Selective green coupling of alkynyltins and allylic halides to trienynes via a tandem double stille reaction

Article abstract of DOI:10.1002/adsc.201000430

The palladium-catalyzed reaction of alkynyltin compounds with allylic chlorides leads to a 2:2 coupling to give trienynes by regio- and stereoselective formation of three new C-C bonds. The reaction can be applied to different alkynyl and allylic fragments, providing a wide range of trienynes with different substitution patterns in very good yields. They can be prepared in a green way using recyclable polymeric tin alkynyls. Copyright

Full text of DOI:10.1002/adsc.201000430

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DOI: 10.1002/adsc.201000430
Selective Green Coupling of Alkynyltins and Allylic Halides to
Trienynes via a Tandem Double Stille Reaction
Isabel Meana,a Ana C. Albꢀniz,a,* and Pablo Espineta,*
a
IU CINQUIMA/Quꢁmica Inorgꢂnica, Universidad de Valladolid, 47071 Valladolid, Spain
Fax : (+34)-983-423-013; e-mail: albeniz@qi.uva.es or espinet@qi.uva.es
Received: June 1, 2010; Published online: October 27, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000430.
3
ꢀ
Abstract: The palladium-catalyzed reaction of alky-
nyltin compounds with allylic chlorides leads to a
2:2 coupling to give trienynes by regio- and stereo-
The reactions of allylic halides with Bu3Sn
(C CR )
(1a–i) catalyzed by 2 (5% mol), lead to the formation
of trienynes (Scheme 1). The vicinal-trans isomer
(trans in Scheme and Table for short) is the only or
the major reaction product. Two other isomers (gem
and vicinal-cis) were also formed in several reactions
(Scheme 1).
No 1,1-coupling product (allyl-alkynyl) was ob-
served in any case. The reactions can be more con-
veniently carried out in a preparative scale using the
polymeric tin reagents 11. They were synthesized
from copol-NB-NBSn(Bu)2Cl, a vinylic polynorbor-
nene functionalized with tin groups that we developed
recently for its use in green Stille couplings.[3] This
procedure allows the efficient purification of the reac-
À
selective formation of three new C C bonds. The
reaction can be applied to different alkynyl and al-
lylic fragments, providing a wide range of trienynes
with different substitution patterns in very good
yields. They can be prepared in a green way using
recyclable polymeric tin alkynyls.
À
Keywords: C C coupling; enynes; green chemistry;
palladium; stannanes
À
The Stille reaction is one of the most powerful C C
building tools in organic synthesis.[1] It is still the reac-
tion of choice for many transformations carried out in
the presence of sensitive functional groups, since it is
versatile and proceeds under mild conditions.[2] Its
main drawback is the generation of toxic tin by-prod-
ucts, but there are some recent alternatives to over-
come or alleviate this problem using polymeric recy-
clable tin reagents.[3,4] Although Stille couplings are
well understood, certain combinations of reagents still
give unexpected results. We report here the Pd-cata-
lyzed reaction of alkynyltin compounds and allylic
chlorides, a coupling that deviates from routine and
results in the formation of trienynes, formally dimers
of the expected 1:1 cross-coupling product.
There is increasing interest in the metal-catalyzed
synthesis of enynes and oligoenynes, since highly un-
saturated derivatives of this kind are useful building
blocks for the synthesis of cyclic compounds, natural
products, and materials.[5] The new reaction reported
here provides a new and efficient tool for the synthe-
À
sis of polyunsaturated molecules through C C cou-
pling, which complements the Sonogashira-type pro-
cesses.[5,6]
Scheme 1. Synthesis of the trienynes and possible isomers.
Adv. Synth. Catal. 2010, 352, 2887 – 2891
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Isabel Meana et al.
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3
[a]
ꢀ
Table 1. Reactions of Bu3SnC CR (1) and allylic halides catalyzed by 2 (entries n), and preparative reactions of copol-
3
[b]
ꢀ
NB-NBSn(Bu)2C CR (11) and allylic halides catalyzed by 2 (entries nPol).
Entry
Tin reagent, R3
R1, R2, X
3–10,% (258C, 8 h)[c]
Ratio trans:gem:cis
3–10,% (508C, h)[d]
1
1Pol
2
2Pol
3
4
4Pol
5
5Pol
6
7
8
8Pol
9
9Pol
10
10Pol
11
12
12Pol
13
13Pol
1a, n-Bu
11a, n-Bu
1b, t-Bu
11b, t-Bu
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
H, H, Cl
Me, H, Cl
Me, H, Cl
H, Me, Cl
H, Ph, Cl
H, Ph, Cl
H, CO2Me, Br
H, CO2Me, Br
90
34
1:0:0
1:0:0
100 (8)
98 (24)
58 (24)[e]
85 (24)
40 (96)
63 (24)[e]
75 (24)
92 (8)[e]
97 (24)
100 (8)
94 (8)[e]
100 (8)
98 (24)
100 (24)
98 (24)
100 (8)
97 (24)
100 (24)
100 (24)
70 (24)
81 (24)[e]
98 (24)
18:1:0
5.3:1:0
1:0:0
2.2:1:0
1:0:0
5.3:1:0
1:0:0
1:0:0
10:1:0
1:0:0
1:0:0
3.6:1:1.7
6.8:1:0
1:0:0
1c, Me3Si
1
39
1d, 1-cyclohexenyl
11d, 1-cyclohexenyl
1e, Ph
11e, Ph
1f, o-tolyl
73
59
85
100
1g, p-tolyl
1h, p-MeO-C6H4
11h, p-MeO-C6H4
1i, p-CF3-C6H4
11i, p-CF3-C6H4
1a, n-Bu
11a, n-Bu
1a, n-Bu
1a, n-Bu
11a, n-Bu
1a, n-Bu
11a, n-Bu
37
55
1:0:0
2.3:1:0
1:0:0
1:0:0
1:0:0
16
45
43
1:0:0
[a]
1
Reactions in CDCl3. The conversion to 3–10 (%) was determined by H NMR relative integration of the allyl protons in
the allylic halide and in the products.
Reactions in THF. Isolated yields.
Molar ratio Sn:allyl halide=1:1.
Molar ratio Sn:allyl halide=1.5:1.
Total conversion was observed to give 3–10 in the% given, plus a monoallyl by-product (16% for entry 2, 8% for entry 5,
6% for entry 7 and 19% for entry 13), 23% of R C C
for entry 2 and 14% for entry 4).
[b]
[c]
[d]
[e]
3
3
3
ꢀ
ꢀ
ACHTUNGTREN(NUNG allyl)C=C(R )C CR for entry 4 and allyltributylstannane (26%
tion products, and the polymeric by-product can be 8 h when 2 is used). The 1,1-coupling product is not
recycled following the protocol reported before.[3]
an intermediate in the reaction: When CH2=CH
À
À ꢀ À
Table 1 collects the conversions and isomeric ratio CH2 C C Bu-n (12) was introduced as reactant in a
of the products for the reactions of several monomer- coupling under conditions of entry 8, Table 1, the allyl
ic alkynyltins and allylic halides (entries n), as ob- chloride and 1h were converted to 3h, while 12 re-
served by NMR, at 258C (molar ratio 1:allyl halide= mained unaltered and no mixed-R (n-Bu/C6H4OMe)
1:1), and under more stringent conditions (508C and trienyne was formed (Scheme 2). The reaction does
1:allyl halide=1.5:1). Benzoquinone was added as not occur via previous homocoupling of two alkynyl
coupling promoter.[7,8] The reactions at 258C are fairly fragments. Thus the dialkyne n-Bu C C C C Bu-n
À ꢀ À ꢀ À
slow, which allows us to compare the reactivity of dif-
ferent substrates. An increase in the size of R3 leads
to lower rates (cf. entries 1 vs. 2, and 6 vs. 7). For R=
aryl (entries 5–9), electron-donating substituents in
the ring accelerate the reaction, while electron-with-
drawing groups slow the reaction down. The reactions
with polymers 11 give very good isolated yields (en-
tries nPol) and in most cases (entries 4, 5, 9) the selec-
tivity is even improved in comparison with the reac-
tions of 1.
The reaction is favored by the use of a labile ligand
such as AsPh3. Thus, complex [Pd
is less active than 2, and the reaction of entry 1
(Table 1) takes 2 days to reach 90% conversion (cf. coupling product 12.
(h3-C3H5)Cl
ACHUTGTNRENNUG HCATUNGTERN(NUNG PPh3)]
Scheme 2. Coupling experiments in the presence of the 1:1
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Adv. Synth. Catal. 2010, 352, 2887 – 2891

Selective Green Coupling of Alkynyltins and Allylic Halides to Trienynes
Figure 1. Plots of conversion (%) vs. time in the formation
of 3 for alkynyltin derivatives 1e–i (258C; molar ratio 1:allyl
halide=1:1).
bond of the alkynylstannane. In this respect, the rate
of formation of 3 was monitored for different aryl-
substituted alkynyltins and the results confirm that
electron-donating substituents accelerate the reaction
(p-OMe>p-Me>H@CF3), whereas, for electronical-
ly equivalent substituents, an increase of the steric
hindrance slows the reaction down (p-Me>o-Me)
(Figure 1). The loss of selectivity with formation of 4
or 5 in some of the reactions can be explained at this
point, by 1,2 insertion (see Scheme 3 for C labels) of
the alkynyltin (giving 4) or trans-2,1 insertion (giving
5). Both types of regio- and sterochemistry have been
Scheme 3. Proposed catalytic cycle for the synthesis of 3. A
monomeric alkynyltin and allyl chloride are depicted for
simplicity. L is AsPh3 or other ligand present (e.g., allyl
chloride, benzoquinone, solvent, etc.) and can be different
in each step.
À
observed in the insertion reactions of alkynes into M
C bonds.[11] The inclusion of the alkynyltin in a poly-
meric framework (Table 1, entries Pol) improves the
selectivity to the cis-2,1 insertion, affording 3; this is
(13) does not react with allyl chloride in the presence probably due to steric constraints in the p-coordina-
of 2.
A plausible pathway for the formation of 3 is
tion of the alkynyl stannane in A.
The last steps in the proposed pathway of Scheme 3
shown in the tandem process in Scheme 3. This pro- were checked by carrying out the Stille coupling of
posal assumes that allyl-alkynyl couplings are allyl chloride with two types of vinyltin derivatives
slow,[8a,9] compared to allyl-vinyl couplings,[10] which is with substitution patterns close to those of intermedi-
well known in the literature. The first step of the reac- ate C (Scheme 3). These were synthesized by hydro-
tion could be confirmed by monitoring the reactions stannation of 12, which leads to a mixture of two iso-
1
of 2 and five equivalents of 1a, d by H NMR at meric compounds (15a and 15b), or by hydrostanna-
243 K. Complete transformation of 2 into [Pd
(h3- tion of the dialkyne 13, which affords 16 (Scheme 4).
ꢀ
C3H5)
G
N
d) was immediately observed. Complex 14a was also none, and 2 they give the coupling products in a fast
1
detected by H NMR when the catalytic reaction of reaction, confirming the feasibility of cycle II.
Table 1, entry 1 was monitored, showing that it is an
intermediate preceding the rate-determining step.
It is interesting to note that less selective results are
obtained using other sources of alkynyl. When a mix-
Since the evolution of the reaction from A should ture of 1-hexyne and a base such as potassium phos-
be independent of L, the differences in rate of reac- phate was used instead of the alkynyltin 1a, only mix-
tion observed will be due to the different displace- tures of 3a and the 1:1 coupling product were ob-
ment of the equilibrium 14QA, and it is expected to tained in low conversions (16% after 12 h at 508C).
be slower for stronger L donors (as observed in PPh3 When the copper acetylide was used instead of 1a the
vs. AsPh3). For the same L, the reaction rate should reaction also led to low conversions (24% after two
increase with the coordinating ability of the triple days at 508C) and formation of equimolar mixtures of
Adv. Synth. Catal. 2010, 352, 2887 – 2891
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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Isabel Meana et al.
COMMUNICATIONS
prior to use. The reactants Bu3SnCl, Bu3SnH, phenylethynyl-
tributyltin, dodeca-5,7-diyne, the organic halides and the ter-
minal alkynes were obtained from commercial suppliers and
used without further purification. The compounds
Copol-NB-NB-Sn(Bu)2Cl,[3]
[PdCl2A
(PPh3)2],[14] [{Pd(h3-C3H5)
[Pd
(h3-C3H5)Cl(AsPh3)],[16] and [Pd
cuprous
(m-Cl)}2],[15]
(h3-C3H5)Cl
ACHTUNGTRENNUNG
butylacetylide,[13]
G
E
R
ACHTUNGTRENNUNG
G
E
N
(PPh3)][16]
were prepared according to literature methods.
2:2 Coupling Reactions using Copol-NB-NB-
Sn(Bu)2R: Preparation of 1,4-Dibutyl-3-
propenylhept-6-en-1-yne (3a)
ꢀ À
(C C Bu-n)
To
a suspension of Copol-NB-NB-Sn(Bu)2ACHTUTGNENRNUG
(2.400 g, 4.786 mmol), benzoquinone (0.0172 g, 0.160 mmol)
and [Pd (AsPh3)] (2, 0.0780 g, 0.160 mmol) in
A
ACHTUNGTRENNUNG
THF (75 mL), under N2 was added the allyl chloride
(0.2240 g, 3.191 mmol). The reaction mixture was heated at
508C for 18 h giving a dark solution. It was evaporated to
dryness at room temperature, and the residue was washed
with a mixture of n-hexane and MeOH and stirred for
30 min. The copolymer copol-NB-NBSn(Bu)2Cl recovered
was filtered, washed with MeOH, and air-dried; yield:
1.9839 g (83%). The filtrate was concentrated to 5 mL and
filtered through activated carbon and silica gel. After distil-
lation to remove the solvents, 3a was obtained as a dark
liquid; yield: 0.382 g (98%).The other 2:2 coupling products
were obtained in a similar way starting from the correspond-
ing copolymer and organic halide as collected in Table 1.
Scheme 4. Stille coupling of vinyltin derivatives modelling
the proposed intermediate C.
3a and the 1:1 coupling product.[12] This result can be
fit in the frame of Scheme 3, considering that for al-
kynyls with slower coordination-insertion rates than
alkynylstannanes, or with low solubility (such as the
sparingly soluble copper alkynyls that makes them
unlikely species as ligands) the 1:1 allyl-alkynyl cou-
pling can become competitive with the process report-
ed here.
In summary, a selective synthesis of trienynes, by
the regio- and stereoselective coupling of alkynylstan-
nanes and allyl halides, has been found. The reaction
can be carried out in an environmentally clean way,
using recyclable polymeric tin alkynyls. The trienyne
products correspond to a 2:2 cross-coupling of the re-
agents, which occurs via a double Stille tandem reac-
tion. The mechanistic study shows that the selectivity
is due to the slowness of the allyl-alkynyl reductive
elimination, compared to the fast rates of insertion of
coordinated alkynylstannanes, and reductive elimina-
tion of allyl-vinyl fragments.
ꢀ À
2:2 Coupling Reactions using Bu3SnACTHNUTRGNE(UNG C C R):
Preparation of 3a
ꢀ À
(C C Bu-n) (0.1362 g, 0.3674 mmol),
To a solution of Bu3SnACHTUNGTRENNUNG
benzoquinone (0.0020 g, 0.018 mmol) and the complex [Pd-
A
ACHTUNGTRENNUNG
(6 mL), under N2 was added the allyl chloride (0.0281 g,
0.3674 mmol). The reaction mixture was heated at 508C for
15 h giving a black solution. It was filtered thought activated
carbon and Celite and evaporated to dryness at room tem-
perature. The product was separated by column chromatog-
raphy with silica gel using hexane as solvent. Treatment of
the product with a saturated KF aqueous solution was neces-
sary to separate Bu3SnCl byproduct. After vigorous stirring
for 30 min SnBu3F precipitated. The organic phase was ex-
tracted, dried with anhydrous MgSO4, filtered through
Celite and evaporated to dryness to afford a yellowish liquid
(3a); yield: 0.0213 g (43%).
Experimental Section
Supporting Information
Experimental details for the preparation of the tin deriva-
tives 1, copolymers 11 and compounds 15–18, detection and
characterization of complexes 14, and characterization data
of all compounds and selected NMR spectra are given in
the Supporting Information.
General Considerations
1H, 13C{1H}, 19F and 119Sn NMR spectra were recorded on
Bruker AC-300, ARX-300 and AV-400 spectrometers.
Chemical shifts (in d units, ppm) were referenced to Me4Si
(1H and 13C), CFCl3 (19F), H3PO4 (85%, 31P) and SnMe4
(
119Sn). The spectral data were recorded at 293 K unless oth-
erwise noted. Mass spectra of the products were recorded
on Agilent Tech. 5973 MS system. All the manipulations
were carried out under an atmosphere of nitrogen using
standard Schlenk techniques. Solvents were dried over and
distilled from appropriate drying agents under nitrogen,
Acknowledgements
Financial support from the Spanish MEC (DGI, Grant
CTQ2007-67411/BQU; Consolider Ingenio 2010, Grant
2890
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ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2887 – 2891

Selective Green Coupling of Alkynyltins and Allylic Halides to Trienynes
INTECAT, CSD2006–0003; FPU fellowship to IM) and the
Junta de Castilla y Leꢀn (Grupos de Excelencia GR169) is
gratefully acknowledged.
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Adv. Synth. Catal. 2010, 352, 2887 – 2891
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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