Metal free fluoroamination of allylsilanes: A route to 3-fluoropyrrolidines

Article abstract of DOI:10.1016/j.jfluchem.2012.05.013

The intramolecular fluoroamination of homoallylic amines activated by a triisopropylsilyl or p-tolyldiisopropylsilyl group was successfully performed in the presence of Selectfluor in acetonitrile leading to anti or syn 3-fluoropyrrolidines. The stereoche

Full text of DOI:10.1016/j.jfluchem.2012.05.013

Journal of Fluorine Chemistry 143 (2012) 167–176
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Metal free fluoroamination of allylsilanes: A route to 3-fluoropyrrolidines
*
´
Lorraine E. Combettes, Oscar Lozano, Veronique Gouverneur
University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom
A R T I C L E I N F O
A B S T R A C T
Article history:
The intramolecular fluoroamination of homoallylic amines activated by a triisopropylsilyl or p-
tolyldiisopropylsilyl group was successfully performed in the presence of Selectfluor1 in acetonitrile
leading to anti or syn 3-fluoropyrrolidines. The stereochemical outcome of these fluorocyclizations is
dictated by the geometry of the alkene precursor. In comparison with oxygen nucleophile, the use of N-
tosyl or N-Boc nucleophiles benefits from superior control over stereoselectivity but suffers from
competitive fluorodesilylation.
Received 15 April 2012
Received in revised form 12 May 2012
Accepted 14 May 2012
Available online 23 May 2012
Dedicated to Professor David O’Hagan,
recipient of the 2012 ACS Award for
Creative Work in Fluorine Chemistry.
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
Fluorocyclization
Allylsilane
1,2-Dipole
Selectfluor
Pyrrolidine
1. Introduction
purpose, the triisopropylsilylmethyl and diisopropylphenylsilyl-
methyl groups were used as activating groups instead of
Organosilanes are valuable starting materials for the prepara-
tion of fluorinated targets when reacted in the presence of
electrophilic sources of fluorine [1]. Arylsilanes are amenable to
fluorination upon ipso-substitution, a reaction leading to fluori-
nated aromatics in modest yields [2]. Recently, Ritter and Tang
reported an improved regiospecific silver-mediated electrophilic
fluorination of aryltriethoxysilanes [3]. Since our first report in
2001, we have expanded significantly the scope of this chemistry
to non aromatic systems with the demonstration that vinylsilanes,
allylsilanes, allenylsilanes and allenylmethylsilanes are superior to
arylsilanes in terms of reactivity and in some cases, product
selectivity [4]. When these organosilanes were subjected to
fluorination, fluoroalkenes, fluorodienes, allylic and propargylic
fluorides became accessible in moderate to excellent yields.
Numerous enantiopure products were synthesized including
biologically relevant targets [5]. For these applications, the
presence of the silyl group is critical to increase the nucleophilicity
of the proximal alkene and dictate the regiochemistry of the
fluorination [6]. More recently, we exploited a new mode of
reactivity for allylsilanes with ‘‘F+’’ sources by allowing them to act
as 1,2-dipoles instead of the equivalent of an allyl anion [7]. For this
trimethylsilylmethyl. Based on these principles, the fluoroether-
ification of silyl-activated homoallylic alcohols was performed in
the presence of 1-chloromethyl-4-fluoro-1,4-diazoniabicy-
clo[2.2.2]octane bis tetrafluoroborate (Selectfluor1) or N-fluor-
obenzenesulfonimide (NFSI) and led to a series of fluorinated
tetrahydrofurans [8]. The stereochemical outcome of these
reactions is consistent with an overall syn addition to the double
bond; this stereospecific transformation led to syn- and anti-
cyclized products using E- and Z-allylsilanes respectively. The
importance of fluorinated N-heterocycles encouraged us to expand
the scope of these silyl-induced fluoroetherifications by examining
the reactivity of allylsilanes substituted with pending N-nucleo-
philes as potential substrates for fluoroamination. Herein, we
report that 3-fluoropyrrolidines are accessible upon fluorocycliza-
tion of N-protected homoallylic amines and we discuss the
efficiency of this process versus the fluoroetherification of the
corresponding homoallylic alcohols (Fig. 1).
2. Results and discussion
We began our studies with the fluorocyclization of the linear
homoallylic amines 1a–f. The purpose of this preliminary
investigation was to identify the optimum silyl substituent and
N-protecting group for fluorocyclization to occur in preference to
fluorodesilylation. Based on our previous work [8], we selected the
* Corresponding author.
E-mail address: veronique.gouverneur@chem.ox.ac.uk (V. Gouverneur).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.05.013

168
L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
A. Fluorination of Allylsilanes (Allylsilane as Allyl Anion)
SiMe3
The homoallylic amines 1a–f were subjected to fluorocycliza-
tion in acetonitrile using either Selectfluor (1.1 equiv.) or NFSI
(1.1 equiv.). The reactions were typically performed in the
presence of NaHCO3 (1.1 equiv.) or K2CO3 (1.1 equiv.) to minimize
protodesilylation and facilitate cyclization by deprotonation of the
protected nitrogen nucleophile. Amines 1c–e did not undergo
fluorination-cyclization but led exclusively to the allylic fluoride 2.
The homoallylic amine 1b with the pending diisopropyltolylsilyl
group gave the cyclized product 4b in 23% isolated yield along with
50% of the undesired product 2 resulting fluorodesilylation (entry
5). The triisopropylsilyl group was found to be optimum; indeed 1a
gave the pyrrolidine 4a in isolated yields up to 58% (entries 1–4);
competitive fluorodesilylation could however not be avoided. The
N-Boc protected precursor 1f underwent cyclization but this
protecting group did not lead to a more favorable product
distribution towards the fluorinated pyrrolidine 4f (entry 12).
The cyclized products were produced as inseparable mixtures of
syn and anti isomers with diastereomeric ratio superior to the E/Z
ratio of the starting allylsilanes; the syn isomer was consistently
found to be predominant. The use of Selectfluor1 and NaHCO3 in
acetonitrile at room temperature gave better results and was
retained for further investigation. All together, these results
highlight clear differences with the corresponding fluoroether-
ification of silyl-activated homoallylic alcohols [8]. The fluorocy-
clization of the N-protected homoallylic amines 1a–f was less
efficient as competitive fluorodesilylation could not be eradicated
or was the predominant reaction pathway, but the level of
stereocontrol for the fluoroamination was superior (Table 1).
To further investigate the difference in reactivity of silyl-
activated homoallylic alcohols and amines, we examine the
cyclization of (Z)-1a, (Z)-1b, (Z)-1g and (E)-1h. The synthesis of
these allylsilanes is presented in Scheme 2. Compounds (Z)-1a, (Z)-
1b and (Z)-1g were prepared by substituting the corresponding
activated alcohols with tosyl amine in DMF. The Z geometry of all
precursors was secured through a key ring closing metathesis as
previously reported in the literature [8,13,14]. The preparation of
(E)-1h began with the known (E)-2,2-dimethyl-5-(triisopropylsi-
lyl)pent-3-enoic acid [8]. This precursor was obtained by cross-
metathesis reaction of deconjugated tiglic acid with triisopropy-
lallylsilane followed by methylation under basic condition
applying literature procedures [8]. Amination with tosyl isocya-
nate gave the amide (E)-5 with no erosion of stereochemistry (E:Z
ratio > 20:1). The reduction of (E)-5 with lithium aluminium
F
Me3Si
R'
R'
"F+" source
R
R
B. Fluoroetherification of Allylsilanes (Allylsilane as 1,2-Dipole)
F
SiR3
SiR3
R3Si
OH
"F+" source
O
SiR3
C. Fluoroamination of Allylsilanes (this work)
F
SiR3
R3Si
NHP
"F+" source
N
P
P = protecting group
Fig. 1. Fluorination of allylsilanes used as allyl anion or 1,2-dipole equivalent.
triisopropylsilyl, p-tolyldimethylsilyl, triphenylsilyl, dimethylphe-
nylsilyl and the benzhydryldimethylsilyl groups as a replacement
to trimethylsilyl in order to favor 1,2-dipole reactivity; all these
groups with the exception of the triisopropylsilyl group are
amenable to oxidative cleavage [9]. Both the tosyl and Boc groups
were chosen to protect the pending amino nucleophile towards
direct N-fluorination [10], yet allowing for cyclization. All
homoallylic amines, with the exception of 1b, were prepared by
cross-metathesis of the corresponding allylsilanes with homo-
allylic tosylamine or tert-butyl but-3-en-1-ylcarbamate in the
presence of Grubbs catalyst 2nd generation and 1,4-benzoquinone.
For 1b, it was preferable to perform the cross-metathesis reaction
with but-3-enol then convert the primary alcohol group into the
tosylated amine [11]. The required allylsilanes were either
commercially available or obtained by substitution of the
chloroallylsilane with the necessary organolithium following
literature procedures [12]. All cross-metathesis reactions gave
the desired allylsilanes as inseparable mixture of
E and Z
geometrical isomers (E major) with isolated yields ranging from
54 to 89% (Scheme 1).
5 mol% 2nd Grubbs
SiR1R2R3
(3 equiv.)
SiR1R2R3
TsHN
+
TsHN
(1 equiv.)
0.5 equiv. BQ
1a SiR1R2R3 = Si(iPr)3
1c SiR1R2R3 = SiPh3
DCM
89% E:Z = 5:1
64% E:Z = 3:1
54% E:Z = 2:1
58% E:Z = 4:1
BQ = benzoquinone
1d SiR1R2R3 = SiMe2Ph
1e SiR1R2R3 = SiMe2(CHPh2)
5 mol% 2nd Grubbs
Si(iPr)2ptolyl
Si(iPr)2ptolyl
(3 equiv.)
HO
+
HO
(1 equiv.)
0.5 equiv. BQ
DCM
88% E:Z = 2:1
1) MeSO2Cl, NEt3, CH2Cl2
2) KOH, TsNH2, DMF, 120 °C
Si(iPr)2ptolyl
TosNH
BocHN
1b, 51% E:Z = 2:1
5 mol% 2nd Grubbs
Si(iPr)3
+
Si(iPr)3
1f, 89% E:Z = 5:1
BocHN
(1 equiv.)
0.5 equiv. BQ
DCM
(3 equiv.)
Scheme 1. Synthesis of amines 1a–f.

L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
169
Table 1
Fluorocyclization of allylsilanes 1a–f.
Entry
Allylsilanes (E:Z)
Condition (time)a
Yield [%] of 2 or 3b
Yield [%] of 4a-f (syn:anti)c
1
1a (5:1)
1a (5:1)
1a (5:1)
1a (5:1)
1b (2:1)
1c (3:1)
1c (3:1)
1d (2:1)
1d (2:1)
1e (4:1)
1e (4:1)
1f (5:1)
A (24 h)
B (48 h)
C (48 h)
D (24 h)
A (24 h)
A (16 h)
E (72 h)
A (16 h)
E (16 h)
A (48 h)
E (72 h)
A (24 h)
2, 34
2, 17
2, 22
2, 18
2, 50
2, 44
2, 56
2, 72
2, 63
2, 34
2, 46
3, 43
4a 58 (9:1)
4a 55 (7:1)
4a 53 (7:1)
4a 50 (9:1)
4b 23 (5:1)
2
3
4
5
d
6
–
d
7
–
d
8
–
d
9
–
d
10
11
12
–
d
–
4f 54 (5:1)
a
Conditions: A = Selectfluor (1.1 equiv.), NaHCO3 (1.1 equiv.) CH3CN, r.t.; B = Selectfluor (1.1 equiv.), K2CO3 (1.1 equiv.), CH3CN, r.t.; C = Selectfluor (1.1 equiv.), CH3CN, r.t.;
D = NFSI (1.1 equiv.), NaHCO3 (1.1 equiv.), CH3CN, reflux; E = NFSI (1.1 equiv.), NaHCO3 (1.1 equiv.), CH3CN, r.t.
b
Yield of the isolated product.
c
d.r., determined by 19F NMR analysis of the crude product.
d
Fluorodesilylation only.
hydride gave (E)-1h in 48%. This reaction led to detectable
isomerization of the double bond (E:Z ratio = 16:1).
(entry 5) but in contrast, the linear allylsilane (Z)-1b gave 4b with a
chemical yield of only 14% (entry 4). The gem-dimethyl substitu-
tion of (E)-1h did not encourage further cyclization vs. competitive
fluorodesilylation (entry 6). For (E)-1h, the allylic fluoride 7 was
isolated as the major product (45%) and the 3-fluoropyrrolidine 4h
was obtained in 36%. The stereochemical outcome of the
cyclization is consistent with an overall syn addition to the double
bond; this stereospecific transformation led to syn- and anti-
cyclized products using E- and Z-allylsilanes respectively. For the E
and Z linear precursors (E)-1a, (E)-1b, (Z)-1a and (Z)-1b, the
diastereomeric ratio of the products was superior to the E:Z ratio of
the starting allylsilanes (entries 1–4) [8]. In contrast, erosion was
observed for the substituted amines (Z)-1g and (E)-1h (entries 5
and 6). Steady state NOE/HOESY experiments were conducted for
all cyclized products for the assignment of syn or anti-stereo-
chemistry. A strong NOE interaction was found between the H3 and
All homoallylic amines were subjected to fluorocyclization
using Selectfluor1 and NaHCO3 in acetonitrile at room tempera-
ture (Table 2). These reactions gave the desired fluorinated
pyrrolidines with yields ranging from 14 to 61%. Competitive
fluorodesilylation was observed for all substrates; the allylic
fluoride side-products could be separated from the desired 3-
fluoropyrrolidines 4 by silica gel column chromatography. Several
trends emerge from this study. The cyclization of triisopropylal-
lylsilanes was more efficient than the corresponding precursors
presenting with the diisopropyltolylsilyl group; this stands true
both for the E and Z series (entries 1 and 2 vs. entries 3 and 4). In the
Z series, the presence of an alkene methyl substituent proximal to
the silyl group was beneficial in terms of product distribution. The
branched amine (Z)-1g gave the product of cyclization in 61% yield
TsHN
HO
SiR1R2R3
SiR1R2R3
R
R
(Z)-1a R = H, SiR1R2R3 = Si(iPr)3
54% E:Z = 1:12
58% E:Z = 1:12
45% E:Z = 1:2
(Z)-1b R = H, SiR1R2R3 = Si(iPr)2p-tolyl
(Z)-1g R = Me, SiR1R2R3 = Si(iPr)3
O
O
TsNCO
HO
Si(iPr)3
TsHN
Si(iPr)3
5, 25% E:Z > 20:1
NEt3, THF
r.t. 16h
(E)-
LiAlH4 (5 eq.)
TsHN
Si(iPr)3
Et2O, 0°C, 1h
then r.t. 16h
(E)-1h, 48% E:Z = 16:1
Scheme 2. Synthesis of amines (Z)-1a and b, (Z)-1g and (E)-1h.

170
L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
Table 2
Fluorocyclisation of Allylsilanes 1a and b and 1g and h.a
Entry
1
Allylsilane 1
Product 4
Yield (%)b
Product 2, 6 or 7
Yield (%)b
34%
d.r. (syn:anti)c
58%
(9:1)
2
3
34%
38%
50%
(1:>20)
23%
(5:1)
4
14%
56%
(1:23)
5
6
a
61%
27%
45%
(1:1.3)
36%
(6:1)
Conditions: Selectfluor1 (1.1 equiv.), NaHCO3 (1.1 equiv.), CH3CN, r.t., up to 48 h.
Yield of isolated product.
The d.r. was determined by 19F NMR analysis on the crude product.
b
c
H2 protons for the syn-pyrrolidines. HOESY analysis showed a
strong interaction between the fluorine and one the isopropyl
substituent of the silyl group. These observations are consistent
with a syn spatial arrangement of these two substituents. In
contrast, the anti 3-fluoropyrrolidines showed a strong HOESY
interaction between the fluorine and H2 proton, and a weak NOE
interaction between H3–H2, which is diagnostic of an anti relation-
ship between the fluorine and silylmethyl substituent. This study
revealed that the pending nucleophile has a clear influence on the
efficiency of the cyclization process. Chemical yields were signifi-
cantly higher for the O-series [8] vs the N-series. In contrast, control
over stereoselectivity was typically superior for the amines with
respect to the corresponding alcohols, at least for the linear systems.
The branched precursors (Z)-1g and (E)-1h led to significant erosion
ofd.r. upon cyclization. Assumingthatthe cyclizations are kinetically
controlled [15], such stereochemical leakage could arise from two
possible pathways. In a first scenario, competitive syn addition of the
electrophilic fluorination reagent with respect to the silyl group
could take place [16]. Alternatively, the fluorinated carbocation
resulting from an anti attack of ‘‘F+’’ with respect to the bulky
stereodirecting triisopropylsilyl or diisopropyltolylsilyl group could
undergo bond rotation prior to ring closure [16].
3. Conclusions
In summary, this work demonstrates that N-tosyl and N-Boc
homoallylic amines activated by triisopropylsilyl or p-
a
tolyldiisopropylsilyl group are amenable to electrophilic fluor-
ocyclization. The E or Z geometry of the alkene functionality
dictates the preferential syn or anti stereochemical outcome of
these kinetically controlled reactions. Important differences
have been noted between allylsilanes substituted with oxygen
[8] or nitrogen nucleophiles. Competitive fluorination leading to
allylic fluorides could not be avoided with homoallylic amines
but the level of stereocontrol achieved was superior at least for
linear substrates. The fluorocyclization of silyl-activated homo-
allylic amines provides an alternative route to palladium-
catalyzed intramolecular aminofluorination, a method restricted
in scope to styrenes and providing no control over syn or anti
selectivity [17]. The work described herein represents a solid
foundation for further development; these new metal free
fluorocyclizations will however require the development of a
new cleavable silyl group to eradicate competitive fluorodesi-
lylation and thereby allowing this strategy to reach its full
synthetic potential.

L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
171
4. Experimental
(1.5 equiv.) was dissolved in anhydrous DMF [0.5 M] at 120 8C and
tosylamine (1.5 equiv.) added. The mixture was stirred for 30 min,
after which a solution of mesylate (1 equiv.) in anhydrous DMF
[0.5 M] was added. After complete consumption of the starting
material (2–3 h), the reaction mixture was cooled, diluted with
H2O and extracted four times with EtOAc. The combined organic
extracts were washed three times with H2O then brine, dried over
MgSO4, filtered, and the solvent removed in vacuo. The crude
product was purified by flash column chromatography on silica gel.
4.1. General
1H NMR spectra were recorded in deuterated solvents using
Bruker DPX200, DPX400, AV400 and AV500 spectrometers,
calibrated using residual undeuterated solvent as an internal
reference. 13C NMR spectra were recorded in deuterated solvents
using Bruker DPX200, DPX400, AV400 and AV500 spectrometers,
calibrated using residual undeuterated solvent as an internal
reference. 19F spectra were recorded on an AV400 spectrometer,
calibrated using fluorotrichloromethane (CFCl3) as a reference.
4.3.1. (E)-4-Methyl-N-(5-(triisopropylsilyl)pent-3-en-1-
yl)benzenesulfonamide (E)-1a
Chemical shifts (
d
) are quoted in parts per million (ppm) and
Following the general procedure A on 500 mg (2.2 mmol,
1 equiv.) of N-but-3-en-1-yl-4-methylbenzenesulfonamide [18],
the reaction yielded 782 mg of (E)-1a (89%, E:Z = 5:1) as a colorless
oil after flash column chromatography on silica gel (hexane/Et2O
8:2–7:3). Major (E) isomer: Rf = 0.4 (hexane/Et2O 6:4); 1H NMR
coupling constants (J) are measured in hertz (Hz). The following
abbreviations are used to describe multiplicities s = singlet;
d = doublet; t = triplet; q = quartet; br = broad; m = multiplet;
app = apparent. NMR spectra were processed with either Mes-
tRe-C or ACD/SpectManager. IUPAC names were obtained using the
ACD/I-Lab service. High resolution mass spectra (HMRS; m/z) were
recorded on micromass GCT spectrometer using field ionization
(FI) or chemical ionization (CI); or on Autospec-oa Tof and Bruker
MicroTOF instruments for electrospray ionization (ESI). Infrared
spectra were recorded as thin films on NaCl plates in solution in
CH2Cl2 or as solid on KBr disc on a Bruker Tensor 27 FT-IR
(400 MHz, CDCl3) d
= 0.94–1.04 (m, 21H, Si(i-Pr)3), 1.49 (d, 2H, 3JH–
H = 8.1 Hz, CH2Si), 2.08 (q, 2H, 3JH–H = 6.9 Hz, NCH2CH2), 2.40 (s, 3H,
CH3PhNH), 2.88–2.94 (m, 2H, NCH2CH2), 4.88 (t, 1H, 3JH–H = 5.8 Hz,
3
3
4
NH), 5.07 (1H, dtt, JH–H(trans) = 15.0 Hz, JH–H = 6.9 Hz, JH–
3
3
H = 1.4 Hz, NCH2CH2CH), 5.45 (dtt, 1H, JH–H(trans) = 15.0 Hz, JH–
4
3
H = 8.1 Hz, JH–H = 1.4 Hz, CHCH2Si), 7.28 (d, 2H, JH–H = 7.8 Hz,
3
&&&Ar–H), 7.73 (d, 2H, JH–H = 8.3 Hz, Ar–H); 13C NMR (101 MHz,
spectrometer. Absorptions are measured in wavenumbers (cmÀ1
)
CDCl3) d = 10.8 (Si(CH(CH3)2)3), 15.3 (CH2Si), 18.5 (Si(CH(CH3)2)3),
and only peaks of interest are reported. Melting points of solids
were measured on a Griffin apparatus and are uncorrected. All
reactions requiring anhydrous conditions were conducted in dried
apparatus under an inert atmosphere of argon. Solvents were dried
on a column of alumina or purified before use according to
standard procedures. All reactions were monitored by thin layer
chromatography (TLC) using Merck Kiesegel 60 F254 plates.
Visualization of the reaction components was achieved using UV
fluorescence (254 nm) and KMnO4 stain. Silica gel chromatogra-
21.5 (CH3PhNH), 32.6 (NCH2CH2), 42.8 (NCH2CH2), 123.5
(NCH2CH2CH), 127.0 (Ar), 129.5 (Ar), 131.1 (CHCH2Si), 136.9
(Ar), 143.1 (Ar); IR (CH2Cl2):
883; HRMS (CI+) m/z required for C21H38NO2SSi ([M+H]+):
396.2393, found 396.2400, = 1.9 ppm.
n = 2948, 2000, 1699, 1130, 1047, 988,
D
4.3.2. (E)-N-(5-(diisopropyl(p-tolyl)silyl)pent-3-en-1-yl)-4-
methylbenzenesulfonamide (E)-1b
Following the general procedure B on 311.5 mg (1.12 mmol,
1 equiv.) of (E)-5-[diisopropyl(4-methylphenyl)silyl]pent-3-en-1-
ol [8] the reaction yielded 255.2 mg (51% over two steps, E:Z = 2:1)
of (E)-1b as a colorless oil after flash column chromatography on
silica gel (hexane/Et2O 9:1 to 8:2). Note: the synthesis of this
product by direct cross-metathesis of the homoallylic tosyl-amine
with allyl(diisopropyltolyl)silane gave a mixture of the desired
product along up to 50% of the truncated side-product despite the
addition of 1,4-benzoquinone. Major (E) isomer: Rf = 0.2 (hexane/
phy was carried out over Merck silica gel C60 (40–60
eluent systems as described for each experiment.
mm) using
4.2. Synthesis of allylsilanes
Allyldimethylphenylsilane [12], allylbenzhydryldimethylsilane
[12], and allyl(diisopropyl)(4-methylphenyl)silane [8] were syn-
thesized according to the literature procedures. Allyltriisopropyl-
silane and allyltriphenylsilane were commercially available and
used without further purification.
Et2O 7:3); 1H NMR (400 MHz, CDCl3)
d = 0.96–1.05 (m, 12H,
3
Si(CH(CH3)2)2), 1.18–1.30 (m, 2H, Si(CH(CH3)2)2), 1.82 (d, 2H, JH–
H = 7.8 Hz, CH2Si), 2.05–2.12 (m, 2H, NCH2CH2), 2.36 (s, 3H,
CH3PhNH), 2.43 (s, 3H, CH3PhSi), 2.90–2.96 (m, 2H, NCH2CH2),
4.3. Synthesis of organosilanes
3
3
4.35–4.42 (m, 1H, NH), 5.13 (dt,1H, JH–H(trans) = 15.1 Hz, JH–
3
3
General procedure A. To a solution of homoallylic amine
(1 equiv.) and allylsilane (3 equiv.) in dry CH2Cl2 [0.3 M] was
added portion wise over 3 days Grubbs’ 2nd generation catalyst
(5 mol%) and 1,4-benzoquinone (0.5 equiv.) at reflux. The reaction
was maintained at reflux under argon atmosphere until TLC
showed complete consumption of the starting material (3–4 days);
the reaction was stopped and the solvent removed in vacuo. The
resulting crude mixture was purified by flash column chromatog-
raphy on silica gel.
General procedure B. Dry NEt3 (5 equiv.) was added dropwise at
0 8C to a solution of primary alcohol (1 equiv.) and methane
sulfonylchloride (1.2 equiv.) in dry CH2Cl2 [0.2 M]. The reaction
was stirred at ambient temperature under an atmosphere of argon
until TLC showed consumption of the alcohol (2 h). The reaction
mixture was quenched with H2O and extracted three times with
CH2Cl2. The combined organic phases were washed with H2O,
brine, dried over MgSO4, filtered and the solvent removed in vacuo.
The resulting crude mixture was engaged without further
purification to the next step. Finely grinded potassium hydroxide
H = 7.1 Hz, NCH2CH2CH), 5.51 (dtt, 1H, JH–H(trans) = 15.1 Hz, JH–
4
3
H = 7.8 Hz, JH–H = 1.3 Hz, CHCH2Si), 7.19 (d, 2H, JH–H = 7.3 Hz,
3
3
SiAr–H), 7.30 (d, 2H, JH–H = 8.3 Hz, NHAr–H), 7.37 (d, 2H, JH–
H = 7.8 Hz, SiAr–H), 7.72 (d, 2H, 3JH–H = 8.3 Hz, NHAr–H); 13C NMR
(101 MHz, CDCl3)
d = 10.9 (Si(CH(CH3)2)2), 15.6 (CH2Si), 18.0
(Si(CH(CH3)2)2), 21.4 (CH3PhNH), 21.5 (CH3PhSi), 32.6 (NCH2CH2),
42.7 (NCH2CH2), 124.3 (NCH2CH2CH), 127.0 (NHAr), 128.4
(CHCH2Si), 128.5 (SiAr), 129.6 (NHAr), 130.8 (SiAr), 134.8 (SiAr),
137.0 (SiAr), 138.7 (NHAr), 143.2 (NHAr); IR (CH2Cl2)
2864, 1599, 1328, 1100, 882, 814; HRMS (ESI+) m/z required for
25H37NO2SSiNa+ ([M+Na]+): 466.2206, found 466.2209,
= 0.6 ppm.
n = 2942,
C
D
4.3.3. (E)-4-methyl-N-(5-(triphenylsilyl)pent-3-en-1-
yl)benzenesulfonamide (E)-1c
Following the general procedure A on 200 mg (0.9 mmol,
1 equiv.) of N-but-3-en-1-yl-4-methylbenzenesulfonamide [18],
the reaction yielded 343 mg of a mixture containing 64% of (E)-1c
(E:Z = 3:1) and 15% of the truncated side product, as a white solid

172
L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
3
3
after flash column chromatography on silica gel (hexane/Et2O 8:2
then 7:3). Major (E) isomer: Rf = 0.2 (hexane/Et2O 7:3);
H = 6.1 Hz, NH), 4.96 (dt, 1H, JH–H(trans) = 15.1 Hz, JH–H = 6.8 Hz,
3
3
NHCH2CH2CH), 5.28 (dt, 1H, JH–H(trans) = 15.1 Hz, JH–H = 7.7 Hz,
CHCH2Si), 7.12–7.19 (m, 2H, SiCH(Ph–H)2), 7.23–7.34 (m, 10H,
SiCH(Ph–H)2), 7.79 (d, 2H, 3JH–H = 8.1 Hz, NHAr–H), 7.74 (d, 2H, 3JH–
m.p. = 119 8C; 1H NMR (400 MHz, CDCl3)
NHCH2CH2), 2.31 (d, 2H, JH–H = 7.8 Hz, CH2Si), 2.44 (s, 3H,
d = 1.98–2.06 (m, 2H,
3
3
CH3PhNH), 2.80–2.87 (m, 2H, NHCH2CH2), 4.16 (t, 1H, JH–
H = 8.1 Hz, NHAr–H); 13C NMR (101 MHz, CDCl3)
d
= À3.8
3
3
H = 6.1 Hz, NH), 5.08 (dtt, 1H, JH–H(trans) = 15.1 Hz, JH–H = 7.1 Hz,
(Si(CH3)2), 20.7 (CH2Si), 21.3 (CH3PhNH), 32.5 (NHCH2CH2), 42.8
(NHCH2CH2), 44.6 (SiCH(Ph)2), 125.1 (NHCH2CH2CH), 126.9
(NHAr–C), 128.2 (SiCH(Ph–C)2), 128.2 (SiCH(Ph–C)2), 128.6
(SiCH(Ph–C)2), 129.2 (CHCH2Si), 129.5 (NHAr–C), 136.8 (NHAr–
C), 142.2 (SiCH(Ph–C)2), 143.1 (NHAr–C); IR (CH2Cl2)
3090, 1597, 1447; HRMS (CI+) m/z required for C27H34NO2SSi
([M+H]+): 464.2080, found 464.2063,
= 3.6 ppm. Identifiable data
for the minor (Z) isomer: 1H NMR (400 MHz, CDCl3)
= 0.05 (s, 6H,
Si(CH3)2), 1.98–2.06 (m, 2H, NHCH2CH2), 4.89 (t, 1H, 3JH–H = 6.1 Hz,
NH), 5.09 (dt, 1H, 3JH–H(cis) = 10.1 Hz, 3JH–H = 7.3 Hz, NHCH2CH2CH),
5.40 (dt, 1H, 3JH–H(cis) = 10.1 Hz, 3JH–H = 8.8 Hz, CHCH2Si); 13C NMR
4JH–H = 1.4 Hz, NHCH2CH2CH), 5.52 (dtt, 1H, JH–H(trans) = 15.1 Hz,
3
3JH–H = 7.8 Hz, 4JH–H = 1.1 Hz, CHCH2Si), 7.27 (d, 2H, 3JH–H = 8.3 Hz,
3
NHAr–H), 7.35–7.55 (m, 15H, SiAr–H), 7.66 (d, 2H, JH–H = 8.3 Hz,
NHAr–H); 13C NMR (101 MHz, CDCl3)
d
= 19.5 (CH2Si), 21.5
n = 3280,
(CH3PhNH), 32.8 (NHCH2CH2), 42.7 (NHCH2CH2), 126.2
(NHCH2CH2CH), 127.0 (NHAr–C), 127.9 (SiAr–C), 129.0 (CHCH2Si),
129.6 (NHAr–C), 129.6 (SiAr–C), 134.3 (SiAr–C), 135.6 (SiAr–C),
D
d
137.2 (NHAr–C), 143.2 (NHAr–C); IR (CH2Cl2)
1327, 1161, 702; HRMS (ESI+) m/z required for C30H31NO2SSiNa+
([M+Na]+): 520.1737, found 520.1731,
= 1.9 ppm. Identifiable
= 1.87–
n
= 3282, 3068, 1428,
D
data for the minor (Z) isomer 1H NMR (400 MHz, CDCl3)
d
(101 MHz, CDCl3)
d
= À3.7 (Si(CH3)2), 16.4 (CH2Si), 26.9
1.94 (m, 2H, NHCH2CH2), 2.28 (d, 2H, 3JH–H = 7.6 Hz, CH2Si), 2.41 (s,
(NHCH2CH2), 42.7 (NHCH2CH2), 44.6 (SiCH(Ph)2), 124.4
(NHCH2CH2CH).
3
3H, CH3PhNH), 2.73–2.79 (m, 2H, NHCH2CH2), 4.22 (t, 1H, JH–
H = 6.1 Hz, NH), 5.12–5.24 (m, 1H, NHCH2CH2CH), 5.58–5.75 (m,
1H, CHCH2Si); 13C NMR (101 MHz, CDCl3)
(NHCH2CH2), 42.5 (NHCH2CH2), 124.6 (NHCH2CH2CH), 128.0
(CHCH2Si).
d
= 15.4 (CH2Si), 27.1
4.3.6. (E)-tert-butyl (5-(triisopropylsilyl)pent-3-en-1-yl)carbamate
(E)-1f
Following the general procedure A on 500 mg (2.9 mmol,
1 equiv.) of tert-butyl but-3-en-1-ylcarbamate [19], the reaction
yielded 887 mg of (E)-1f (89%, E:Z = 5:1) as a yellow oil after flash
column chromatography on silica gel (hexane/Et2O 9:1). Major (E)
isomer: Rf = 0.7 (hexane/Et2O 9:1); 1H NMR (400 MHz, CDCl3)
4.3.4. (E)-N-(5-(dimethyl(phenyl)silyl)pent-3-en-1-yl)-4-
methylbenzenesulfonamide (E)-1d
Following the general procedure A on 100 mg (0.4 mmol,
1 equiv.) of N-but-3-en-1-yl-4-methylbenzenesulfonamide [18],
the reaction yielded 90 mg of (E)-1d (54%, E:Z = 2:1) as a colorless
oil after flash column chromatography on silica gel (hexane/Et2O
d
= 1.04 (s, 21H, Si(CH(CH3)2)3), 1.43 (s, 9H, COC(CH3)3), 1.56 (d, 2H,
3JH–H = 8.0 Hz, CH2Si), 2.13–2.17 (m, 2H, NHCH2CH2), 3.11 (m, 2H,
NHCH2CH2), 5.22 (d, 1H, 3JH–H(trans) = 14.8 Hz, NHCH2CH2CH), 5.55
(d, 1H, 3JH–H(trans) = 14.8 Hz, CHCH2Si); 13C NMR (101 MHz, CDCl3)
8:2 then 7:3). Major (E) isomer: Rf = 0.2 (hexane/Et2O 7:3); 1H NMR
3
(400 MHz, CDCl3)
d
= 0.28 (s, 6H, Si(CH3)2), 1.66 (d, 2H, JH–
d = 10.9 (Si(CH(CH3)2)3), 15.4 (CH2Si), 18.7 (Si(CH(CH3)2)3), 28.4
H = 7.8 Hz, CH2Si), 2.06–2.12 (m, 2H, NHCH2CH2), 2.44 (s, 3H,
CH3PhNH), 2.88–2.94 (m, 2H, NHCH2CH2), 4.56 (t, 1H, JH–
(CH3PhNH), 33.1 (NHCH2CH2), 40.2 (NHCH2CH2), 78.0 (COC(CH3)3),
124.9 (NHCH2CH2CH), 130.2 (CHCH2Si), 155.9 (CO); IR (CH2Cl2)
3
3
3
H = 6.1 Hz, NH), 5.04 (dtt, 1H, JH–H(trans) = 15.2 Hz, JH–H = 6.8 Hz,
n
C
= 3044, 2322, 1761, 1543; HRMS (CI+) m/z required for
4JH–H = 1.2 Hz, NHCH2CH2CH), 5.40 (dtt, 1H, JH–H(trans) = 15.2 Hz,
19H40NO2Si ([M+H]+): 342.2828, found 342.2845,
D = 4.9 ppm.
3
3JH–H = 7.8 Hz, 4JH–H = 1.2 Hz, CHCH2Si), 7.30 (d, 2H, 3JH–H = 8.1 Hz,
NHAr–H), 7.34–7.40 (m, 3H, SiAr–H), 7.47–7.51 (m, 2H, SiAr–H),
4.3.7. (Z)-4-methyl-N-(5-(triisopropylsilyl)pent-3-en-1-
7.74 (d, 2H, JH–H = 8.1 Hz, NHAr–H); 13C NMR (101 MHz, CDCl3)
yl)benzenesulfonamide (Z)-1a
3
d
= À3.5 (Si(CH3)2), 21.4 (CH3PhNH), 21.9 (CH2Si), 32.6
Following the general procedure B on 164.5 mg (0.68 mmol,
1 equiv.) of (Z)-5-(triisopropylsilyl)pent-3-en-1-ol [8], the reaction
yielded 145.4 mg (54% over two steps, E:Z = 1:10) of (Z)-1a as a
colorless oil after flash column chromatography on silica gel
(hexane/Et2O 9:1 to 7:3). Major (Z) isomer: Rf = 0.5 (hexane/Et2O
(NHCH2CH2), 42.8 (NHCH2CH2), 124.5 (NHCH2CH2CH), 127.0
(NHAr–C), 127.7 (SiAr–C), 129.0 (CHCH2Si), 129.6 (SiAr–C), 129.6
(NHAr–C), 133.5 (SiAr–C), 137.0 (NHAr–C), 138.3 (SiAr–C), 143.2
(NHAr–C); IR (CH2Cl2)
HRMS (ESI+): m/z required for C20H27NO2SSiNa+ ([M+Na]+)
396.1424, found 396.1416,
minor (Z) isomer: 1H NMR (400 MHz, CDCl3)
Si(CH3)2), 1.65 (d, 2H, JH–H = 8.6 Hz, CH2Si), 2.01–2.07 (m, 2H,
NHCH2CH2), 2.42 (s, 3H, CH3PhNH), 2.84–2.90 (m, 2H, NHCH2CH2),
n = 3283, 2956, 1426, 1327, 1161, 836;
6:4); 1H NMR (400 MHz, CDCl3)
d = 0.95–1.05 (m, 21H, Si(i-Pr)3),
1.45 (d, 2H, JH–H = 8.6 Hz, CH2Si), 2.16–2.23 (m, 2H, NCH2CH2),
2.40 (s, 3H, CH3PhNH), 2.92–2.99 (m, 2H, NCH2CH2), 4.86–4.96 (m,
3
D
= 2.0 ppm. Identifiable data for the
d = 0.27 (s, 6H,
3
3
3
4
1H, NH), 5.02 (dtt, 1H, JH–H(cis) = 10.5 Hz, JH–H = 7.3 Hz, JH–
3
3
H = 1.5 Hz, NCH2CH2CH), 5.57 (dt, 1H, JH–H(cis) = 10.5 Hz, JH–
H = 8.8 Hz, CHCH2Si), 7.28 (d, 2H, 3JH–H = 8.3 Hz, Ar–H), 7.76 (d, 2H,
3JH–H = 8.3 Hz, Ar–H); 13C NMR (101 MHz, CDCl3)
d = 10.8 (CH2Si),
3
3
4.62 (t, 1H, JH–H = 6.1 Hz, NH), 5.14 (dtt, 1H, JH–H(cis) = 10.6 Hz,
3JH–H = 7.1 Hz, JH–H = 1.3 Hz, NHCH2CH2CH), 5.51 (dtt, 1H, JH–
4
3
H(cis) = 10.6 Hz, JH–H = 8.6 Hz, JH–H = 1.5 Hz, CHCH2Si); 13C NMR
10.9 (Si(CH(CH3)2)3), 18.5 (Si(CH(CH3)2)3), 21.4 (CH3PhNH), 27.1
(NCH2CH2), 42.8 (NCH2CH2), 122.0 (NCH2CH2CH), 127.0 (Ar), 129.5
3
4
(101 MHz, CDCl3)
(NHCH2CH2), 42.7 (NHCH2CH2), 122.9 (NHCH2CH2CH), 128.5
(CHCH2Si).
d
= À3.4 (Si(CH3)2), 17.9 (CH2Si), 27.1
(Ar), 130.0 (CHC2Si), 136.9 (Ar), 143.1 (Ar); IR (CH2Cl2)
2865, 1463, 1328, 1161, 883, 663; HRMS (ESI+) m/z required for
21H37NO2SSiNa+ ([M+Na]+): 418.2206, found 418.2206,
= 1 ppm.
n = 2942,
C
D
4.3.5. (E)-N-(5-(benzhydryldimethylsilyl)pent-3-en-1-yl)-4-
methylbenzenesulfonamide (E)-1e
Following the general procedure A on 150 mg (0.6 mmol,
1 equiv.) of N-but-3-en-1-yl-4-methylbenzenesulfonamide [18],
the reaction yielded 178 mg of (E)-1e (58%, E:Z = 4:1) as a colorless
oil after flash column chromatography on silica gel (hexane/Et2O
8:2 then 7:3). Major (E) isomer: Rf = 0.2 (hexane/Et2O 7:3); 1H NMR
4.3.8. (Z)-N-(5-(diisopropyl(p-tolyl)silyl)pent-3-en-1-yl)-4-
methylbenzenesulfonamide (Z)-1b
Following the general procedure B on 300 mg (1.1 mmol, 1 equiv.)
of (Z)-5-[diisopropyl(4-methylphenyl)silyl]pent-3-en-1-ol [8], the
reaction yielded 277 mg of (Z)-1b (58% over two steps, E:Z = 1:12) as
a colorless oil after flash column chromatography on silica gel
(hexane/Et2O 9:1 to 8:2). Major (Z) isomer: Rf = 0.2 (hexane/Et2O
(400 MHz, CDCl3)
d = 0.06 (s, 6H, Si(CH3)2), 1.42–1.49 (m, 2H,
CH2Si), 2.06–2.14 (m, 2H, NHCH2CH2), 2.42 (s, 3H, CH3PhNH), 2.86–
3
2.95 (m, 2H, NHCH2CH2), 3.58 (s, 1H, SiCH(Ph)2), 4.85 (t, 1H, JH–
7:3); 1H NMR (400 MHz, CDCl3)
d = 0.96–1.03 (m, 12H,

L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
173
3
Si(CH(CH3)2)2), 1.19–1.29 (m, 2H, Si(CH(CH3)2)2), 1.77 (d, 2H, JH–
H = 8.3 Hz, CH2Si), 2.15–2.23 (m, 2H, NCH2CH2), 2.37 (s, 3H,
CH3PhNH), 2.41 (s, 3H, CH3PhSi), 2.94–2.99 (m, 2H, NCH2CH2),
CH3CCH2Si); 13C NMR (101 MHz, CDCl3)
d
= 11.6 (Si(CH(CH3)2)3),
15.1 (CH2Si), 18.0 (Si(CH(CH3)2)3), 26.4 (CH3CCH2Si), 28.5
(NHCH2CH2), 117.8 (NHCH2CH2CH).
3
3
4.60–4.73 (m, 1H, NH), 5.07 (dt, 1H, JH–H(cis) = 10.1 Hz, JH–
3
3
H = 7.3 Hz, NCH2CH2CH), 5.65 (dt, 1H, JH–H(cis) = 10.1 Hz, JH–
4.3.11. (E)-2,2-dimethyl-N-tosyl-5-(triisopropylsilyl)pent-3-
enamide (E)-5
3
H = 8.7 Hz, CHCH2Si), 7.18 (d, 2H, JH–H = 7.6 Hz, SiAr–H), 7.30 (d,
2H,3JH–H = 8.1 Hz, NHAr–H), 7.37(d, 2H, 3JH–H = 7.8 Hz, SiAr–H), 7.77
To a solution of (E)-2,2-dimethyl-5-(triisopropylsilyl)pent-3-
enoic acid [8] (824 mg, 2,9 mmol, 1 equiv.) in THF (6 mL) under
argon was added tosyl isocyanate (0.45 mL, 2.9 mmol, 1 equiv.).
After stirring at room temperature for 10 minutes, distilled
triethylamine (0.40 mL, 2.9 mmol, 1 equiv.) was added dropwise
totheopenflaskallowingthereleaseofCO2. The reactionwas stirred
overnight. The mixture was then diluted with an equal volume of
EtOAc, washed twice with 2 M HCl and brine, dried over MgSO4,
filtered and the solvent removed in vacuo. The crude product was
purified by flash column chromatography on silica gel (hexane/Et2O
9:1 to 7:3) to yield 322 mg of (E)-5 (25%, E:Z = >20:1) as a colorless
oil. (E) isomer: Rf = 0.3 (hexane/Et2O 7:3); 1H NMR (400 MHz, CDCl3)
(d, 2H, 3JH–H = 8.3 Hz, NHAr–H); 13C NMR (101 MHz, CDCl3)
d = 10.9
(Si(CH(CH3)2)2), 11.2 (CH2Si), 17.9 (Si(CH(CH3)2)2), 21.4 (CH3PhNH),
21.4 (CH3PhSi), 27.2 (NCH2CH2), 42.7 (NCH2CH2), 122.7
(NCH2CH2CH), 127.0 (NHAr), 128.4 (SiAr), 129.5 (CHCH2Si), 129.6
(NHAr), 130.8 (SiAr), 134.8 (SiAr), 137.0 (SiAr), 138.7 (NHAr), 143.2
(NHAr); IR (CH2Cl2):
z required for C25H38NO2SSi ([M+H]+): 444.2393, found 444.2401,
= 1.9 ppm.
n
= 2958, 1717, 1630, 1427, 949; HRMS (CI+) m/
D
4.3.9. (Z)-5-(triisopropylsilyl)-4-methylpent-3-en-1-ol
To a solution of 2,2-diisopropyl-4-methyl-2,3,6,7-tetrahydro-
1,2-oxasilepine [8] (791 mg, 3.7 mmol, 1 equiv.) in anhydrous THF
at À78 8C under argon, was added dropwise a solution of sBuLi
([0.7 M] in pentane, 16 mL, 11.2 mmol, 3 equiv.). The reaction
mixture was stirred at 0 8C for 4 h. It was quenched with a
saturated NH4Cl(aq) solution and the aqueous phase was extracted
with Et2O. The combined organic phases were washed with brine,
dried over MgSO4, filtered and the solvent removed in vacuo. The
crude mixture was purified by flash column chromatography on
silica gel (hexane/Et2O 9:1 to 7:3) to give 405 mg of the
corresponding alcohol (42%, E:Z = 1:2) as a colorless oil. Major
(Z) isomer: Rf = 0.3 (hexane/Et2O 7:3); 1H NMR (400 MHz, CDCl3)
d
= 1.03–1.06 (m, 21H, Si(CH(CH3)2)3), 1.19 (s, 6H, NHCOC(CH3)2),
1.63 (d, 2H, 3JH–H = 8.3 Hz, CH2Si), 2.44 (s, 3H, CH3PhNH), 5.34 (d, 1H,
3JH–H(trans) = 15.6 Hz,
H(trans) = 15.6 Hz, JH–H = 8.3 Hz, CH55CHCH2Si), 7.33 (d, 2H, JH–
H = 8.1 Hz, Ar–H), 7.92 (d, 2H, JH–H = 8.3 Hz, Ar–H), 8.15–8.19 (m,
1H, NH); 13C NMR (101 MHz, CDCl3)
CH55CHCH2Si),
5.70
(dt,
1H,
3JH–
3
3
3
d = 11.0 (Si(CH(CH3)2)3), 16.1
(CH2Si), 18.6 (Si(CH(CH3)2)3), 21.7 (CH3PhNH), 24.6 (NHCOC(CH3)2),
45.8 (NHCOC(CH3)2), 128.4 (Ar–C), 129.5 (Ar–C), 130.4
(CH55CHCH2Si), 130.5 (CH55CHCH2Si), 135.4 (Ar–C), 144.9 (Ar–C),
174.4 (NHCO); IR (CH2Cl2):
853; HRMS (ESI+) m/z required for C23H39NO3SSiNa+ ([M+Na]+):
460.2312, found 460.2293, = 4 ppm.
n = 2949, 1699, 1423, 1239, 1165, 964,
d
= 0.85–0.90 (m, 3H, Si(CH(CH3)2)3), 0.99–1.10 (m, 17 H,
D
Si(CH(CH3)2)3), 1.48–1.52 (m, 1H, OH), 1.58 (s, 2H, CH2Si), 1.76
(s, 3H, CH3CCH2Si), 2.24–2.33 (m, 2H, OHCH2CH2), 3.63 (t, 2H, 3JH–
4.3.12. (E)-N-(2,2-dimethyl-5-(triisopropylsilyl)pent-3-en-1-yl)-4-
methylbenzenesulfonamide (E)-1h
In a flask charged with LiAlH4 (83 mg, 2.2 mmol, 5 equiv.) in dry
Et2O (9 mL) at 0 8C under argon, a solution of (E)-2,2-dimethyl-N-
3
H = 6.5 Hz, OHCH2CH2), 4.96 (t, 1H, JH–H = 7.1 Hz, OHCH2CH2CH);
13C NMR (101 MHz, CDCl3)
d
= 11.9 (Si(CH(CH3)2)3), 16.2 (CH2Si),
18.7 (Si(CH(CH3)2)3), 26.6 (CH3CCH2Si), 33.0 (OHCH2CH2), 62.6
(OHCH2CH2), 117.7 (OHCH2CH2CH), 137.3 (CCH2Si); IR (neat)
tosyl-5-(triisopropylsilyl)pent-3-enamide
(E)-5
(193 mg,
n
= 3329, 2943, 2867, 1465, 1167, 1049, 918; HRMS (FI+) m/z
0.4 mmol, 1 equiv.) in 1 mL of Et2O was added dropwise. The
reaction mixture stirred at 0 8C for 1 h then at room temperature
overnight. H2O was added carefully to the mixture, which was
filtered through Celite and then extracted with Et2O. The combined
organic layers were washed with brine, dried over MgSO4 and the
solvent removed in vacuo. Purification of the resulting residue by
flash column chromatography on silica gel (hexane/Et2O 8:2)
yielded 90.3 mg of the product (E)-1h (48%, E:Z = 16:1) as a
colorless oil. Major (E) isomer: Rf = 0.5 (hexane/Et2O 6:4); 1H NMR
required for C15H32OSi ([M]+) 256.2223, found 256.2228,
= 2.2 ppm. Identifiable data for the minor (E) isomer: 1H NMR
(400 MHz, CDCl3) = 1.62 (s, 2H, CH2Si), 1.79 (s, 3H, CH3CCH2Si);
13C NMR (101 MHz, CDCl3)
= 11.9 (Si(CH(CH3)2)3), 15.3 (CH2Si),
D
d
d
18.3 (Si(CH(CH3)2)3), 26.7 (CH3CCH2Si), 118.1 (OHCH2CH2CH),
137.5 (CH3CCH2Si).
4.3.10. (Z)-4-methyl-N-(4-methyl-5-(triisopropylsilyl)pent-3-en-1-
yl)benzenesulfonamide (Z)-1g
(400 MHz, CDCl3)
d = 0.95 (s, 6H, NHCH2C(CH3)2), 0.99–1.04 (m,
Following the general procedure B on 405 mg (1.6 mmol,
1 equiv.) of (Z)-5-(triisopropylsilyl)-4-methylpent-3-en-1-ol the
reaction yielded 306 mg of (Z)-1g (47% over two steps, E:Z = 1:2) as
a yellow oil after flash column chromatography on silica gel
(hexane/Et2O 9:1 to 7:3). Major (Z) isomer: Rf = 0.6 (hexane/Et2O
21H, Si(CH(CH3)2)3), 1.52 (d, 2H, 3JH–H = 7.9 Hz, CH2Si), 2.42 (s, 3H,
3
CH3PhNH), 2.68 (d, 2H, JH–H = 6.3 Hz, NHCH2), 4.39–4.46 (m, 1H,
NH), 5.05 (d, 1H, 3JH–H(trans) = 15.6 Hz, CH55CHCH2Si), 5.42 (dt, 1H,
3JH–H(trans) = 15.6 Hz, 3JH–H = 7.9 Hz, CH55CHCH2Si), 7.30 (d, 2H, 3JH–
H = 7.8 Hz, Ar–H), 7.72 (d, 2H, JH–H = 8.1 Hz, Ar–H); 13C NMR
3
6:4); 1H NMR (400 MHz, CDCl3)
d
= 0.83–0.86 (m, 3H,
(101 MHz, CDCl3) d = 10.9 (Si(CH(CH3)2)3), 15.6 (CH2Si), 18.6
Si(CH(CH3)2)3), 0.91–0.97 (m, 18H, Si(CH(CH3)2)3), 1.41 (s, 2H,
CH2Si), 1.64 (s, 3H, CH3CCH2Si), 2.06–2.16 (m, 2H, NHCH2CH2), 2.38
(Si(CH(CH3)2)3), 21.4 (CH3PhNH), 25.1 (NHCH2C(CH3)2), 36.5
(NHCH2C(CH3)2), 53.2 (NHCH2), 126.8 (CH55CHCH2Si), 127.0 (Ar–
C), 129.6 (Ar–C), 134.1 (CH55CHCH2Si), 136.9 (Ar–C), 143.1 (Ar–C);
3
(s, 3H, CH3PhNH), 2.86–2.96 (m, 2H, NHCH2CH2), 4.73 (t, 1H, JH–
H = 6.8 Hz, NHCH2CH2CH), 4.98–5.20 (m, 1H, NH), 7.25 (d, 2H, 3JH–
IR (neat)
23H40NO2SSi ([M–H]À): 422.2555, found 422.2548,
Identifiable data for the minor (Z) isomer: 1H NMR (400 MHz, CDCl3)
n
= 1265, 1162, 739, 705; HRMS (ESIÀ) m/z required for
= 1.5 ppm.
3
H = 7.8 Hz, Ar–H), 7.75 (d, 2H, JH–H = 8.1 Hz, Ar–H); 13C NMR
C
D
(101 MHz, CDCl3)
d = 11.7 (Si(CH(CH3)2)3), 16.0 (CH2Si), 18.5
3
3
(Si(CH(CH3)2)3), 21.3 (CH3PhNH), 26.3 (CH3CCH2Si), 28.5
(NHCH2CH2), 42.9 (NHCH2CH2), 117.5 (NHCH2CH2CH), 127.0
(Ar–C), 129.4 (Ar–C), 137.0 (Ar–C), 137.3 (CH3CCH2Si), 142.9
d = 1.45 (d, 2H, JH–H = 8.3 Hz, CH2Si), 2.84 (d, 2H, JH–H = 6.6 Hz,
3
NHCH2), 4.95 (d, 1H, JH–H(cis) = 11.9 Hz, CH55CHCH2Si), 5.47–5.56
(m, 1H, CH55CHCH2Si).
(Ar–C); IR (CH2Cl2)
(ESIÀ) m/z required for C22H38NO2SSi ([M–H]À): 408.2398, found
408.2392,
= 1.4 ppm. Identifiable data for the minor (E) isomer: 1H
NMR (400 MHz, CDCl3) = 0.80–0.83 (m, 3H, Si(CH(CH3)2)3), 0.97–
1.02 (m, 18H, Si(CH(CH3)2)3), 1.44 (s, 2H, CH2Si), 1.66 (s, 2H,
n = 2944, 2866, 1464, 1328, 1161, 883; HRMS
4.4. Fluorocyclization of organosilanes
D
d
General procedure C. NaHCO3 (1.1 equiv.) was added to a
solution of allylsilane (1 equiv.) in dry CH3CN [0.1 M]. Selectfluor

174
L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
(1.1 equiv.) was added and the reaction was stirred for 48 h at r.t.
The solvent was removed in vacuo and the reaction mixture was
treated with a saturated solution of NaHCO3 and extracted three
times with Et2O. The combined organic phases were washed with
H2O, brine, dried over MgSO4, filtered and the solvent removed in
vacuo. The crude product was purified by flash column chroma-
tography on silica gel (hexane/Et2O 8:2).
8.5, 3.8 Hz, CHAHBCHF), 2.09 (m, 1H, CHAHBCHF), 3.40 (dd, 1H, 3JH–
H = 11.0, 6.0 Hz, NCHAHB), 3.71 (m, 1H, NCHAHB), 4.01 (m, 1H,
2
3
NCHCHF), 5.04 (ddt, 1H, JH–F = 52.9 Hz, JH–H = 6.9, 3.8 Hz,
NCHCHF); 13C NMR (125 MHz, CDCl3)
d = 11.6 (Si(CH(CH3)2)3),
18.7 (CH2Si), 18.9 (Si(CH(CH3)2)3), 28.6 (COOC(CH3)3), 31.3 (d, 3JC–
F = 21.0 Hz, CH2CHF), 44.0 (NCH2), 59.4 (d, 3JC–F = 20 Hz, NCHCHF),
1
79.7 (COOC(CH3)3), 94.2 (d, JC–F = 173.7 Hz, NCHCHF), 154.5
(COOC(CH3)3); 19F {1H} NMR (376 MHz, CDCl3)
d
= À188.0; nmax
cmÀ1 (DCM): 2800, 1715, 1352; HRMS (CI+) required for
21H37FNO2SSi 360.2730; found: 360.2734;
([M+H]+):
= 1.1 ppm. Characteristic data for minor anti-isomer: 19F {1H}
/
4.4.1. Syn-3-fluoro-1-tosyl-2-((triisopropylsilyl)methyl)pyrrolidine
syn-4a
Following the general procedure C on 100 mg (0.25 mmol,
1 equiv.) of (E)-1a, the reaction gave 62 mg of syn-4a (58%, d.r.
(syn:anti) 9:1) as a white solid and 22 mg of allylic fluoride 2 (34%).
Major syn isomer: Rf = 0.5 (hexane/Et2O 6:4); m.p. = 73 8C; 1H NMR
C
D
NMR (376 MHz, CDCl3)
d
= À172.7.
4.4.4. Anti-3-fluoro-1-tosyl-2-((triisopropylsilyl)methyl)pyrrolidine
anti-4a
Following the general procedure C on 145 mg (0.37 mmol,
1 equiv.) of (Z)-1a, the reaction gave52 mg of anti-4a (34%, d.r.
(syn:anti) 1:21) as a white solid and 36 mg (38%) of allylic
(400 MHz, CDCl3) d = 1.06–1.13 (m, 21H, Si(CH(CH3)2)3), 1.23–1.47
2
3
(m, 2H, CHAHBCHF + CHAHBSi), 1.53 (ddd, 1H, JH–H = 14.5 Hz, JH–
3
F = 4.3 Hz, JH–H = 3.4 Hz, CHAHBSi), 1.95 (td, 1H, J = 14.9, 5.3 Hz,
CHAHBCHF), 2.43 (s, 3H, CH3PhN), 3.45–3.55 (m, 1H, NCHAHB), 3.68
(dd, 1H, 2JH–H = 11.4 Hz, 3JH–H = 8.3 Hz, NCHAHB), 3.88 (ddt, 1H, 3JH–
fluoride 2. Major anti isomer: Rf = 0.5 (hexane/Et2O 6:4);
3
2
2
F = 25.3 Hz, JH–H = 12.7, 3.4 Hz, NCHCHF), 4.89 (dt, 1H, JH–
m.p. = 70 8C; 1H NMR (400 MHz, C6D6)
d
= 0.62 (ddd, 1H, JH–
3
3
3
4
F = 52.3 Hz, JH–H = 3.1 Hz, NCHCHF), 7.31 (d, 2 H, JH–H = 8.1 Hz,
H = 15.1 Hz, JH–H = 13.4 Hz, JH–F = 1.5 Hz, CHAHBSi), 0.91–1.02
(m, 3H, Si(CH(CH3)2)3), 1.02–1.10 (m, 18H, Si(CH(CH3)2)3), 1.41–
Ar–H), 7.73 (d, 2H, JH–H = 8.3 Hz, Ar–H); 13C NMR (101 MHz,
3
2
4
CDCl3)
d
= 11.3 (Si(CH(CH3)2)3), 11.4 (CH2Si), 11.5 (Si(CH(CH3)2)3),
1.56 (m, 2H, CH2CHF), 1.66 (ddd, 1H, JH–H = 15.1 Hz, JH–
3
18.5 (Si(CH(CH3)2)3), 18.8 (Si(CH(CH3)2)3), 21.5 (CH3PhN), 32.1 (d,
F = 4.8 Hz, JH–H = 2.8 Hz, CHAHBSi), 1.85 (s, 3H, CH3PhN), 3.11
(ddd, 1H, JH–H = 10.6 Hz, JH–H = 9.3 Hz, JH–H = 7.6 Hz, NCHAHB),
3.45 (ddd, 1H, JH–H = 9.3 Hz, JH–H = 7.6, 2.1 Hz, NCHAHB), 4.21
(ddd, 1H, JH–F = 25.3 Hz, JH–H = 13.1, 2.3 Hz, NCHCHF), 4.52 (d,
1H, JH–F = 53.1 Hz, NCHCHF), 6.84 (d, 2H, JH–H = 8.1 Hz, Ar–H),
7.88 (d, 2H, JH–H = 8.3 Hz, Ar–H); 13C NMR (100 MHz, C6D6)
2
3
2
3
2JC–F = 22.4 Hz, CH2CHF), 46.4 (NCH2), 63.3 (d, JC–F = 20.8 Hz,
1
2
3
NCHCHF), 94.1 (d, JC–F = 182.9 Hz, NCHCHF), 127.2 (Ar–C), 129.7
(Ar–C), 135.6 (Ar–C), 143.5 (Ar–C); 19F {1H} NMR (377 MHz, CDCl3)
3
3
2
3
d
= À188.59; IR (CH2Cl2):
(CI+) m/z required for C21H37FNO2SSi ([M+H]+) 414.2298, found
414.2300, = 4.8 ppm.
n
= 3029, 1900, 1400, 902, 760; HRMS
3
3
D
d
= 11.9 (Si(CH(CH3)2)3), 18.4 (d, JC–F = 11.2 Hz, CH2Si), 19.2
(Si(CH(CH3)2)3), 21.5 (CH3PhN), 30.5 (d, 2JC–F = 21.6 Hz, CH2CHF),
2
1
4.4.2. Syn-2-((diisopropyl(p-tolyl)silyl)methyl)-3-fluoro-1-
tosylpyrrolidine syn-4b
Following the general procedure C on 100 mg (0.22 mmol,
1 equiv.) of (E)-1b, the reaction gave 24 mg of syn-4b (23%, d.r.
(syn:anti) 5:1) as a colorless oil and 29 mg (50%) of allylic fluoride 2.
Major syn isomer: Rf = 0.4 (hexane/Et2O 7:3); 1H NMR (500 MHz,
46.4 (NCH2), 65.2 (d, JC–F = 22.4 Hz, NCHCHF), 97.1 (d, JC–
F = 179.7 Hz, NCHCHF), 128.0 (Ar–C), 130.0 (Ar–C), 135.7 (Ar–C),
143.4 (Ar–C); 19F {1H} NMR (377 MHz, C6D6)
d
= À173.33; IR
= 3002, 1923, 1355, 991; HRMS (CI+): m/z required
for C21H37FNO2SSi ([M+H]+) 414.2298, found 414.2310,
= 4.5 ppm.
(CH2Cl2)
n
D
CDCl3)
d = 1.08–1.13 (m, 12H, Si(CH(CH3)2)2), 1.13–1.18 (m, 1H,
CHAHBCHF), 1.29–1.35 (m, 2H, Si(CH(CH3)2)2), 1.56–1.61 (m, 1H,
CHAHBSi), 1.79–1.89 (m, 2H, CHAHBCHF+CHAHBSi), 2.39 (s, 3H,
CH3PhSi), 2.42 (s, 3H, CH3PhN), 3.46–3.54 (m, 1H, NCHAHB), 3.61
(dd, 1H, 2JH–H = 12.0 Hz, 3JH–H = 8.2 Hz, NCHAHB), 3.69 (ddd, 1H, 3JH–
4.4.5. Anti-2-((diisopropyl(p-tolyl)silyl)methyl)-3-fluoro-1-
tosylpyrrolidine anti-4b
Following the general procedure C on 100 mg (0.22 mmol,
1 equiv.) of (Z)-1b, the reaction gave 15 mg of anti-4b (14%, d.r.
(syn:anti) > 1:20) as a colorless oil and 39 mg (57%) of the allylic
fluoride 2. Major anti isomer: Rf = 0.5 (hexane/Et2O 7:3); 1H NMR
3
2
F = 25.8 Hz, JH–H = 12.6, 3.3 Hz, NCHCHF), 4.59 (ddd, 1H, JH–
F = 52.0 Hz, 3JH–H = 3.5, 2.8 Hz, NCHCHF), 7.21 (d, 2H, 3JH–H = 7.2 Hz,
3
3
SiAr–H), 7.25 (d, 2H, JH–H = 7.9 Hz, NAr–H), 7.47 (d, 2H, JH–
(500 MHz, CDCl3)
Si(CH(CH3)2)2), 1.05 (m, 1H, CHAHBSi), 1.15 (dd, 6H, JH–H = 10.7,
d
= 1.04 (dd, 6H, 3JH–H = 10.4, 7.6 Hz,
H = 7.9 Hz, SiAr–H), 7.61 (d, 2H, JH–H = 8.2 Hz, NAr–H); 13C NMR
3
3
3
(125 MHz, CDCl3)
12.1 (d, JC–F = 10.5 Hz, CH2Si), 18.2 (Si(CH(CH3)2)2), 18.3
(Si(CH(CH3)2)2), 21.5 (CH3PhSi), 21.5 (CH3PhN), 31.9 (d, JC–
F = 21.9 Hz, CH2CHF), 46.6 (NCH2), 63.2 (d, JC–F = 21.0 Hz,
d
= 11.5 (Si(CH(CH3)2)2), 11.6 (Si(CH(CH3)2)2),
7.6 Hz, Si(CH(CH3)2)2), 1.26 (p, 1H, JH–H = 7.6 Hz, Si(CH(CH3)2)2),
3
3
2
1.41 (p, 1H, JH–H = 7.6 Hz, Si(CH(CH3)2)2), 1.74 (ddd, 1H, JH–
2
4
3
H = 15.1 Hz, JH–F = 4.4 Hz, JH–H = 3.1 Hz, CHAHBSi), 1.92–2.14 (m,
2H, CH2CHF), 2.37 (s, 3H, CH3PhSi), 2.42 (s, 3H, CH3PhN), 3.11 (ddd,
2
1
3
2
3
NCHCHF), 93.7 (d, JC–F = 183.1 Hz, NCHCHF), 127.3 (NAr–C),
1H, JH–H = 11.4 Hz, JH–H = 9.5 Hz, JH–H = 6.2 Hz, NCHAHB), 3.62
2
3
128.6 (SiAr–C), 129.6 (NAr–C), 130.9 (SiAr–C), 135.1 (NAr–C),
135.2 (SiAr–C), 138.7 (SiAr–C), 143.4 (NAr–C); 19F {1H} NMR
(dd, 1H, JH–H = 9.5 Hz, JH–H = 1.0 Hz, NCHAHB), 3.97 (dddd, 1H,
3JH–F = 25.2 Hz, 3JH–H = 13.2, 3.1, 1.1 Hz, NCHCHF), 4.56 (dd, 1H, 2JH–
3
3
(377 MHz, CDCl3)
1349, 1161, 1099, 817, 737; HRMS (ESI+) m/z required for
25H36FNO2SSiNa+ ([M+Na]+): 484.2112, found 484.2096,
= 3.2 ppm.
d
= À188.77; IR (CH2Cl2)
n
= 2944, 2866, 1599,
F = 51.7 Hz, JH–H = 2.5 Hz, NCHCHF), 7.21 (d, 2H, JH–H = 7.6 Hz,
3
3
SiAr–H), 7.28 (d, 2H, JH–H = 8.2 Hz, NAr–H), 7.40 (d, 2H, JH–
H = 7.8 Hz, SiAr–H), 7.65 (d, 2H, JH–H = 8.2 Hz, NAr–H); 13C NMR
3
C
D
(125 MHz, CDCl3) d = 10.8 (Si(CH(CH3)2)2), 11.5 (Si(CH(CH3)2)2),
3
18.0 (Si(CH(CH3)2)2), 18.2 (Si(CH(CH3)2)2), 18.4 (d, JC–F = 11.4 Hz,
2
4.4.3. Syn-tert-butyl-3-fluoro-2-
CH2Si), 21.5 (CH3PhSi), 21.5 (CH3PhN), 30.1 (d, JC–F = 21.0 Hz,
2
((triisopropylsilyl)methyl)pyrrolidine-1-carboxylate syn-4f
Following the general procedure C on 100 mg (0.29 mmol,
1 equiv.) of (E)-1f, the reaction gave 56 mg of syn-4f (54%, d.r.
(syn:anti) 5:1) as a colorless oil and 27 mg (43%) of allylic fluoride 3.
Major syn isomer: Rf = 0.6 (hexane/Et2O 9:1); 1H NMR (500 MHz,
CH2CHF), 45.7 (NCH2), 64.6 (d, JC–F = 21.9 Hz, NCHCHF), 96.1 (d,
1JC–F = 179.3 Hz, NCHCHF), 127.6 (NAr–C), 128.8 (SiAr–C), 129.5
(NAr–C), 130.5 (SiAr–C), 133.8 (NAr–C), 134.8 (SiAr–C), 139.0
(SiAr–C), 143.3 (NAr–C); 19F {1H} NMR (377 MHz, CDCl3)
d
= À174.06; IR (CH2Cl2)
739; HRMS (CI+) m/z required for C25H37FNO2SSi ([M+H]+):
462.2298, found 462.2311, = 2.7 ppm.
n = 2945, 2866, 1599, 1345, 1161, 1099,
CDCl3)
d = 1.08 (m, 23H, Si(CH(CH3)2)3 + CH2Si), 1.48 (s, 9H,
3
3
COOC(CH3)3), 1.88 (ddddd, 1H, JH–F = 39.1 Hz, JH–H = 11.3, 11.0,
D

L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
175
3
2
4.4.6. Anti-3-fluoro-2-methyl-1-tosyl-2-
4JH–H = 1.3 Hz, CH255CHCHF), 5.23 (dt, 1H, JH–H(cis) = 10.6 Hz, JH–
4
3
((triisopropylsilyl)methyl)pyrrolidine anti-4g
H = 1.3 Hz, JH–H = 1.3 Hz, CHAHB55CHCHF), 5.30 (ddt, 1H, JH–
H(trans) = 17.2 Hz, 4JH–F = 3.3 Hz, 2JH–H = 1.3 Hz, 4JH–H = 1.3 Hz,
CHAHB55CHCHF), 5.82 (dddd, 1H, JH–F = 14.9 Hz, JH–H = 17.2,
10.6, 5.8 Hz, CH255CHCHF), 7.32 (d, 2H, JH–H = 8.1 Hz, NHAr–H),
7.76 (d, 2H, JH–H = 8.1 Hz, NHAr–H); 13C NMR (101 MHz, CDCl3)
Following the general procedure C on 163 mg (0.39 mmol,
1 equiv.) of (Z)-1g, the reaction gave 102 mg of anti-4g (61%, d.r.
(syn:anti) 1:1) as a yellow oil and 29 mg (27%) of the allylic fluoride
6. Major anti isomer: Rf = 0.6 (hexane/Et2O 6:4); 1H NMR
3
3
3
3
2
(500 MHz, C6D6)
d
= 0.78–0.87 (m, 1H, CHAHBSi), 0.89–1.09 (m,
d
= 21.5 (CH3PhNH), 35.0 (d, JC–F = 21.6 Hz, NHCH2CH2), 39.3 (d,
3JC–F = 4.0 Hz, NHCH2CH2), 91.5 (d, JC–F = 167.8 Hz, CH255CHCHF),
3
1
21H, Si(CH(CH3)2)3), 1.55–1.80 (m, 2H, CH2CHF), 1.72 (d, 3H, JH–
H = 4.7 Hz, NC(CH3)), 1.93 (s, 3H, CH3PhN), 2.12 (dd, 1H, JH–
H = 15.1 Hz, 4JH–F = 6.3 Hz, CHAHBSi), 3.34 (ddd, 1H, 2JH–H = 16.8 Hz,
2
3
117.6 (d, JC–F = 12.0 Hz, CH255CHCHF), 127.1 (NHAr–C), 129.8
(NHAr–C), 135.4 (d, 2JC–F = 19.2 Hz, CH255CHCHF), 136.7 (NHAr–C),
3JH–H = 9.7, 7.3 Hz, NCHAHB), 3.56 (ddd, 1H, JH–H = 16.8 Hz, JH–
H = 9.1, 2.5 Hz, NCHAHB), 4.59 (ddd, 1H, 2JH–F = 53.0 Hz, 3JH–H = 3.8,
1.9 Hz, NCCHF), 6.83 (d, 2H, 3JH–H = 8.5 Hz, NAr–H), 7.80 (d, 2H, 3JH–
143.6 (NHAr–C); 19F {1H} NMR (377 MHz, CDCl3)
d
= À180.3; IR
= 3250, 3061, 2821, 1645, 1432; HRMS (CI+) m/z required
for C12H20FN2O2S ([M+NH4]+) 275.1230, found 275.1243,
= 4.9 ppm.
2
3
(neat)
n
H = 8.2 Hz, NAr–H); 13C NMR (125 MHz, C6D6)
(Si(CH(CH3)2)3), 19.5 (Si(CH(CH3)2)3), 21.5 (CH3PhN), 22.4 (d, JC–
d
= 12.7
3
D
3
2
F = 12.4 Hz, NC(CH3)), 24.4 (d, JC–F = 5.7 Hz, CH2Si), 29.3 (d, JC–
4.5.2. N-tert-butyl (3-fluoropent-4-en-1-yl)carbamate 3
2
F = 22.9 Hz, CH2CHF), 46.4 (NCH2), 72.0 (d, JC–F = 19.1 Hz,
Rf = 0.4 (hexane/Et2O 7:3); 1H NMR (400 MHz, CDCl3)
d
= 1.44
1
3
NC(CH3)), 99.7 (d, JC–F = 186.0 Hz, NCCHF), 127.7 (NAr–C), 129.9
(sbr, 9H, COOC(CH3)3), 1.81–1.95 (m, 2H, JH–F = 25.7 Hz,
NHCH2CH2), 3.28 (d, 2H, JH–H = 6.3 Hz, NHCH2CH2), 4.74 (sbr,
1H, NH), 4.98 (dddd, 1H, JH–F = 48.5 Hz, JH–H = 11.0, 5.8 Hz, JH–
H = 1.3 Hz, CH255CHCHF), 5.24 (dt, 1H, JH–H(cis) = 10.9, JH–
H = 1.3 Hz, JH–H = 1.3 Hz, CHAHB55CHCHF), 5.34 (ddt, 1H, JH–
H(trans) = 17.2 Hz, 4JH–F = 3.3 Hz, 2JH–H = 1.3 Hz, 4JH–H = 1.3 Hz,
CHAHB55CHCHF), 5.89 (dddd, 1H, JH–H(trans) = 17.2 Hz, JH–
F = 14.9 Hz, JH–H(cis) = 10.9 Hz, JH–H = 5.8 Hz, CH255CHCHF); 13C
(NAr–C), 140.3 (NAr–C), 142.8 (NAr–C); 19F {1H} NMR (377 MHz,
3
2
3
4
CDCl3)
d
= À181.97; IR (CH2Cl2)
n
= 2952, 1464, 1341, 1158, 1011,
3
2
814, 711; HRMS (ESI+) m/z required for C22H38FNO2SSiNa+
4
3
([M+Na]+): 450.2269, found 450.2261,
D
= 1.4 ppm. Identifiable
data for minor syn isomer: 1H NMR (500 MHz, C6D6)
d
= 1.74 (d, 3H,
2
4
3
3
3JH–H = 5.3 Hz, NC(CH3)), 2.20 (dd, 1H, JH–H = 15.4 Hz, JH–
2
3
3
3
F = 6.9 Hz, CHAHBSi), 4.62 (ddd, 1H, JH–F = 53.0 Hz, JH–H = 3.5,
2
1.3 Hz, NCCHF); 13C NMR (125 MHz, C6D6)
d
= 12.6 (Si(CH(CH3)2)3),
NMR (101 MHz, CDCl3)
d
= 28.3 (COOC(CH3)3), 35.3 (d, JC–
F = 21.6 Hz, NHCH2CH2), 36.7 (d, JC–F = 3.2 Hz, NHCH2CH2), 79.2
(COOC(CH3)3), 91.5 (d, 1JC–F = 167.0 Hz, CH255CHCHF), 117.1 (d, 3JC–
19.4 (Si(CH(CH3)2)3), 22.3 (d, 3JC–F = 12.4 Hz, NC(CH3)), 24.3 (d, 3JC–
3
2
F = 5.7 Hz, CH2Si), 29.4 (d, JC–F = 21.9 Hz, CH2CHF), 46.4 (NCH2),
72.3 (d, 2JC–F = 18.1 Hz, NC(CH3)), 99.7 (d, 1JC–F = 186.0 Hz, NCCHF);
F = 12.0 Hz, CH255CHCHF), 135.9 (d, JC–F = 19.2 Hz, CH255CHCHF),
2
19F {1H} NMR (377 MHz, CDCl3)
d
= À181.75.
155.9 (COOC(CH3)3); 19F {1H} NMR (377 MHz, CDCl3)
d
= À179.90;
= 3351, 2979, 1694, 1521, 1367, 1174, 989; HRMS (ESI+)
m/z required for C10H18FNO2Na+ ([M+Na]+) 226.1214, found
226.1214, = 0.2 ppm.
IR (neat)
n
4.4.7. Syn-3-fluoro-4,4-dimethyl-1-tosyl-2-
((triisopropylsilyl)methyl)pyrrolidine syn-4h
D
Following the general procedure C on 90 mg (0.22 mmol,
1 equiv.) of (E)-1h, the reaction gave 35 mg of syn-4h (36%, d.r.
(syn:anti) 6.6:1) as a yellow oil and 28 mg (45%) of the allylic
fluoride 7. Major syn isomer: Rf = 0.6 (hexane/Et2O 6:4); 1H NMR
4.5.3. N-(3-fluoro-4-methylpent-4-en-1-yl)-4-methylbenzene
sulfonamide 6
Rf = 0.2 (hexane/Et2O 6:4); 1H NMR (500 MHz, C6D6)
d = 1.43 (s,
(500 MHz, C6D6)
d
= 0.43 (d, 3H, 4JH–F = 1.7 Hz, NCH2C(CH3)2), 0.80
3H, CH255C(CH3)CHF), 1.40–1.61 (m, 2H, NHCH2CH2), 1.89 (s, 3H,
CH3PhNH), 2.78–2.89 (m, 2H, NHCH2CH2), 4.49–4.54 (m, 1H, NH),
4.57 (ddd, 1H, 2JH–F = 48.0 Hz, 3JH–H = 8.5, 3.8 Hz, CH255C(CH3)CHF),
(d, 3H, 4JH–F = 1.9 Hz, NCH2C(CH3)2), 1.01–1.03 (m, 3H,
3
Si(CH(CH3)2)3), 1.10 (d, 9H, JH–H = 6.9 Hz, Si(CH(CH3)2)3), 1.15
(d, 9H, 3JH–H = 7.2 Hz, Si(CH(CH3)2)3), 1.41 (dd, 1H, 2JH–H = 13.2 Hz,
3JH–H = 12.9 Hz, CHAHBSi), 1.85 (s, 3H, CH3PhN), 1.86–1.92 (m, 1H,
4.69 (d, 1H, JH–H = 1.6 Hz, CHAHB55C(CH3)CHF), 4.85 (s, 1H,
2
3
CHAHB55C(CH3)CHF), 6.79 (d, 2H, JH–H = 7.9 Hz, NHAr–H), 7.78
2
2
CHAHBSi), 3.22 (d, 1H, JH–H = 10.7 Hz, NCHAHB), 3.41 (d, 1H, JH–
H = 10.4 Hz, NCHAHB), 4.19 (dd, 1H, JH–F = 52.6 Hz, JH–H = 3.5 Hz,
C(CH3)2CHF), 4.36 (ddt, 1H, JH–F = 27.4, JH–H = 16.6, 3.1 Hz,
NCHCHF), 6.81 (d, 2H, JH–H = 7.9 Hz, NAr–H), 7.84 (d, 2H, JH–
H = 8.2 Hz, NAr–H); 13C NMR (125 MHz, C6D6)
(d, 2H, 3JH–H = 8.2 Hz, NHAr–H); 13C NMR (125 MHz, C6D6)
d
= 17.6
2
2
3
3
(d, JC–F = 3.8 Hz, CH255C(CH3)CHF), 21.4 (CH3PhNH), 34.2 (d, JC–
F = 21.9 Hz, NHCH2CH2), 39.9 (d, 3JC–F = 3.8 Hz, NHCH2CH2), 93.6 (d,
1JC–F = 170.7 Hz, CH255C(CH3)CHF), 113.1 (d, 3JC–F = 9.5 Hz,
CH255C(CH3)CHF), 127.8 (NHAr–C), 130.1 (NHAr–C), 138.6
3
3
3
3
3
d = 11.9 (d, JC–
2
F = 12.4 Hz, CH2Si), 12.3 (Si(CH(CH3)2)3), 19.2 (Si(CH(CH3)2)3), 19.4
(NHAr–C), 143.3 (d, JC–F = 17.2 Hz, CH255C(CH3)CHF), 143.3
3
(Si(CH(CH3)2)3), 19.7 (d, JC–F = 7.6 Hz, NCH2C(CH3)2), 21.4
(NHAr–C); 19F {1H} NMR (377 MHz, C6D6)
n
d
= À180.54; IR (neat)
= 3441, 3054, 1641, 1422, 1265, 896, 737; HRMS (CI+) m/z
required for C13H19FNO2S ([M+H+]) 272.1121, found 272.1133,
= 4.6 ppm.
3
2
(CH3PhN), 23.3 (d, JC–F = 6.7 Hz, NCH2C(CH3)2), 42.1 (d, JC–
2
F = 19.1 Hz, NCH2C(CH3)2), 58.0 (NCH2), 63.6 (d, JC–F = 21.9 Hz,
1
NCHCHF), 101.1 (d, JC–F = 189.8 Hz, NCHCHF), 127.9 (NAr–C),
D
130.0 (NAr–C), 139.2 (NAr–C), 143.1 (NAr–C); 19F {1H} NMR
(377 MHz, C6D6)
1265, 1156, 739; HRMS (ESI+) m/z required for C23H40FNO2SSiNa+
([M+Na]+): 464.2425, found 464.2413,
= 2.7 ppm. Identifiable
data for minor anti isomer: 19F {1H} NMR (377 MHz, CDCl3)
= À197.73.
d
= À192.61; IR (CH2Cl2)
n
= 2945, 2868, 1470,
4.5.4. N-(3-fluoro-2,2-dimethylpent-4-en-1-yl)-4-methylbenzene
sulfonamide 7
D
Rf = 0.3 (hexane/Et2O 6:4); m.p. = 81 8C; 1H NMR (400 MHz,
4
CDCl3)
d
= 0.89 (d, 3H, JH–F = 0.8 Hz, NHCH2C(CH3)2), 0.90 (d, 3H,
d
4JH–F = 1.3 Hz, NHCH2C(CH3)2), 2.43 (s, 3H, CH3PhNH), 2.79 (dd, 1H,
2JH–H = 12.6 Hz, JH–H = 7.1 Hz, NHCHAHBC(CH3)2), 2.88 (dd, 1H,
3
3
4.5. Allylic fluorides
2JH–H = 12.6 Hz, JH–H = 6.6 Hz, NHCHAHBC(CH3)2), 4.62 (ddt, 1H,
2JH–F = 47.5 Hz, JH–H = 6.3 Hz, JH–H = 1.3 Hz, CH255CHCHF), 4.93
3
4
3
3
4.5.1. N-(3-fluoropent-4-en-1-yl)-4-methylbenzenesulfonamide 2
Rf = 0.3 (hexane/Et2O 6:4); m.p. = 73 8C; 1H NMR (400 MHz,
(dd, 1H, JH–H = 7.1, 6.6 Hz, NH), 5.30 (dd, 1H, JH–H(cis) =10.9 Hz,
2JH–H = 1.5 Hz, 3JH–
CHAHB55CHCHF), 5.31 (dddd, 1H,
H(trans) = 17.2 Hz, 4JH–F = 3.1 Hz, 2JH–H = 1.5 Hz, 4JH–H = 1.3 Hz,
CHAHB55CHCHF), 5.83 (dddd, 1H, JH–H(trans) = 17.2 Hz, JH–
F = 15.9 Hz, JH–H(cis) = 10.9 Hz, JH–H = 6.3 Hz, CH255CHCHF), 7.31
CDCl3)
d
= 1.81–1.94 (m, 2H, 3JH–F = 21.2 Hz, NHCH2CH2), 2.43 (sbr,
3
3
3
3H, CH3PhNH), 3.05–3.19 (m, 2H, NHCH2CH2), 4.70 (t, 1H, JH–
H = 5.7 Hz, NH), 4.97 (dddt, 1H, JH–F = 48.6 Hz, JH–H = 7.2, 5.8 Hz,
2
3
3
3

176
L.E. Combettes et al. / Journal of Fluorine Chemistry 143 (2012) 167–176
(d, 2H, 3JH–H = 8.4 Hz, NHAr–H), 7.75 (d, 2H, 3JH–H = 8.4 Hz, NHAr–
(f) G.T. Giuffredi, S. Purser, M. Sawicki, A.L. Thompson, V. Gouverneur, Tetrahe-
dron: Asymmetry 21 (2010) 123–127;
(g) G.T. Giuffredi, S. Purser, M. Sawicki, A.L. Thompson, V. Gouverneur, Tetrahe-
dron: Asymmetry 20 (2009) 910–920;
(h) G.T. Giuffredi, B. Bernet, V. Gouverneur, European Journal of Organic Chem-
istry (2011) 3825–3836;
(i) G.T. Giuffredi, L.E. Jennings, B. Bernet, V. Gouverneur, Journal of Fluorine
Chemistry 132 (2011) 772–778.
3
H); 13C NMR (101 MHz, CDCl3)
d
= 20.0 (d, JC–F = 3.2 Hz,
NHCH2C(CH3)2), 21.5 (CH3PhNH), 21.5 (d, 3JC–F = 6.4 Hz,
2
NHCH2C(CH3)2), 38.1 (d, JC–F = 19.2 Hz, NHCH2C(CH3)2), 50.4 (d,
3JC–F = 3.2 Hz,
NHCH2C(CH3)2),
98.1
(d,
1JC–F = 174.2 Hz,
3
CH255CHCHF), 119.4 (d, JC–F = 12.8 Hz, CH255CHCHF), 127.0
(NHAr–C), 129.7 (NHAr–C), 132.1 (d, 2JC–F = 19.2 Hz, CH255CHCHF),
CHCHF), 136.9 (NHAr–C), 143.3 (NHAr–C); 19F {1H} NMR
[6] (a) J.B. Lambert, Y. Zhao, R.W. Emblidge, L.A. Salvador, X. Liu, J.-H. So, E.C. Chelius,
Accounts of Chemical Research 32 (1999) 183–190;
(b) I. Fleming, A. Barbero, D. Walter, Chemical Reviews 97 (1997) 2063–2192;
(c) M.C. Curtis-Long, Y. Aye, Chemistry: A European Journal 15 (2009) 5402–5416.
[7] (a) R.H. Bates, J.B. Shotwell, W.R. Roush, Organic Letters 10 (2008) 4343–4346;
(b) G.C. Micalizio, W.R. Roush, Organic Letters 2 (2000) 461–464;
(c) J.M. Tinsley, W.R. Roush, Journal of the American Chemical Society 127 (2005)
10818–10819;
(377 MHz, CDCl3)
d
= À186.10; IR (KBr)
n = 3418, 2975, 1644,
1427, 1326, 1161, 664; HRMS (CI+) m/z required for C14H24N2O2FS
([M+NH4+]) 303.1543, found 303.1549,
D = 3.5 ppm.
(d) M. Dressel, P. Restorp, P. Somfai, Chemistry: A European Journal 14 (2008)
3072–3077;
Acknowledgments
(e) P. Restorp, A. Fischer, P. Somfai, Journal of the American Chemical Society 128
(2006) 12646–12647;
(f) G. Adiwidjaja, H. Flo¨rke, A. Kirshning, E. Schaumann, Liebigs Annalen (1995)
501–507.
This research was supported by the EPSRC (EP/F019467/1, LEC)
and the European Community (PIEF-GA-2008-220034, OL). We
thank Dr. Marie Schuler and Mr Rakesh Patel for preliminary
experiments, and Dr. Barbara Odell for NMR studies.
[8] S.C. Wilkinson, O. Lozano, M. Schuler, M. Pacheco, R. Salmon, V. Gouverneur,
Angewandte Chemie International Edition 48 (2009) 7083–7086.
[9] (a) K. Tamao, Advances in Silicon Chemistry 3 (1996) 1–62;
(b) G.R. Jones, Y. Landais, Tetrahedron 52 (1996) 7599–7662;
(c) I. Fleming, R. Henning, D.C. Parker, H.E. Plaut, P.E.J. Sanderson, Journal of the
Chemical Society, Perkin Transactions 1 (1995) 317–337;
(d) T. Akiyama, E. Hoshi, S. Fujiyoshi, Journal of the Chemical Society, Perkin
Transactions 1 (1998) 2121–2122.
[10] R.P. Singh, J.M. Shreeve, Chemical Communications (2001) 1196–1197.
[11] The cross-metathesis of the homoallylic tosylamine with allyl(diisopropyl)(4-
methylphenyl)silane led to a truncated side-product resulting from double bond
isomerisation/reversible cross-metathesis.
[12] Allyldimethylphenylsilane, see J.A. Soderquist, A. Hassner, Journal of Organic
Chemistry 48 (1983) 1801–1810.;
Allylbenzhydryldimethylsilane, see Z.-H. Peng, K.A. Woerpel, Organic Letters 2
(2000) 1379–1381; Allyl(diisopropyl)(4-methylphenyl)silane, see reference [8].
[13] R.E. Taylor, F.C. Engelhardt, M.J. Schmitt, H. Yuan, Journal of the American
Chemical Society 123 (2001) 2964–2969.
References
[1] (a) M.C. Pacheco, S. Purser, V. Gouverneur, Chemical Reviews 108 (2008) 1943–
1981;
(b) M. Tredwell, V. Gouverneur, Organic and Biomolecular Chemistry 4 (2006)
26–32.
[2] V. Gouverneur, B. Greedy, Chemistry: A European Journal 8 (2002) 766–771,
references therein.
[3] P. Tang, T. Ritter, Tetrahedron 67 (2011) 4449–4454.
[4] B. Greedy, V. Gouverneur, Chemical Communications (2001) 233–234;
S. Thibaudeau, V. Gouverneur, Organic Letters 5 (2003) 4891–4893;
(b) L. Carroll, M.C. Pacheco, L. Garcia, V. Gouverneur, Chemical Communications
(2006) 4113–4115;
(c) B. Greedy, J.-M. Paris, T. Vidal, V. Gouverneur, Angewandte Chemie Interna-
tional Edition 42 (2003) 3291–3294;
[14] We noted a significant E:Z isomerisation upon ring opening of the silylated 2,2-
diisopropyl-4-methyl-2,3,6,7-tetrahydro-1,2-oxasilepine[8] with s-BuLi.
[15] 3-Fluoropyrrolidine anti-4a was subjected to the standard condition for fluor-
ocyclisation; no anti–syn isomerisation was observed after 72 h.
[16] (a) M.J.C. Buckle, I. Fleming, S. Gil, Tetrahedron Letters 33 (1992) 4479–4482;
(b) M.J.C. Buckle, I. Fleming, S. Gil, K.L.C. Pang, Organic and Biomolecular Chem-
istry 2 (2004) 749–769.
(d) L. Carroll, S. McCullough, T. Rees, T.D.W. Claridge, V. Gouverneur, Organic and
Biomolecular Chemistry 6 (2008) 1731–1733;
(e) M.C. Pacheco, V. Gouverneur, Organic Letters 7 (2005) 1267–1270.
[5] (a) S. Purser, B. Odell, D.W. Claridge, P.R. Moore, V. Gouverneur, Chemistry: A
European Journal 12 (2006) 9176–9185;
(b) G. Giuffredi, C. Bobbio, V. Gouverneur, Journal of Organic Chemistry 71 (2006)
5361–5364;
[17] T. Xu, S. Qiu, G. Liu, Chinese Journal of Chemistry 29 (2011) 2785–2790.
[18] (a) T. Mizutani, Y. Ukaji, K. Inomata, Bulletin of the Chemical Society of Japan 76
(2003) 1251–1256;
(b) R.C. Larock, H. Yang, S.M. Weinreb, R.J. Herr, Journal of Organic Chemistry 59
(1994) 4172–4178.
[19] C. Taillier, T. Hameury, V. Bellosta, J. Cossy, Tetrahedron 63 (2007) 4472–4490.
(c) H. Teare, F. Huguet, M. Tredwell, S. Thibaudeau, S. Luthra, V. Gouverneur,
Arkivoc 10 (2007) 232–244;
(d) Y.-H. Lam, C. Bobbio, I.R. Cooper, V. Gouverneur, Angewandte Chemie Inter-
national Edition 46 (2007) 5106–5110;
(e) S. Purser, T.D.W. Claridge, B. Odell, P.R. Moore, V. Gouverneur, Organic Letters
10 (2008) 4263–4266;