Copper-catalyzed hydrostannation of activated alkynes

Article abstract of DOI:10.1021/ol052129p

(Chemical Equation Presented) [(Ph₃P)CuH]₆ effectively catalyzes the hydrostannation of activated alkynes with exclusive regioselectivity for α-stannation. Syn hydrostannation is observed exclusively for alkynoates. Anti or syn hydrostannation adducts are obtained as products for alkynone substrates.

Full text of DOI:10.1021/ol052129p

ORGANIC
LETTERS
2
005
Vol. 7, No. 23
249-5252
Copper-Catalyzed Hydrostannation of
Activated Alkynes
5
Lai To Leung, Sze Kar Leung, and Pauline Chiu*
Department of Chemistry, The UniVersity of Hong Kong, Pokfulam Road,
Hong Kong, P. R. China
pchiu@hku.hk
Received September 3, 2005
ABSTRACT
3 6
[(Ph P)CuH] effectively catalyzes the hydrostannation of activated alkynes with exclusive regioselectivity for r-stannation. Syn hydrostannation
is observed exclusively for alkynoates. Anti or syn hydrostannation adducts are obtained as products for alkynone substrates.
While a variety of palladium-catalyzed carbon-carbon bond
forming reactions have been developed, the Stille reaction
remains as one of the most extensively utilized processes,
and examples of these reactions of functionalized vinylstan-
tolerated by vinylstannanes and prolonged adsorption on
silica leads to eventual decomposition and diminished returns.
Currently, the most commonly used strategy to synthesize
vinylstannanes is the hydrostannation of alkynes.3 Hy-
drostannations of alkynes have been mediated by various
1
nanes in the syntheses of natural products abound.
4
5
5,6
5
5
5
The success of the Stille vinylation reaction is intimately
dependent on the ability to acquire vinylstannanes of high
transition metals, including Mo, Rh, Ni, Co, Pt, Ru,
and Pd, with Pd being the most popular metal catalyst.4
a,7
2
purity. The challenge in the synthesis of vinylstannanes is
Although palladium- or molybdenum-catalyzed hydrostan-
nations of alkynes occur efficiently in very good yields, the
direction provided by the steric and electronic factors of
alkyne substrates is often insufficiently high, resulting in
diastereomeric mixtures of vinylstannanes as products. For
activated alkynes, although the regioselectivity favors R-stan-
nation, this is frequently accompanied by the formation of a
to directly produce these compounds with high regio- and
stereoselectivity, because diastereomeric mixtures of vinyl-
stannanes are typically very nonpolar and tedious to separate.
Moreover, silica gel column chromatography is not well-
(1) Some recent examples: (a) Overman, L. E.; Peterson, E. A. Angew.
Chem., Int. Ed. 2003, 42, 2525. (b) Nicolaou, K. C.; Li, Y.; Sugita, K.;
Monenschein, H.; Guntupalli, P.; Mitchell, H. J.; Fylaktakidou, K. C.;
Vourloumis, D.; Giannakakou, P.; O’Brate, A. J. Am. Chem. Soc. 2003,
8
minor, â-stannated vinylstannane. Therefore, finding new
1
25, 15443. (c) Lebsack, A. D.; Link, J. T.; Overman, L. E.; Stearns, B. A.
(3) Smith, N. D.; Mancuso, J.; Lautens, M. Chem. ReV. 2000, 100, 3257.
(4) (a) Zhang, H. X.; Guibe, F.; Balavoine, G. J. Org. Chem. 1990, 55,
1857. (b) Kazmaier, U.; Schauss, D.; Pohlman, M. Org. Lett. 1999, 1, 1017.
(c) Kazmaier, U.; Pohlman, M.; Schauss, D. Eur. J. Org. Chem. 2000, 2761.
(5) Kikukawa, K.; Umekawa, H.; Wada, F.; Matsuda, T. Chem. Lett.
1988, 881.
J. Am. Chem. Soc. 2002, 124, 9008. (d) Trost, B. M.; Gunzner, J. L.; Dirat,
O.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124, 10396. (e) Fuwa, H.;
Kainuma, N.; Tachibana, K.; Sasaki, M. J Am Chem Soc. 2002, 124, 14983.
(
f) Govek, S. P.; Overman, L. E. J. Am. Chem. Soc. 2001, 123, 9468. (g)
White, J. D.; Carter, R. G.; Sundermann, K. F.; Wartmann, M. J. Am. Chem.
Soc. 2001, 123, 5407.
(6) Bamba, M.; Nishikawa, T.; Isobe, M. Tetrahedron Lett. 1996, 37,
8199.
(2) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b) Davies,
A. G. Organotin Chemistry; Wiley-VCH: Weinheim, Germany, 2004. (c)
Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic Synthesis; Butter-
worth: London, UK, 1987. (d) Orita, A.; Otera, J. In Main Group Metals
in Organic Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH:
Weinheim, Germany, 2004; Chapter 12, p 621.
(7) (a) Ichinose, Y.; Oda, H.; Oshima, K.; Utimoto, K. Bull. Chem. Soc.
Jpn. 1987, 60, 3468. (b) Miyake, H.; Yamamura, K. Chem. Lett. 1989,
981. (c) Rossi, R.; Carpita, A.; Cossi, P. Tetrahedron Lett. 1992, 33, 4495.
(d) Cochran, J. C.; Bronk, B. S.; Terrence, K. M.; Phillips, H. K.
Tetrahedron Lett. 1990, 31, 6621.
1
0.1021/ol052129p CCC: $30.25
© 2005 American Chemical Society
Published on Web 10/12/2005

catalysts and conditions to achieve more selective hydrostan-
nations of alkynes remains a challenge with implications for
the applications of the Stille coupling reaction in total
synthesis.
best of our knowledge, this is the first report in the literature
of copper as a transition metal for the catalysis of hydrostan-
1
6
nation. (E)-R-Tributylstannanylbut-2-enoate 3a was ob-
tained as the sole stannylated product, with no (Z)-dia-
stereomer or â-stannylation product 4a observed (Figure 1).
The only side product detected (<10%) was the saturated
ester 5a.
We disclose herein a novel, regioselective hydrostannation
reaction of activated alkynes catalyzed by Stryker’s reagent
3 6
(Ph P)CuH]
(1).9 At 1 mol % catalysis, 1 mediates
,10
[
hydrostannation with exclusive R-stannation. With respect
to conventional catalysis by palladium, copper-catalyzed
hydrostannation typically generates vinylstannanes with
comparable yields but higher regioselectivities, and is a
useful, alternative method for the selective synthesis of
vinylstannanes.
In the course of our investigations on the copper-catalyzed
reductive aldol cyclization reaction,11 we found that 1
efficiently catalyzed the syn addition of Bu
3
SnH to alkynyl
esters such as 2a (Table 1).1
2,13
Stryker’s reagent (1), a
Figure 1. Side products of hydrostannation.
Catalyst levels of 1-10 mol % of 1 were found to be
effective in mediating hydrostannation of 2a (Table 1, entries
Table 1. Hydrostannation of 2a with Various Amounts of 1
1-3). However, high levels of catalyst resulted in decreased
yields of the hydrostannation product 3a, with a concomitant
accumulation of saturated ester 5a (Table 1, entries 4-5).
Ester 5a is presumably derived from the conjugate reduction
of destannylated alkenoate 6a by 1. This is consistent with
previous observations which suggested that 1 quenches and
entry
mol % of 1a
yield of 3a (%)
1
2
3
4
5
1
5
10
50
100
81
81
83
50
44
10d
reduces vinylcopper intermediates. The reduction of the
intermediate by 1 can also account for some destannylation
1
7
that always accompanies hydrostannation.
A study of the hydrostannation reaction of alkynoate 2a
with respect to solvent effects was conducted (Table 2).
a
mol % calculated on the basis of Cu.
copper(I) hydride complex,14 was found to be an effective
catalyst, whereas other copper complexes, including CuCl,
Table 2. Hydrostannation of 2a in Various Solvents
1
5
CuBr, CuCN, Cu(OAc)
2 2 4
, Cu(acac) , and Cu(PF )MeCN,
did not facilitate hydrostannation to any great extent. To the
(
8) On occasion, the diastereomeric mixture of vinylstannanes had to be
entry
solvent
yield of 3a (%)
used in the synthesis because the isomers were inseparable, see: Rossi, R.;
Carpita, A.; Cossi, P. Synth. Commun. 1993, 23, 143.
1
2
3
4
5
6
PhMe
PhH
cyclohexane
THF
CH2Cl2
MeCN:PhMe (1:1)
83
76
64
76
76
78
(9) Stryker’s reagent (1) is commercially available, and is also conve-
niently prepared in the laboratory: (a) Brestensky, D. M.; Stryker, J. M.
Tetrahedron Lett. 1988, 29, 3749. (b) Chiu, P.; Li, Z.; Fung, C. M.
Tetrahedron Lett. 2003, 44, 455. (c) Lee, D.; Yun, J. Tetrahedron Lett.
a
2
005, 46, 2037.
10) (a) Mahoney, W. S.; Brestensky, D. M.; Stryker, J. M. J. Am. Chem.
Soc. 1988, 110, 291. (b) Mahoney, W. S.; Stryker, J. M. J. Am. Chem. Soc.
(
b
1
1
989, 111, 8818. (c) Brestensky, D. M.; Stryker, J. M. Tetrahedron Lett.
989, 30, 5677. (d) Daeuble, J. F.; McGettigan, C.; Stryker, J. M.
a
was moderately soluble in C6H12. b 1 was insoluble in neat MeCN.
1
Tetrahedron Lett. 1990, 31, 2397. (e) Koenig, T. M.; Daeuble, J. F.;
Brestensky, D. M.; Stryker, J. M. Tetrahedron Lett. 1990, 31, 3237.
(
11) (a) Chiu, P.; Leung, S. K. Chem. Commun. 2004, 2308. (b) Chiu,
Toluene was a good solvent for this reaction, as had been
found in many other reactions involving 1. Other solvents
tried led to satisfactory but inferior yields.
P.; Chung, W. K. Synlett 2005, 55. (c) Chiu, P.; Szeto, C. P.; Geng. Z.;
Cheng, K. F. Org. Lett. 2001, 3, 1901. (d) Chiu, P.; Chen, B.; Cheng, K.
F. Tetrahedron Lett. 1998, 39, 9229.
(12) The cis-reduction of unactivated alkynes with stoichiometric and
catalytic 1 has been reported: ref 10d. High reaction temperatures (ambient
to 80 °C) and catalyst loadings (∼50 mol %) were required for these
reductions.
(15) The copper complexes were not very soluble in PhMe or THF;
Cu(PF4)MeCN, though soluble in MeCN, also did not catalyze hydrostan-
nation.
(13) Bu3SnH has stoichiometrically induced the conjugate reduction of
activated olefins under catalysis by 1: Lipshutz, B. H.; Keith, J.; Papa, P.;
Vivian, R. Tetrahedron 1998, 39, 4627.
(16) However, Cu(I) is a common transition metal catalyst for the related
stannylmetalation reaction: (a) Hibino, J.; Matsubara, S.; Morizawa, Y.;
Oshima, K. Tetrahedron Lett. 1984, 25, 2151. (b) Aksela, R.; Oehlschlager,
A. C. Tetrahedron 1991, 47, 1163.
(14) Hexameric 1 exists as lower aggregates in solution; the monomers
or dimers are likely to be the actual catalytic species.
5250
Org. Lett., Vol. 7, No. 23, 2005

Having surveyed the reaction conditions, the hydrostan-
nation of other alkynyl esters was investigated (Table 3).
Table 4. Hydrostannation of Alkynyl Ketones Catalyzed by 1
Table 3. Hydrostannation of Alkynyl Esters and Amides
Catalyzed by 1
comparison
yield of 8 + 9 with cat. Pd,
entry
substrate
(8:9)
% yield (8:9)
1
2
3
4
7a (R ) Et, R′ ) Me)
7b (R ) n-C6H13, R′ ) Me) 48 (0:100)
7c (R ) n-Bu, R′ ) Et)
7d (R ) n-Bu, R′ ) t-Bu)
55 (0:100)
58 (0:100)a
0 (100:0)
comparison
with cat. Pd,
% yield (3:4)
b
yield of
3 (%)
c,e
69 (12:88)
61 (21:79)
entry
substrate
d,e
a
1
2
2a (R ) TBSOCH2, X ) OEt)
2b (R ) Me, X ) OMe)
83
62
86-92 (>10:1)
a
Reference 7d. Me3SnH used instead of Bu3SnH. b Reference 4a, total
b
67 (5:1)
destannylation occurred upon isolation, but in situ DIBAL-H reduction gave
the alcohol derived from 8a in 61% yield. 8c could not be obtained pure.
c
c
7
9 (2.8:1)
d
e
d
8d/9d could not be separated. Ratios were determined by integration of
3
4
5
6
2c (R ) n-Bu, X ) OEt)
75
70
77
83 (3:1)
75 (4:1)
83 (2:1)
1
c
c
the H NMR spectra of the product mixtures, see the Supporting Information.
2d (R ) n-C6H13, X ) OMe)
2e (R ) n-C6H13, X ) Oi-Bu)
2f (R ) Me, X ) N(CH2)5)
e
c
41
87 (>10:1)
No â-stannation was observed for any of the alkynones
examined. The major stannylated enone diastereomers re-
sulted from the anti addition of Bu SnH, in contrast to the
3
a
Reference 7c. b Reference 7d. Me3SnH used instead of Bu3SnH. Ratio
c
1
d
determined by integration of the H NMR of the mixture. Reference 4a.
7% of 6f and 28% of unreacted 2f recovered.
e
1
syn-selective hydrostannation of alkynyl esters and amides.
While syn and anti addition of tin hydride were reported for
the palladium-catalyzed hydrostannation of 7a and 7b,
The hydrostannations catalyzed by 1 are generally com-
plete within 1 h at room temperature. As in palladium-
catalyzed hydrostannations, only syn adducts are formed in
4
a,7d
respectively,
anti hydrostannation was found for both
18
substrates under catalysis by 1. Syn and anti addition appears
to be governed in part by the steric demands of the R′ group
comparably good yields. However, compared to Pd- or Mo-
catalyzed hydrostannations, the selectivity for R-stannation
was superior, and in fact exclusive under catalysis by 1. Even
for the challenging case of an alkynyl ester bearing a bulky
OR′ group (Table 3, entry 5), in which directions by steric
and electronic factors are working in opposition, the hy-
drostannation catalyzed by 1 showed exclusive selectivity
for stannation at the R-position, compared to a dramatic
decrease in the regioselectivity in the palladium-catalyzed
hydrostannation.
(Table 4, entries 3 and 4). Increasing the steric bulk of R′
corresponded to increased addition via the syn mode.
Protodestannylation on silica gel was mainly responsible for
the lower yields of products.
The alkynes that undergo hydrostannation in the presence
of 1 are electron-deficient, activated alkynes.The hydrostan-
nation of unpolarized alkynes, e.g., diphenylacetylene, fails
altogether under catalysis by 1 returning only unreacted
2
0
starting materials.
An alkynyl amide 2f was hydrostannated also with
excellent regioselectivity, but at a very slow reaction rate
The excellent regioselectivity of the hydrostannation
catalyzed by 1 for R-stannation correlates to the concomitant
regioselective delivery of hydride to the electron-deficient
â-position. The active species reacting with the alkyne is
presumably more polarized and hydridic in nature than the
corresponding palladium hydrides. The failure to induce
hydrostannation of unactivated alkynes, and the attenuated
reactivity toward the less electrophilic alkynyl amides further
support the regiochemical pathway being dominated by
hydride addition.
(Table 3, entry 6). After 18 h, only a 41% yield of 3f was
obtained, with 28% of the starting material being recovered.
With this particular substrate, the Pd-catalyzed hydrostan-
nation was much more efficient.
To explore the scope of the reaction further, we then
examined the hydrostannation of alkynyl ketones 7 (Table
4). These studies are technically more challenging due to
the known vulnerability of stannylated enone products to
decomposition by protodestannylation.4 Under palladium
catalysis, syn and anti hydrostannation of alkynyl ketone
substrates have been reported, the selectivity for R-stannation
a
The observation that the treatment of a red solution of 1
with Bu SnH induces a color change from red to dark brown
3
1
9
being good to exclusive (Table 4, entries 1 and 2).
infers the disappearance of 1 and the formation of a new
species. Since the chemistry of the new catalytic species
parallels the reactivity of 1 as a hydride source for the
reduction of activated alkenes and alkynes, it is possible that
Under catalysis by 1, high regioselectivity for R-stannation
is maintained in the hydrostannation of alkynones (Table 4).
2
1
(17) Reduced esters 5d and 6d were detected in the course of the
the active species resembles copper hydrides.
hydrostannation of 2d catalyzed by 1 in anhydrous C6D6 as monitored by
1
H NMR.
1
(
18) The configurations of vinylstannanes were elucidated by H NMR
(19) For the same propargyl ketone HCdCCOMe, a 51% yield of 1:1
E:Z R-stannated products by cat. Pd/Me3SnH (ref 7d) and a 65% yield of
82:18 R: â stannation by cat. Pd/Bu3SnH (ref 4a) have been reported.
3
spectroscopy. The JSnH values for cis and trans H-CdC-Sn bonds are
5
8-62 and 112-118 Hz, respectively.
Org. Lett., Vol. 7, No. 23, 2005
5251

Scheme 1. Proposed Mechanism for the Hydrostannation of Alkynones and Alkynoates Induced by 1
We propose that the Cu-catalyzed hydrostannation follows
decreased facility of isomerization to the allenolate 12 with
a hydrometalation mechanism (Scheme 1). Thus 1 enters the
increasing steric demands of R′.
catalytic cycle and reacts with Bu
3
SnH to generate the
We have described a novel copper-catalyzed hydrostan-
nation of alkynoates which produces high yields of single
diastereomers of (E)-R-stannylated alkenoates. Hydrostan-
nation of alkynones catalyzed by 1 occurs with superior
diastereoselectivities compared with the Pd-catalyzed process.
This method complements the selectivity of stannylcupration
reactions for both (E)- and (Z)-â-stannylated alkenoates,22
and should find use in the preparation of this class of
vinylstannanes. Further investigations on the scope and
mechanism of this reaction are being pursued.
catalytic species 10, a stannylated copper hydride. Hydro-
cupration by 10 occurs as directed by the polarization of the
triple bond. When the substrate is an alkynyl ester (X )
OR′), transmetalation then takes place in the (E)-vinylcopper
intermediate 11, thereby producing the vinylstannane, and
regenerating the copper catalyst to complete the cycle.
For alkynones, the (E)-vinylcopper intermediate 11 (X )
R′) isomerizes to the (Z)-vinylcopper intermediate 13 before
transmetalation to tin to give 9.22 This pathway is made
kinetically viable by the electron-withdrawing ability of the
ketone via the formation of allenolate 12, and thermody-
namically favorable by the alleviation of 1,3-allylic strain
between the alkanoyl group and the R group in the (E)-
intermediate 11. The appearance of (E)-8c and (E)-8d infers
the relative stabilities of their precursors 11, and may reflect
Acknowledgment. This work is supported by the Uni-
versity of Hong Kong (CRCG), and by a grant from the
Research Grants Council of Hong Kong SAR, P. R. China
(Project No. HKU 7102/02P). S.K.L. thanks the University
of Hong Kong for a conference travel grant.
Supporting Information Available: Experimental pro-
cedures, full characterization, and H, C NMR spectra for
e, 3a-f, 7b,c, and 9a-c. This material is available free of
1
13
(
20) Complex mixtures of vinylstannane isomers and reduction products
were obtained for propargylic alcohol derivatives, unactivated alkyl and
aryl alkynes.
2
(
21) However, the possibility of the active species being dimeric
Ph3PCuH2SnBu3”, as suggested by one reviewer, cannot be precluded.
22) Piers, E.; Morton, H. E. J. Org. Chem. 1980, 45, 4263.
charge via the Internet at http://pubs.acs.org.
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Org. Lett., Vol. 7, No. 23, 2005