Convenient synthesis of non-conjugated alkynyl ketones from keto aldehydes by a chemoselective one-pot nonaflation - Base catalyzed elimination sequence

Article abstract of DOI:10.1016/j.tet.2011.05.095

Keto aldehydes were selectively converted to non-conjugated alkynyl ketones possessing an unsubstituted alkyne terminus using one-pot nonaflation - base catalyzed elimination reaction sequences. Consecutive one-pot nonaflation of keto aldehydes with perfluorobutane-1-sulfonyl fluoride and elimination of the nonaflyl group using the P₁ phosphazene base resulted in the formation of a terminal CC triple bond with the keto group remaining intact. Careful optimization of the reaction conditions enabled a highly chemoselective conversion of the aldehyde function in the presence of unprotected keto groups exploiting a minor difference in acidity of their α-hydrogen atoms. Scope and limitations of the protocol as well as possible implementation of these substrates in Sonogashira coupling were explored.

Full text of DOI:10.1016/j.tet.2011.05.095

Tetrahedron 67 (2011) 5382e5388
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Convenient synthesis of non-conjugated alkynyl ketones from keto aldehydes by
a chemoselective one-pot nonaflationdbase catalyzed elimination sequence
,
Ekaterina V. Boltukhina, Andrey E. Sheshenev y, Ilya M. Lyapkalo
*
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Keto aldehydes were selectively converted to non-conjugated alkynyl ketones possessing an un-
substituted alkyne terminus using one-pot nonaflationdbase catalyzed elimination reaction sequences.
Consecutive one-pot nonaflation of keto aldehydes with perfluorobutane-1-sulfonyl fluoride and elim-
ination of the nonaflyl group using the P1 phosphazene base resulted in the formation of a terminal C^C
triple bond with the keto group remaining intact. Careful optimization of the reaction conditions enabled
a highly chemoselective conversion of the aldehyde function in the presence of unprotected keto groups
Received 31 January 2011
Received in revised form 10 May 2011
Accepted 23 May 2011
Available online 30 May 2011
This article is dedicated to the memory of
Dr. Ilya Lyapkalo who passed away on
September 10, 2010
exploiting a minor difference in acidity of their a-hydrogen atoms. Scope and limitations of the protocol
as well as possible implementation of these substrates in Sonogashira coupling were explored.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Nonaflation
Elimination
Alkynyl ketones
Cross-coupling
Phosphazene base
1. Introduction
the conversion of bifunctional substratesdketo aldehydesdhaving
their carbonyl groups separated by a spacer to non-conjugated
In line with our ongoing research devoted to the extension of
Pd(0) catalyzed cross-coupling methodology to carbonyl group
chemistry,1a we have recently described a general and straightfor-
ward synthesis of alkynes from aliphatic aldehydes and ketones,1b
where carbonyl functionality underwent conversion into the enol
nonaflate intermediate, followed by elimination of the nonaflyl
group to give a C^C triple bond in one synthetic operation. These
one-pot transformations were uniformly induced by phosphazene
bases combined with mildly electrophilic nonafluorobutane-1-
sulfonyl fluoride.2 On the other hand, it was noticed in an earlier
study that conversion of aldehydes to enol nonaflates proceeded
appreciably faster than that of ketones, apparently owing to the
alkynyl ketones. These alkynyl ketones comprise functionalities
with essentially orthogonal reactivities: the keto group represents
an electrophile or an enolate nucleophile, whereas the acetylenic
terminus can be subjected to Pd(0) catalyzed cross coupling (i.e.
Sonogashira coupling reactions) or [3þ2] cycloaddition reactions
with nitrile oxides4 or azides5 (click chemistry).
We have shown the feasibility of this transformation previously
for a single example, the conversion of 6-oxoheptanal 1a to hept-6-
yn-2-one 2a (Scheme 1), which participated further in a Sonaga-
shira coupling in situ.1a The formation and stereochemistry of an
intermediate 6-oxoheptenyl nonaflate A (E/Z ratio 5:1) was de-
scribed as well.3
higher acidity of the
a-hydrogen atoms of aldehydes compared to
O
ONf
P1-base, rt
those of ketones.3
·
P1-base, NfF
This difference in reactivity could allow the chemoselective
transformation of a CH2CH]O functionality to a terminal C^C
triple bond in the presence of an unprotected keto group. From
a synthetic viewpoint, this could result in a new protocol allowing
E2 elimination
DMF, –30 °C
O
1a
O
A
O
2a
N P N
P1-base:
NfF:
3
Sonogashira
coupling
* Corresponding author. Tel.: þ44 2075945708; fax: þ44 2075945804; e-mail
CF3(CF2)3SO2F
Scheme 1.
address: a.sheshenev@imperial.ac.uk (A.E. Sheshenev).
y
Present address: Department of Chemistry, Imperial College London, Exhibition
Road, South Kensington, London SW7 2AZ, UK.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.095

E.V. Boltukhina et al. / Tetrahedron 67 (2011) 5382e5388
5383
In this paper, we report a systematic study on the scope and limi-
tations of the chemoselective one-step transformation of keto al-
dehydes 1 into non-conjugated alkynyl ketones 2. This protocol will
open up an easy approach to non-conjugated alkynyl ketones
which, in turn, could serve as versatile cross-linking reagents
connecting various pharmacologically relevant structural elements
in the future.5
1H NMR data of the crude reaction mixtures. The observed losses
were most likely due to the volatility of the products during
workup and isolation on a small scale. Substrate 1b was an ex-
ception, since it was impossible to isolate product 2b despite high
conversion according to the 1H NMR spectrum of the crude reaction
mixture due to its extremely high volatility (Table 1, entry 2).
To overcome these losses an additional series of experiments
was carried out, in which products (2) were subjected in situ to
a Sonogashira coupling reaction1a with cyclopentenyl nonaflate
(Table 1, entries 11e17). Products (3) were isolated for all substrates
in good to excellent yields, which exceeded those of their pre-
cursors (2) considerably, thus demonstrating the efficiency of the
protocol.
The reactivity of some substrates deserves further comment.
The transformation of 6-oxo-6-phenylhexanal 1e to the desired
alkynyl ketone 2e (Table 1, entry 5) was accompanied by an intra-
molecular aldol condensation, furnishing phenyl cyclopentenyl
ketone as a side product. The ratio of 2e/cyclopentenyl ketone
amounted to 89/11 by 1H NMR of the crude reaction mixture. This
was a unique example among the substrates examined. This result
can be rationalized by the somewhat higher acidity of alkyl aryl
ketones in comparison with the dialkyl analogs (e.g., the pKa values
in DMSO for ethyl phenyl ketone and diethyl ketone are 24.4 and
27.1, respectively).6 However, the existing difference in acidity of
keto and aldehyde groups in 1e is still sufficient for the reaction to
proceed with a reasonable degree of chemoselectivity. A com-
pletely different situation was observed in the case of substrate 1h
possessing a cyclopentanone fragment (Table 1, entry 8). The re-
action afforded only a small amount of desired 2h accompanied by
a complex mixture of unidentified products. The acidity difference
2. Results and discussion
To ensure the desired chemoselectivity of sulfonylation for the
aldehyde group, the intermediate enol nonaflates were generated
at ꢀ30 ꢁC. Once the O-sulfonylation was complete, the reaction
mixtures were allowed to gradually warm to rt to allow the re-
quired E2 elimination to occur (Scheme 2).
O
O
O
H
H
(R)n
H
O
E2
a
·
(R)n
(R)n
ONf
1
2
E2
O
O
·
b
·
·
(R)n
(R)n
3
Scheme 2. Reagents and conditions: (a) tert-Butylimino-tris(1-pyrrolidinyl)phos-
phorane [hereinafter referred to as P1-base] (ꢂ2 equiv), NfF (1 equiv), DMF, ꢀ30 ꢁC; E2:
P1-base, rt; (b) cyclopentenyl nonaflate, i-Pr2NH (4 equiv), Pd(OAc)2 (5 mol %), PPh3
(10 mol %), CuI (10 mol %), rt.
As evidenced by 1H NMR analyses of the reaction mixtures upon
completion, transformation of keto aldehydes 1 into alkynyl ke-
tones 2 proceeded cleanly. Alkynyl ketones were isolated in good
yields in most cases (Table 1, entries 1, 3e6, 9, 10). The isolated
yields of products (2) were slightly lower than expected from the
of keto and aldehyde a-carbonyl hydrogen atoms in 1h was prob-
ably not high enough to induce the desired chemoselectivity. In-
deed, cyclopentanone (pKa value in DMSO is 25.8)7 is known to be
Table 1
Yields of alkynyl ketones 2 and Sonogashira coupling products 3 obtained from keto aldehydes 1 according Scheme 2
Entry
Substrate 1
Product 2
Yield %
76a (85)b
(93)b,c
Entry
Substrate 1
Product 3
Yielda
%
O
O
O
O
1
2
1a
1b
2a
2b
d
O
O
·
( )3
( )3
( )2
O
O
11
12
13
14
15
1b
1c
1d
1e
1f
3b
92
88
94
86
92
·
·
·
( )2
·
( )2
O
O
3
4
5
6
1c
2c
2d
2e
2f
64a (90)b
86a (96)b
60a,d (89)b
60a (96)b
3c
3d
3e
3f
O
·
( )4
O
( )4
·
( )4
O
O
1d
·
O
·
( )4
( )4
·
n-Bu
n-Bu
( )4
n-Bu
O
O
O
1e
1f
·
O
·
( )3
( )3
·
( )3
Ph
Ph
O
Ph
O
·
·
·
O
O
O
O
7e
1g
1h
2g
2h
18a (23)b
d
d
·
O
O
O
8
(30)b,f
·
O
(continued on next page)

5384
E.V. Boltukhina et al. / Tetrahedron 67 (2011) 5382e5388
Table 1 (continued )
Entry
9
Substrate 1
Product 2
Yield %
Entry
16
Substrate 1
Product 3
Yielda
94
%
O
O
O
O
1i
1j
2i
60a (95)b
1i
3i
·
O
O
·
·
·
·
O
O
·
10
2j
77a (92)b
17
1j
3j
89
a
Isolated yield.
b
c
Conversion determined by 1H NMR of the crude reaction mixture.
Product 2b was not isolated due to its high volatility.
d
Isolated product 2e contained ca. 6 mol % (by 1H NMR) of phenyl cyclopentenyl ketone as an admixture (the ratio of 2e/cyclopentenyl ketone in the crude reaction mixture
was 89/11 by 1H NMR, see text).
e
Reaction was carried out in THF, see text.
Product 2h was not isolated in a pure state due to the presence of a considerable amount of unidentified side products.
f
R
the most acidic of all cycloalkanones and the outcome of the re-
action points out that the acidity of keto and aldehyde groups is
comparable. An attempt to improve the yield for substrate 1h by
carrying out the reaction in less polar THF did not bring about
a better result.
O3, –78 °C, CH2Cl2,
then PPh3, –50 °C to rt
R
O
Y
1a–g (see Table 1)
X
X
Y
61–84%
O
Scheme 4.
The conversion of keto aldehyde 1g to alkynyl ketone 2g under
standard conditions in DMF was accompanied by the formation of
an unexpected product, which was identified as (E)-5,5-
dimethylocta-3,6,7-trien-2-one 4 (2g/4 ratio¼2.7:1). The latter is
proposed to be formed by a P1-base induced rearrangement of 2g.
The rate of this rearrangement proved to be remarkably solvent
dependent (Scheme 3). A mixture of 2g and 4 remained unchanged
in the presence of P1-base in C6D6 upon overnight storage at rt and
only insignificant conversion (ca. 5%) to 4 was observed by heating
at 50 ꢁC overnight. However, 2g was fully converted into allenic
enone 4 upon overnight storage in DMSO-d6 at rt.
Alicyclic keto aldehydes 1hej were obtained by Michael addi-
tion of enamines derived from cycloalkanones to acrolein followed
by acidic hydrolysis (Scheme 5).10
1.sec. amine, reflux, p-TSA
O
2. acrolein, Et2O
3.1N HCl
O
O
1h-j
28–65%
n = 0,1,2
n
n
Scheme 5.
P1-base, solvent
·
O
·
·
The P1-base was synthesized according to a synthetic protocol
developed by our group as depicted in Scheme 6. This method in-
cludes phosphorylation of pyrrolidine with PCl3 leading to the
O
2g
O
H
N
4
P+(NR2)3
formation of tris(1-pyrrolidinyl)phosphine and
a subsequent
Staudinger reaction11 with tert-butyl azide.
Scheme 3. Solvent dependent rearrangement of alkynyl ketone 2g in the presence of
P1-base.
1. PCl3, THF, –40 °C to rt, Ar
2. t-BuN3, 5 °C to rt, then 85 °C
3. 140 °C, 40 h
H
N
The ring openingdrearrangement process is proposed to occur
via anionic enolate intermediate as depicted in Scheme 3. Since the
enolate intermediate is more polar than starting 2g and P1-base, it
should be better stabilized by a more polar solvent, hence the ob-
served rate acceleration in DMSO or in DMF (to some extent). Only
one example of a related transformation exists in the literature
described by van Tamelen and co-workers for the rearrangement of
car-3-ene-2-one to eucarvone.8
N
P N
3
64 %
P1-base
Scheme 6.
Based on this conclusion the transformation of 1g to 2g was
repeated in less polar THF. Although the ring-opening product 4
was no longer detected in the 1H NMR spectrum of the reaction
mixture, the reaction was sluggish and led to incomplete conver-
sion of the intermediate enol nonaflate and the formation of some
unidentified side products. Therefore, a low overall yield of alkynyl
ketone 2g resulted (Table 1, entry 7).
The starting keto aldehydes 1aeg were synthesized from readily
available cyclic alkenes by ozonolysis as shown in Scheme 4.9
Generally, PPh3 afforded products 1 in higher yields and purities
compared to Me2S, which is due to a more efficient cleavage of the
trioxolane intermediates by PPh3.
3. Conclusion
With the exception of very acidic ketones, the developed
methodology represents a general and convenient approach to
non-conjugated alkynyl ketones. Robustness, good reproducibility,
easy up-scaling and availability of starting materials lend value to
the synthesis. The combination of distinctly basic and mildly elec-
trophilic reagents enabled a clear kinetic discrimination between
aldehyde and non-activated aliphatic keto groups, allowing for
structural elaborations to be achieved orthogonally. Last but not
least, the phosphazene base can be easily recovered from its salts,12
thus reducing the cost of the process.

E.V. Boltukhina et al. / Tetrahedron 67 (2011) 5382e5388
5385
4. Experimental
4.1. General
4.2.1.4. 7-Oxoundecanal (1d) Yield 1.33 g (72%) starting from 1-
n-butylcyclohept-1-ene (1.53 g, 10.0 mmol); bp 135e137 ꢁC
(0.7 mbar); 1H NMR (CDCl3)
d
9.75 (t, 1H, J¼1.7 Hz, CHO), 2.45e2.36
(m, 6H),1.67e1.50 (m, 6H),1.35e1.25 (m, 4H), 0.89(t, 3H, J¼7.3 Hz, H-
All reactions were carried out in pre-dried glassware equipped
with PTFE-coated magnetic stirring bars in anhydrous solvents
under an atmosphere of dry argon. Solvents were dried by stan-
dard procedures: hexane and dichloromethane were distilled
over P2O5; THF was distilled over Na/K alloy with addition of
Ph2CO; DMF was distilled over CaH2 in vacuo. Ozonolysis was
carried out using an ozone generator OzoneLabÔ OL80W (Yanco
Industries LTD). 1H NMR spectra of the reaction mixtures were
routinely performed to ensure complete conversion of the start-
ing materials. NMR spectra were recorded on a Bruker Avance IÔ
400 (Bruker BioSpin GmbH) spectrometer (400 MHz for 1H,
100 MHz for 13C, 162 MHz for 31P) in C6D6 or CDCl3. Chemical
11); 13C NMR (CDCl3)
d 211.2, 202.5, 43.8, 42.7, 42.5, 28.9, 26.1, 23.6,
22.5, 22.0, 14.0; ESI-HRMS: m/z [MþNa]þ calcd for C11H20NaO2:
207.1361, found: 207.1356; IR (neat): 1714 (C]O) cmꢀ1
.
4.2.1.5. 6-Oxo-6-phenylhexanal (1e).16 Yield 0.85 g (71%) start-
ing from 1-phenylcyclohex-1-ene (1.00 g, 6.3 mmol); 1H NMR
(CDCl3)
d
9.79 (t, 1H, J¼1.6 Hz, CHO), 7.95e7.93 (m, 2H), 7.57e7.53
(m, 1H), 7.47e7.43 (m, 2H), 3.01 (t, 2H, J¼6.8 Hz, H-5), 2.51 (td, 2H,
J¼1.6, 7.2 Hz, H-2), 1.82e1.67 (m, 4H); 13C NMR (CDCl3)
d 202.1,
199.6, 136.9, 133.0, 128.6, 128.0, 38.1, 43.7, 23.6, 21.7.
4.2.1.6. [(1R,3R)-3-Acetyl-2,2-dimethylcyclobutyl]acetaldehyde
shifts were reported as
d
scale in parts per million relative to
(1f).17 Yield 1.67 g (67%) starting from (ꢀ)-
a-pinene (2.00 g,
9.22 (t, J¼1.4 Hz, 1H, CHO), 2.33e2.28
SiMe4
(
d
¼0) as an internal standard for 1H NMR, to CDCl3
14.7 mmol); 1H NMR (C6D6)
d
(
(
d
¼77.16) or C6D6
(
d
¼128.06) for 13C NMR and to (MeO)3PO
(m, 1H), 2.00e1.87 (m, 2H), 1.83e1.68 (m, 2H), 1.67e1.62 (m, 1H),
d
¼3.7 ppm in C6D6)13 as an internal standard for 31P NMR. IR
1.60 (s, 3H, COMe), 0.99 (s, 3H, Me-2), 0.57 (s, 3H, Me-2); 13C NMR
spectra were recorded on a Bruker Equinox 55 IR spectrometer
(Bruker BioSpin GmbH) in films or in CDCl3. High-resolution mass
spectra were taken on GTC Premier spectrometer (WATERS) using
EI ionization method or on LTQ Orbitrap XL spectrometer
(Thermo Fisher Scientific) using ESI ionization method in meth-
anol or acetonitrile. Melting points (mp, uncorrected) were de-
(C6D6) d 205.1, 199.8, 54.1, 45.1, 42.7, 35.9, 30.3, 29.7, 23.1, 17.6.
4.2.1.7. [(1R,3S)-2,2-Dimethyl-3-(2-oxo-propyl)cyclopropyl]acet-
aldehyde (1g).18 Yield 1.13 g (61%) starting from (þ)-3-carene
(1.50 g, 11.0 mmol); 1H NMR (C6D6)
d
9.39 (t, 1H, J¼1.8 Hz, CHO),
1.81e1.78 (m, 2H), 1.76e1.72 (m, 2H), 1.70 (s, 3H, COMe), 0.96 (s, 3H,
termined using Wagner
& Munz PolyTherm A apparatus.
Me-2), 0.77e0.70 (m,1H), 0.64e0.58 (m, 1H), 0.60 (s, 3H, Me-2); 13C
Preparative separations were performed by silica gel gravity
column chromatography (Silica gel 60, Fluka, 12479). Column
chromatography was monitored by TLC (Silica gel 60, Glass plates,
Merck, 105631) and visualized using 5% phosphomolybdic acid
solution in ethanol. All the obtained products were of more than
95% purity by NMR unless otherwise noted.
NMR (C6D6) d 205.9, 200.2, 39.6, 39.1, 29.1, 28.5, 21.6, 19.7, 17.0, 15.1.
4.2.2. Synthesis of starting keto aldehydes by Michael reaction. Keto
aldehydes 1hej were prepared according to a literature procedure.10
4.2.2.1. 3-(2-Oxocyclopentyl)propanal (1h).10 Yield 1.2 g (28%); 1H
NMR (C6D6)
d
9.28 (t, 1H, J¼1.4 Hz, CHO), 1.96e1.92 (m, 2H),
1.88e1.80 (m, 1H), 1.79e1.70 (m, 1H), 1.65e1.55 (m, 1H), 1.53e1.45
4.2. Synthesis of starting keto aldehydes 1
(m, 2H), 1.39e1.24 (m, 2H), 1.16e1.05 (m, 1H), 0.87e0.80 (m, 1H); 13C
NMR (100 MHz, C6D6)
d 217.7, 200.3, 47.7, 41.6, 37.6, 29.6, 22.3, 20.6.
4.2.1. Synthesis of starting keto aldehydes by ozonolysis.9 Typical
procedure: A stream of ozone was passed through a solution of al-
kene (1 mol equiv) in dry CH2Cl2 (30 mL per 6 mmol of starting
alkene) at ꢀ78 ꢁC until the resulting solution became blue-violet.
The excess of ozone was removed by passing a stream of oxygen
followed by argon through the solution. The resulting mixture was
allowed to reach ꢀ50 ꢁC and carefully quenched by addition of Ph3P
(1.2 mol equiv) in dry CH2Cl2 (5 mL per 2 g of Ph3P). After 24 h at rt
the reaction mixture was concentrated and the residue was sub-
jected to chromatography on SiO2 (hexane/Et2O) or distillation in
vacuo to provide keto aldehydes 1aeg as colorless liquids.
4.2.2.2. 3-(2-Oxocyclohexyl)propanal (1i).10 Yield 3.6 g (65%); 1H
NMR (C6D6) 9.34 (t, 1H, J¼1.4 Hz, CHO), 2.18e1.70 (m, 6H),
1.55e1.46 (m, 2H), 1.33e1.01 (m, 4H), 0.94e0.83 (m, 1H); 13C NMR
(C6D6) 210.2, 200.7, 49.6, 42.0, 41.8, 34.2, 27.9, 25.1, 22.5.
d
d
4.2.2.3. 3-(2-Oxocycloheptyl)propanal (1j)10 Yield 4.2 g (60%);
1H NMR (C6D6)
9.31 (t, 1H, J¼1.4 Hz, CHO), 2.21e2.07 (m, 3H),
d
2.01e1.85 (m, 2H), 1.82e1.73 (m, 1H), 1.47e1.29 (m, 5H), 1.25e1.15
(m, 1H), 1.02e0.90 (m, 3H); 13C NMR (C6D6)
d 213.0, 200.5, 51.0,
42.9, 41.8, 31.7, 29.5, 28.7, 24.8, 24.4.
4.2.1.1. 6-Oxoheptanal (1a).14 Yield 8.00 g (62%) starting from 1-
4.3. Synthesis of P1-base
methylcyclohex-1-ene (9.68 g, 101 mmol); 1H NMR (CDCl3)
d 9.77
(t, 1H, J¼1.6 Hz, CHO), 2.50e2.43 (m, 4H), 2.15 (s, 3H, COMe),
4.3.1. tert-Butylimino-tris(1-pyrrolidinyl)phosphorane.12 Note: All
operations were performed using freshly distilled dry solvents
under a positive atmosphere of dry argon. Freshly distilled pyrro-
lidine (85.20 g, 1.198 mol) and THF (300 mL) were placed into a 1 L
three-neck round-bottom flask equipped with a PTFE-coated
magnetic stirring bar, thermometer, dropping funnel, and argon
inlet and cooled to ꢀ40 ꢁC. Then solution of PCl3 (20.05 g,
0.146 mol) in THF (200 mL) was added dropwise at ꢀ40 ꢁC. After
completion of the addition the reaction mixture was warmed
slowly to rt and stirred at ambient temperature for 18 h. The solvent
was removed from the reaction flask in vacuo (rt, 50 mbar) and the
solid residue was washed twice with hexane (2ꢃ100 mL). The
combined hexane fractions were concentrated in vacuo (rt,
50 mbar) to afford tris(1-pyrrolidinyl)phosphine (29.34 g,
0.122 mol) as colorless liquid. The obtained phosphine was placed
1.66e1.58 (m, 4H); 13C NMR (CDCl3)
d 208.5, 202.2, 43.7, 43.3, 29.9,
23.1, 21.5.
4.2.1.2. 5-Oxohexanal (1b).9 Yield 1.16 g (84%) starting from 1-
methylcyclopent-1-ene (1.00 g, 12.2 mmol); 1H NMR (CDCl3)
d
9.77 (t, 1H, J¼1.4 Hz, CHO), 2.50e2.44 (m, 4H), 2.11 (s, 3H, COMe),
1.86 (quintet, 2H, J¼7.1 Hz, H-3); 13C NMR (CDCl3)
d 207.8, 201.7,
42.8, 42.2, 29.8, 16.0.
4.2.1.3. 7-Oxooctanal (1c).15 Yield 1.38 g (68%) starting from 1-
methylcyclohept-1-ene (1.56 g, 14.2 mmol); 1H NMR (CDCl3)
d
9.77 (t, 1H, J¼1.5 Hz, CHO), 2.48e2.42 (m, 4H), 2.14 (s, 3H, COMe),
1.68e1.56 (m, 4H), 1.37e1.29 (m, 2H); 13C NMR (CDCl3)
d 208.6,
202.3, 43.6, 43.3, 29.8, 28.5, 23.3, 21.7.

5386
E.V. Boltukhina et al. / Tetrahedron 67 (2011) 5382e5388
into a 250 mL three-necked round-bottom flask equipped with
a PTFE-coated magnetic stirring bar, thermometer, dropping fun-
nel, and argon inlet, cooled to 5 ꢁC and tert-butyl azide19 (14.5 g,
0.146 mol) was added dropwise. The reaction mixture was stirred
overnight at rt, heated at 85 ꢁC for 1 h and cooled to rt. Volatiles
were removed at 50 mbar for 30 min. BaO (1.0 g) was added and the
reaction mixture was heated at 140 ꢁC for 40 h. Vacuum distillation
over BaO afforded the P1-base (29.1 g, 64%) as a viscous colorless
oil; bp 112e114 ꢁC (0.15 mbar) [lit.12 bp 108 ꢁC (0.05 Torr)]; 1H NMR
EtOAc, 20:1) afforded 2f (0.124 g, 60%) as a white solid; Rf 0.40; mp
44e45 ꢁC; 1H NMR (CDCl3)
d
2.88 (dd, 1H, J¼10.5, 7.6 Hz, H-1), 2.69
(ddd, 1H, J¼10.7, 8.5, 2.4 Hz, H-3), 2.40e2.31 (m, 1H, H-4), 2.16 (d,
1H, J¼2.4 Hz, ^CH), 2.11e2.06 (m, 1H, H-4), 2.05 (s, 3H, COMe), 1.34
(s, 3H, Me-2),1.04 (s, 3H, Me-2); 13C NMR (CDCl3)
d 206.8, 83.5, 71.6,
54.3, 44.2, 32.8, 30.1, 30.0, 24.3, 19.1; EI-HRMS: m/z [MꢀH]þ calcd
for C10H13O: 149.0966, found: 149.0967; IR (CDCl3): 3305 (^CeH),
1979 (C^C), 1704 (C]O) cmꢀ1
.
(C6D6)
b
d
3.08e3.12 (m, 12H,
a
-H-pyrrolidinyl), 1.60e1.50 (m, 12H,
4.4.1.6. Mixture of 1-[(1S,3S)-3-ethynyl-2,2-dimethylcyclopropyl]
propan-2-one (2g) and (E)-5,5-dimethylocta-3,6,7-trien-2-one
(4). The reaction was carried out according to GP1 using 1g
(0.219 g, 1.30 mmol), NfF (0.397 g, 1.32 mmol), and P1-base (0.818 g,
2.62 mmol). Column chromatography on SiO2 (hexane to hexane/
EtOAc, 30:1 to 20:1 to 10:1) afforded a mixture of 2g and 4 (0.05 g,
26%, ratio 2g/4¼2.7/1 by 1H NMR) as a pale yellow oil; Rf 0.41; 1H
-H-pyrrolidinyl), 1.56 (s, 9H, t-Bu); 31P NMR (C6D6)
d
8.8.
4.4. Synthesis of alkynyl ketones 2
4.4.1. General procedure (GP1). Starting keto aldehyde
1
(1.00 mmol), NfF (0.305 g, 1.01 mmol) and DMF (1 mL) were placed
in a round-bottom flask. The flask was cooled to ꢀ30 ꢁC whereupon
the P1-base (0.628 g, 2.01 mmol) was added dropwise. The reaction
mixture was allowed to warm up gradually to rt and stirred for
16e18 h (NMR monitoring). It was quenched with saturated aq
NH4Cl (15 mL) and extracted with Et2O (3ꢃ15 mL). The combined
organic layers were washed with water (15 mL), brine (15 mL),
dried over MgSO4, and concentrated. Products 2 were isolated by
column chromatography on SiO2.
NMR (CDCl3) for compound 2g (from the mixture with 4) d 2.58 (dd,
1H, J¼18.1, 7.5 Hz, H-1), 2.42 (dd, 1H, J¼18.1, 6.3 Hz, H-1), 2.17 (s, 3H,
COMe),1.91 (d,1H, J¼2.2 Hz, ^CH),1.29 (dd,1H, J¼8.6, 2.2 Hz, H-30),
1.15e1.10 (m, 1H, H-10), 1.10 (s, 3H, Me-20), 1.03 (s, 3H, Me-20); 1H
NMR (CDCl3) for compound 4 (from the mixture with 2g) d 6.74 (d,
1H, J¼16.2 Hz, H-3), 6.02 (d, 1H, J¼16.2 Hz, H-4), 5.09 (t, 1H,
J¼6.6 Hz, H-6), 4.79 (d, 2H, J¼6.6 Hz, H-8), 2.24 (s, 3H, COMe), 1.18
(s, 6H, 2Me-5); 13C NMR (CDCl3) for the mixture of 2g and 4
d 208.0,
206.9, 199.0,155.4, 127.4, 98.4, 82.6, 77.7, 68.7, 40.2, 37.0, 30.0, 27.23,
27.20, 27.19, 24.2, 21.4, 17.4, 16.2.
4.4.1.1. Hept-6-yn-2-one (2a).20 The reaction was carried out
according to GP1 using 1a (0.259 g, 2.02 mmol), NfF (0.715 g,
2.37 mmol), and P1-base (1.455 g, 4.66 mmol). Column chroma-
tography on SiO2 (pentane/Et2O, 5:1) afforded 2a (0.169 g, 76%) as
4.4.1.7. 1-[(1S,3S)-3-Ethynyl-2,2-dimethylcyclopropyl]propan-2-
one (2g). The reaction was carried out according to GP1 using 1g
(0.185 g, 1.10 mmol), NfF (0.336 g, 1.11 mmol), and P1-base (0.691 g,
2.21 mmol) in THF as the reaction medium. Column chromatogra-
phy on SiO2 (hexane/EtOAc, 30:1 to 20:1 to 10:1) afforded 2g
a colorless liquid; Rf 0.35; 1H NMR (CDCl3)
d
2.59 (t, 2H, J¼7.2 Hz, H-
3), 2.24 (dt, 2H, J¼6.9, 2.6 Hz, H-5), 2.16 (s, 3H, COMe), 1.97 (t, 1H,
J¼2.6 Hz, ^CH), 1.79 (quint, 2H, J¼7.01 Hz, H-4); 13C NMR (CDCl3)
d
208.2, 83.5, 69.0, 42.0, 30.0, 22.2, 17.7.
(0.03 g, 18%) as a pale yellow oil; Rf 0.35; 1H NMR (C6D6)
d 2.34 (dd,
1H, J¼18.0, 7.3 Hz, H-1), 2.17 (dd,1H, J¼18.0, 6.5 Hz, H-1),1.73 (s, 3H,
COMe), 1.72 (d, 1H, J¼2.2 Hz, ^CH), 1.10 (dd, 1H, J¼8.6, 2.2 Hz, H-30),
0.98 (s, 3H, Me-20), 0.98e0.93 (m, 1H, H-10), 0.82 (s, 3H, Me-20); 13C
4.4.1.2. Oct-7-yn-2-one (2c).21 The reaction was carried out
according to GP1 using 1c (0.142 g, 1.00 mmol), NfF (0.305 g,
1.01 mmol), and P1-base (0.628 g, 2.01 mmol). Column chroma-
tography on SiO2 (pentane/Et2O, 10:1 to 5:1) afforded 2c (0.079 g,
NMR (C6D6) d 205.4, 82.7, 69.0, 40.0, 29.4, 27.0, 24.6, 21.3, 17.6, 16.3;
EI-HRMS: m/z [MꢀH]þ calcd for C10H13O: 149.0966, found:
64%) as a colorless liquid; Rf 0.40; 1H NMR (CDCl3)
d
2.46e2.42 (m,
149.0971; IR (neat): 3294 (CeH), 2110 (C^C), 1715 (C]O) cmꢀ1
.
2H), 2.19 (td, 2H, J¼7.0, 2.7 Hz, H-6), 2.13 (s, 3H, COMe), 1.93 (t, 1H,
J¼2.7 Hz, H-8), 1.72e1.64 (m, 2H), 1.55e1.47 (m, 2H); 13C NMR
4.4.1.8. 2-(Prop-2-ynyl)cyclohexanone (2i).24 The reaction was
carried out according to GP1 using 1i (0.154 g, 1.00 mmol), NfF
(0.305 g, 1.01 mmol), and P1-base (0.628 g, 2.01 mmol). Column
chromatography on SiO2 (hexane/EtOAc, 10:1 to 5:1) afforded 2i
(0.082 g, 60%) as a pale yellow oil; Rf 0.32; 1H NMR (CDCl3)
(CDCl3)
d 208.6, 84.1, 68.7, 43.2, 29.9, 28.0, 23.0, 18.4.
4.4.1.3. Undec-10-yn-5-one (2d).22 The reaction was carried out
according to GP1 using 1d (0.184 g, 1.00 mmol), NfF (0.305 g,
1.01 mmol), and P1-base (0.628 g, 2.01 mmol). Column chroma-
tography on SiO2 (hexane/EtOAc, 20:1 to 10:1) afforded 2d (0.143 g,
d
2.62e2.55 (m, 1H), 2.52e2.25 (m, 4H), 2.20e2.13 (m, 1H),
2.10e2.05 (m, 1H), 1.94 (t, 1H, J¼2.6 Hz, ^CH), 1.94e1.87 (m, 1H),
86%) as a colorless liquid; Rf 0.37; 1H NMR (CDCl3)
d
2.43e2.47 (m,
1.74e1.57 (m, 2H), 1.44e1.34 (m, 1H); 13C NMR (C6D6)
d 210.8, 82.7,
4H), 2.19 (td, 2H, J¼7.0, 2.7 Hz, H-9), 1.93 (t, 1H, J¼2.7 Hz, H-11),
69.5, 49.6, 42.0, 33.3, 27.9, 25.2, 18.9.
1.72e1.64 (m, 2H), 1.58e1.47 (m, 4H), 1.34e1.24 (m, 2H), 0.89 (t, 3H,
J¼7.3 Hz, H-1); 13C NMR (CDCl3)
d
211.0, 84.2, 68.6, 42.7, 42.2, 28.1,
4.4.1.9. 2-(Prop-2-ynyl)cycloheptanone (2j).25 The reaction was
carried out according to GP1 using 1j (0.168 g, 1.00 mmol), NfF
(0.305 g, 1.01 mmol), and P1-base (0.628 g, 2.01 mmol). Column
chromatography on SiO2 (hexane/EtOAc, 5:1 to 2:1) afforded 2j
(0.115 g, 77%) as a pale yellow liquid; Rf 0.37; 1H NMR (CDCl3)
26.1, 23.0, 22.5, 18.4, 13.9.
4.4.1.4. 1-Phenylhex-5-yn-1-one (2e).23 The reaction was carried
out according to GP1 using 1e (0.194 g, 1.02 mmol), NfF (0.311 g,
1.03 mmol), and P1-base (0.640 g, 2.05 mmol). Column chroma-
tography on SiO2 (pentane to pentane/Et2O, 20:1) afforded 2e
d
2.77e2.70 (m, 1H), 2.59e2.42 (m, 3H), 2.24 (ddd, 1H, J¼17.0, 4.4,
2.7 Hz, H-1), 2.03e1.99 (m, 1H), 1.94 (t, 1H, J¼2.7 Hz, ^CH),
(0.104 g, 61%) as a yellow oil; Rf 0.33; 1H NMR (CDCl3)
d 7.99e7.97
1.94e1.81 (m, 3H), 1.70e1.60 (m, 1H), 1.53e1.31 (m, 3H); 13C NMR
(m, 2H), 7.59e7.55 (m, 1H), 7.49e7.45 (m, 2H), 3.14 (t, 2H, J¼7.2 Hz,
(CDCl3) d 213.9, 82.8, 69.4, 50.9, 43.5, 30.5, 29.5, 29.0, 24.0, 21.0.
H-2), 2.34 (td, 2H, J¼6.8, 2.7 Hz, H-4), 2.02e1.95 (m, 3H); 13C NMR
(CDCl3)
d
199.7, 137.1, 133.2, 128.7, 128.2, 83.9, 69.2, 37.2, 22.9, 18.1.
4.5. Synthesis of cyclopentenyl nonaflate
nonaflate.26 Cyclopentanone
4.4.1.5. 1-[(1R,3R)-3-Ethynyl-2,2-dimethylcyclobutyl]ethanone
(2f). The reaction was carried out according to GP1 using 1f
(0.231 g, 1.37 mmol), NfF (0.419 g, 1.39 mmol), and P1-base (0.862 g,
2.76 mmol). Column chromatography on SiO2 (hexane to hexane/
4.5.1. Cyclopentenyl
(1.00
g,
11.9 mmol) and NfF (4.13 g, 13.7 mmol) were mixed in dry DMF
(12 mL), and the resulting solution was cooled to 0 ꢁC, followed by
dropwise addition of P1-base (4.28 g, 13.7 mmol). The reaction

E.V. Boltukhina et al. / Tetrahedron 67 (2011) 5382e5388
5387
mixture was stirred at rt for 18 h, quenched with saturated NH4Cl
solution (20 mL) and extracted with hexane (3ꢃ25 mL). The com-
bined organic layers were washed with water (25 mL), brine
(25 mL), dried over Na2SO4, and concentrated. Flash chromatog-
raphy on SiO2 (hexane/EtOAc, 20:1) afforded cyclopent-1-enyl
nonaflate (3.98 g, 91%) as a colorless oil; 1H NMR (CDCl3)
1.94 mmol), PPh3 (0.016 g, 0.06 mmol), PdCl2 (0.005 g, 0.03 mmol),
CuI (0.012 g, 0.06 mmol), cyclopent-1-enyl nonaflate (0.220 g,
0.60 mmol), and i-Pr2NH (0.244 g, 2.41 mmol). Column chroma-
tography on SiO2 (hexane/EtOAc, 30:1) and further purification by
preparative TLC (hexane/EtOAc¼10:1) afforded 3e (0.128 g, 86%) as
a beige solid; Rf 0.45; mp 33e34 ꢁC; 1H NMR (CDCl3)
d 8.00e7.97
d
5.65e5.63 (m, 1H, H-2), 2.60e2.55 (m, 2H), 2.45e2.39 (m, 2H),
(m, 2H, o-Ph), 7.58e7.54 (m, 1H, p-Ph), 7.48e7.45 (m, 2H, m-Ph),
5.95e5.93 (m,1H, ]CH), 3.13 (t, 2H, J¼7.3 Hz), 2.47 (t, 2H, J¼6.8 Hz),
2.43e2.39 (m, 4H), 2.02e1.95 (m, 2H), 1.92e1.84 (m, 2H); 13C NMR
2.07e2.00 (m, 2H); 13C NMR (CDCl3)
d
149.9, 117.9, 31.1, 28.1, 21.0.
4.6. One-pot palladium catalyzed Sonogashira coupling
(CDCl3) d 199.9, 137.2, 136.5, 133.1, 129.0, 128.7, 128.3, 128.2, 125.0,
90.5, 78.9, 37.5, 36.8, 33.2, 23.45, 23.43, 19.2; EI-HRMS: m/z [M]þ
calcd for C17H18O: 238.1358, found: 238.1362; IR (CDCl3): 1684 (C]
4.6.1. General procedure for Sonogashira coupling (GP2) exemplified
by the synthesis of 6-cyclopentenylhex-5-yn-2-one (3b). Keto alde-
hyde 1b (0.220 g, 1.93 mmol), NfF (0.588 g, 1.95 mmol), and DMF
(2 mL) were placed in a round-bottom flask. The flask was cooled to
ꢀ30 ꢁC whereupon the P1-base (1.210 g, 3.87 mmol) was added
dropwise. The reaction mixture was allowed to warm gradually to
rt and stirred for 16e18 h (NMR monitoring). It was purged with
argon. Subsequently PPh3 (0.032 g, 0.12 mmol), a mixture of PdCl2
(0.011 g, 0.06 mmol) and CuI (0.023 g, 0.12 mmol), cyclopentenyl
nonaflate (0.441 g, 1.20 mmol) and i-Pr2NH (0.487 g, 4.82 mmol)
were added. The reaction mixture was stirred overnight, quenched
with saturated aq NH4Cl (15 mL) and extracted with Et2O
(4ꢃ15 mL). The combined ethereal extracts were washed with
water (15 mL), brine (15 mL), dried over MgSO4, and concentrated.
O), 1645 (C]C) cmꢀ1
.
4 . 6 .1. 5 . 1 - [ ( 1 R , 3 S ) - 3 - ( C yc l o p e n t e nyl e t h y nyl ) - 2 , 2 -
dimethylcyclobutyl]ethanone (3f). The reaction was carried out
according to GP2 using 1f (0.239 g, 1.42 mmol), NfF (0.433 g,
1.44 mmol), P1-base (0.892 g, 2.86 mmol), PPh3 (0.023 g,
0.09 mmol), PdCl2 (0.008 g, 0.04 mmol), CuI (0.017 g, 0.09 mmol),
cyclopent-1-enyl nonaflate (0.325 g, 0.89 mmol), and i-Pr2NH
(0.359 g, 3.55 mmol). Column chromatography on SiO2 (hexane/
EtOAc, 30:1 to 20:1) afforded 3f (0.176 g, 92%) as a tan solid; Rf 0.35;
mp 32e33 ꢁC; 1H NMR (CDCl3)
d 5.95e5.94 (m, 1H, ]CH), 2.87 (dd,
1H, J¼10.6, 7.6 Hz), 2.80 (dd, 1H, J¼10.6, 8.6 Hz), 2.42e2.31 (m, 5H),
2.13e2.08 (m, 1H), 2.05 (s, 3H, COMe), 1.91e1.84 (m, 2H), 1.33 (s, 3H,
Me-2),1.02 (s, 3H, Me-2); 13C NMR (CDCl3)
d 207.1,136.7,124.9, 90.2,
4.6.1.1. 6-Cyclopentenylhex-5-yn-2-one (3b). Column chroma-
tography on SiO2 (hexane to hexane/EtOAc, 20:1 to 10:1) afforded
3b (0.180 g, 92%) as a colorless oil; Rf 0.40; 1H NMR (CDCl3)
81.3, 54.4, 44.9, 36.8, 33.3, 30.11, 30.06, 23.4, 19.2; EI-HRMS: m/z
[M]þ calcd for C15H20O: 216.1514, found: 216.1519; IR (CDCl3): 1706
(C]O), 1612 (C]C) cmꢀ1
.
d
5.95e5.93 (m, 1H, ]CH), 2.71e2.68 (m, 2H), 2.60e2.56 (m, 2H),
2.42e2.37 (m, 4H), 2.18 (s, 3H, COMe), 1.91e1.84 (m, 2H); 13C NMR
(CDCl3) 206.7, 136.7, 124.8, 89.7, 78.4, 42.8, 36.7, 33.2, 30.0, 23.4,
14.3; EI-HRMS: m/z [M]þ calcd for C11H14O: 162.1045, found:
162.1047; IR (neat): 1716 (C]O), 1612 (C]C) cmꢀ1
4.6.1.6. 2-(3-Cyclopentenylprop-2-ynyl)cyclohexanone (3i). The
reaction was carried out according to GP2 using 1i (0.154 g,
1.00 mmol), NfF (0.305 g, 1.01 mmol), P1-base (0.628 g, 2.01 mmol),
PPh3 (0.016 g, 0.063 mmol), PdCl2 (0.006 g, 0.031 mmol), CuI
(0.012 g, 0.063 mmol), cyclopent-1-enyl nonaflate (0.229 g,
0.625 mmol), and i-Pr2NH (0.253 g, 2.50 mmol). Column chroma-
tography on SiO2 (hexane/EtOAc, 10:1) afforded 3i (0.118 g, 94%) as
a pale yellow solid; Rf 0.33; mp 29e30 ꢁC; 1H NMR (CDCl3)
d
.
4.6.1.2. 8-Cyclopentenyloct-7-yn-2-one (3c). The reaction was
carried out according to GP2 using 1c (0.142 g, 1.00 mmol), NfF
(0.305 g, 1.01 mmol), P1-base (0.628 g, 2.01 mmol), PPh3 (0.018 g,
0.067 mmol), PdCl2 (0.006 g, 0.034 mmol), CuI (0.013 g,
0.067 mmol), cyclopent-1-enyl nonaflate (0.244 g, 0.67 mmol), and
i-Pr2NH (0.271 g, 2.68 mmol). Column chromatography on SiO2
(hexane/EtOAc, 10:1 to 5:1) afforded 3c (0.113 g, 88%) as a yellow
d
5.93e5.92 (m, 1H, ]CH), 2.75 (dd, 1H, J¼17.2, 4.2 Hz), 2.53e2.25
(m, 9H), 2.10e2.05 (m, 1H), 1.92e1.82 (m, 3H), 1.73e1.59 (m, 3H),
1.43e1.33 (m, 1H); 13C NMR (CDCl3)
d 211.1, 136.4, 125.0, 89.3, 79.1,
50.0, 42.1, 36.7, 33.5, 33.2, 28.0, 25.2, 23.4,19.9; ESI-HRMS: m/z [M]þ
calcd for C14H19O: 203.1436 [MþþH], found: 203.1430; IR (CDCl3):
oil; Rf 0.37; 1H NMR (CDCl3)
d 5.93e5.92 (m, 1H, ]CH), 2.45 (t, 2H,
J¼7.3 Hz), 2.42e2.36 (m, 4H), 2.33 (t, 2H, J¼7.1 Hz), 2.13 (s, 3H,
1708 (C]O) cmꢀ1
.
COMe), 1.90e1.83 (m, 2H), 1.73e1.63 (m, 2H), 1.57e1.49 (m, 2H); 13C
NMR (CDCl3)
28.4, 23.4, 23.2, 19.4; EI-HRMS: m/z [M]þ calcd for C13H18O:
190.1358, found: 190.1356; IR (neat): 1713 (C]O) cmꢀ1
d
208.8, 136.3, 125.0, 90.8, 78.3, 43.3, 36.8, 33.2, 30.0,
4.6.1.7. 2-(3-Cyclopentenylprop-2-ynyl)cycloheptanone (3j). The
reaction was carried out according to GP2 using 1j (0.168 g,
1.00 mmol), NfF (0.305 g, 1.01 mmol), P1-base (0.628 g, 2.01 mmol),
PPh3 (0.022 g, 0.083 mmol), PdCl2 (0.007 g, 0.042 mmol), CuI
(0.016 g, 0.083 mmol), cyclopent-1-enyl nonaflate (0.305 g,
0.830 mmol), and i-Pr2NH (0.336 g, 3.32 mmol). Column chroma-
tography on SiO2 (hexane/EtOAc, 10:1 to 5:1) afforded 3j (0.160 g,
89%) as a beige solid; Rf 0.37; mp 39e41 ꢁC; 1H NMR (CDCl3)
.
4.6.1.3. 11-Cyclopentenylundec-10-yn-5-one (3d). The reaction
was carried out according to GP2 using 1d (0.184 g, 1.00 mmol), NfF
(0.305 g, 1.01 mmol), P1-base (0.628 g, 2.01 mmol), PPh3 (0.024 g,
0.09 mmol), PdCl2 (0.008 g, 0.045 mmol), CuI (0.017 g, 0.09 mmol),
cyclopent-1-enyl nonaflate (0.330 g, 0.90 mmol), and i-Pr2NH
(0.364 g, 3.60 mmol). Column chromatography on SiO2 (pentane/
Et2O, 30:1 to 20:1) afforded 3d (0.196 g, 94%) as a pale yellow oil; Rf
d
5.93e5.92 (m, 1H, ]CH), 2.75e2.66 (m, 1H), 2.65e2.61 (m, 1H),
2.57e2.36 (m, 7H), 2.04e2.00 (m, 1H), 1.90e1.82 (m, 5H), 1.69e1.59
(m, 1H), 1.51e1.31 (m, 3H); 13C NMR (CDCl3)
214.3, 136.5, 124.9,
d
0.40; 1H NMR (CDCl3)
d
5.94e5.92 (m,1H, ]CH), 2.44e2.31 (m,10H),
89.3, 79.0, 51.3, 43.5, 36.7, 33.2, 30.5, 29.6, 29.0, 24.2, 23.4, 22.1; EI-
1.91e1.83 (m, 2H), 1.72e1.65 (m, 2H), 1.58e1.49 (m, 4H), 1.35e1.26
HRMS: m/z [M]þ calcd for C15H20O: 216.1514, found: 216.1511; IR
(m, 2H), 0.90 (t, 3H, J¼7.3 Hz, H-1); 13C NMR (CDCl3)
d
211.2, 136.3,
(CDCl3): 1699 (C]O), 1613 (C]C) cmꢀ1
.
125.0, 90.9, 78.3, 42.7, 42.4, 36.8, 33.2, 28.5, 26.2, 23.4, 23.2, 22.5,
19.5, 14.0; EI-HRMS: m/z [M]þ calcd for C16H24O: 232.1827, found:
Acknowledgements
232.1833; IR (neat): 1712 (C]O), 1612 (C]C) cmꢀ1
.
Financial support by IOCB grant No Z4 055 0506 and an IOCB
postdoctoral fellowship for E.V.B. are gratefully acknowledged. We
thank Lanxess Deutschland GmbH for generous donation of
nonafluorobutane-1 sulfonyl fluoride. The authors are grateful to
4.6.1.4. 6-Cyclopentenyl-1-phenylhex-5-yn-1-one (3e). The re-
action was carried out according to GP2 using 1e (0.184 g,
0.965 mmol), NfF (0.295 g, 0.98 mmol), P1-base (0.606 g,

5388
E.V. Boltukhina et al. / Tetrahedron 67 (2011) 5382e5388
8. van Tamelen, E. E.; McNary, J.; Lornitzo, F. A. J. Am. Chem. Soc. 1957, 79,
1231e1236.
9. Hsu, J.-L.; Fang, J.-M. J. Org. Chem. 2001, 66, 8573e8584.
Dr. Mimi Hii (Imperial College London) and Dr. Ullrich Jahn (IOCB
Prague) for kind help in the preparation of this manuscript.
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