Steric tuning of silylacetylenes and chiral phosphine ligands for rhodium-catalyzed asymmetric conjugate alkynylation of enones

Article abstract of DOI:10.1021/ja710540s

Rhodium-catalyzed asymmetric conjugate alkynylation of α,β-unsaturated ketones giving β-alkynylketones took place in high yields with high enantioselectivity. The reaction was realized by use of (triisopropylsilyl)acetylene combined with (R)-DTBM-segphos as a chiral phosphine ligand, where the sterically bulky substituents on the silicon and phosphorus atoms suppress the alkyne dimerization. Copyright

Full text of DOI:10.1021/ja710540s

Published on Web 01/16/2008
Steric Tuning of Silylacetylenes and Chiral Phosphine Ligands for
Rhodium-Catalyzed Asymmetric Conjugate Alkynylation of Enones
Takahiro Nishimura,* Xun-Xiang Guo, Nanase Uchiyama, Taisuke Katoh, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Kyoto 606-8502, Japan
Received November 22, 2007; E-mail: tnishi@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Rhodium-catalyzed asymmetric conjugate addition to R,â-
unsaturated ketones and related compounds is now well-recognized
to be one of the most efficient methods of introducing aryl and
alkenyl groups with high enantioselectivity.1 On the other hand,
asymmetric conjugate addition of alkynyl groups has not been well-
developed in spite of its high synthetic utility.2 A most straight-
forward and convenient reaction scheme should be the addition of
terminal acetylenes to enones, but it faces an inherent problem that
terminal acetylene is more reactive than enone toward the alkynyl-
Figure 1.
rhodium intermediate, which results in the predominant formation
Table 1. Rhodium-Catalyzed Asymmetric Conjugate Addition of
of acetylene dimers rather than â-alkynylketones (Scheme 1).3,4 One
Silylacetylenes to Enone 1aa
solution to this problem is the rhodium-catalyzed 1,3-rearrangement
of an alkynyl group from alkynyl alkenyl carbinols, where the
concentration of acetylene is kept minimal during the reaction,
leading to high yields of the â-alkynylketones.5 In this communica-
tion, we wish to report another solution to the rhodium-catalyzed
asymmetric conjugate alkynylation, which is realized by use of
(triisopropylsilyl)acetylene combined with DTBM-segphos6 as a
chiral phosphine ligand. The sterically bulky substituents on the
silicon and phosphorus atoms should hinder the acetylene from
approaching the alkynyl-rhodium intermediate (Figure 1).
entry
ligand
Si
product
yield (%)b
t
1
2
3
4
5
6
7c
(R)-binap
(R)-binap
(R)-binap
(R)-segphos
(R)-DMM-binap
(R)-DTBM-segphos
(R)-DTBM-segphos
SiMe2 Bu
SiEt3
2a
3a
4a
4a
4a
4a
4a
9
10
35
36
SiiPr3
SiiPr3
SiiPr3
SiiPr3
SiiPr3
49
Scheme 1.
87
99 (91)d
a Reaction conditions: enone 1a (0.20 mmol), silylacetylene (0.40 mmol),
[Rh(µ-OAc)(C2H4)2]2 (5 mol % of Rh), ligand (5.5 mol %), 1,4-dioxane
(0.4 mL) at 80 °C for 12 h. b NMR yield. c For 24 h. d Enantiomeric excess
(%) determined by HPLC analysis with a chiral stationary phase column:
Chiralcel OJ-H.
Table 2. Rhodium-Catalyzed Dimerization of Silylacetylenesa
The effects of the alkyl substituents on the silylacetylenes and
chiral bisphosphine ligands were examined for the addition to
1-phenyl-2-buten-1-one (1a) (Table 1). In the presence of 5 mol
7
% of a Rh/(R)-binap catalyst generated from [Rh(µ-OAc)(C2H4)2]2
and (R)-binap,8 the reaction of 1a with 2 equiv of (tert-butyldim-
ethylsilyl)acetylene at 80 °C for 12 h gave only 9% yield of
entry
ligand
Si
conversion (%)b
t
1
2
3
4
(R)-binap
(R)-binap
(R)-DTBM-segphos
(R)-DTBM-segphos
SiEt3
SiiPr3
SiEt3
SiiPr3
95
86
25
4
â-alkynylketone 2a (Si ) SiMe2 Bu), where a major product was
the dimer of the silylacetylene (entry 1).9 Similarly, the reaction of
(triethylsilyl)acetylene gave a low yield (10%) of â-alkynylketone
3a (Si ) SiEt3; entry 2). By use of sterically more bulky (tri-
isopropylsilyl)acetylene, the yield of conjugate addition was
increased to 35% (entry 3). This yield is still not satisfactory but
substantially higher than that with other silylacetylenes. The results
obtained for the reaction with binap, segphos, and their modified
derivatives showed that the yield of 4a (Si ) SiiPr3) is strongly
dependent on the steric bulkiness of the diarylphosphino groups,
with the more bulky aryl group giving the higher yield. The reaction
with segphos6 (Ar ) Ph) resulted in the formation of 4a in 36%
yield (entry 4), which is comparable to that observed with binap.
The yield of 4a was increased to 49% by use of (R)-DMM-binap,10
where the Ar on phosphorus is 3,5-Me2-4-MeOC6H2 (entry 5), and
the highest yield (87%) was obtained by use of (R)-DTBM-segphos,
where Ar is very bulky 3,5-t-Bu2-4-MeOC6H2 (entry 6). The
a Reaction conditions: silylacetylene (0.40 mmol), [Rh(µ-OAc)(C2H4)2]2
(2.5 mol % of Rh), ligand (2.8 mol %), 1,4-dioxane (0.8 mL) at 40 °C for
0.5 h. b Determined by GC.
reaction for a prolonged period of time (24 h) gave a quantitative
yield of 4a, whose enantiomeric excess was 91% (entry 7).
The high yield of â-alkynylketone 4a obtained by the combina-
tion of (triisopropylsilyl)acetylene and DTBM-segphos ligand is
caused by effective suppression of the dimerization of silylacetylene,
which is demonstrated by reference experiments of alkyne dimer-
ization carried out in the absence of enones (Table 2). The Rh/
binap catalyst was very active for the dimerization, especially for
(triethylsilyl)acetylene, giving high yields of the acetylene dimers
9
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J. AM. CHEM. SOC. 2008, 130, 1576-1577
10.1021/ja710540s CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. a
which gave the target compounds in high yields (Scheme 2, c and
d).
The present rhodium-catalyzed asymmetric alkynylation using
(triisopropylsilyl)acetylene and DTBM-segphos was successfully
applied to several types of R,â-unsaturated ketones (Table 3). The
reaction of 1-propenyl ketones 1a-1f bearing aryl, alkenyl, or alkyl
substituents on the carbonyl all proceeded well under standard
conditions to give the corresponding â-alkynylketones 4a-4f in
high yields, the enantioselectivity ranging between 91 and 95% ee
(entries 1-6). Linear enones 1g and 1h, which are substituted with
a longer alkyl chain at the â-position, are also good substrates
(entries 7 and 8). Although their reactivity is somewhat lower
toward the present alkynylation, cyclic enones 1i and 1j gave the
corresponding â-alkynylketones 4i and 4j with high ee (entries 9
and 10).
a Conditions: (a) TBAF, THF; (b) cat. RhCl(PPh3)3, EtOH, H2 (1 atm);
(c) iodobenzene, cat. Pd(PPh3)4, cat. CuI, Et3N, 60 °C; (d) 1-azido-4-
chlorobenzene, cat. CuSO4‚5H2O, Na-ascorbate, CH3CN, H2O.
Table 3. Asymmetric Conjugate Addition of
(Triisopropylsilyl)acetylene to Enonesa
In summary, we have succeeded in a conjugate addition of
(triisopropylsilyl)acetylene to R,â-unsaturated ketones with high
enantioselectivity by use of a rhodium/(R)-DTBM-segphos catalyst,
where the sterically bulky substituents on the silicon and phosphorus
atoms suppress the alkyne dimerization.
Acknowledgment. This work was supported in part by a 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.
Supporting Information Available: Experimental procedures 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.
References
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a Reaction conditions: enone 1 (0.20 mmol), (triisopropylsilyl)acetylene
(0.40 mmol), [Rh(µ-OAc)(C2H4)2]2 (5 mol % of Rh), (R)-DTBM-segphos
(5.5 mol %), 1,4-dioxane (0.4 mL) at 80 °C for 24 h. b Enantiomeric excess
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were assigned by consideration of the stereochemical pathway. c For 42 h.
(8) Binap; 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl.
at the reaction temperature of 40 °C (entries 1 and 2). The
dimerization was much slower with the Rh/DTBM-segphos catalyst,
the conversion of (triisopropylsilyl)acetylene being only 4% under
the same reaction conditions (entries 3 and 4).
The silyl group of 4a obtained here with 91% ee was readily
removed by treatment with tetrabutylammonium fluoride (TBAF)
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binaphthyl.
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D
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