Rhodium-catalyzed asymmetric conjugate alkynylation of enones with alkynylsilanols

Article abstract of DOI:10.1021/ol901119d

Asymmetric conjugate alkynylation of α,β-unsaturated ketones with (triisopropylsilyl)ethynylsilanols giving β-alkyny I ketones took place in high yields with high enantioselectivity in the presence of chiral rhodium catalysts.

Full text of DOI:10.1021/ol901119d

ORGANIC
LETTERS
2009
Vol. 11, No. 15
3222-3225
Rhodium-Catalyzed Asymmetric
Conjugate Alkynylation of Enones with
Alkynylsilanols
Takahiro Nishimura,* Sumito Tokuji, Takahiro Sawano, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo-ku, Kyoto 606-8502, Japan
tnishi@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Received May 21, 2009
ABSTRACT
Asymmetric conjugate alkynylation of r,ꢀ-unsaturated ketones with (triisopropylsilyl)ethynylsilanols giving ꢀ-alkynylketones took place in
high yields with high enantioselectivity in the presence of chiral rhodium catalysts.
Catalytic asymmetric conjugate alkynylation of R,ꢀ-unsatur-
ated carbonyl compounds is one of the significant challenges
in asymmetric carbon-carbon bond formation.1 Despite the
recent progress of transition metal-catalyzed asymmetric
conjugate alkylation, arylation, and alkenylation,2 asymmetric
conjugate addition of alkynyl groups has not been well
developed. There have been a few reports on catalytic
asymmetric alkynyl conjugate addition by Carreira (Cu),3
Corey (Ni),4 and Chong (chiral 1,1′-binapthols).5-7 Recently,
we reported a rhodium-catalyzed reaction that realizes the
asymmetric conjugate addition of terminal alkynes to R,ꢀ-
unsaturated ketones by use of a bulky silylacetylene in the
presence of a bulky bisphosphine-rhodium complex as a
catalyst (Scheme 1).8,9 Although high yields and high
enantioselectivities were obtained in the rhodium-catalyzed
(4) Kwak, Y.-S.; Corey, E. J. Org. Lett. 2004, 6, 3385.
(5) Wu, T. R.; Chong, J. M. J. Am. Chem. Soc. 2005, 127, 3244.
(6) For selected examples of enantioselective conjugate alkynylations,
see: (a) Chong, J. M.; Shen, L.; Taylor, N. J. J. Am. Chem. Soc. 2000, 122,
1822. (b) Yamashita, M.; Yamada, K.; Tomioka, K. Org. Lett. 2005, 7,
2369.
(7) For examples of metal-catalyzed conjugate alkynylation of electron-
deficient alkenes, see: (a) Schwartz, J.; Carr, D. B.; Hansen, R. T.; Dayrit,
F. M. J. Org. Chem. 1980, 45, 3053. (b) Picquet, M.; Bruneau, C.; Dixneuf,
P. H. Tetrahedron 1999, 55, 3937. (c) Chang, S.; Na, Y.; Choi, E.; Kim, S.
Org. Lett. 2001, 3, 2089. (d) Kno¨pfel, T. F.; Carreira, E. M. J. Am. Chem.
Soc. 2003, 125, 6054. (e) Kno¨pfel, T. F.; Boyall, D.; Carreira, E. M. Org.
Lett. 2004, 6, 2281. (f) Fujimori, S.; Carreira, E. M. Angew. Chem., Int.
Ed. 2007, 46, 4964. (g) Chen, L.; Li, C.-J. Chem. Commun. 2004, 2362.
(h) Nishimura, T.; Washitake, Y.; Nishiguchi, Y.; Maeda, Y.; Uemura, S.
Chem. Commun. 2004, 1312. (i) Nishimura, T.; Washitake, Y.; Uemura, S.
AdV. Synth. Catal. 2007, 349, 2563. For examples of conjugate alkynylations,
see: (j) Hooz, J.; Layton, R. B. J. Am. Chem. Soc. 1971, 93, 7320. (k)
Pappo, R.; Collins, P. W. Tetrahedron Lett. 1972, 13, 2627. (l) Bruhn, M.;
Brown, H. C.; Collins, P. W.; Palmer, J. R.; Dajani, E. Z.; Pappo, R.
Tetrahedron Lett. 1976, 17, 235. (m) Sinclair, J. A.; Molander, G. A.;
Brown, H. C. J. Am. Chem. Soc. 1977, 99, 954. (n) Kim, S.; Lee, J. M.
Tetrahedron Lett. 1990, 31, 7627. (o) Bergdahl, M.; Eriksson, M.; Nilsson,
M.; Olsson, T. J. Org. Chem. 1993, 58, 7238. (p) Eriksson, M.; Iliefski, T.;
Nilsson, M.; Olsson, T. J. Org. Chem. 1997, 62, 182.
(1) For recent reviews of asymmetric alkynylation, see: (a) Fujimori,
S.; Kno¨pfel, T. F.; Zarotti, P.; Ichikawa, T.; Boyall, D.; Carreira, E. M.
Bull. Chem. Soc. Jpn. 2007, 80, 1635. (b) Zani, L.; Bolm, C. Chem.
Commun. 2006, 4263. (c) Cozzi, P. G.; Hilgraf, R.; Zimmermann, N. Eur.
J. Org. Chem. 2004, 4095. (d) Wei, C.; Li, Z.; Li, C.-J. Synlett 2004, 1472.
(e) Pu, L. Tetrahedron 2003, 59, 9873. (f) Frantz, D. E.; Fa¨ssler, R.;
Tomooka, C. S.; Carreira, E. M. Acc. Chem. Res. 2000, 33, 373.
(2) For reviews, see: (a) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003,
103, 2829. (b) Hayashi, T. Bull. Chem. Soc. Jpn. 2004, 77, 13. (c) Hayashi,
T. Pure Appl. Chem. 2004, 76, 465. (d) Darses, S.; Genet, J.-P. Eur. J.
Org. Chem. 2003, 4313. (e) Fagnou, K.; Lautens, M. Chem. ReV. 2003,
103, 169. (f) Christoffers, J.; Koripelly, G.; Rosiak, A.; Ro¨ssle, M. Synthesis
2007, 1279. (g) Lo´pez, F.; Minnaard, A. J.; Feringa, B. L. Acc. Chem. Res.
2007, 40, 179. (h) Harutynyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard,
A. J.; Feringa, B. L. Chem. ReV. 2008, 108, 2824.
(3) Kno¨pfel, T. F.; Zarotti, P.; Ichikawa, T.; Carreira, E. M. J. Am. Chem.
Soc. 2005, 127, 9682.
10.1021/ol901119d CCC: $40.75
Published on Web 07/02/2009
 2009 American Chemical Society

(OH)((R)-binap)]212 (5 mol % of Rh) at 80 °C for 12 h gave
ꢀ-alkynylketone 3a in 26% yield with the formation of a
large amount of 1,4-bis(triisopropylsilyl)-1-buten-3-yne,
which is a head-to-head dimer of 2m (Table 1, entry 1).13
Scheme 1
Table 1. Rhodium-Catalyzed Conjugate Alkynylation of Enone
1aa
asymmetric addition,8 the reaction has the drawback that the
scope of the enone substrates is rather narrow. Thus the yields
of the ꢀ-alkynylation products are low for the conjugate
enones substituted with aryl groups at the ꢀ-position and
cyclic enones. This is mainly due to the low reactivity of
such enones, resulting in the predominant formation of
acetylene dimers rather than ꢀ-alkynylketones. To realize
the alkynylation of less reactive enones, more effective
suppression of the dimerization of terminal alkynes is
important. One solution of the problem is to use internal
alkynes bearing bulky substituents, which can provide the
alkynylrhodium intermediates, because the bulky internal
alkynes are expected to be less reactive than enones toward
the alkynylrhodium species (Scheme 2). Here, we report the
entry
R
temp (°C)
yield (%)b
ee (%)c
1
H (2m)
80
80
80
60
60
60
26
27
78
73
93
89
90
88
88
95
96
96
2
CMe2(OH) (2n)
CMe2(OH) (2n)
SiMe2(OH) (2o)
SiMe2(OH) (2o)
SiMe2(OH) (2o)
3d
4
5e
6e f
,
a Reaction conditions: 1a (0.20 mmol), 2 (0.30 mmol), [Rh(OH)((R)-
binap)]2 (5 mol % of Rh) in 1,4-dioxane (0.4 mL). b Isolated yield.
c Determined by HPLC analysis with a chiral stationary phase column
(Chiralcel OD-H). d Reaction time 63 h. e Performed in dioxane/H2O (10:1).
f The reaction of enone 1a (1.0 mmol)) and 2o (1.5 mmol).
This result clearly indicates that the dimerization of 2m
catalyzed by the rhodium/binap complex is a major problem
even in the use of the terminal alkyne bearing a bulky
triisopropylsilyl group. We next focused on the propargylic
alcohol 2n, whose analogues are known to provide alkynyl-
rhodium species by reaction with a hydroxorhodium
complex,9,10a,14 but the reactivity of 2n as an alkynylating
reagent was low under the reaction conditions (entries 2 and
3). Alkynylsilanols15 are another synthetic equivalent to
terminal alkynes in the palladium-catalyzed coupling reac-
tions.16 A unique feature of organosilanols is their high ability
of transmetalation to late transition metals.17 An alkynylsilanol
was successfully applied to the rhodium-catalyzed asymmetric
conjugate alkynylation of enones. Thus, the use of alkynyl(dim-
ethyl)silanol 2o in the reaction of 1a gave 3a in 73% yield with
95% ee (entry 4). The reaction in aqueous dioxane gave higher
yield (93%) of 3a with 96% ee (entry 5).
Scheme 2
use of alkynylsilanols for the asymmetric conjugate alkynylation
of enones. The reaction is applicable to a wide scope of enones
including ꢀ-aryl-substituted ones and cyclic enones.10,11
Treatment of 1-pheny-2-buten-1-one (1a) with (triisopro-
pylsilyl)acetylene (2m; 1.5 equiv) in the presence of [Rh-
Table 2 summarizes the results obtained for the reaction
of several enones 1 with alkynylsilanols 2. The reaction of
1-propenyl ketones 1a-1d, substituted with aryl or alkenyl
groups on the carbonyl, proceeded well to give the corre-
sponding ꢀ-alkynylketones 3a-3d in high yields, the enan-
tioselectivity ranging between 94% and 97% ee (entries
(8) Nishimura, T.; Guo, X.-X.; Uchiyama, N.; Katoh, T.; Hayashi, T.
J. Am. Chem. Soc. 2008, 130, 1576.
(9) As an alternative method, rhodium-catalyzed asymmetric 1,3-
rearrangement of alkynyl group from alkynyl alkenyl carbinols has been
also reported: Nishimura, T.; Katoh, T.; Takatsu, K.; Shintani, R.; Hayashi,
T. J. Am. Chem. Soc. 2007, 129, 14158
.
(10) For examples of our recent studies of rhodium-catalyzed alkyny-
lations, see: (a) Nishimura, T.; Guo, X.-X.; Ohnishi, K.; Hayashi, T. AdV.
Synth. Catal. 2007, 349, 2669. (b) Shintani, R.; Takatsu, K.; Katoh, T.;
Nishimura, T.; Hayashi, T. Angew. Chem., Int. Ed. 2008, 47, 1447. (c)
Nishimura, T.; Guo, X.-X.; Hayashi, T. Chem. Asian J. 2008, 3, 1505. (d)
Nishimura, T.; Tsurumaki, E.; Kawamoto, T.; Guo, X.-X.; Hayashi, T. Org.
(12) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am.
Chem. Soc. 2002, 124, 5052.
Lett. 2008, 10, 4057
.
(13) Similar results have been reported in ref 8.
(11) For examples of rhodium-catalyzed alkynylation of CdC or CdO
bonds, see: (a) Nikishin, G. I.; Kovalev, I. P. Tetrahedron Lett. 1990, 31,
7063. (b) Yamaguchi, M.; Omata, K.; Hirama, M. Tetrahedron Lett. 1994,
35, 5689. (c) Lerum, R. V.; Chisholm, J. D. Tetrahedron Lett. 2004, 45,
6591. (d) Dhondi, P. K.; Chisholm, J. D. Org. Lett. 2006, 8, 67. (e) Dhondi,
P. K.; Carberry, P.; Chisholm, J. D. Tetrahedron Lett. 2007, 48, 8743. (f)
Dhondi, P. K.; Carberry, P.; Choi, L. B.; Chisholm, J. D. J. Org. Chem.
2007, 72, 9590. (g) Crotti, S.; Bertolini, F.; Macchia, F.; Pineschi, M. Chem.
Commun. 2008, 3127.
(14) Funayama, A.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2005, 127,
15354
.
(15) (a) Lee, M.; Ko, S.; Chang, S. J. Am. Chem. Soc. 2000, 122, 12011.
(b) Lee, Y.; Seomoon, D.; Kim, S.; Han, H.; Chang, S.; Lee, P. H. J. Org.
Chem. 2004, 69, 1741.
(16) (a) Chang, S.; Yang, S. H.; Lee, P. H. Tetrahedron Lett. 2001, 42,
4833. (b) Denmark, S. E.; Tymonko, S. A. J. Org. Chem. 2003, 68, 9151.
(c) Yoshida, H.; Yamaryo, Y.; Ohshita, J.; Kunai, A. Chem. Commun. 2003,
1510.
Org. Lett., Vol. 11, No. 15, 2009
3223

The reactivity of 2-cyclohexen-1-one (1i) in the present
rhodium-catalyzed alkynylation is very different from that
of linear enones (Table 3). Thus, the reaction of enone 1i
Table 2. Asymmetric Conjugate Alkynylation of Enonesa
Table 3. Conjugate Alkynylation of 2-Cyclohexen-1-one (1i)a
yield
entry
catalyst
R
(%)b
1
2
3
4
5
[Rh(OH)((R)-binap)]2
SiMe2(OH) (2o)
2
22
69
83
5
c
[Rh(OH)((R)-DTBM-segphos)]2 SiiPr2(OH) (2p)
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
SiMe2(OH) (2o)
SiiPr2(OH) (2p)
H (2m)
a Reaction conditions: 1i (0.20 mmol), 2 (0.40 mmol), Rh catalyst (5
mol % of Rh) in 1,4-dioxane (0.4 mL) at 80 °C for 12 h. b Determined by
1H NMR. c In situ generated from [Rh(OH)(cod)]2 (5 mol % of Rh) and
(R)-DTBM-segphos (6 mol %).
with alkynylsilanol 2o in the presence of [Rh(OH)(binap)]2
at 80 °C for 12 h gave only 2% of ꢀ-alkynylketone 3i (entry
1). The reaction with bulky silanol 2p in the presence of the
rhodium/DTBM-segphos catalyst also gave a low yield of
3i (22%) (entry 2). On the other hand, it was found that the
rhodium complex bearing a diene as a ligand was effective
in the alkynylation of 1i. The use of [Rh(OH)(cod)]2 (cod
) 1,5-cyclooctadiene) gave 3i in 69% yield (entry 3). Higher
yield of 3i was obtained by use of silanol 2p as an
alkynylating reagent (entry 4). The use of terminal alkyne
2m resulted in a low yield of 3i here again (entry 5).
On the basis of the high catalytic activity of cod complex
[Rh(OH)(cod)]2 as demonstrated in Table 3, chiral diene
ligands20 were tested for the asymmetric alkynylation of
cyclic enones. The use of (R,R)-Bn-bod*20c,d enabled the
alkynylation to proceed with high enantioselectivity. Thus,
the reaction of cyclic enones 1i-1k with alkynylsilanol 2p
in the presence of Cs2CO3 (10 mol %) and a chiral diene-
rhodium catalyst, in situ generated from [RhCl(C2H4)2]2 (5
a Reaction conditions: 1 (0.20 mmol), 2o (0.30 mmol), [Rh(OH)((R)-
binap)]2 (5 mol % of Rh) in 1,4-dioxane/H2O (10:1, 0.4 mL). b Determined
by chiral HPLC analysis. c ee was not determined. d Performed with 2p
(0.4 mmol) in 1,4-dioxane (0.4 mL) at 80 °C for 24 h in the presence of
[Rh(OH)(cod)]2 (5 mol % of Rh) and (R)-DTBM-segphos (6 mol %).
1-4). Linear enones 1e and 1f, bearing a longer alkyl chain
at the ꢀ position, are also good substrates (entries 5 and 6).
On the other hand, the yield of ꢀ-alkynylation product was
low for the enone 1g, which is substituted with a phenyl
group at the ꢀ-position (entry 7). The alkynylation of
ꢀ-arylenones was greatly improved by use of (R)-DTBM-
segphos18 as a ligand and more bulky silanol 2p having two
isopropyl groups. Thus, the reaction of ꢀ-arylenones 1g and
1h with alkynylsilanol 2p gave ꢀ-alkynylketones 3g and 3h,
respectively, in good yields (82% and 73%) with high
enantioselectivity (96% and 98% ee; entries 8 and 9).19
(18) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. AdV. Synth. Catal. 2001, 343, 264.
(19) The reaction of 1g with 2p in the presence of [Rh(OH)((R)-binap)]2
at 80 °C for 24 h gave 3g in 52% yield with 8% ee. On the other hand, the
reaction of 1g with 2o catalyzed by in situ generated [Rh(OH)((R)-DTBM-
segphos)]2 gave 3g in 14% yield.
(20) For a review of chiral diene ligands, see: (a) Defieber, C.; Gru¨tzmacher,
H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482 For selected
examples of the asymmetric reactions using chiral diene ligands, see: (b) Hayashi,
T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125,
11508. (c) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani,
R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. (d) Otomaru, Y.;
Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503. (e)
Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem. Soc.
2004, 126, 1628. (f) Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.; Carreira,
E. M. J. Am. Chem. Soc. 2005, 127, 10850. (g) La¨ng, F.; Breher, F.; Stein,
D.; Gru¨tzmacher, H. Organometallics 2005, 24, 2997. (h) Helbig, S.; Sauer,
S.; Cramer, N.; Laschat, S.; Baro, A.; Frey, W. AdV. Synth. Catal. 2007,
349, 2331. (i) Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, G.-Q. J. Am. Chem.
Soc. 2007, 129, 5336. (j) Noe¨l, T.; Vandyck, K.; Van der Eycken, J.
Tetrahedron 2007, 63, 12961. (k) Gendrineau, T.; Chuzel, O.; Eijsberg, H.;
Genet, J.-P.; Darses, S. Angew. Chem., Int. Ed. 2008, 47, 7669.
(17) For examples of transition-metal-catalyzed coupling reactions using
organosilanols, see: (a) Hirabayashi, K.; Nishihara, Y.; Mori, A.; Hiyama,
T. Tetrahedron Lett. 1998, 39, 7893. (b) Hirabayashi, K.; Kawashima, J.;
Nishihara, Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1, 299. (c) Hirabayashi,
K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishihara, Y.; Hiyama, T. J.
Org. Chem. 2000, 65, 5342. (d) Hirabayashi, K.; Ando, J.; Kawashima, J.;
Nishihara, Y.; Mori, A.; Hiyama, T. Bull. Chem. Soc. Jpn. 2000, 73, 1409.
(e) Mori, A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am.
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K. Synlett 2002, 295. (g) Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett
2002, 298. (h) Denmark, S. E.; Neuville, L. Org. Lett. 2000, 2, 565. (i)
Denmark, S. E.; Wehrli, D. Org. Lett. 2000, 2, 3221. (j) Demmark, S. E.;
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Org. Lett., Vol. 11, No. 15, 2009

mol % of Rh) and (R,R)-Bn-bod*, at 60 °C for 48 h gave
the corresponding 1,4-addition products 3i-3k in 77-91%
yield with 78-91% ee (Scheme 3).
In summary, we have developed a rhodium-catalyzed
asymmetric conjugate alkynylation of enones with alkynyl-
silanols giving ꢀ-alkynylketones with high enantioselectivity.
Acknowledgment. This work was supported by Grant-
in-Aid for Scientific Research (S) (19105002) and Grant-
in-Aid for Scientific Research on Priority Areas “Advanced
Molecular Transformations of Carbon Resources” from
MEXT, Japan. We thank Takasago International Corporation
for the gift of (R)-DTBM-segphos.
Scheme 3
.
Asymmetric Conjugate Alkynylation of Cyclic
Enones
Supporting Information Available: Experimental pro-
cedures and spectroscopic and analytical data for the
substrates and products. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL901119D
Org. Lett., Vol. 11, No. 15, 2009
3225