Carbonylative Suzuki-Miyaura coupling reaction of lactam-, lactone-, and thiolactone-derived enol triflates for the synthesis of unsymmetrical dienones

Article abstract of DOI:10.1002/ejoc.200601089

A thorough study of the carbonylative Suzuki-Miyaura cross-coupling reaction of enol triflates with alkenylboronic acids for the synthesis of unsymmetrical dienones is reported. Conditions were found that enabled the coupling of structurally different eno

Full text of DOI:10.1002/ejoc.200601089

FULL PAPER
DOI: 10.1002/ejoc.200601089
Carbonylative Suzuki–Miyaura Coupling Reaction of Lactam-, Lactone-, and
Thiolactone-Derived Enol Triflates for the Synthesis of Unsymmetrical
Dienones
Laura Bartali,[a] Antonio Guarna,[a] Paolo Larini,[a] and Ernesto G. Occhiato*[a]
Keywords: Carbonylation / Cross-coupling / Boronic acids / Triflates / Enones
A thorough study of the carbonylative Suzuki–Miyaura cross-
coupling reaction of enol triflates with alkenylboronic acids
for the synthesis of unsymmetrical dienones is reported. Con-
ditions were found that enabled the coupling of structurally
different enol triflates derived from lactams, lactones, and
thiolactones (i.e., cyclic ketene aminal, acetal, and thioacetal
triflates, respectively) with various alkenylboronic acids at
room temperature under 1 atm of CO pressure with 1–5%
palladium catalyst; the carbonylated products were obtained
in 50–86% overall yields. The methodology allows for a con-
vergent and rapid preparation of substrates useful in conju-
gate additions and Nazarov reactions.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Lactam- and lactone-derived enol triflates (Figure 1) and
the corresponding phosphates are synthetically useful inter-
mediates that have been widely used as electrophiles in
metal-catalyzed coupling processes for the synthesis of nat-
ural products and heterocyclic compounds.[1,2] These com-
pounds undergo palladium- and nickel-mediated coupling
reactions with organotin, -zinc, and -boron derivatives, as
well as Sonogashira and Heck reactions, exchange with
metals, and coupling with organocuprates.[3,4] Carbon-
ylative coupling reactions are powerful synthetic tools, how-
ever, only methoxycarbonylation reactions have been car-
ried out on these triflates so far.[1d,1e,1i,1j,5] Nevertheless, the
possibility of forming new C–C bonds through carbon-
ylative cross-coupling reactions involving organometallic
reagents (Scheme 1) would certainly expand the utility and
scope of these reactions in organic synthesis. Stille carbon-
ylative processes are well known and widely used, however,
tin compounds are toxic and not many of them are com-
mercially available.[6] Therefore, and also because of our
previous experience of Suzuki–Miyaura coupling reactions
of lactam-derived enol triflates,[7] we opted to investigate
the carbonylative palladium-catalyzed coupling reactions of
these triflates with boronic acids, which are safe, easily pre-
pared, and widely available.
Figure 1. Enol triflates and boronic acids.
Scheme 1. Carbonylative processes involving enol triflates.
We started this study by evaluating the use of vinylbo-
ronic acids as coupling partners in the carbonylative reac-
tion that leads to unsymmetrical divinyl ketones that we[1c,8]
and others[9] have employed as substrates in the Nazarov
reaction.[10] Quite surprisingly, a survey of the literature re-
vealed that vinylboronic acids have never been used in car-
bonylative cross-coupling processes with a single exception
in which arenediazonium salts were used as the electro-
philes.[11] Moreover, only four papers dealing with the car-
[a] Department of Organic Chemistry “U. Schiff” and Laboratory
of Design, Synthesis and Study of Biologically Active Heterocy-
cles (HeteroBioLab), Università di Firenze,
Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy
Fax: +39-055-4573531
2152
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Carbonylative Suzuki–Miyaura Reaction of Enol Triflates
FULL PAPER
bonylative coupling of (carbocyclic) enol triflates with or- temperatures (60–90 °C) to occur,[12] with triflate 1 the ra-
ganoboron compounds such as sodium tetraphenylborate, pid formation of the carbonylative coupling product 12
2-indolylborates,[12] and an arylboronic acid[13] have been with (E)-pent-1-enylboronic acid (11a, Figure 1) was ob-
published. In this manuscript we therefore disclose the re- served when carrying out the reaction at room temperature
sults of our investigation of the carbonylative Suzuki– and under atmospheric pressure of carbon monoxide. In
Miyaura reaction of structurally different enol triflates 1–8 order to generate the negatively charged, four-coordinate
(Figure 1) derived from lactams and lactones, (i.e., cyclic boron “ate” complex that is required for the transmet-
ketene aminal and acetal triflates, respectively) with vinyl- alation step, KF was first used (Entry 1), but soon we found
boronic acids for a convergent and rapid approach to un- that CsF was by far superior for such a purpose (Entry 7).
symmetrical divinyl ketones.[14] We also report the extension This is consistent with the observation that caesium salts
of the methodology to thiolactone-derived enol triflate 9, are often the best choice in palladium-catalyzed coupling
the simplest representative of a class of electrophiles that reactions involving organoboron compounds under anhy-
have never been used in any kind of metal-catalyzed coup- drous conditions.[16] We also tested some carbonates as the
ling process.
base but the results were worse. In particular, the reaction
in the presence of 3 equiv. of Cs2CO3 (Entry 4) furnished
12 in 39% yield after chromatography, whereas under the
same conditions in the presence of CsF (Entry 3) the yield
was 71% after chromatography.
Results and Discussion
An initial survey (Table 1) of the conditions used for the
carbonylative coupling of alkenylboronic acids with these
All reactions were very fast with consumption (by TLC)
triflates was carried out with cyclic ketene aminal triflate 1 of most of the triflate in the first 2 hours.[17] We tried two
(Figure 1) and revealed Pd(OAc)2/Ph3P to be the best cata- different protocols. In method A, triflate, boronic acid, CsF,
lyst system.[15]
and the catalyst [5% Pd(OAc)2/10% Ph3P] were mixed in
While the reactions of cyclohexenyl triflates with lithium anhydrous THF and the resulting mixture saturated with
2-indolylborates and sodium tetraphenylborate have been CO. In method B, a solution of the triflate was added to a
reported to require either medium CO pressure (15 atm) or CO-saturated mixture of the other reagents and the catalyst
Table 1. Carbonylative Suzuki–Miyaura reaction of vinyl triflate 1 with alkenylboronic acids.[a]
Entry
Boronic ac-
id[b]
Amount of
boronic acid
(equiv.)
Base
Amount of base Time [h]
(equiv.)
T [°C]
Method[c]
Products
(% yield)[d]
1
2
3
4
5
6
7
8
11a
11a
11a
11a
11a
11a
11a
11b
11b[g]
11c
11c
11d
11e
2
1.5
2
KF
4
1.5
3
3
2.25
3
3
3
3
3
4
4
4
3
4
3
3
4
3
3
4
4
4
18
20
20
20
20
25
25
25
25
25
21
18
22
A
B
B
B
A
A
A
A
A
A
B
B
B
12 (46)
CsF
CsF
Cs2CO3
CsF
CsF
CsF
CsF
CsF
CsF
CsF
CsF
CsF
12 (29)
12 (71), 13 (10)[e]
12 (39)
2
1.5
1.5
2
2.2
1.5
1.5
2.5
2.5
2.5
12 (66), 13 (12)[e]
12 (76),[f] 13 (15)[e,f]
12 (79), 13 (12)[e]
14 (46)
9
14 (67), 15 (5)[e]
16 (76)[h]
10
11
12
13
3.75
3.75
3
16 (83)[f,h]
17 (70)[h]
18 (68)[h]
[a] Reactions carried out with 0.3–1.5 mmol of the substrates. [b] Commercial boronic acids were used. [c] Method A: The mixture
prepared by mixing triflate, catalyst, and boronic acid in THF was flushed with CO and then left under static CO pressure (balloon).
Method B: A mixture of boronic acid and catalyst in THF was flushed with CO and then a solution of triflate in THF was added, the
solution flushed again with CO, and then left under static CO pressure. [d] Yield after chromatography. [e] Evaluated by 1H NMR analysis
of the crude reaction mixture. [f] Average yield of two runs. [g] Freshly prepared. [h] The relative amount of the non-carbonylated product
1
could not be evaluated by H NMR analysis of the crude reaction mixture.
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L. Bartali, A. Guarna, P. Larini, E. G. Occhiato
FULL PAPER
in THF. This second protocol in general provided (slightly) ylated product 25 was formed (18%). With both triflates 5
higher yields as it prevents to a certain extent direct coup- and 6 we tried to suppress the unwanted, slower secondary
ling before saturation of the mixture with CO. Two observa- process that leads to direct coupling products by decreasing
tions are worth mentioning. Degradation of either the tri- the amount of catalyst to 1 mol-%. Although only the car-
flate or the acyl-palladium intermediate complex could be bonylative process then apparently took place under these
the cause of the low yields obtained after chromatography conditions, compounds 24 and 26 were obtained in low
in some cases (Entries 1, 2, 4, and 8). In particular, the yields (46 and 41%, respectively) mainly as a result of the
water present in the commercial boronic acids can hy- decomposition of the triflate back to the lactam. (In the
drolyze the acyl-palladium complex before transmetalation case of the N–CO2Me-protected triflate 6 we determined
occurs.[12b] As an example, the reaction in Entry 8, which that about 30% of the triflate was hydrolyzed to the corre-
was carried out with a very moist commercial hex-1-enyl- sponding lactam.) The reactions of triflates 5 and 6 with
boronic acid (11b), afforded 14 in 46% yield, whereas with a boronic acid 11a were eventually carried out in the presence
freshly prepared boronic acid[18] the yield increased to 67% of dppf [1,1Ј-bis(diphenylphosphanyl)ferrocene] as ligand,
(Entry 9). The second observation is that despite the reac- which is reported to increase the relative amount of the car-
tions being carried out under 1 atm of CO, the non-carbon- bonylated product in the Suzuki–Miyaura carbonylative
ylative Suzuki–Miyaura coupling appears to be a minor process,[19] obtaining compounds 24 and 26 in good chro-
problem with triflate 1 as non-carbonylated products were matographic yields (62 and 61%, respectively, Entries 5 and
always obtained albeit in less than 15% yield. In most cases 6) together with smaller amounts of the byproducts 25 and
an excess of the commercial boronic acid was needed to 27 (11–13%).
give good yields and 2.5 equiv. were necessary to give the
The first attempt at carbonylative coupling of the crude
best yields in the case of arylvinylboronic acids 11c–e (En- reaction mixture containing cyclic ketene acetal triflate 7
tries 11–13). Steric hindrance had little effect on the reac- was performed under standard conditions (Method B) with
tion outcome because with α-phenyl-substituted vinylbo- 5 mol-% Pd(OAc)2. The reaction with boronic acid 11a was
ronic acid 11e (Entry 13) the reaction provided the coupling as fast as with the lactam derivatives but provided a smaller
product 18 in 68% yield. Also, the presence of electron- relative amount of the carbonylated product 28, which was
withdrawing substituents on the aromatic ring (fluorine in obtained in 42% yield after chromatography. (This experi-
11d) is not detrimental to the success of the reaction.
ment was repeated a number of times without appreciable
In order to explore the scope of the reaction, we pre- variation of the reaction outcome.) Reducing the amount
pared a series of structurally different vinyl triflates by of catalyst (1 mol-%) did not change the product ratio. Thus
quenching with N-phenyltriflimide the enolates generated the reaction was carried out in the presence of dppf as li-
by treatment of lactams, lactones, and one thiolactone with gand (Entry 7) and with 2.5 equiv. of boronic acid, which
KHMDS [potassium bis(trimethylsilyl)amide] (Figure 1). In provided, as in the case of N-heterocyclic triflates 5 and 6,
contrast with six- and seven-membered lactam-derived vinyl a higher ratio of 28 (50%) to 29 (6%). These conditions
triflates, which can be purified by chromatography, triflates were applied to the coupling of 7 with boronic acids 11c
3, 4, 7 and 8 are unstable compounds that tend to decom- and 11e; in both cases the carbonylated products were ob-
pose quickly. Therefore they were used without purification tained in acceptable yields following chromatography after
just after their preparation. With all these triflates we de- two steps (Entries 8 and 9). As for the seven-membered
cided to apply protocol B using pent-1-enyl- (11a) and sty- triflate 8, this was best prepared according to Milne and
rylboronic acid (11c) as representative boronic acids (in Kocienski’s procedure[4c] in which the aqueous work up is
some cases also 11e). The results are reported in Table 2.
avoided. However, the carbonylative coupling of crude trifl-
The results of the carbonylative coupling of triflates 2–6 ate 8 with boronic acid 11a in the presence of dppf provided
derived from differently protected (N-tosyl, N-Cbz, N- 34 in only 32% yield together with less than 6% of the non-
CO2Me, N-CO2Ph) five-, six-, and seven-membered lactams carbonylated product (Entry 10). Considerable degradation
were satisfactory, although we had in some cases to opti- of the unstable triflate 8 took place under these conditions.
mize the reaction conditions. We were particularly pleased The corresponding phosphate 10 (Figure 1) did not react at
to obtain the coupling product between five-membered het- all under these conditions.
erocyclic triflate 3 and pent-1-enylboronic acid (Entry 3) in
Finally, carbonylative coupling of dihydrothiopyranyl
77% yield as this procedure could represent a better alter- triflate 9 with both boronic acids 11a and 11c under the
native to those previously proposed for the preparation of conditions of protocol B provided an almost equimolar
a roseophilin synthetic precursor.[1c] The reaction carried mixture of the carbonylative and non-carbonylative prod-
out on triflate 4 under the same conditions provided instead ucts.[20] Carbonylated products 36 and 38 were both ob-
the carbonylated product 23 in low yield (31%) as a result tained in 40% yield after chromatography and the corre-
of the very low thermal stability of the triflate (which in sponding non-carbonylative compounds in yields of 30–
fact rapidly decomposes after its isolation and, presumably, 33%. Better results in terms of product ratio were obtained
during the reaction).
by using CsOAc as base (Entries 11 and 12) and com-
The yield of carbonylative coupling under standard con- pounds 36 and 38 could then be isolated in good overall
ditions was barely acceptable with seven-membered ring yields (56 and 57%, respectively) after the two reaction
triflate 5 (48%) as a relatively large amount of non-carbon- steps.
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Carbonylative Suzuki–Miyaura Reaction of Enol Triflates
FULL PAPER
Table 2. Carbonylative Suzuki–Miyaura reactions of lactam-, lactone-, and thiolactone-derived vinyl triflates with alkenylboronic acids.[a]
[a] Reactions carried out with 0.5–1.5 mmol of the substrates by method B at 18–22 °C in the presence of 5 mol-% of the catalyst Pd-
(OAc)2, 10 mol-% of Ph3P, 2 equiv. of the boronic acid, and 3 equiv. of CsF. All reactions were complete after 3–4 h by TLC. [b] Commer-
cial boronic acids were used. [c] Yield after chromatography. [d] The relative amount of non-carbonylated product could not be evaluated
1
by H NMR analysis of the crude reaction mixture. [e] 2.5 Equiv. of boronic acid. [f] Overall yield over two steps after chromatography.
1
[g] Conversion calculated by H NMR analysis of the crude reaction mixture. [h] Reaction carried out in the presence of 6.25 mol-% of
dppf as ligand. [i] Reaction carried out in the presence of CsOAc as base.
The results reported in Table 1 and Table 2 show that lactones (9), the highest ratios being observed with the N-
under standard conditions [5 mol-% of Pd(OAc)2, 10 mol- heterocyclic triflates and the lowest with oxygen- and sul-
% of Ph3P, and 2–2.5 equiv. of pent-1-enylboronic acid] fur-containing vinyl triflates. In particular, we observed a
there is a noticeable difference in the ratio between carbony- carbonylated/non-carbonylated product ratio of 1.6 with
lated and non-carbonylated products obtained with triflates triflate 7 (Table 3, Entry 2). This ratio grew to a value in
of six-membered lactams (e.g., 1), lactones (7), and thio- excess of 7 with triflate 1 (Entry 1) and decreased to 1.3
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L. Bartali, A. Guarna, P. Larini, E. G. Occhiato
FULL PAPER
with sulfur-containing triflate 9 (Entry 3). Thus it seems
that the heteroatom has a certain influence on the reaction
outcome.
Table 3. Comparison of the carbonylative Suzuki–Miyaura reaction
of vinyl triflates 1, 7, and 9 with boronic acid 11a.[a]
Entry
Triflate
Products (Yield [%])
Product ratio
1
2
3
1
7
9
12 (71)/13 (10)
28 (42)/29 (27)
36 (40)/37 (30)
7.1
1.6
1.3
[a] Reactions carried out with 0.5–1.5 mmol of substrates by
method B at 18–22 °C in the presence of 5 mol-% of catalyst
Pd(OAc)2, 10 mol-% of Ph3P, 2 equiv. of boronic acid, and 3 equiv.
of CsF.
The mechanism of the carbonylative processes has been
the subject of several studies.[19] The ratio between carbony-
lated product VI and non-carbonylated compound VIII de-
pends on the relative rates of formation of the acyl-palla-
dium complex IV (path a) and the transmetalated complex
VII (path b), as reported in Scheme 2. The formation of a
pentacoordinate intermediate after CO adsorption has been
suggested and in some cases demonstrated with Ar–M–X
complexes in which M is NiII, PdII, and PtII.[21,22] This
would lead to the formation of complex II which should be
favored by the presence of an electronegative atom X in the
R ring. The removal of electron density from the metal cen-
ter by the heteroatom should stabilize II because the metal
center can better accommodate another unshared electron
pair from the new CO ligand.[21] As this effect should be
primarily inductive, as shown by Garrou and Heck,[21]
changing from sulfur (lowest electronegativity) to nitrogen
and then to oxygen (highest electronegativity), as in this
case, should greatly influence the equilibrium towards inter-
mediate II and thus favor path a, leading to the carbony-
lated product VI. (The formation of the acyl-palladium
complex IV could then occur either by direct migration of
the alkenyl residue or by a dissociative process.)[21–23] The
same inductive effect could also favor the coordination of
the boronic acid to complex I and consequently the forma-
tion of the non-carbonylated product VIII through path b.
However, formation of V is likely to be preceded by dissoci-
ation of the triflate anion to form cationic complex III[24]
which should be less favored in the presence of an electro-
negative atom in R such as nitrogen and oxygen.
Scheme 2. Mechanism of the carbonylative coupling reaction.
carbonylated product increases. As the best ratios in favor
of the carbonylated products are obtained with N-heterocy-
cle triflates 1 and 2 (and 3), there must be in these cases an
optimal electron density on C-2 such that CO adsorption is
still fast and migration of R to form the acyl-palladium
complex is not too slow.[25]
From a practical point of view, direct transmetalation
(path b) could be retarded by reducing the reactivity of the
boronic acid with a consequential increase in the relative
amount of the carbonylated product. This actually occurred
with thiolactone-derived triflate 9 when CsOAc was used as
base (Entries 11 and 12, Table 2) which is less efficient in
boron quaternization than CsF. Also, reducing the amount
of catalyst in some cases helped to suppress the unwanted
secondary pathway, although in this case degradation of the
triflate occurred. Finally, bidentate ligands with a large bite
angle such as dppf were effective in increasing the rate of
the carbonylation reaction (path a) of the lactone-derived
triflate 7 (Table 2, Entries 7–9) as well as seven-membered
N-heterocycle derivatives (Table 2, Entries 5 and 6).
Conclusions
In conclusion, the carbonylative Suzuki–Miyaura coup-
On the other hand, too low an electron density on the ling reaction of structurally different vinyl triflates derived
C-2 carbon atom of R, as in 7, due to the high electronega- from lactams, lactones, and thiolactones with alkenyl-
tivity of the heterocyclic oxygen atom could be detrimental boronic acids occur at room temperature and under 1 atm
to the rate of migration of the R group to form the acyl- of CO pressure, that is, under operationally simple condi-
palladium complex IV, in accordance with the observation tions, using 5 mol-% of Pd(OAc)2 and either 10 mol-% of
that for aromatic halides the migration step that forms the Ph3P or 6.25 mol-% of dppf as ligand to give unsymmetri-
acyl-palladium complex is critically influenced by the elec- cal dienones. Good-to-excellent yields (60–86%) were ob-
tron density of the aryl moiety.[19,21,23] Thus the migration tained in particular with N-heterocyclic vinyl triflates.
step that leads to VI is retarded and either degradation of Good overall yields over two steps (50–57%) were also ob-
the acyl-palladium complex or direct coupling to give 29 tained with lactone- and thiolactone-derived enol triflates.
becomes competitive. Instead, in the coupling of sulfur-con- We observed that the relative amounts of the carbonylated
taining triflate 9, the higher electron density on C-2 retards products (with respect to the corresponding non-carbony-
the adsorption of CO and the relative amount of the non- lated ones) could be related to the electron density on C-2,
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Carbonylative Suzuki–Miyaura Reaction of Enol Triflates
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5-Methyl-1-(4-methylphenylsulfonyl)-4,5-dihydro-1H-pyrrol-2-yl
Trifluoromethanesulfonate (3):[8b] A solution of 5-methyl-N-tosyl-
pyrrolidin-2-one (253 mg, 1.0 mmol) in THF (2 mL) was added to
a solution of KHMDS (2.5 mL of a 0.5  solution in toluene,
1.25 mmol) in THF (5.5 mL), cooled to –78 °C and under nitrogen,
and the resulting mixture was stirred for 1.5 h. Afterwards a solu-
tion of PhNTf2 (447 mg, 1.25 mmol) in THF (1.5 mL) was quickly
added and the mixture was stirred for 1 h at –78 °C before the
temperature was allowed to rise to 0 °C. Then a 10% NaOH solu-
tion (10 mL) was added, the mixture was extracted with Et2O
which in turn greatly depends on the electronegativity of
the heteroatom present in the ring. The highest ratios were
obtained with five- and six-membered N-heterocyclic vinyl
triflates. In the case of the six-membered O-heterocycle 7,
the low electron density on C-2 could retard the migration
step that generates the acyl-palladium complex. With sul-
fur-containing heterocyclic triflate 9, the high electron den-
sity on C-2 could instead slow down the adsorption of CO
by the palladium complex. This methodology allows for the
rapid preparation of unsymmetrical divinyl ketones which (3ϫ10 mL), washed with water (10 mL) and brine (2ϫ10 mL),
and then dried with anhydrous K2CO3. After filtration and evapo-
ration of the solvent, crude vinyl triflate 3 was obtained as a yellow-
ish oil and used directly in the next coupling reaction. This triflate
must be stored in a refrigerator and used within 24 h of its prepara-
are useful as substrates for a variety of reactions such as
conjugate additions and Nazarov reactions.
1
tion. H NMR (200 MHz, CDCl3): δ = 7.76 (d, J = 8.1 Hz, 2 H,
Experimental Section
CHarom), 7.35 (d, J = 8.1 Hz, 2 H, CHarom), 5.09 (br. s, 1 H,
C=CH), 4.19 (m, 1 H, N-CH), 2.46 (s, 3 H, CH3-Carom), 2.27 (td,
J = 7.3, 2.2 Hz, 1 H, CH-CH2), 1.87 (dt, J = 16.8, 2.9 Hz, 1 H,
1H NMR spectra were recorded at 200 and 400 MHz at 25 °C. 13
C
NMR spectra were recorded at 50.33 MHz at 25 °C. Mass spectra
were carried out by EI at 70 eV. Chromatographic separations were CH-CH2), 1.39 (d, J = 6.6 Hz, 3 H, CH3-CH) ppm.
performed under pressure on silica gel using flash column chroma-
tographic techniques; Rf values refer to TLC carried out on
0.25 mm silica gel plates with the same eluent as indicated for col-
Benzyl 7-(Trifluoromethylsulfonyloxy)-2,3,4,5-tetrahydro-1H-azep-
ine-1-carboxylate (5):[7a] A solution of benzyl 2-oxoazepane-1-car-
boxylate (988 mg, 4 mmol) in THF (8 mL) was added to a solution
of KHMDS (10 mL of a 0.5  solution in toluene, 5 mmol) in THF
(22 mL) cooled to –78 °C and under nitrogen and the resulting mix-
ture was stirred for 1.5 h. Afterwards a solution of PhNTf2
umn chromatography. Boronic acids were purchased or prepared as
reported previously.[18] THF was distilled from Na/benzophenone.
Dichloromethane and 1,2-dichloroethane were distilled from CaH2.
Methyl 6-(Trifluoromethylsulfonyloxy)-1,2,3,4-tetrahydropyridine-1-
carboxylate (1):[26] A solution of methyl 2-oxopiperidine-1-carbox-
ylate (1.76 g, 11.2 mmol) in THF (20 mL) was added to a solution
prepared by diluting a 0.5  solution of KHMDS [potassium bis-
(trimethylsilyl)amide] in toluene (28 mL, 14 mmol), cooled to
–78 °C and under nitrogen, with THF (70 mL) and the resulting
mixture was stirred for 1.5 h. Afterwards a solution of PhNTf2
(14 mmol) in THF (20 mL) was added dropwise and after 1 h the
reaction mixture was warmed to room temperature. After 16 h,
water (100 mL) was added, the mixture was extracted with Et2O
(3ϫ60 mL), and the combined organic layers were washed with
10% NaOH (100 mL) and dried for 1 h with anhydrous K2CO3.
After filtration and evaporation of the solvent the crude oil was
purified by chromatography (EtOAc/petroleum ether 1:8, 1.5%
Et3N, Rf = 0.38) providing 1 as a colorless oil (2.57 g, 79%). 1H
NMR (200 MHz, CDCl3): δ = 5.32 (t, J = 3.8 Hz, 1 H, C=CH),
3.80 (s, 3 H, CO2CH3), 3.67 (m, 2 H, N-CH2), 2.28 (m, 2 H,
C=CH-CH2), 1.80 (m, 2 H, CH2CH2CH2) ppm.
(1.786 g, 5 mmol) in THF (6 mL) was quickly added and then left
to stir for 1 h at –78 °C before allowing the temperature to rise to
0 °C. Then a 10% NaOH solution (40 mL) was added, the mixture
was extracted with Et2O (3ϫ40 mL), washed with water (40 mL)
and brine (2ϫ40 mL), and then dried with anhydrous K2CO3. Af-
ter filtration and evaporation of the solvent, the crude reaction
mixture was purified by chromatography (EtOAc/petroleum ether
1:2, 1.5% Et3N, Rf = 0.90) providing 5 as a colorless oil (951 mg,
82%). 1H NMR (200 MHz, CDCl3): δ = 7.43–7.25 (m, 5 H,
CHarom), 5.71 (t, J = 6.2 Hz, 1 H, C=CH), 5.22 (s, 2 H, CH2Ph),
3.80–3.45 (m, 2 H, N-CH2), 2.21–2.05 (m, 2 H, C=CH-CH2), 1.82–
1.65 (m, 2 H, CH2CH2), 1.48–1.64 (m, 2 H, CH2CH2) ppm.
Methyl 7-(Trifluoromethylsulfonyloxy)-2,3,4,5-tetrahydro-1H-azep-
ine-1-carboxylate (6): A solution of methyl 2-oxoazepane-1-carbox-
ylate (822 mg, 4.8 mmol) in THF (8 mL) was added to a solution
of KHMDS (12 mL of a 0.5  solution in toluene, 6 mmol) in THF
(30 mL) cooled to –78 °C and under nitrogen and the resulting mix-
ture was stirred for 1.5 h. Afterwards a solution of PhNTf2 (2.14 g,
6 mmol) in THF (7 mL) was quickly added and left to stir for 1 h
at –78 °C before allowing the temperature to rise to 0 °C. Then a
10% NaOH solution (40 mL) was added, the mixture was extracted
with Et2O (3ϫ40 mL), washed with water (40 mL) and brine
(2ϫ40 mL), and then dried with anhydrous K2CO3. After filtration
and evaporation of the solvent, the crude reaction mixture was
purified by chromatography (EtOAc/petroleum ether 1:4, 1.5%
1-(4-Methylphenylsulfonyl)-1,4,5,6-tetrahydropyridin-2-yl Trifluoro-
methanesulfonate (2):[3c] A solution of 1-(toluene-4-sulfonyl)piperi-
din-2-one (547 mg, 2.16 mmol) in THF (8 mL) was added dropwise
to a solution prepared by diluting a 0.5  solution of KHMDS in
toluene (5.8 mL, 2.9 mmol), cooled to –78 °C and under nitrogen,
with THF (14 mL) and the resulting mixture was stirred for 1.5 h.
Afterwards a solution of PhNTf2 (2.68 mmol) in THF (4 mL) was
added dropwise and after 1 h the reaction mixture was warmed to
room temperature. After 16 h, water (50 mL) was added, the mix-
ture was extracted with Et2O (3ϫ30 mL), and the combined or-
ganic layers were washed with 10% NaOH (50 mL) and dried for
1 h with anhydrous K2CO3. After filtration and evaporation of the
solvent the crude oil was purified by chromatography (EtOAc/pe-
1
Et3N, Rf = 0.53) providing 6 as a colorless oil (880 mg, 60%). H
NMR (200 MHz, CDCl3): δ = 5.70 (t, J = 6.6 Hz, 1 H, C=CH),
3.79 (s, 3 H, CO2CH3), 3.75–3.37 (m, 2 H, N-CH2), 2.29–2.04 (m,
2 H, C=CH-CH2), 1.90–1.69 (m, 2 H, CH2CH2), 1.66–1.41 (m, 2
H, CH2CH2) ppm.
troleum ether 1:4, 1.5% Et3N, Rf = 0.31) providing 2 as a white 2-Methyl-3,4-dihydro-2H-pyran-6-yl
Trifluoromethanesulfonate
1
solid (666 mg, 80%). H NMR (200 MHz, CDCl3): δ = 7.78 (d, J (7):[8b] A 0.5  solution of KHMDS in toluene (3.8 mL, 1.88 mmol)
= 8.14 Hz, 2 H, CHarom), 7.34 (d, J = 8.14 Hz, 2 H, CHarom), 5.45
(t, J = 4.0 Hz, 1 H, C=CH), 3.68–3.61 (m, 2 H, N-CH2), 2.45 (s, 3
was added dropwise in about 10 min to a solution of 6-methyltetra-
hydropyran-2-one (171 mg, 1.5 mmol) in anhydrous THF (3 mL)
H, CH3-Carom), 2.18–2.08 (m, 2 H, C=CH-CH2), 1.52–1.41 (m, 2 cooled to –78 °C and under nitrogen. Afterwards a solution of
H, CH2CH2CH2) ppm.
PhNTf2 (672 mg, 1.88 mmol) in THF (1.5 mL) was added and the
Eur. J. Org. Chem. 2007, 2152–2163
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2157

L. Bartali, A. Guarna, P. Larini, E. G. Occhiato
FULL PAPER
resulting mixture left to stir at –78 °C for 2 h before allowing the
temperature to rise to 0 °C. Then a 10% NaOH solution (6 mL)
was added and the mixture was extracted with Et2O (3ϫ6 mL) and
dried with anhydrous K2CO3 for about 30 min. After filtration, the
solution of crude triflate 7 was concentrated under vacuum to a
small volume (about 1.5 mL) and immediately used in the next
coupling step. It is important not to remove the solvent completely,
as the triflate quickly decomposes if exposed to air.[4d] 1H NMR
(200 MHz, CDCl3): δ = 4.75 (t, J = 2.5 Hz, 1 H, C=CH), 4.31–
4.15 (m, 1 H, O-CH), 2.25–2.15 (m, 2 H, C=CH-CH2), 1.94–1.77
(m, 1 H,=CHCH2CH2), 1.69–1.47 (m, 1 H, =CHCH2CH2), 1.35
(d, J = 6.5 Hz, 3 H, CH3-CH) ppm.
CH3CH2CH2CH2), 0.88 (t, J = 6.6 Hz, 3 H, CH3CH2CH2-
CH2) ppm. 13C NMR (CDCl3): δ = 188.2 (s), 154.2 (s), 148.0 (d),
139.6 (s), 126.3 (d), 121.0 (d), 52.8 (q), 43.6 (t), 32.5 (t), 30.3 (t),
23.0 (t), 22.7 (t), 22.3 (t), 13.9 (q) ppm. MS: m/z (%) = 251 (20)
[M]+, 208 (24), 194 (84), 55 (100). C14H21NO3 (251.32): calcd. C
66.91, H 8.42, N 5.57; found C 66.71, H 8.13, N 5.36.
Methyl 6-[(2E)-3-Phenylprop-2-enoyl]-1,2,3,4-tetrahydropyridine-1-
carboxylate (16): A suspension prepared by mixing (E)-styrylbo-
ronic acid (11c) (370 mg, 2.5 mmol), Pd(OAc)2 (11 mg, 0.05 mmol),
Ph3P (26 mg, 0.1 mmol), and CsF (570 mg, 3.75 mmol) in anhy-
drous THF (10 mL) was flushed with CO whilst stirring. After
10 min, a solution of triflate 1 (290 mg, 1 mmol) in THF (6 mL)
was slowly added by syringe, the resulting mixture was flushed
again with CO, and finally left under static pressure of CO (1 atm)
for 4 h at room temperature. Usual work up gave a crude oil which
was purified by chromatography (EtOAc/petroleum ether 1:3, Rf =
0. 23) to give 16 (233 mg) in 86% yield as a pale yellow oil. 1H
NMR (200 MHz, CDCl3): δ = 7.67 (d, J = 15.8 Hz, 1 H,
COCH=CH), 7.61–7.47 (m, 2 H, CHarom), 7.46–7.32 (m, 3 H,
CHarom), 6.92 (d, J = 15.8 Hz, 1 H, COCH=CH), 5.98 (t, J =
3.7 Hz, 1 H, C=CH), 3.75–3.66 (m, 2 H, N-CH2), 3.64 (s, 3 H,
CO2CH3), 2.36–2.23 (m, 2 H, C=CH-CH2), 1.95–1.79 (m, 2 H,
CH2CH2CH2) ppm. 13C NMR (CDCl3): δ = 187.9 (s), 154.5 (s),
143.2 (d), 139.8 (s), 134.6 (s), 130.2 (d), 128.7 (d, 2 C), 128.2 (d, 2
C), 122.5 (d), 121.6 (d), 53.0 (q), 43.6 (t), 23.0 (t), 22.6 (t) ppm.
3,4-Dihydro-2H-thiopyran-6-yl Trifluoromethanesulfonate (9):
A
solution of tetrahydrothiopyran-2-one[27] (348 mg, 3 mmol) in THF
(6 mL) was added to a solution of KHMDS (7.5 mL of a 0.5 
solution in toluene, 3.75 mmol) in THF (16.5 mL) cooled to –78 °C
and under nitrogen and the resulting mixture was stirred for 1.5 h.
Afterwards a solution of PhNTf2 (1.340 g, 3.75 mmol) in THF
(4.5 mL) was quickly added and then left to stir for 1 h at –78 °C
before allowing the temperature to rise to room temperature. Then
a 10% NaOH solution (30 mL) was added, the mixture was ex-
tracted with Et2O (3ϫ30 mL), washed with water (30 mL) and
brine (2ϫ30 mL), and then dried with anhydrous K2CO3. After
filtration and evaporation of the solvent, crude triflate 9 (762 mg)
was obtained as a pale yellowish oil and used directly in the next
step. 1H NMR (200 MHz, CDCl3): δ = 5.84 (t, J = 4.4 Hz, 1 H, MS: m/z (%) = 271 (64) [M]+, 212 (41), 131 (40), 103 (67), 77 (100),
C=CH), 3.06–3.01 (m, 2 H, S-CH2), 2.41–2.32 (m, 2 H, C=CH- 59 (44), 51 (64). C16H17NO3 (271.31): calcd. C 70.83, H 6.32, N
CH2), 2.06–1.95 (m, 2 H, CH2CH2CH2) ppm. 13C NMR (CDCl3):
δ = 154.3 (s), 114.9 (d), 29.2 (t), 23.7 (t), 21.7 (t) ppm.
5.16; found C 70.99, H 6.01, N 4.87.
Methyl 6-[(2E)-3-(4-Fluorophenyl)prop-2-enoyl]-1,2,3,4-tetrahydro-
pyridine-1-carboxylate (17): Prepared as reported above for 16. A
suspension prepared by mixing boronic acid 11d (415 mg,
2.5 mmol), Pd(OAc)2 (11 mg, 0.05 mmol), Ph3P (26 mg, 0.1 mmol),
Methyl 6-[(2E)-Hex-2-enoyl]-1,2,3,4-tetrahydropyridine-1-carboxyl-
ate (12): Pd(OAc)2 (5.6 mg, 0.025 mmol), Ph3P (13 mg, 0.05 mmol),
(E)-pent-1-enylboronic acid (11a) (115 mg, 1.0 mmol), and CsF
(228 mg, 1.5 mmol) were added to a solution of triflate 1 (145 mg, and CsF (570 mg, 3.75 mmol) in anhydrous THF (10 mL) was
0.5 mmol) in anhydrous THF (8 mL) under nitrogen. The flask was
flushed with CO and then stirred under a static pressure of CO
(1 atm). After 3 h, Et2O (30 mL) was added to the dark orange
solution which was washed with water (20 mL). The aqueous phase
was extracted with Et2O (20 mL) and the combined organic layers
were dried with Na2SO4. After filtration and evaporation of the
solvent, the crude oil was purified by chromatography (EtOAc/pe-
flushed with CO whilst stirring. After 10 min, a solution of triflate
1 (290 mg, 1 mmol) in THF (6 mL) was slowly added by syringe,
the resulting mixture was flushed again with CO, and finally left
under static pressure of CO (1 atm) for 4 h at room temperature.
Usual work up gave a crude oil which was purified by chromatog-
raphy (EtOAc/petroleum ether 1:2, Rf = 0.32) to give 17 (202 mg)
1
in 70% yield as a pale yellow oil. H NMR (200 MHz, CDCl3): δ
troleum ether 1:3, Rf = 0.40) yielding 12 (94 mg, 79%) as a pale = 7.64 (d, J = 16.1 Hz, 1 H, COCH=CH), 7.57–7.47 (m, 2 H,
yellow oil. 1H NMR (200 MHz, CDCl3): δ = 6.87 (dt, J = 15.8,
6.6 Hz, 1 H, COCH=CH), 6.23 (dt, J = 15.8, 1.5 Hz, 1 H,
COCH=CH), 5.83 (t, J = 4.0 Hz, 1 H, C=CH), 3.67–3.58 (m, 2 H,
CHarom), 7.11–6.99 (m, 2 H, CHarom), 6.83 (d, J = 16.1 Hz, 1 H,
COCH=CH), 5.98 (t, J = 3.7 Hz, 1 H, C=CH), 3.75–3.66 (m, 2 H,
N-CH2), 3.64 (s, 3 H, CO2CH3), 2.35–2.22 (m, 2 H, C=CH-CH2),
N-CH2), 3.61 (s, 3 H, CO2CH3), 2.29–2.08 (m, 4 H, C=CH-CH2, 1.95–1.77 (m, 2 H, CH2CH2CH2) ppm. 13C NMR (CDCl3): δ =
CH3CH2CH2), 1.89–1.73 (m, 2 H, CH2CH2CH2), 1.56–1.35 (m, 2 187.6 (s), 166.1 and 161.1 (both d, 1JCF = 251.0 Hz, 1 C), 154.5 (s),
H, CH3CH2CH2), 0.89 (t, J = 6.9 Hz, 3 H, CH3CH2CH2) ppm. 13
C
141.8 (d), 139.8 (s), 130.8 (s), 130.1 and 129.9 (both d, JCF = 8.4
3
2
NMR (CDCl3): δ = 188.2 (s), 154.3 (s), 147.6 (d), 139.6 (s), 126.3
Hz, 2 C), 122.2 (d), 121.7 (d), 116.0 and 115.6 (both d, JCF
=
(d), 120.9 (d), 52.8 (q), 43.5 (t), 34.7 (t), 23.0 (t), 22.7 (t), 21.4 (t),
22.1 Hz, 2 C), 53.0 (q), 43.6 (t), 23.1 (t), 22.7 (t) ppm. MS: m/z (%)
13.7 (q) ppm. MS: m/z (%) = 237 (24) [M]+, 208 (22), 194 (57), 55 = 289 (69) [M]+, 261 (15), 230 (56), 214 (58), 149 (100), 121 (54).
(100). C13H19NO3 (237.29): calcd. C 65.80, H 8.07, N 5.90; found
C 65.69, H 7.93, N 5.95.
C16H16FNO3 (289.30): calcd. C 66.43, H 5.57, N 4.84; found C
66.11, H 5.62, N, 4.71.
Methyl 6-[(2E)-Hept-2-enoyl]-1,2,3,4-tetrahydropyridine-1-carboxyl-
ate (14): Prepared as reported above for 12 starting from 1 (87 mg,
0.3 mmol) and freshly prepared (E)-hex-1-enylboronic acid (11b)
Methyl 6-(2-Phenylprop-2-enoyl)-1,2,3,4-tetrahydropyridine-1-car-
boxylate (18): Prepared as reported above for 16. A suspension pre-
pared by mixing boronic acid 11e (185 mg, 1.25 mmol), Pd(OAc)2
(56 mg, 0.45 mmol). Chromatography (EtOAc/petroleum ether 1:3, (5.6 mg, 0.025 mmol), Ph3P (13 mg, 0.05 mmol), and CsF (228 mg,
1
Rf = 0.34) afforded 14 (58 mg) in 67% yield. H NMR (200 MHz,
CDCl3): δ = 6.90 (dt, J = 16.1, 6.6 Hz, 1 H, COCH=CH), 6.24 (d,
J = 16.1 Hz, 1 H, COCH=CH), 5.84 (t, J = 3.7 Hz, 1 H, C=CH),
1.5 mmol) in anhydrous THF (5 mL) was flushed with CO whilst
stirring. After 10 min, a solution of triflate 1 (145 mg, 0.5 mmol)
in THF (3 mL) was slowly added by syringe, the resulting mixture
3.71–3.57 (m, 2 H, N-CH2), 3.63 (s, 3 H, CO2CH3), 2.33–2.12 was flushed again with CO, and finally left under static pressure of
(m, 4 H, C=CH-CH2, CH3CH2CH2CH2), 1.92–1.73 (m, 2 H, CO (1 atm) for 4 h at room temperature. Usual work up gave a
CH2CH2CH2), 1.59–1.18 (m,
4
H, CH3CH2CH2CH2,
crude oil which was purified by chromatography (EtOAc/petroleum
2158
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2152–2163

Carbonylative Suzuki–Miyaura Reaction of Enol Triflates
FULL PAPER
ether 1:2, 0.5% Et3N, Rf = 0.4) to give 18 (92 mg) in 68% yield as
a pale yellow oil. H NMR (200 MHz, CDCl3): δ = 7.50–7.30 (m,
THF (10 mL) was flushed with CO whilst stirring. After 10 min, a
solution of crude triflate 3 (1 mmol) in THF (6 mL) was slowly
1
5 H, CHarom), 5.93 (s, 1 H, C=CH2), 5.91 (t, J = 3.7 Hz, 1 H, added by syringe, the resulting mixture was flushed with CO, and
C=CH-CH2), 5.85 (s, 1 H, C=CH2), 3.59 (s, 3 H, CO2CH3), 3.53– finally left under static pressure of CO (1 atm) for 18 h at room
3.47 (m, 2 H, N-CH2), 2.30–2.21 (m, 2 H, C=CH-CH2), 1.89–1.80 temperature. Usual work up gave a crude oil which was purified by
(m, 2 H, CH2CH2CH2) ppm. 13C NMR (CDCl3): δ = 191.5 (s),
153.8 (s), 146.5 (s), 139.0 (s), 136.6 (s), 128.0 (d, 2 C), 127.9 (d, 2
C), 127.4 (d), 123.1 (t), 122.4 (d), 52.9 (q), 42.9 (t), 23.0 (t), 22.5
chromatography (EtOAc/petroleum ether 1:4, 0.5% Et3N, Rf =
0.42) to give 21 (256 mg, 77%) as a pale yellow oil. 1H NMR
(200 MHz, CDCl3): δ = 7.66 (d, J = 8.4 Hz, 2 H, CHarom), 7.29 (d,
(t) ppm. MS: m/z (%) = 271 (100) [M]+, 226 (29), 198 (25), 168 (42), J = 8.4 Hz, 2 H, CHarom), 7.06 (dt, J = 15.8, 6.8 Hz, 1 H,
154 (60), 103 (43), 77 (58). C16H17NO3 (271.31): calcd. C 70.83, H
6.32, N 5.16; found C 70.71, H 5.99, N 4.98.
COCH=CH), 6.58 (dt, J = 15.8, 1.4 Hz, 1 H, COCH=CH), 5.95
(t, J = 3.3 Hz, 1 H, C=CH), 4.25–4.06 (m, 1 H, N-CH), 2.41 (s, 3
H, CH3-Carom), 2.26 (qd, J = 7.4, 1.4 Hz, 2 H, CH3CH2CH2), 2.10
(ddd, J = 18.0, 8.4, 2.2 Hz, 1 H,=CHCH2CH), 1.82 (ddd, J = 18.0,
3.3, 2.6 Hz, 1 H, =CHCH2CH), 1.63–1.44 (m, 2 H, CH3CH2CH2),
1.31 (d, J = 6.6 Hz, 3 H, CH3-CH–N), 0.96 (t, J = 7.4 Hz, 3 H,
CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 185.4 (s), 148.4 (d),
143.9 (s), 143.4 (s), 133.2 (s), 129.4 (d, 2 C), 127.9 (d), 127.6 (d),
125.3 (d), 58.9 (d), 36.2 (t), 34.7 (t), 22.6 (q), 21.7 (q), 21.5 (t), 13.8
(q) ppm. MS: m/z (%) = 333 (66) [M]+, 290 (85), 178 (99), 91 (100).
C18H23NO3S (333.45): calcd. C 64.84, H 6.95, N 4.20; found C
64.71, H 7.12, N, 3.86.
(2E)-1-[1-(4-Methylphenylsulfonyl)-1,4,5,6-tetrahydropyridin-2-yl]-
hex-2-en-1-one (19): A suspension prepared by mixing boronic acid
11a (114 mg, 1 mmol), Pd(OAc)2 (6 mg, 0.025 mmol), Ph3P (13 mg,
0.05 mmol), and CsF (228 mg, 1.5 mmol) in anhydrous THF
(5 mL) was flushed with CO whilst stirring. After 10 min, a solu-
tion of triflate 2 (193 mg, 0.5 mmol) in THF (3 mL) was slowly
added by syringe, the resulting mixture was flushed with CO, and
finally left under static pressure of CO (1 atm) for 3 h at room
temperature. Usual work up gave a crude oil which was purified by
chromatography (EtOAc/petroleum ether 1:2, 0.5% Et3N, Rf =
0.48) to give 19 (115 mg, 69 %) as a pale yellow oil. 1H NMR
(200 MHz, CDCl3): δ = 7.69 (d, J = 8.4 Hz, 2 H, CHarom), 7.26 (d,
J = 8.4 Hz, 2 H, CHarom), 7.02–6.87 (dt, J = 16.1, 7.3 Hz, 1 H,
COCH=CH), 6.51 (d, J = 16.1 Hz, 1 H, COCH=CH), 6.03 (t, J =
3.7 Hz, 1 H, C=CH), 3.45–3.39 (m, 2 H, N-CH2), 2.37 (s, 3 H,
CH3-Carom), 2.19 (q, J = 7.0 Hz, 2 H, C=CH-CH2), 2.06–1.98 (m,
2 H, CH3CH2CH2), 1.57–1.38 (m, 2 H, CH3CH2CH2), 1.32–1.08
( m , 2 H , C H 2 C H 2 C H 2 ) , 0 . 9 1 ( t , J = 7 . 3 H z , 3 H ,
CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 188.6 (s), 147.4 (d),
143.9 (s), 139.1 (s), 135.2 (s), 129.6 (d, 2 C), 127.7 (d, 2 C), 127.1
(d), 125.2 (d), 44.9 (q), 34.5 (t), 22.3 (t), 21.5 (t), 21.3 (t), 19.3 (t),
13.7 (q) ppm. MS: m/z (%) = 333 (15) [M]+, 290 (66), 226 (64), 178
(82), 135 (56), 97 (50), 91 (88), 65 (44), 55 (100). C18H23NO3S
(333.45): calcd. C 64.84, H 6.95, N 4.20; found C 64.91, H 6.69, N
4.31.
Phenyl 5-[(2E)-Hex-2-enoyl]-2,3-dihydro-1H-pyrrole-1-carboxylate
(23): A solution of phenyl 2-oxopyrrolidine-1-carboxylate (205 mg,
1.0 mmol) in THF (2 mL) was added to a solution of KHMDS
(2.5 mL of a 0.5  solution in toluene, 1.25 mmol) in THF (5.5 mL)
cooled to –78 °C and under nitrogen and the resulting mixture was
stirred for 1.5 h. Afterwards a solution of PhNTf2 (447 mg,
1.25 mmol) in THF (1.5 mL) was quickly added and the mixture
was left to stir for 1 h at –78 °C before allowing the temperature to
rise to 0 °C. Then a 10% NaOH solution (10 mL) was added, the
mixture was extracted with Et2O (3ϫ10 mL), washed with water
(10 mL) and brine (2ϫ10 mL), and dried with anhydrous K2CO3
for 30 min. After filtration and evaporation of the solvent, crude
vinyl triflate 4 was dissolved in anhydrous THF (2 mL) and added
to a CO-saturated suspension prepared by mixing boronic acid 11a
(228 mg, 2.0 mmol), Pd(OAc)2 (11 mg, 0.05 mmol), Ph3P (26 mg,
0.1 mmol), and CsF (456 mg, 3 mmol) in anhydrous THF (8 mL).
The resulting mixture was flushed with CO and finally left under
static pressure of CO (1 atm) for 18 h at room temperature. Usual
work up gave a crude oil which was purified by chromatography
(EtOAc/petroleum ether 1:5, 0.5% Et3N, Rf = 0.14) to give 23
(88 mg, 31%) as a colorless oil. 1H NMR (200 MHz, CDCl3): δ
= 7.37–7.07 (m, 5 H, CHarom), 6.95 (dt, J = 15.8, 7.0 Hz, 1 H,
COCH=CH), 6.31 (d, J = 15.8 Hz, 1 H, COCH=CH), 5.79 (t, J =
3.3 Hz, 1 H, C=CH), 4.14 (t, J = 8.8 Hz, 2 H, N-CH2), 2.78 (td, J
= 8.8, 3.3 Hz, 2 H, C=CH-CH2), 2.28–2.13 (m, 2 H, CH3CH2CH2),
1.58–1.40 (m, 2 H, CH3CH2CH2), 0.91 (t, J = 7.3 Hz, 3 H,
CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 185.5 (s), 150.5 (s),
149.4 (d), 147.6 (s), 142.7 (s), 129.1 (d, 2 C), 128.6 (d), 125.3 (d),
121.2 (d, 2 C), 119.7 (d), 48.7 (t), 34.6 (t), 28.7 (t), 21.4 (t), 13.8
(q) ppm. MS: m/z (%) = 285 (5) [M]+, 192 (69), 138 (96), 55 (100).
C17H19NO3 (285.34): calcd. C 71.56, H 6.71, N 4.91; found C
71.33, H 7.02, N 4.53.
(2E)-1-[1-(4-Methylphenylsulfonyl)-1,4,5,6-tetrahydropyridin-2-yl]-
3-phenylprop-2-en-1-one (20): A suspension prepared by mixing bo-
ronic acid 11c (148 mg, 1 mmol), Pd(OAc)2 (6 mg, 0.025 mmol),
Ph3P (13 mg, 0.05 mmol), and CsF (228 mg, 1.5 mmol) in anhy-
drous THF (5 mL) was flushed with CO whilst stirring. After
10 min, a solution of triflate 2 (193 mg, 0.5 mmol) in THF (3 mL)
was slowly added by syringe, the resulting mixture was flushed with
CO, and finally left under static pressure of CO (1 atm) for 3 h at
room temperature. Usual work up gave a crude oil which was puri-
fied by chromatography (EtOAc/petroleum ether 1:2, 0.5% Et3N,
Rf = 0.52) to give 20 (110 mg, 60%) as a pale yellow oil. 1H NMR
(200 MHz, CDCl3): δ = 7.75–7.68 (m, 3 H, COCH=CH, CHarom),
7.61–7.56 (m, 2 H, CHarom), 7.37–7.25 (m, 5 H, CHarom), 7.20 (d,
J = 16.1 Hz, 1 H, COCH=CH), 6.17 (t, J = 3.7 Hz, 1 H, C=CH),
3.54–3.49 (m, 2 H, N-CH2), 2.40 (s, 3 H, CH3-Carom), 2.15–2.06
(m, 2 H, C=CH-CH2), 1.39–1.22 (m, 2 H, CH2CH2CH2) ppm. 13C
NMR (CDCl3): δ = 188.2 (s), 144.0 (d), 142.3 (d), 139.4 (s), 135.2
(s), 134.8 (s), 130.1 (d), 129.6 (d, 2 C), 128.6 (d, 2 C), 128.3 (d, 2
C), 127.8 (d, 2 C), 125.7 (d), 123.4 (d), 45.1 (q), 22.4 (t), 21.5 (t),
19.3 (t) ppm. MS: m/z (%) = 367 (4) [M]+, 303 (19), 212 (100), 131
(43), 103 (43), 91 (50), 77 (38), 65 (22). C21H21NO3S (367.46):
calcd. C 68.64, H 5.76, N 3.81; found C 68.52, H 5.48, N 4.02.
Benzyl 7-[(2E)-Hex-2-enoyl]-2,3,4,5-tetrahydro-1H-azepine-1-car-
boxylate (24): A suspension prepared by mixing boronic acid 11a
(114 mg, 1 mmol), Pd(OAc)2 (1 mg, 0.005 mmol), Ph3P (2.6 mg,
0.01 mmol), and CsF (228 mg, 1.5 mmol) in anhydrous THF
(6 mL) was flushed with CO whilst stirring. After 10 min, a solu-
tion of triflate 5 (190 mg, 0.5 mmol) in THF (2 mL) was slowly
added by syringe, the resulting mixture was flushed with CO, and
finally left under static pressure of CO (1 atm) for 3 h at room
(2E)-1-[5-Methyl-1-(4-methylphenylsulfonyl)-4,5-dihydro-1H-pyrrol-
2-yl]hex-2-en-1-one (21): A suspension prepared by mixing boronic
acid 11a (284 mg, 2.5 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), Ph3P
(26.2 mg, 0.1 mmol), and CsF (455.7 mg, 3.0 mmol) in anhydrous temperature. Usual work up gave an oil which was purified by
Eur. J. Org. Chem. 2007, 2152–2163
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2159

L. Bartali, A. Guarna, P. Larini, E. G. Occhiato
FULL PAPER
chromatography (EtOAc/petroleum ether 1:4, 0.5% Et3N) to give
CH3CH2CH2), 1.89–1.74 (m, 2 H, CH2CH2), 1.65–1.38 (m, 4 H,
24 (Rf = 0.31, 78 mg, 48%) as a pale yellow oil.
CH2CH2, CH3CH2CH2), 0.91 (t,
J
=
7.7 Hz,
3
H,
CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 187.4 (s), 154.8 (s),
148.7 (d), 143.6 (s), 133.7 (d), 124.8 (d), 52.8 (q), 47.9 (t), 34.7 (t),
29.4 (t), 27.4 (t), 23.3 (t), 21.6 (t), 13.8 (q) ppm. MS: m/z (%) = 251
(16) [M]+, 208 (98), 136 (44), 55 (100). C14H21NO3 (251.32): calcd.
C 66.91, H 8.42, N 5.57; found C 70.22, H 8.78, N, 5.33.
The same reaction was carried out also as follows: A suspension
prepared by mixing boronic acid 11a (228 mg, 2 mmol), Pd-
(OAc)2 (9 mg, 0.04 mmol), dppf [1,1Ј-bis(diphenylphosphanyl)fer-
rocene] (27 mg, 0.05 mmol), and CsF (374 mg, 2.46 mmol) in anhy-
drous THF (6 mL) was flushed with CO whilst stirring. After
10 min, a solution of triflate 5 (303 mg, 0.8 mmol) in THF (2 mL)
was slowly added by syringe, the resulting mixture was flushed with
CO, and finally left under static pressure of CO (1 atm) for 4 h at
room temperature. Usual work up and chromatography gave 24
(162 mg, 62%) and 25 (Rf = 0.67, 31 mg, 13%).
27: 1H NMR (CDCl3, 200 MHz): δ = 5.91 (d, J = 15.4 Hz, 1 H,
=C-CH=CH), 5.65 (t, J = 6.6 Hz, 1 H, C=CH), 5.51 (dt, J = 15.4,
6.6 Hz, 1 H, =C-CH=CH), 3.64 (s, 3 H, CO2CH3), 3.60–3.40 (br.
s, 2 H, N-CH2), 2.10–1.95 (m, 4 H, C=CH-CH2, CH3CH2CH2),
1.83–1.71 (m, 2 H, CH2CH2), 1.60–1.32 (m, 4 H, CH2CH2,
CH3CH2CH2), 0.88 (t, J = 7.7 Hz, 3 H, CH3CH2CH2) ppm. 13C
NMR (CDCl3): δ = 143.0 (s), 129.5 (d), 126.6 (d), 125.9 (d), 52.6
(q), 47.4 (t), 34.3 (t), 29.9 (t), 26.9 (t), 24.6 (t), 22.6 (t), 13.7 (q) ppm.
MS: m/z (%) = 223 (39) [M]+, 164 (100).
24: 1H NMR (CDCl3, 200 MHz) (3:1 mixture of rotamers): δ
(major rotamer) = 7.30–7.20 (m, 5 H, CHarom), 6.86 (dt, J = 15.4,
7.0 Hz, 1 H, COCH=CH), 6.54 (t, J = 6.6 Hz, 1 H, C=CH), 6.31
(d, J = 15.4 Hz, 1 H, COCH=CH), 5.04 (s, 2 H, CH2Ph), 3.53–
3.65 (m, 2 H, N-CH2), 2.38–2.28 (m, 2 H, C=CH-CH2), 2.21–2.04 (2E)-1-(2-Methyl-3,4-dihydro-2H-pyran-6-yl)hex-2-en-1-one (28): A
(m, 2 H, CH3CH2CH2), 1.90–1.79 (m, 2 H, CH2CH2), 1.59–1.50 suspension prepared by mixing boronic acid 11a (342 mg, 3 mmol),
(m, 2 H, CH3CH2CH2), 1.50–1.32 (m, 2 H, CH2CH2), 0.89 (t, J = Pd(OAc)2 (17 mg, 0.075 mmol), Ph3P (39 mg, 0.15 mmol), and CsF
7.7 Hz, 3 H, CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 187.4 (s),
154.1 (s), 148.7 (d), 143.5 (s), 135.7 (s), 133.8 (d), 127.9 (d, 2 C),
127.7 (d, 2 C), 127.6 (d), 124.9 (d), 67.4 (t), 47.8 (t), 34.5 (t), 29.3
(684 mg, 4.5 mmol) in anhydrous THF (15 mL) was flushed with
CO whilst stirring. After 10 min, a solution of crude triflate 7
(1.5 mmol) in THF (9 mL) was slowly added by syringe, the re-
(t), 27.3 (t), 23.3 (t), 21.3 (t), 13.7 (q) ppm. MS: m/z (%) = 327 (1) sulting mixture was flushed with CO, and finally left under static
[M]+, 240 (19), 91 (100). C20H25NO3 (327.42): calcd. C 73.37, H
7.70, N 4.28; found C 72.98, H 7.56, N 4.11.
pressure of CO (1 atm) for 18 h at room temperature. Usual work
up gave an oil which was purified by chromatography (EtOAc/pe-
troleum ether 1:10, 0.5% Et3N) to give 28 (Rf = 0.31, 116 mg, 42%)
as a colorless oil and 29 (Rf = 0.91, 65 mg, 27%) as a pale yellow
oil.
25: 1H NMR (CDCl3, 200 MHz) (3:1 mixture of rotamers): δ
(major rotamer) = 7.30–7.20 (m, 5 H, CHarom), 5.92 (d, J =
15.4 Hz, 1 H, =C-CH=CH), 5.72–5.42 (m, 1 H, 1 H, C=CH, =C-
CH=CH), 5.11 (s, 2 H, CH2Ph), 3.50–3.30 (m, 2 H, N-CH2), 2.20–
The same reaction was carried out as follows: A suspension pre-
2.09 (m, 2 H, C=CH-CH2), 2.09–1.94 (m, 2 H, CH3CH2CH2), pared by mixing boronic acid 11a (285 mg, 2.5 mmol), Pd(OAc)2
1.89–1.81 (m, 2 H, CH2CH2), 1.60–1.20 (m, 4 H, CH3CH2CH2, (11.2 mg, 0.05 mmol), dppf (34.6 mg, 0.0625 mmol), and CsF
CH2CH2), 0.84 (t, J = 7.3 Hz, 3 H, CH3CH2CH2) ppm. 13C NMR
(CDCl3): δ = 154.2 (s), 147.5 (s), 143.0 (s), 136.8 (d), 129.5 (d),
128.1 (d, 2 C), 127.6 (d, 2 C), 126.7 (d), 125.9 (d), 66.7 (t), 47.4 (t),
34.3 (t), 29.8 (t), 26.8 (t), 24.6 (t), 22.4 (t), 13.8 (q) ppm. MS: m/z
(%) = 299 (7) [M]+, 208 (10), 164 (26), 91 (100).
(456 mg, 3 mmol) in anhydrous THF (8 mL) was flushed with CO
whilst stirring. After 10 min, a solution of crude triflate 7 (1 mmol)
in THF (1.3 mL) was slowly added by syringe, the resulting mixture
was flushed with CO, and finally left under static pressure of CO
(1 atm) for 18 h at room temperature. Usual work up and
chromatography afforded 28 (97 mg, 50%) and 29 (10 mg, 6%).
Methyl 7-[(2E)-Hex-2-enoyl]-2,3,4,5-tetrahydro-1H-azepine-1-car-
boxylate (26): A suspension prepared by mixing boronic acid 11a
1
28: H NMR (CDCl3, 200 MHz): δ = 6.98 (dt, J = 15.4, 6.9 Hz, 1
(114 mg, 1 mmol), Pd(OAc)2 (1 mg, 0.005 mmol), Ph3P (2.6 mg, H, COCH=CH), 6.66 (d, J = 15.4 Hz, 1 H, COCH=CH), 5.97 (t,
0.01 mmol), and CsF (228 mg, 1.5 mmol) in anhydrous THF
(6 mL) was flushed with CO whilst stirring. After 10 min, a solu-
tion of triflate 6 (152 mg, 0.5 mmol) in THF (2 mL) was slowly
added by syringe, the resulting mixture was flushed with CO, and
finally left under static pressure of CO (1 atm) for 18 h at room
temperature. Usual work up gave an oil which was purified by
chromatography (EtOAc/petroleum ether 1:8, 0.5% Et3N) to give
26 (Rf = 0.13, 52 mg, 41%) as a pale yellow oil.
J = 3.7 Hz, 1 H, C=CH), 4.05–3.95 (m, 1 H, O-CH), 2.28–2.12 (m,
H, C=CH-CH2, CH3CH2CH2), 1.90–1.76 (m, H,
4
1
=CHCH2CH2), 1.65–1.40 (m, 3 H,=CHCH2CH2, CH3CH2CH2),
1.36 (d, J = 6.2 Hz, 3 H, CH3-CH), 0.92 (t, J = 7.3 Hz, 3 H,
CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 185.5 (s), 151.4 (s),
148.4 (d), 124.2 (d), 109.7 (d), 72.2 (d), 34.8 (t), 28.4 (t), 21.6 (t),
21.1 (t), 20.9 (q), 13.9 (q) ppm. MS: m/z (%) = 194 (2) [M]+, 97
(65), 55 (100). C12H18O2 (194.27): calcd. C 74.19, H 9.34; found C
74.47, H 9.01.
The same reaction was carried out also as follows: A suspension
prepared by mixing boronic acid 11a (228 mg, 2 mmol), Pd-
(OAc)2 (9 mg, 0.04 mmol), dppf (27 mg, 0.05 mmol), and CsF
(374 mg, 2.46 mmol) in anhydrous THF (6 mL) was flushed with
CO whilst stirring. After 10 min, a solution of triflate 6 (244 mg,
0.8 mmol) in THF (2 mL) was slowly added by syringe, the re-
sulting mixture was flushed with CO, and finally left under static
pressure of CO (1 atm) for 4 h at room temperature. Usual work
up and chromatography gave 26 (122 mg, 61%) and 27 (Rf = 0.45,
19 mg, 11%).
1
29: H NMR (CDCl3, 200 MHz): δ = 5.96 (dt, J = 15.4, 6.6 Hz, 1
H, =C-CH=CH), 5.74 (d, J = 15.4 Hz, 1 H, =C-CH=CH), 4.67 (t,
J = 4.0 Hz, 1 H, C=CH), 4.02–3.90 (m, 1 H, O-CH), 2.20–2.00 (m,
4
H, C=CH-CH2, CH3CH2CH2), 1.90–1.75 (m,
1
H,
=CHCH2CH2), 1.63–1.40 (m, 3 H,=CHCH2CH2, CH3CH2CH2),
1.33 (d, J = 6.2 Hz, 3 H, CH3-CH), 0.92 (t, J = 7.3 Hz, 3 H,
CH3CH2CH2) ppm. 13C NMR (CDCl3): δ = 150.6 (s), 128.3 (d),
125.8 (d), 99.1 (d), 71.5 (d), 34.6 (t), 29.4 (t), 22.5 (t), 21.2 (q), 13.9
(q) ppm. MS: m/z (%) = 166 (3) [M]+, 55 (100)
1
26: H NMR (CDCl3, 200 MHz): δ = 6.94 (dt, J = 15.5, 7.0 Hz, 1
(2E)-1-(2-Methyl-3,4-dihydro-2H-pyran-6-yl)-3-phenylprop-2-en-1-
one (30): A suspension prepared by mixing boronic acid 11c
(555 mg, 3.75 mmol), Pd(OAc)2 (17 mg, 0.075 mmol), dppf (52 mg,
H, COCH=CH), 6.54 (t, J = 6.6 Hz, 1 H, C=CH), 6.36 (d, J =
15.5 Hz, 1 H, COCH=CH), 3.58 (s, 3 H, CO2CH3), 3.62–3.50 (m,
2 H, N-CH2), 2.37–2.27 (m, 2 H, C=CH-CH2), 2.23–2.10 (m, 2 H, 0.094 mmol), and CsF (684 mg, 4.5 mmol) in anhydrous THF
2160 Eur. J. Org. Chem. 2007, 2152–2163
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Carbonylative Suzuki–Miyaura Reaction of Enol Triflates
FULL PAPER
(12 mL) was flushed with CO whilst stirring. After 10 min, a solu-
tion of crude triflate 7 (1.5 mmol) in THF (2 mL) was slowly added
by syringe, the resulting mixture flushed with CO, and finally left
under static pressure of CO (1 atm) for 18 h at room temperature.
Usual work up gave an oil which was purified by chromatography
(EtOAc/petroleum ether 1:10, 0.5% Et3N) to give 30 (Rf = 0.22,
MS: m/z (%) = 194 (17) [M]+, 151 (75), 97 (64), 55 (100). C12H18O2
(194.27): calcd. C 74.19, H 9.34; found C 74.44, H 9.08.
(2E)-1-(3,4-Dihydro-2H-thiopyran-6-yl)hex-2-en-1-one (36): A sus-
pension prepared by mixing boronic acid 11a (80 mg, 0.7 mmol),
Pd(OAc)2 (3.9 mg, 0.0175 mmol), Ph3P (9.2 mg, 0.035 mmol), and
CsOAc (202 mg, 1.05 mmol) in anhydrous THF (3.5 mL) was
flushed with CO whilst stirring. After 10 min, a solution of crude
triflate 9 (0.35 mmol) in THF (2 mL) was slowly added by syringe,
the resulting mixture flushed with CO, and finally left under static
pressure of CO (1 atm) for 3 h at room temperature. Usual work
up gave an oil which was purified by chromatography (EtOAc/pe-
troleum ether 1:8, 0.5% Et3N) to give 36 (Rf = 0.33, 38 mg, 56%)
as a pale yellow oil and 37 (Rf = 0.68, 13 mg, 22%) as a pale yellow
oil. Both compounds tend to be quickly oxidized on exposure to
air.
1
176 mg, 51%) as a colorless oil. H NMR (CDCl3, 200 MHz): δ =
7.75 (d, J = 16.1 Hz, 1 H, COCH=CH), 7.62–7.58 (m, 2 H,
CHarom), 7.45–7.25 (m, 3 H, CHarom), 7.36 (d, J = 16.1 Hz, 1 H,
COCH=CH), 6.10 (t, J = 4.03 Hz, 1 H, C=CH), 4.19–4.01 (m, 1
H, O-CH), 2.30–2.12 (m, 2 H, C=CH-CH2), 1.97–1.81 (m, 1 H,
=CHCH2CH2), 1.68–1.50 (m, 1 H, =CHCH2CH2), 1.41 (d, J =
6.2 Hz, 3 H, CH3-CH) ppm. 13C NMR (CDCl3): δ = 185.2 (s),
151.5 (s), 143.4 (d), 134.8 (s), 130.0 (d), 128.6 (d, 2 C), 128.2 (d, 2
C), 120.5 (d), 109.7 (d), 72.2 (d), 28.4 (t), 21.0 (q), 20.9 (t) ppm.
MS: m/z (%) = 228 (59) [M]+, 200 (22), 131 (100), 103 (62), 77 (45).
C15H16O2 (228.29): calcd. C 78.92, H 7.06; found C 79.16, H 6.88.
1
36: H NMR (CDCl3, 200 MHz): δ = 6.95 (dt, J = 15.4, 7.0 Hz, 1
H, COCH=CH), 6.91 (t, J = 4.7 Hz, 1 H, C=CH), 6.62 (dt, J =
15.4, 1.47 Hz, 1 H, COCH=CH), 2.92–2.86 (m, 2 H, S-CH2), 2.40
(q, J = 6. 2 Hz, 2 H, C=CH-CH2 ) , 2 . 2 8– 2. 15 (m, 2 H,
CH3CH2CH2), 2.5–1.93 (m, 2 H, =CHCH2CH2), 1.60–1.42 (m, 2
1-(2-Methyl-3,4-dihydro-2H-pyran-6-yl)-2-phenylprop-2-en-1-one
(32): A suspension prepared by mixing boronic acid 11e (370 mg,
2.5 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), dppf (34.6 mg,
0.0625 mmol), and CsF (456 mg, 3 mmol) in anhydrous THF
(8 mL) was flushed with CO whilst stirring. After 10 min, a solu-
tion of crude triflate 7 (1 mmol) in THF (1.3 mL) was slowly added
by syringe, the resulting mixture flushed with CO, and finally left
under static pressure of CO (1 atm) for 18 h at room temperature.
Usual work up gave an oil which was purified by chromatography
(EtOAc/petroleum ether 1:10, 0.5% Et3N) to give 32 (Rf = 0.13,
H, CH3CH2CH2), 0.94 (t, J = 7.4 Hz, 3 H, CH3CH2CH2) ppm. 13
C
NMR (CDCl3): δ = 187.3 (s), 148.4 (d), 136.9 (s), 132.3 (d), 123.5
(d), 34.8 (t), 26.3 (t), 25.2 (t), 21.6 (t), 21.5 (t), 13.8 (q) ppm. MS:
m/z (%) = 196 (15) [M]+, 167 (21), 153 (20), 97 (23), 55 (100).
C11H16OS (196.31): calcd. C 67.30, H 8.22; found C 67.66, H 8.13.
37: 1H NMR (CDCl3, 200 MHz): δ = 6.04 (d, J = 15.4 Hz, 1 H,
=C-CH=CH), 5.76 (dt, J = 15.4, 6.6 Hz, 1 H, =C-CH=CH), 5.73
(t, J = 4.0 Hz, 1 H, C=CH), 2.92–2.85 (m, 2 H, S-CH2), 2.30–2.10
(m, 2 H), 2.10–1.91 (m, 4 H), 1.52–1.33 (m, 2 H, CH3CH2CH2),
0.91 (t, J = 7.0 Hz, 3 H, CH3CH2CH2) ppm. 13C NMR (CDCl3):
δ = 130.6 (d), 130.5 (s), 129.2 (d), 121.1 (d), 76.4 (t), 34.8 (t), 26.6
(t), 24.8 (t), 22.8 (t), 22.6 (t), 13.8 (q) ppm. MS: m/z (%) = 168 (7)
[M]+, 139 (19), 55 (100).
1
118 mg, 52%) as a colorless oil. H NMR (CDCl3, 200 MHz): δ =
7.40–7.23 (m, 5 H, CHarom), 6.00 (t, J = 7.8 Hz, 1 H, C=CH), 5.86
(s, 1 H, C=CH2), 5.58 (s, 1 H, C=CH2), 4.02–3.94 (m, 1 H, O-CH),
2 . 2 9– 2 . 01 (m , 2 H , C = C H - C H 2 ) , 1 . 9 4– 1 . 7 8 ( m , 1 H ,
=CHCH2CH2), 1.69–1.45 (m, 1 H, =CHCH2CH2), 1.33 (d, J =
6.2 Hz, 3 H, CH3-CH–O) ppm. 13C NMR (CDCl3): δ = 192.2 (s),
151.1 (s), 147.2 (s), 136.8 (s), 128.3 (d, 2 C), 128.0 (d), 126.3 (d, 2
C), 118.9 (t), 116.6 (d), 72.3 (d), 28.2 (t), 21.3 (d), 20.7 (q) ppm.
MS: m/z (%) = 228 (69) [M]+, 174 (65), 156 (59), 103 (100), 77 (54).
C15H16O2 (228.29): calcd. C 78.92, H 7.06; found C 78.73, H 7.48.
(2E)-1-(3,4-Dihydro-2H-thiopyran-6-yl)-3-phenylprop-2-en-1-one
(38): A suspension prepared by mixing boronic acid 11c (444 mg,
2.0 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), Ph3P (26.2 mg,
0.1 mmol), and CsOAc (577 mg, 3 mmol) in anhydrous THF
(10 mL) was flushed with CO whilst stirring. After 10 min, a solu-
tion of crude triflate 9 (1.0 mmol) in THF (6 mL) was slowly added
by syringe, the resulting mixture flushed with CO, and finally left
under static pressure of CO (1 atm) for 3 h at room temperature.
Usual work up gave an oil which was purified by chromatography
(EtOAc/petroleum ether 1:7, 0.5% Et3N) to give 38 (Rf = 0.47,
131 mg, 57 %) as a pale yellow oil. Compound 38 tends to be
(2E)-1-(4,5,6,7-Tetrahydrooxepin-2-yl)hex-2-en-1-one (34): A solu-
tion of ε-caprolactone (114 mg, 1.0 mmol) and PhNTf2 (429 mg,
1.2 mmol) in anhydrous THF (5 mL) was added dropwise, in about
60 min, to a cooled (–78 °C) solution of KHMDS (0.5  in toluene,
2.8 mL, 1.40 mmol) in THF (3.5 mL) whilst stirring and under ni-
trogen. The resulting mixture was left to stir at –78 °C for 15 min
before allowing the temperature to rise to –10 °C. Then the solution
was concentrated under vacuum to about 1͞3 of the original volume
and used directly in the coupling step as follows: A suspension
prepared by mixing boronic acid 11a (285 mg, 2.5 mmol), Pd-
(OAc)2 (11.2 mg, 0.05 mmol), dppf (34.6 mg, 0.0625 mmol), and
CsF (456 mg, 3 mmol) in anhydrous THF (8 mL) was flushed with
CO whilst stirring. After 10 min, the above solution of crude triflate
8 (≈1 mmol) was slowly added by syringe, the resulting mixture
flushed with CO, and finally left under static pressure of CO
(1 atm) for 2 h at room temperature. Usual work up gave an oil
which was purified by chromatography (EtOAc/petroleum ether
1:10, 0.5% Et3N) to give 34 (Rf = 0.33, 61 mg, 32%) as a colorless
1
quickly oxidized on exposure to air. H NMR (CDCl3, 200 MHz):
δ = 7.70 (d, J = 15.4 Hz, 1 H, COCH=CH), 7.61–7.56 (m, 2 H,
CHarom), 7.42–7.37 (m, 3 H, CHarom), 7.28 (d, J = 15.4 Hz, 1 H,
COCH=CH), 7.05 (t, J = 4.4 Hz, 1 H, C=CH), 2.96–2.91 (m, 2
H, S-CH2), 2.51–2.41 (m, 2 H, C=CH-CH2), 2.09–1.97 (m, 2 H,
=CHCH2CH2) ppm. 13C NMR (CDCl3): δ = 187.2 (s), 143.8 (d),
134.5 (s), 134.8 (s), 132.7 (d), 130.3 (d), 128.8 (d, 2 C), 128.3 (d, 2
C), 119.8 (d), 26.4 (t), 25.2 (t), 21.5 (t) ppm. MS: m/z (%) = 230
(77) [M]+, 131 (100), 103 (80), 77 (70). C14H14OS (230.33): calcd.
C 73.01, H 6.13; found C 72.82, H 5.77.
1
oil. H NMR (CDCl3, 200 MHz): δ = 6.97 (dt, J = 15.7, 7.0 Hz, 1
H, COCH=CH), 6.70 (d, J = 15.7 Hz, 1 H, COCH=CH), 6.30 (t,
J = 6.2 Hz, 1 H, C=CH), 4.00 (t, J = 5.1 Hz, 2 H, O-CH2), 2.40–
2.11 (m, 4 H, C=CH-CH2, CH3CH2CH2), 1.98–1.79 (m, 2 H,
CH2CH2), 1.76–1.57 (m, 2 H, CH3CH2CH2), 1.56–1.40 (m, 2 H,
CH2CH2), 0.92 (t, J = 7.3 Hz, 3 H, CH3CH2CH2) ppm. 13C NMR
(CDCl3): δ = 187.1 (s), 156.9 (s), 148.6 (d), 124.5 (d), 120.2 (d),
72.7 (t), 34.8 (t), 31.4 (t), 26.5 (t), 24.8 (t), 21.5 (t), 13.8 (t) ppm.
Acknowledgments
We thank the Ministero dell’Università e della Ricerca (MIUR)
and the University of Florence for financial support and the Cassa
di Risparmio di Firenze for granting a 400 MHz NMR spectrome-
ter. We also thank Prof. Cristina Prandi (University of Turin) for
Eur. J. Org. Chem. 2007, 2152–2163
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2161

L. Bartali, A. Guarna, P. Larini, E. G. Occhiato
FULL PAPER
[8]
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providing a sample of tetrahydrothiopyran-2-one and Dr. Gloria
Menchi for carrying out some experiments at high CO pressure.
Maurizio Passaponti and Brunella Innocenti are acknowledged for
their technical support.
[9]
Substituted 1-(5,6-dihydro-4H-pyran-2-yl)propenones have
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[13]
[14]
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As we have already shown, the carbonylative Stille coupling of
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solution containing the catalyst and boronate, consistent with a
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negatively charged Pd0 species [(Ph3P)Pd(OAc)]. The solution
then gradually turned orange again.
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and bromides.
Compounds 36–39 suffer form rapid oxidation to the corre-
sponding sulfoxides (by MS analysis) if not stored under nitro-
gen. Compound 39 in particular could not be properly charac-
terized although the following 1H NMR signals outside the
aromatic region can be assigned: 1H NMR (CDCl3, 200 MHz):
δ = 5.99 (t, J = 4.7 Hz, 1 H), 3.01–2.94 (m, 2 H), 2.45–2.30 (m,
2 H), 1.15–1.00 (m, 2 H); MS: m/z (%) = 202 (100) [M]+, 77
(36).
[20]
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Eur. J. Org. Chem. 2007, 2152–2163

Carbonylative Suzuki–Miyaura Reaction of Enol Triflates
FULL PAPER
[23] B. A. Markies, P. Wijkens, A. Dedieu, J. Boersma, A. L. Spek,
G. van Koten, Organometallics 1995, 14, 5628–5641.
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[25] The approximate relative electron density on the C-2 carbon
atom could be evaluated on the basis of its 13C NMR chemical
shift in the coupling products. For example, in 28, C-2 reso-
nates at δ = 151.4 ppm, which should correspond to a very low
electron density on the carbon atom as it is linked to the most
electronegative oxygen atom. The electron density on C-2
should increase on moving to the N-heterocyclic compound 12
(δ = 139.6 ppm). Finally, the resonance of C-2 in the sulfur-
containing compound 36 has the lowest value at 136.9 ppm,
consistent with the highest electron density.
[26] E. G. Occhiato, C. Prandi, A. Ferrali, A. Guarna, A. Deagos-
tino, P. Venturello, J. Org. Chem. 2002, 67, 7144–7146.
[27] Prepared according to the procedure reported in: I. Roling, H.-
G. Schamrr, W. Eisenreich, K.-H. Engel, J. Agric. Food Chem.
1998, 46, 668–672.
Received: December 15, 2006
Published Online: March 13, 2007
Eur. J. Org. Chem. 2007, 2152–2163
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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