Gold-catalyzed diastereoselective synthesis of α-fluoroenones from propargyl acetates

Article abstract of DOI:10.1055/s-0030-1258992

A diastereoselective preparation of -fluoroenones from propargyl acetates has been developed proceeding via a gold-catalyzed rearrangement-fluorination cascade. Control reactions are consistent with a mechanism involving a gold-mediated 3,3-sigmatropic shift followed by a direct, nongold-catalyzed electrophilic fluorination of the allenyl acetate intermediate.

Full text of DOI:10.1055/s-0030-1258992

LETTER
2737
Gold-Catalyzed Diastereoselective Synthesis of a-Fluoroenones from
Propargyl Acetates
a
-Fluoroenone
s
atthew N. Hopkinson,a Guy T. Giuffredi,a Antony D. Gee,b,1 Véronique Gouverneur*a
b
Received 6 August 2010
routes towards a-fluoroenones are scarce and are limited
to multistep protocols.13 In this paper, we report the dia-
stereoselective synthesis of these biologically relevant
compounds directly from propargyl acetates. In addition,
Abstract: A diastereoselective preparation of a-fluoroenones from
propargyl acetates has been developed proceeding via a gold-cata-
lyzed rearrangement–fluorination cascade. Control reactions are
consistent with a mechanism involving a gold-mediated 3,3-sigma-
tropic shift followed by a direct, nongold-catalyzed electrophilic control experiments suggest that a mechanistic scenario
fluorination of the allenyl acetate intermediate.
involving a cascade gold-catalyzed rearrangement fol-
lowed by an electrophilic fluorination not involving an or-
ganogold intermediate is operational.
Key words: gold, fluorine, catalysis, diastereoselectivity, rear-
rangement
As a preliminary study, propargyl acetate 1a was synthe-
sized and treated with Selectfluor (1.2 equiv), Ph3PAuCl
(2 mol%), and AgOTf (5 mol%) in acetonitrile–water
(800:1, 0.05 M) at room temperature for 48 hours. Pleas-
ingly, a-fluoroenones (E)-2a and (Z)-2a, resulting from a
cascade [3,3]-sigmatropic rearrangement–fluorination
process were observed as the major products and isolated
in 45% yield. The reaction proceeded with high diastere-
oselectivity delivering the E-isomer as the major product
(crude E/Z ratio = 10.4:1).14 Importantly, the E- and Z-iso-
mers could be easily separated by column chromatogra-
phy. The protonated enone (E)-3a was also isolated from
the reaction mixture in 25% yield (E/Z > 20:1) whilst trace
amounts of products resulting from homocoupling of the
propargyl acetate and oxidative cross-coupling with an
acetate group were observed by NMR and mass spectrom-
etry (Scheme 1).10
Fluorinated compounds are becoming increasingly impor-
tant as pharmaceuticals and agrochemicals.2 As such,
methods for the introduction of fluorine into complex or-
ganic molecules are in high demand. In recent years, sig-
nificant research attention has focused on the
development of transition-metal-catalyzed approaches to
C–F bond formation.3 In 2007, Sadighi and co-workers re-
ported the direct gold-catalyzed hydrofluorination of
alkynes with Et3N·3HF4 whilst, the following year, our
group reported the first gold-catalyzed fluorination proto-
col using an electrophilic source of fluorine.5 Therein, tri-
fluorinated pyranones were obtained upon the gold(I)-
mediated cascade cyclization–fluorination of b-hydroxy-
a,a-difluoroynones in the presence of Selectfluor. More
recently, gold(I) catalysts have been used in combination
with Selectfluor to perform oxidative coupling reactions6
between in situ generated organogold intermediates and
benzoates,7 arylboronic acids,8 and nonactivated arenes.9
These transformations are thought to involve AuI/AuIII
redox cycles where Selectfluor acts as a stoichiometric
oxidant.
OAc
Cl
N+
N+
Ph
+
2 BF4
n-C6H13
F
1a
Selectfluor
1.2 equiv
In 2009, Zhang and coworkers reported the cascade [3,3]-
sigmatropic rearrangement–homodimerization of propar-
gyl acetates catalyzed by gold(I) complexes in the pres-
ence of Selectfluor.10 In the course of this study, a-
fluoroenones were observed as minor side products. This
observation led us to investigate whether, through optimi-
zation of the reaction conditions, a-fluoroenones could be
efficiently prepared via this method.11 These compounds,
which contain a C(sp2)–F moiety, are important synthetic
intermediates towards fluoroalkenes, which have found
applications as peptidomimetics.12 Currently, synthetic
PPh3AuCl (2 mol%)
AgOTf (5 mol%)
MeCN–H2O (800:1, 0.05 M)
r.t., 48 h
F
O
Ph
+
+
Ph
n-C6H13
O
n-C6H13
2a
45% (E/Z = 10.4:1)
(E)-3a
25% (E/Z > 20:1)
n-C6H13
O
OAc
Ph
Ph
Ph
O
n-C6H13
trace
O
n-C6H13
SYNLETT 2010, No. 18, pp 2737–2742
x
x
.x
x
.2
0
1
0
trace
Advanced online publication: 08.10.2010
DOI: 10.1055/s-0030-1258992; Art ID: D21310ST
Scheme 1 Preliminary studies
© Georg Thieme Verlag Stuttgart · New York

2738
M. N. Hopkinson et al.
LETTER
With the aim of identifying standard reaction conditions, In order to investigate the effect of the propargyl acetate
optimization studies were carried out using 1a as a model substitution, substrates 1a–k were prepared according to
substrate (Table 1). SIPrAuCl/AgOTf [SIPr = 1,3- literature procedures11a and treated with Selectfluor and
bis(2,6-diisopropylphenyl)imidazolin-2-ylidene],
was SIPrAuCl/AgOTf in acetonitrile (Table 2).15 In most cas-
identified as the catalytic system of choice for this trans- es, the reactions were heated to 40 °C to encourage com-
formation, delivering 2a in 53% isolated yield (68% yield plete conversion of the starting material in a reasonable
estimated by 19F NMR, entry 2) when heated with Select- reaction time (<72 h). For propargyl acetates 1a–h, which
fluor in acetonitrile at 80 °C for two hours. Whilst the re- contain only one substituent at the propargylic position,
action was still successful with SIPrAuCl in the absence the rearrangement–fluorination process was found to pro-
of the silver co-catalyst, this system resulted in a lower ceed with preferential E selectivity. The best diastereose-
yield of fluoroenones (entry 3). AuCl and AuCl3 were less lectivity was observed for substrates bearing a phenyl
effective catalysts for the rearrangement–fluorination pro- group (entries 1, 2). In all cases, the E- and Z-isomers
cess whilst no fluorinated products were observed in the were separable by column chromatography. The p-nitro-
absence of catalyst or when using 2 mol% of AgOTf or phenyl substituted substrate 1c was well-tolerated, afford-
PtCl2 (entries 4–8). Alternative electrophilic fluorinating ing the corresponding (E)-a-fluoroenone in 64% yield
reagents such as N-fluorobenzenesulfonimide (NFSI) and with an estimated E/Z ratio of 9.4:1 (entry 3). By contrast,
1-fluoro-2,4,6-trimethylpyridinium
tetrafluoroborate the p-methoxyphenyl-substituted variant 1d led to a com-
were not suitable (entries 12, 13). The yield of fluo- plex mixture of products (entry 4). Substrates 1e and 1f,
roenones and the E/Z selectivity could be improved upon bearing alkyl substituents at the propargylic position, re-
lowering the reaction temperature to room temperatue and acted successfully with the highest yield and the best dia-
increasing the amount of catalyst (5 mol%), silver co-cat- stereoselectivity being observed for the cyclohexyl-
alyst (12.5 mol%) and fluorinating reagent (2 equiv). Un- substituted compound (yield 80%, E/Z ratio = 5.2:1, en-
der these conditions, a-fluoroenones 2a were isolated in tries 5, 6). The process was less tolerant of propargyl ace-
70% overall yield in a crude E/Z ratio of 12.5:1 after 48 tates with alkyl substituents at both the propargylic and
hours (entry 14).
alkynyl positions. For these compounds, the correspond-
Table 1 Optimization Studies
OAc
F
oxidant, catalyst
solvent
Ph
Ph
O
n-C6H13
n-C6H13
1a
2a
Entry
1
Catalyst (mol%)
Conditionsa
Yield (%)b
E/Zc
4.4:1
4.2:1
4.0:1
3.6:1
Z only
–
Ph3PAuCl (2), AgOTf (5)
SIPrAuCl (2), AgOTf (5)
SIPrAuCl (2)
Selectfluor, MeCN, 80 °C, 2 h
Selectfluor, MeCN, 80 °C, 2 h
Selectfluor, MeCN, 80 °C, 2 h
Selectfluor, MeCN, 80 °C, 2 h
Selectfluor, MeCN, 80 °C, 2 h
Selectfluor, MeCN, 80 °C, 66 h
Selectfluor, MeCN, 80 °C, 66 h
Selectfluor, MeCN, 80 °C, 66 h
Selectfluor, MeCN, r.t., 48 h
Selectfluor, MeCN, r.t., 48 h
Selectfluor, acetone, r.t., 48 h
NFSI, CH2Cl2, r.t., 48 h
64 (40)
2
68 (53)
3
59
4
AuCl (2)
40
5
AuCl3 (2)
4
6
AgOTf (2)
–
7
PtCl2 (2)
trace
–
8
no catalyst
–
–
9
SIPrAuCl (2), AgOTf (5)
SIPrAuCl (5), AgOTf (12.5)
SIPrAuCl (5), AgOTf (12.5)
SIPrAuCl (5), AgOTf (12.5)
SIPrAuCl (5), AgOTf (12.5)
SIPrAuCl (5), AgOTf (12.5)
71
11.6:1
10.2:1
1:4
10
11
12
13
14
81
5
–
–
[A],d MeCN, r.t., 48 h
–
–
Selectfluor (2 equiv), MeCN, r.t., 48 h
100 (70)
12.5:1
a Solvent concentration = 0.05 M; 1.2 equiv of oxidant unless otherwise stated.
b Yield of 2a estimated by 19F NMR on the crude reaction mixture with fluorobenzene as internal reference. Isolated yields are in parentheses.
c E/Z ratio determined by 19F NMR on the crude reaction mixture.
d [A] = 1-Fluoro-2,4,6-trimethylpyridinium tetrafluoroborate.
Synlett 2010, No. 18, 2737–2742 © Thieme Stuttgart · New York

LETTER
a-Fluoroenones
2739
Table 2 Rearrangement–Fluorination of Propargyl Acetates 1a–k
O
Cl
R1
O
N+
N+
SIPrAuCl (5 mol%)
+
O
N
N
R2
R3
AgOTf (12.5 mol%)
MeCN (0.05 M)
40 °C, 1.5–72 h
R1
R2
2BF4
••
F
F
Selectfluor
(2 equiv)
R3
2a–k
SIPr
1a–k
Entry
1c
Propargyl R1
acetate
R2
H
R3
Time
(h)
Major product
Yield
(%)a
E/Zb
70
(E)-2a 64
(Z)-2a 6
F
1a
1b
Ph
Ph
n-C6H13
48
24
12.5:1
12.2:1
O
O
n-C6H13
F
62
2
H
Ph
(E)-2b only
F
64
3
4
1c
4-O2NC6H4
4-MeOC6H4
H
H
n-C6H13
n-C6H13
20
20
9.4:1
–
(E)-2c only
O2N
MeO
O
O
n-C6H13
F
d
1d
–
O
n-C6H13
F
F
F
80
(E)-2e 68
(Z)-2e 12
5
6
1e
1f
Cy
H
H
Ph
Ph
48
72
5.2:1
2:1
63
(E)-2f 42
(Z)-2f 21
n-Pr
O
O
29
7
8
1g
1h
Cy
H
H
n-C6H13
n-Bu
72
72
3.3:1
1.4:1
(E)-2g only
n-C6H13
F
39
(E)-2h 19
(Z)-2h 18
n-Pr
O
O
9
1i
-(CH)5-
Ph
1.5
2i 85
–
F
O
10
11
1j
-(CH)5-
Ph
n-C6H13
3.5
24
2j 58
–
–
n-C6H13
F
Ph
O
1k
Ph
Ph
2k 58
Ph
F
a Isolated yield.
b Crude E/Z ratio determined by 19F NMR. The E- and Z-isomers were separable by column chromatography.
c Reaction performed at r.t.
d Complex reaction mixture.
Synlett 2010, No. 18, 2737–2742 © Thieme Stuttgart · New York

2740
M. N. Hopkinson et al.
LETTER
ing a-fluoroenones were isolated in low yields with poor erated upon treatment with silver(I), to the alkyne (inter-
E/Z selectivities (entries 7, 8). Notably, unlike (E)-2a,14 mediate A) followed by a [3,3]-sigmatropic shift affords
when (E)-2g (E/Z > 20:1) was subjected to the reaction the allenyl intermediate B. DFT calculations on similar
conditions, isomerization was observed (E/Z = 4:1). Sub- substrates have suggested that this intermediate features
strates 1i–k, bearing two identical substituents at the pro- the gold(I) coordinated to the external double bond.17 At
pargylic position, reacted readily affording the this stage, decomplexation of the gold could lead to the
corresponding a-fluoroenones 2i–k in moderate to high uncoordinated allenyl acetate 4a, which, in the presence
yields up to 85% (entries 9–11). Compound 2k was crys- of Selectfluor could deliver 2a upon electrophilic fluori-
talline and allowed for unambiguous assignment of the nation (path I). Alternatively, intermediate B could under-
structure by X-ray crystallographic analysis (Figure 1).
go a rearrangement involving the loss of an acetyl group
to afford the vinylgold(I) complex C. Direct electrophilic
‘fluorodeauration’ of this species by Selectfluor would
deliver the a-fluoroenones 2a and regenerate the catalyst
(path II). The third pathway involves the oxidation of in-
termediate C by Selectfluor to the square planar gold(III)
fluoride complex D. The C–F bond-forming reductive
elimination from this species would again deliver the de-
sired product and regenerate the gold(I) catalyst (path III).
To distinguish between path I and paths II/III, the allenyl
acetate 4a was prepared independently from 1a18 and
treated with Selectfluor in acetonitrile without gold. After
72 hours at room temperature, a-fluoroenones 2a were
isolated in 51% yield in a crude E/Z ratio of 9.8:1. In ad-
dition, allenyl acetate 4l19 led cleanly to the expected a-
fluoroenone 2l in 73% yield when exposed to Selectfluor
in acetonitrile at 40 °C for 3.5 hours (Scheme 3). These
control reactions suggest that path I, a direct, nongold-
catalyzed fluorination pathway is operative for these two
compounds. This observation stands in contrast to the
mechanism proposed (path III) in a recent report by
Nevado et al. which was published during the preparation
of this manuscript.20 The E selectivity observed through-
Figure 1 Crystal structure of 2k
With the scope and limitations of the process established,
our attention turned to the reaction mechanism. We envis-
age three possible mechanistic pathways, all proceeding
via an initial gold-catalyzed rearrangement (Scheme 2).16
Initial coordination of a cationic [SIPrAu]+ species, gen-
+
O
O
O
O
SIPrAu+
Ph
Ph
n-C6H13
n-C6H13
Au
PrIS
1a
A
[3,3]-sigmatropic
rearrangement
+
Ph
O
SIPr
Au
SIPr
– SIPrAu+
+ SIPrAu+
Au
– Ac
Ph
•
OAc
Ph
OAc
n-C6H13
n-C6H13
n-C6H13
C
4a
B
Selectfluor electrophilic
– Ac
fluorination
Selectfluor
oxidation Selectfluor
electrophilic
fluorodeauration
– SIPrAu+
path II
path I
+
Ph
O
L
F
SIPr
Ph
Au
C-F reductive elimination
– SIPrAu+
F
path III
O
n-C6H13
n-C6H13
2a
D
Scheme 2 Plausible reaction mechanisms
Synlett 2010, No. 18, 2737–2742 © Thieme Stuttgart · New York

LETTER
a-Fluoroenones
2741
Vigalok, A. J. Am. Chem. Soc. 2010, 132, 10626.
out this study is also consistent with a direct electrophilic
fluorination mechanism where Selectfluor approaches the
allene from the least hindered face. Indeed, previous stud-
ies involving intermediates of type C would predict a Z-
selective fluorination if paths II or III were operating.11
Although gold(III) fluoride complexes of type D have
been suggested in the literature, these have not been iso-
lated or spectroscopically characterized. Studies to deter-
mine the extent to which a gold-catalyzed fluorination
pathway (paths II and III) competes with direct electro-
philic fluorination (path I) are ongoing in our laboratory.
(4) (a) Akana, J. A.; Bhattacharyya, K. X.; Müller, P.; Sadighi,
J. P. J. Am. Chem. Soc. 2007, 129, 7736. (b) Gorske, B. C.;
Mbofana, C. T.; Miller, S. J. Org. Lett. 2009, 11, 4318.
(5) Schuler, M.; Silva, F.; Bobbio, C.; Tessier, A.; Gouverneur,
V. Angew. Chem. Int. Ed. 2008, 47, 7927.
(6) For a report on oxidative homocoupling of stoichiometric
gold(I) complexes with Selectfluor, see: Hashmi, A. S. K.;
Ramamurthi, T. D.; Rominger, F. J. Organomet. Chem.
2009, 694, 592.
(7) Yu, P.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc.
2009, 131, 5062.
(8) (a) Zhang, G.; Peng, Y.; Cui, L.; Zhang, L. Angew. Chem.
Int. Ed. 2009, 48, 3112. (b) Zhang, G.; Cui, L.; Wang, Y.;
Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474. (c) Melhado,
A. D.; Brenzovich, W. E. Jr.; Lackner, A. D.; Toste, F. D.
J. Am. Chem. Soc. 2010, 132, 8885. (d) Brenzovich, W. E.
Jr.; Benitez, D.; Lackner, A. D.; Shunatona, H. P.;
Tkatchouk, E.; Goddard, W. A. III.; Toste, F. D. Angew.
Chem. Int. Ed. 2010, 49, 5519.
F
Selectfluor (2 equiv)
OAc
Ph
Ph
•
MeCN (0.05 M)
r.t., 72 h
O
n-C6H13
n-C6H13
4a
2a
51% (E/Z = 9.8:1)
(9) Hopkinson, M. N.; Tessier, A.; Salisbury, A.; Giuffredi,
G. T.; Combettes, L. E.; Gee, A. D.; Gouverneur, V. Chem.
Eur. J. 2010, 16, 4739.
Ph
Ph
F
Selectfluor (2 equiv)
Ph
•
OAc
Ph
(10) Cui, L.; Zhang, G.; Zhang, L. Bioorg. Med. Chem. Lett.
2009, 19, 3884.
(11) For analogous Z-selective gold-catalyzed rearrangement–
halogenation reactions of propargyl acetates with Br and I,
see: (a) Yu, M.; Zhang, G.; Zhang, L. Org. Lett. 2007, 9,
2147. (b) Yu, M.; Zhang, G.; Zhang, L. Tetrahedron 2009,
65, 1846.
(12) Urban, J. J.; Tillman, B. G.; Cronin, W. A. J. Phys. Chem. A
2006, 110, 11120.
(13) (a) Dutheuil, G.; Couve-Bonnaire, S.; Pannecoucke, X.
Angew. Chem. Int. Ed. 2007, 46, 1290. (b) Dutheuil, G.;
Couve-Bonnaire, S.; Pannecoucke, X. Tetrahedron 2009,
65, 6034. (c) Ghosh, A. K.; Banerjee, S.; Sinha, S.; Kang,
S. B.; Zajc, B. J. Org. Chem. 2009, 74, 3689.
MeCN (0.05 M)
40 °C, 3.5 h
n-C6H13
O
n-C6H13
4l
2l
73%
Scheme 3 Electrophilic fluorination of allenes 4a and 4l
In conclusion, we have developed a diastereoselective
preparation of a-fluoroenones from propargyl acetates via
a gold-catalyzed cascade rearrangement–fluorination pro-
cess. Control reactions support a mechanism involving a
gold-mediated 3,3-sigmatropic shift followed by a direct,
nongold-catalyzed electrophilic fluorination of the allenyl
acetate intermediate.
(14) Compounds (E)-2a and (Z)-2a were stable towards
isomerization under the reaction conditions implying that
the observed diastereoselectivity is under kinetic control.
(15) General Procedure for Rearrangement–Fluorination
Process
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Selectfluor (2 equiv), SIPrAuCl (5 mol%), and silver
trifluoromethanesulfonate (12.5 mol%) were added to a
solution of the propargyl acetate (1 equiv) in MeCN (0.05
M). The mixture was stirred at r.t. or 40 °C until TLC
showed consumption of the propargyl acetate (1.5–72 h).
H2O was added, and the mixture was extracted with EtOAc
(3×). The combined organic fractions were washed with
brine, dried with anhyd MgSO4, filtered, and the solvents
removed in vacuo. The crude mixture was purified by
column chromatography on silica gel.
Acknowledgment
We thank GlaxoSmithKline and the EPSRC for financial support,
Dr. B. Odell for NMR studies and Dr. A. L. Thompson (Oxford
Chemical Crystallography Service) for crystallographic services.
References and Notes
(1) New address: A. D. Gee, Division of Imaging Sciences,
School of Medicine, King’s College London, The Rayne
Institute, 4th Floor Lambeth Wing, St Thomas’ Hospital,
Lambeth Palace Rd., London, SE1 7EH, UK.
Preparation of 2a
The general procedure was followed using 1a (500 mg, 1.94
mmol), Selectfluor (1.37 g, 3.87 mmol), SIPrAuCl (60 mg,
0.10 mmol), and AgOTf (62 mg, 0.24 mmol) in MeCN (39
mL). The reaction was stirred for 48 h at r.t. 19F NMR
analysis on the crude reaction mixture indicated an E/Z ratio
of 12.5:1. Purification by column chromatography on silica
gel (hexane–Et2O = 20:1) afforded the product (E)-2a as a
yellow oil (290 mg, yield 64%) as well as (Z)-2a as a yellow
solid (24 mg, yield 6%).
(E)-2-Fluoro-1-phenylnon-1-en-3-one [(E)-2a]
Rf = 0.50 (hexane–Et2O = 9:1). 1H NMR (400 MHz, CDCl3):
d = 7.60–7.64 (m, 2 H), 7.35–7.40 (m, 3 H), 6.70 (d, 1 H,
J = 25.3 Hz), 2.65 (dt, 2 H, J = 7.1, 3.5 Hz), 1.63 (tt, 2 H,
J = 7.3, 7.1 Hz), 1.27–1.36 (m, 6 H), 0.90 (dd, 3 H, J = 6.8,
(2) (a) Kirsch, P. Modern Organofluorine Chemistry; Wiley-
VCH: Weinheim, 2004. (b) Purser, S.; Moore, P. R.;
Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
(3) For a recent highlight, see: (a) Brown, J. M.; Gouverneur,
V. Angew. Chem. Int. Ed. 2009, 48, 8610. For selected
recent examples, see: (b) Hull, K. L.; Anani, W. Q.; Sanford,
M. S. J. Am. Chem. Soc. 2006, 128, 7134. (c) Furuya, T.;
Kaiser, H. M.; Ritter, T. Angew. Chem. Int. Ed. 2008, 47,
5993. (d) Watson, D. A.; Su, M.; Teverovskiy, G.; Zhang,
Y.; García-Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science
2009, 325, 1661. (e) Wang, X.; Mei, T.-S.; Yu, J.-Q. J. Am.
Chem. Soc. 2009, 131, 7520. (f) Kaspi, A. W.; Goldberg, I.;
Synlett 2010, No. 18, 2737–2742 © Thieme Stuttgart · New York

2742
M. N. Hopkinson et al.
LETTER
6.5 Hz). 13C NMR (101 MHz, CDCl3): d = 195.6 (d, J = 38
Hz), 153.1 (d, J = 258 Hz), 130.9 (d, J = 10 Hz), 130.0 (d,
J = 2 Hz), 129.2, 128.2, 119.7 (d, J = 27 Hz), 40.2 (d, J = 2
Hz), 31.6, 28.8, 23.2 (d, J = 2 Hz), 22.5, 14.0. 19F NMR (377
MHz, CDCl3): d = –114.9 (dt, J = 25, 4 Hz). IR (neat): 1708
(C = O). HRMS (ESI+): m/z calcd for C15H19FNaO+ [M +
Na]+: 257.1314; found: 257.1312.
(CH2Cl2): 1697 (C = O). HRMS (FI+): m/z calcd for
C15H19FO [M]+: 234.1420; found: 234.1414.
(16) For a review, see: Marion, N.; Nolan, S. P. Angew. Chem.
Int. Ed. 2007, 46, 2750.
(17) (a) Correa, A.; Marion, N.; Fensterbank, L.; Malacria, M.;
Nolan, S. P.; Cavallo, L. Angew. Chem. Int. Ed. 2008, 47,
718. (b) Gandon, V.; Lemière, G.; Hours, A.; Fensterbank,
L.; Malacria, M. Angew. Chem. Int. Ed. 2008, 47, 7534.
(c) Garayalde, D.; Gómez-Bengoa, E.; Huang, X.; Göeke,
A.; Nevado, C. J. Am. Chem. Soc. 2010, 132, 4720.
(18) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 8414.
(19) Allenyl acetate 4l was isolated as the only acetylated product
during the attempted preparation of the corresponding
propargyl acetate 1l according to the procedure of ref. 11a.
This compound is presumably formed via a spontaneous
3,3-sigmatropic rearrangement of 1l.
(Z)-2-Fluoro-1-phenylnon-1-en-3-one [(Z)-2a]
Mp 30 °C. Rf = 0.42 (hexane–Et2O = 9:1). 1H NMR (400
MHz, CDCl3): d = 7.66–7.70 (m, 2 H), 7.38–7.44 (m, 3 H),
6.83 (d, 1 H, J = 36.9 Hz), 2.74 (dt, 2 H, J = 7.3, 2.3 Hz),
1.69 (tt, 2 H, J = 7.5, 7.3 Hz), 1.27–1.41 (m, 6 H), 0.91 (dd,
3 H, J = 7.0, 6.8 Hz). 13C NMR (101 MHz, CDCl3): d =
195.1 (d, J = 32 Hz), 154.1 (d, J = 272 Hz), 131.2 (d, J = 4
Hz), 130.6 (d, J = 9 Hz), 129.7 (d, J = 3 Hz), 128.8, 114.9 (d,
J = 6 Hz), 38.0, 31.6, 28.8, 23.5 (d, J = 2 Hz), 22.5, 14.0. 19
NMR (377 MHz, CDCl3): d = –125.0 (d, J = 37 Hz). IR
F
(20) de Haro, T.; Nevado, C. Chem. Commun. 2010, in press;
DOI: 10.1039/c002679d.
Synlett 2010, No. 18, 2737–2742 © Thieme Stuttgart · New York

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