F3O2Si [M + H]+: 279.1028, found: 279.1032.
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General Procedure for Alkene Synthesis:
(3-(trifluoromethyl)but-3-en-1-yl)benzene (3a)7 To a 100 mL one neck round bottom was
equipped with stirbar was added the carbinol, 2a (1.45 g, 5 mmol, 1 equiv) and CH2Cl2 (25 mL,
0.2 M in the alcohol).34 The solution was cooled to 0 oC via an iceꢀwater bath and stirred for ten
minutes at this temperature. After this time, TMSOTf (0.167 g, 0.14 mL, 0.15 equiv) was added
to the flask dropwise over one minute. The flask was then equipped with a reflux condenser and
heated to reflux for 4 h.35 After this time, the flask was cooled to room temperature and
quenched with 50 mL of aqueous saturated NaHCO3. The reaction mixture was transferred to a
separatory funnel and diluted with pentane (≈150 mL). The layers were separated and the
aqueous layer was extracted with pentane (3 x 75 mL). The combined organic layers were
washed with brine (≈150 mL) and dried with Na2SO4. The solvent was removed in vacuo by
rotary evaporation. The crude product was gently added atop a silica gel plug and eluted with
pentane36 (2ꢀ3 column volumes). The solvent was removed in vacuo by rotary evaporation
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affording the pure alkene (0.745 g, 74%) as a clear, colorless oil. H NMR (CDCl3, 400 MHz) δ
ppm 2.53 (t, J = 8.07 Hz, 2 H) 2.81 ꢀ 2.89 (m, 2 H) 5.30 (d, J = 1.22 Hz, 1 H) 5.69 (s, 1 H) 7.18 ꢀ
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7.25 (m, 3 H) 7.28 ꢀ 7.35 (m, 2 H); C NMR (CDCl3, 100 MHz) δ ppm 31.5 (CH2) 34.1 (CH2)
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118.5 (q, JCꢀCꢀCꢀF = 5.9 Hz, CH2) 124.1 (q, JCꢀF = 273.6 Hz, CF3) 126.5 (CH) 128.7 (CH) 128.8
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(CH) 138.1 (q, JCꢀCꢀF = 29.3 Hz, C) 140.9 (C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ71.49; GCꢀ
MS (EI) 200 ([M]+, 24%) 161 (6%) 128 (4%) 115 (4%) 91 (100%) 69 (4%) 51 (5%).
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1-(tert-butyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (3b)12 (0.868 g, 86%) was prepared
according to the representative procedure for the synthesis of 3a from 2ꢀ(4ꢀ(tertꢀbutyl)phenyl)ꢀ
1,1,1ꢀtrifluoroꢀ3ꢀ(trimethylsilyl)propanꢀ2ꢀol, 2b (1.40 g, 4.4 mmol), with the following
modification: (a) Reaction was stirred for 15 min at room temperature. The pure CF3 alkene was
obtained as a clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm 1.38 ꢀ 1.40 (m, 9 H) 5.80 (q,
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J = 1.70 Hz, 1 H) 5.96 (q, J = 1.40 Hz, 1 H) 7.46 (s, 4 H); C NMR (CDCl3, 100 MHz) δ ppm
31.5 (CH3) 34.9 (C) 119.85 (q, JCꢀCꢀCꢀF = 5.9 Hz, CH2) 123.8 (q, JCꢀF = 273.8 Hz, CF3) 125.8
(CH) 127.3 (CH) 131.0 (C) 139.1 (q, JCꢀCꢀF = 30.5 Hz, C) 152.5 (C); 19F NMR (CDCl3, 377
MHz) δ ppm ꢀ67.87; GCꢀMS (EI) 228 ([M]+, 20%) 213 (100%) 185 (45%) 128 (8%) 115 (11%)
77 (4%) 69 (2%).
1-methoxy-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (3c)37 (0.811 g, 80%) was prepared
according to the representative procedure for the synthesis of 3a from 1,1,1ꢀtrifluoroꢀ2ꢀ(4ꢀ
methoxyphenyl)ꢀ3ꢀ(trimethylsilyl)propanꢀ2ꢀol, 2c (1.46 g, 5 mmol, with the following
modification: (a) Reaction was stirred for 15 min at room temperature. The pure CF3 alkene was
obtained as a clear, pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm 3.82 ꢀ 3.85 (m, 3 H) 5.71
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(q, J = 1.71 Hz, 1 H) 5.86 ꢀ 5.90 (m, 1 H) 6.89 ꢀ 6.95 (m, 2 H) 7.42 (d, J = 8.31 Hz, 2 H); C
NMR (CDCl3, 100 MHz) δ ppm 55.5 (CH3) 114.2 (CH) 119.1 (q, JCꢀCꢀCꢀF = 5.6 Hz, CH2) 123.8
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(q, JCꢀF = 273.2 Hz, CF3) 126.3 (CH) 128.91 (C) 138.7 (q, JCꢀCꢀF = 30.1 Hz, C) 160.5 (C); F
NMR (CDCl3, 377 MHz) δ ppm ꢀ67.91; GCꢀMS (EI) 202 ([M]+, 98%) 183 (5%) 159 (7%) 133
(100%) 118 (13%) 109 (30%) 103 (11%) 89 (16%) 69 (5%) 63 (13%).
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N,N-dimethyl-4-(3,3,3-trifluoroprop-1-en-2-yl)aniline (3d) (1.33 g, 95%) was prepared
according to the representative procedure for the synthesis of 3a from 2ꢀ(4ꢀ
(dimethylamino)phenyl)ꢀ1,1,1ꢀtrifluoroꢀ3ꢀ(trimethylsilyl)propanꢀ2ꢀol, 2d (1.99 g, 6.5 mmol, with
the following modifications: (a) Reaction was heated at reflux in DCE for 4.5 h. (b) 0.3 equiv of
TMSOTf was used. (c) A silica gel plug was not required. The pure CF3 alkene was obtained as
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an orange, crystalline solid (m.p. 49ꢀ50 C). H NMR (CDCl3, 400 MHz) δ ppm 3.01 (s, 6 H)
5.69 (d, J = 1.71 Hz, 1 H) 5.80 (d, J = 0.98 Hz, 1 H) 6.73 (d, J = 9.05 Hz, 2 H) 7.40 (d, J = 8.56
Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ ppm 40.5 (CH3) 112.2 (CH) 116.8 (q, JCꢀCꢀCꢀF = 5.9 Hz,
CH2) 124.1 (q, JCꢀF = 274.4 Hz, CF3) 121.4 (C) 128.3 (CH) 138.7 (q, JCꢀCꢀF = 29.3 Hz, C) 151.00
(C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ67.52; GCꢀMS (EI) 215 ([M]+, 100%) 199 (19%) 151
(7%) 146 (23%) 130 (11%) 102 (8%) 69 (4%); HRMS (ESI+), calcd for C11H12F3N [M + H]+:
216.1000, found: 216.0984.
1-(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (3e)8
(0.759 g, 63%) was prepared according to the representative procedure for the synthesis of 3a
from 1,1,1ꢀtrifluoroꢀ2ꢀ(4ꢀ(trifluoromethyl)phenyl)ꢀ3ꢀ(trimethylsilyl)propanꢀ2ꢀol, 2e (1.65 g, 5
mmol) affording the pure CF3 alkene as a clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm
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5.85 (q, J = 1.47 Hz, 1 H) 6.04 ꢀ 6.10 (m, 1 H) 7.55 ꢀ 7.61 (m, 2 H) 7.63 ꢀ 7.69 (m, 2 H); C
NMR (CDCl3, 100 MHz) δ ppm 122.4 (q, JCꢀCꢀCꢀF = 5.9 Hz, CH2) 123.3 (q, JCꢀF = 272.9 Hz, CF3)
124.2 (q, JCꢀF = 272.2 Hz, CF3) 125.9 (q, JCꢀCꢀCꢀF = 3.7 Hz, CH) 128.2 (d, JCꢀCꢀCꢀCꢀF = 1.5 Hz, CH)
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131.4 (q, JCꢀCꢀF = 32.3 Hz, C) 137.4 (C) 138.4 (q, JCꢀCꢀF = 30.8 Hz, C); F NMR (CDCl3, 377
MHz) δ ppm ꢀ68.01 (s, 3 F) ꢀ66.03 (s, 3 F); GCꢀMS (EI) 240 ([M]+, 86%) 221 (40%) 201 (4%)
171 (100%) 169 (14%) 151 (95%) 145 (12%) 102 (15%) 75 (12%) 69 (12%).
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1-(benzyloxy)-2-(3,3,3-trifluoroprop-1-en-2-yl)benzene (3f) (1.18g, 85%) was prepared
according to the representative procedure for the synthesis of 3a from 2ꢀ(2ꢀ(benzyloxy)phenyl)ꢀ
1,1,1ꢀtrifluoroꢀ3ꢀ(trimethylsilyl)propanꢀ2ꢀol, 2f (1.84 g, 5 mmol), with the following
modification: (a) Reaction was stirred for 15 min at room temperature. The pure CF3 alkene was
obtained as a clear, pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm 5.07 (s, 2 H) 5.64 (d, J =
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1.19 Hz, 1 H) 6.07 (d, J = 1.19 Hz, 1 H) 6.90 ꢀ 6.98 (m, 2 H) 7.19 ꢀ 7.39 (m, 7 H); C NMR
(CDCl3, 100 MHz) δ ppm 70.6 (CH2) 113.0 (CH) 120.9 (C) 123.5 (q, JCꢀF = 273.6 Hz, CF3)
123.7 (q, JCꢀCꢀCꢀF = 5.1 Hz, CH2) 124.0 (CH) 127.3 (CH) 128.1 (CH) 128.8 (CH) 130.5 (CH)
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131.1 (CH) 136.3 (q, JCꢀCꢀF = 31.5 Hz, C) 137.2 (CH) 156.8 (C); F NMR (CDCl3, 377 MHz) δ
ppm ꢀ68.49; GCꢀMS (EI) 279 ([M]+, 7%) 258 (4%) 209 (2%) 186 (5%) 118 (3%) 109 (7%) 91
(100%) 69 (12%); HRMS (DART), calcd for C16H13F3O [M + NH4]+: 296.1262, found:
296.1279.
1-(3,3,3-trifluoroprop-1-en-2-yl)naphthalene (3g)11 (1.01 g, 91%) was prepared according to
the representative procedure for the synthesis of 3a from 1,1,1ꢀtrifluoroꢀ2ꢀ(naphthalenꢀ1ꢀyl)ꢀ3ꢀ
(trimethylsilyl)propanꢀ2ꢀol, 2g (1.56 g, 5 mmol), with the following modification: (a) Reaction
was stirred for 15 min at room temperature. The pure CF3 alkene was obtained as a clear,
colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm 5.72 (d, J = 0.98 Hz, 1 H) 6.39 (d, J = 1.47 Hz,
1 H) 7.47 ꢀ 7.62 (m, 4 H) 7.87 ꢀ 7.97 (m, 2 H) 7.98 ꢀ 8.06 (m, 1 H); 13C NMR (CDCl3, 100 MHz)
δ ppm 123.5 (q, JCꢀF = 273.6 Hz, CF3) 124.4 (q, JCꢀCꢀCꢀF = 5.9 Hz, CH2) 125.2 (CH) 125.6 (CH)
126.4 (CH) 126.9 (CH) 127.7 (CH) 128.6 (CH) 129.6 (CH) 131.8 (C) 132.4 (C) 134.0 (C) 137.6
(q, JCꢀCꢀF = 31.2 Hz, C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ69.79; GCꢀMS (EI) 222 ([M]+,
39%) 201 (22%) 183 (7%) 153 (100%) 151 (20%) 126 (6%) 69 (5%).
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2-(3,3,3-trifluoroprop-1-en-2-yl)benzofuran (3i) (0.967 g, 86%) was prepared according to the
representative procedure for the synthesis of 3a from 2ꢀ(benzofuranꢀ2ꢀyl)ꢀ1,1,1ꢀtrifluoroꢀ3ꢀ
(trimethylsilyl)propanꢀ2ꢀol, 2i (1.60 g, 5.3 mmol), with the following modification: (a) Reaction
was stirred for 15 min at room temperature. The pure CF3 alkene was obtained as a clear,
colorless oil. 1H NMR (CDCl3, 500 MHz) δ ppm 6.06 (s, 1 H) 6.36 (s, 1 H) 6.97 (s, 1 H) 7.32 (t,
J = 7.60 Hz, 1 H) 7.41 (t, J = 7.40 Hz, 1 H) 7.55 (d, J = 8.20 Hz, 1 H) 7.65 (d, J = 7.72 Hz, 1 H);
13C NMR (CDCl3, 125 MHz) δ ppm 106.5 (q, JCꢀCꢀCꢀCꢀF = 1.7 Hz, CH) 111.4 (CH) 118.3 (q, JCꢀCꢀ
CꢀF = 5.1 Hz, CH2) 122.8 (q, JCꢀF = 272.1 Hz, CF3) 122.0 (CH) 123.6 (CH) 126.0 (CH) 128.7 (C)
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129.7 (q, JCꢀCꢀF = 32.2 Hz, C) 148.7 (C) 155.0 (C) F NMR (CDCl3, 377 MHz) δ ppm ꢀ68.70;
GCꢀMS (EI) 212 ([M]+, 100%) 183 (3%) 143 (54%) 133 (7%) 115 (49%) 89 (9%) 69 (6%);
HRMS (DART), calcd for C11H7F3O [M]+: 212.0449, found: 212.0443.
2-(trifluoromethyl)tridec-1-ene (3j) (1.10 g, 88%) was prepared according to the representative
procedure for the synthesis of 3a from 1,1,1ꢀtrifluoroꢀ2ꢀ((trimethylsilyl)methyl)tridecanꢀ2ꢀol, 2j
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(1.70 g, 5 mmol) affording the pure CF3 alkene as a clear, colorless oil. H NMR (CDCl3, 500
MHz) δ ppm 0.89 (t, J = 7.10 Hz, 3 H) 1.21 ꢀ 1.38 (m, 16 H) 1.47 ꢀ 1.56 (m, 2 H) 2.19 (t, J =
7.80 Hz, 2 H) 5.29 (q, J = 1.40 Hz, 1 H) 5.65 (d, J = 1.42 Hz, 1 H); 13C NMR (CDCl3, 125 MHz)
δ ppm 14.4 (CH3) 23.0 (CH2) 27.7 (CH2) 29.4 (CH2) 29.7 (CH2) 29.7 (CH2) 29.7 (CH2) 29.9
(CH2) 29.9 (CH2) 30.0 (CH2) 32.2 (CH2) 117.5 (q, JCꢀCꢀCꢀF = 5.9 Hz, CH2) 124.2 (q, JCꢀF = 273.8
Hz, CF3) 139.1 (q, JCꢀCꢀF = 28.8 Hz, C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ71.75; GCꢀMS (EI)
250 ([M]+, 2%) 194 (4%) 165 (7%) 131 (7%) 111 (30%) 97 (49%) 83 (48%) 70 (65%) 57 (91%)
43 (100%); HRMS (DART), calcd for C14H25F3 [M – C4H9]+: 193.1199, found: 193.1233; FTIR
(cm‐1, neat, ATR) = 2926, 2855, 1467, 1168, 1125, 937, 792, 637.
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(2-(trifluoromethyl)allyl)cyclohexane (3k) (0.622 g, 65%) was prepared according to the
representative procedure for the synthesis of 3a from 3ꢀcyclohexylꢀ1,1,1ꢀtrifluoroꢀ2ꢀ
((trimethylsilyl)methyl)propanꢀ2ꢀol, 2k (1.42 g, 5 mmol) affording the pure CF3 alkene as a
clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm 0.82 ꢀ 0.93 (m, 2 H) 1.10 ꢀ 1.31 (m, 3 H)
1.46 ꢀ 1.57 (m, 1 H) 1.63 ꢀ 1.79 (m, 5 H) 2.08 (d, J = 7.25 Hz, 2 H) 5.27 (s, 1 H) 5.69 (s, 1 H);
13C NMR (CDCl3, 100 MHz) δ ppm 26.4 (CH2) 26.7 (CH2) 33.3 (CH2) 35.9 (CH) 38.1 (CH2)
119.1 (q, JCꢀCꢀCꢀF = 5.9 Hz, CH2) 124.2 (q, JCꢀF = 273.8 Hz, CF3) 137.2 (q, JCꢀCꢀF = 28.8 Hz, C);
19F NMR (CDCl3, 377 MHz) δ ppm ꢀ71.39; GCꢀMS (EI) 192 ([M]+, 3%) 153 (3%) 133 (6%) 127
(2%) 115 (3%) 109 (6%) 83 (100%) 69 (4%) 55 (70%) 41 (22%); HRMS (DART), calcd for
C10H15F3 [M – C3H4 + H]+: 153.0891, found: 153.0917; FTIR (cm‐1, neat, ATR) = 2926, 2854,
1450, 1167, 1123, 936, 842.
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(2-methyl-3-(trifluoromethyl)but-3-en-1-yl)benzene (3l) (0.900 g, 84%) was prepared
according to the representative procedure for the synthesis of 3a from 1,1,1ꢀtrifluoroꢀ3ꢀmethylꢀ4ꢀ
phenylꢀ2ꢀ((trimethylsilyl)methyl)butanꢀ2ꢀol, 2l (1.52 g, 5 mmol) affording the pure CF3 alkene
as a clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm 1.17 (d, J = 6.85 Hz, 3 H) 2.64 (dd, J
= 13.33, 8.93 Hz, 1 H) 2.74 ꢀ 2.84 (m, 1 H) 3.03 (dd, J = 13.45, 5.38 Hz, 1 H) 5.39 ꢀ 5.44 (m, 1
H) 5.81 (q, J = 1.47 Hz, 1 H) 7.21 ꢀ 7.26 (m, 2 H) 7.26 ꢀ 7.31 (m, 1 H) 7.33 ꢀ 7.39 (m, 2 H); 13C
NMR (CDCl3, 100 MHz) δ ppm 19.8 (CH3) 35.7 (CH) 42.9 (CH2) 117.7 (q, JCꢀF = 5.9 Hz, CH2)
124.5 (q, JCꢀF = 274.4 Hz, CF3) 126.5 (CH) 128.6 (CH) 129.5 (CH) 140.0 (C) 143.7 (q, JCꢀCꢀF
=
27.9 Hz, C); 19F NMR (CDCl3, 377 MHz) δ ppm ꢀ70.44; GCꢀMS (EI) 214 ([M]+, 11%) 175 (5%)
128 (6%) 91 (100%) 69 (7%); HRMS (DART), calcd for C12H13F3 [M + H]+: 215.1048, found:
215.1032.
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(4,4,5,5,5-pentafluoro-3-methylenepentyl)benzene (3n) (0.772 g, 75%) was prepared
according to the representative procedure for the synthesis of 3a from 1,1,1,2,2ꢀpentafluoroꢀ5ꢀ
phenylꢀ3ꢀ((trimethylsilyl)methyl)pentanꢀ3ꢀol, 2n (1.40 g, 4.11 mmol), with the following
modification: (a) Reaction was heated for 4 h at reflux in DCE. The pure CF3 alkene was
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obtained as a clear, colorless oil. H NMR (CDCl3, 400 MHz) δ ppm 2.58 (t, J = 8.07 Hz, 2 H)
2.90 (t, J = 7.80 Hz, 2 H) 5.54 (s, 1 H) 5.78 (s, 1 H) 7.23 ꢀ 7.31 (m, 3 H) 7.33 ꢀ 7.40 (m, 2 H);
13C NMR (CDCl3, 100 MHz) δ ppm 31.7 (CH2) 34.5 (CH2) 113.7 (tq, JCꢀF = 253.1, JCꢀCꢀF = 37.4
Hz, CF2) 119.5 (qt, JCꢀF = 286.8, JCꢀCꢀF = 38.9 Hz, CF3) 121.3 (t, JCꢀCꢀCꢀF = 8.8 Hz, CH2) 126.6
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(CH) 128.7 (CH) 128.8 (CH) 137.6 (t, JCꢀCꢀF = 21.3 Hz, C) 140.8 (C); F NMR (CDCl3, 377
MHz) δ ppm ꢀ119.29 (s, 2 F) ꢀ86.87 (s, 3 F); GCꢀMS (EI) 250 ([M]+, 25%) 211 (5%) 191 (3%)
91 (100%) 69 (3%) 65 (13%); HRMS (DART), calcd for C12H11F5 [M – C5H6F5 ꢀ H]+: 91.0548,
found: 91.0579; FTIR (cm‐1, neat, ATR) = 3066, 3030, 2931, 2362, 1605, 1453, 1332, 1202,
1122, 1023, 940, 698.
(3-(difluoromethyl)but-3-en-1-yl)benzene (3o)9 (0.838 g, 92%) was prepared according to the
representative procedure for the synthesis of 3a from 1,1ꢀdifluoroꢀ4ꢀphenylꢀ2ꢀ
((trimethylsilyl)methyl)butanꢀ2ꢀol, 2o (1.36 g, 5 mmol), with the following modification: (a)
Reaction was stirred for 15 min at room temperature. The pure CF3 alkene was obtained as a
clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ ppm 2.58 (t, J = 8.07 Hz, 2 H) 2.92 (t, J = 8.30
Hz, 2 H) 5.26 ꢀ 5.31 (m, 1 H) 5.44 (s, 1 H) 6.09 (t, J = 56.00 Hz, 1 H) 7.26 ꢀ 7.33 (m, 3 H) 7.34 ꢀ
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7.42 (m, 2 H); C NMR (CDCl3, 100 MHz) δ ppm 30.5 (t, JCꢀCꢀCꢀF = 1.5 Hz, CH2) 34.2 (CH2)
117.8 (q, JCꢀF = 237.7 Hz, CF2H) 117.9 (t, J = 10.00 Hz, CH2) 126.4 (CH) 128.7 (CH) 128.7
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(CH) 141.4 (C) 142.3 (t, J = 20.5 Hz, C); F NMR (CDCl3, 377 MHz) δ ppm ꢀ118.44 (d, J =
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