Cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to α,β-enones

Article abstract of DOI:10.1021/ol051335u

(Chemical Equation Presented) We have developed a cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to α,β-enones. The asymmetric variant of this reaction, a kinetic resolution of secondary propargylic alcohols, was also developed with good selectivity. The mechanistic study revealed that the isomerization proceeds through intramolecular 1,3- and 1,2-hydrogen migration pathways.

Full text of DOI:10.1021/ol051335u

ORGANIC
LETTERS
2005
Vol. 7, No. 16
3561-3563
Cationic Rhodium(I)/BINAP
Complex-Catalyzed Isomerization of
Secondary Propargylic Alcohols to
r,â-Enones
Ken Tanaka* and Takeaki Shoji
Department of Applied Chemistry, Graduate School of Engineering, Tokyo UniVersity
of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received June 8, 2005
ABSTRACT
We have developed a cationic rhodium(I)/BINAP complex-catalyzed isomerization of secondary propargylic alcohols to
r,â-enones. The
asymmetric variant of this reaction, a kinetic resolution of secondary propargylic alcohols, was also developed with good selectivity. The
mechanistic study revealed that the isomerization proceeds through intramolecular 1,3- and 1,2-hydrogen migration pathways.
R,â-Unsaturated carbonyl compounds are useful building
blocks in organic synthesis. For their preparation, isomer-
ization of propargylic alcohols to R,â-enones or R,â-enals
is one of the most efficient methods due to the easy access
to propargylic alcohols and high atom economy.1 However,
such isomerizations are relatively rare compared with well
established isomerizations of allylic alcohols.2
catalyzed isomerizations of allylic alcohols,7 only one
example of rhodium-catalyzed isomerization of propargylic
alcohols was reported. The isomerization of hydroxy alkyne
esters proceeded in the presence of 3% RhCl(PPh3)3 and 5%
n-Bu3P in toluene at 110 °C.8 In this paper, we describe a
cationic rhodium(I)/BINAP complex-catalyzed isomerization
of secondary propargylic alcohols to R,â-enones.
Table 1 shows various rhodium(I) catalysts (5% based on
propargylic alcohols) that we examined for their ability to
isomerize propargylic alcohol 1a at room temperature.
Among the catalysts examined, [Rh(rac-BINAP)]BF4 was
the most effective (entry 7). The best result was obtained
by using [Rh(rac-BINAP)]BF4 as a catalyst at 80 °C for 1
h, which furnished the desired R,â-enone 2a in >95% yield
with complete trans:cis selectivity (100:0, entry 8).
The isomerization of propargylic alcohols to R,â-enones
or R,â-enals was developed by using Ru,3,4 Ir,5 and Pd6
catalysts. Although there are many examples of rhodium-
(1) (a) Trost, B. M. Science 1991, 254, 1471-1477. (b) Trost, B. M.
Angew. Chem., Int. Ed. Engl. 1995, 34, 259-281.
(2) For reviews, see: (a) Uma, R.; Cre´visy, C.; Gre´e, R. Chem. ReV.
2003, 103, 27-51. (b) Van der Drift, R. C.; Bouwman, E.; Drent, E. J.
Organomet. Chem. 2002, 650, 1-24.
(3) Ruthenium-catalyzed isomerization of 2-butyne-1,4-diol to butyro-
lactone via R,â-unsaturated aldehyde, see: Shvo, Y.; Blum, Y.; Reshef, D.
J. Organomet. Chem. 1982, 238, C79-C81.
(7) (a) Bianchini, C.; Meli, A.; Oberhauser, W. New J. Chem. 2001, 25,
11-12. (b) de Bellefon, C.; Tanchoux, N.; Caravieilhes, S.; Grenouillet,
P.; Hessel, V. Angew. Chem., Int. Ed. 2000, 39, 3442-3445. (c) Boons,
G.-J.; Burton, A.; Isles, S. Chem. Commun. 1996, 141-142. (d) Takeuchi,
R.; Nitta, S.; Watanabe, D. J. Org. Chem. 1995, 60, 3045-3051. (e)
Bergens, S.; Bosnich, B. J. Am. Chem. Soc. 1991, 113, 958-967. (f) Sato,
S.; Matsuda, I.; Izumi, Y. J. Organomet. Chem. 1988, 344, 71-88. (g)
Strohmeier, W.; Weigelt, L. J. Organomet. Chem. 1975, 86, C17-C19.
(8) Eddine, M. K.; Pellicciari, R. Tetrahedron Lett. 1995, 36, 4497-
4500.
(4) (a) Ma, D.; Lu, X. J. Chem. Soc., Chem. Commun. 1989, 890-891.
(b) Trost, B. M.; Livingston, R. C. J. Am. Chem. Soc. 1995, 117, 9586-
9587. (c) Trost, B. M.; Lee, C. J. Am. Chem. Soc. 2001, 123, 12191-
12201.
(5) Ma, D.; Lu, X. Tetrahedron Lett. 1989, 30, 2109-2112.
(6) (a) Lu, X.; Ji, J.; Ma, D.; Shen, W. J. Org. Chem. 1991, 56, 5774-
5778. (b) Lu, X.; Ji, J.; Guo, C.; Shen, W. J. Organomet. Chem. 1992,
428, 259-266.
10.1021/ol051335u CCC: $30.25
© 2005 American Chemical Society
Published on Web 07/15/2005

Table 1. Screening of Catalysts for Rhodium-Catalyzed
Isomerization of Propargylic Alcohol 1a
Table 3. Screening of Catalysts for Rhodium-Catalyzed
Kinetic Resolution of Secondary Propargylic Alcohol 1a
% ee of
conversion
(%)a
yield
(%)a
unreacted
s
entry
alcohol
trans:cis
41:59
time
alcohol
(selectivity
entry
catalyst
(h) (% conversiona)
factor)
1
2
3
4
5
6
7
8b
RhCl(PPh3)3
<1
<1
<1
<1
40
<1
27
100
<1
<1
<1
<1
32
<1
27
>95
1
[Rh((R)-BINAP)]BF4
78
47 (46)
22 (34)
33 (46)
9 (14)
10 (20)
8 (70)
5.2
3.1
3.1
3.8
2.5
1.2
3.3
7.3
[Rh(PPh3)2]BF4
[Rh(n-Bu3P)2]BF4
[Rh(dppe)]BF4
[Rh(dcpe)]BF4
[Rh(dppf)]BF4
2
[Rh((R)-Tol-BINAP)]BF4 40
3
[Rh((R)-H8-BINAP)]BF4
[Rh((S)-Segphos)]BF4
[Rh((R)-BINAP)]Cl
[Ir((R)-BINAP)]BF4
[Rh((R)-BINAP)]SbF6
[Rh((R)-BINAP)]OTf
40
88
38
15
40
72
4
5b
6b
7
41 (52)
76 (59)
[Rh(rac-BINAP)]BF4
[Rh(rac-BINAP)]BF4
91:9
100:0
8
a Determined by 1H NMR. b Reaction was conducted in (CH2Cl)2 at 80
°C.
a Determined by 1H NMR. b Reaction was conducted in (CH2Cl)2 at 80
°C for 1 h.
modified-BINAP complexes (Table 3).11-14 Among the
modified BINAP ligands examined (Figure 1), BINAP was
A series of secondary propargylic alcohols 1a-h was
subjected to the above optimal reaction conditions (Table
2). Primary (entries 1-3), secondary (entry 4), and tertiary
Table 2. Cationic Rhodium(I)/BINAP Complex-Catalyzed
Isomerization of Propargylic Alcohols
yield
Figure 1. Structures of modified BINAP ligands.
entry alcohol
Ar
R
ketone (%)a trans:cis
1
2
3
4
5
6
7
8
1b
1a
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Me
Et
n-Bu
i-Pr
t-Bu
2b
2a
2c
2d
2e
2f
99
98
95
98
96
98
99
94
100:0
100:0
100:0
100:0
100:0
100:0
100:0
67:33
the most effective (Table 3, entry 1). The use of a neutral
rhodium(I) complex or a cationic iridium(I) complex led to
(9) Isomerization of 3-octyn-2-ol gave a mixture of olefinic ketones.
(10) The isomerization of 1-phenyl-2-heptyn-1-ol gave a complex mixture
of the products contaning olefinic ketones and 3-butylindan-1-one. For the
formation of indanones utilizing rhodium 1,4-migration, see: (a) Yamabe,
H.; Mizuno, A.; Kusama, H.; Iwasawa, N. J. Am. Chem. Soc. 2005, 127,
3248-3249. (b) Shintani, R.; Okamoto, K.; Hayashi, T. J. Am. Chem. Soc.
2005, 127, 2872-2873.
4-MeOC6H4 Et
4-CF3C6H4
2-MeC6H4
1g
1h
Et
Et
2g
2h
a Isolated yield.
(11) For examples of transition-metal-catalyzed enantioselective isomer-
izations of allylic alcohols, see: (a) Ito, M.; Kitahara, S.; Ikariya, T. J. Am.
Chem. Soc. 2005, 127, 6172-6173. (b) Tanaka, K.; Fu, G. C. J. Org. Chem.
2001, 66, 8177-8186. (c) Tanaka, K.; Qiao, S.; Tobisu, M.; Lo, M. M.-C.;
Fu, G. C. J. Am. Chem. Soc. 2000, 122, 9870-9871. (d) Chapuis, C.; Barthe,
M.; de Saint Laumer, J.-Y. HelV. Chim. Acta 2001, 84, 230-242. (e) Otsuka,
S.; Tani, K. Synthesis 1991, 665-680. (f) Tani, K. Pure Appl. Chem. 1985,
57, 1845-1854. (g) Botteghi, C.; Giacomelli, G. Gazz. Chim. Ital. 1976,
106, 1131-1134.
(12) For examples of transition-metal-catalyzed kinetic resolutions of
allylic alcohols, see: (a) Kitamura, M.; Manabe, K.; Noyori, R. Tetrahedron
Lett. 1987, 28, 4719-4720. (b) Wiles, J. A.; Lee, C. E.; McDonald, R.;
Bergens, S. H. Organometallics 1996, 15, 3782-3784.
(13) For a kinetic resolution of propargylic alcohols with a planar-chiral
DMAP derivative, see: Tao, B.; Ruble, C.; Hoic, D. A.; Fu, G. C. J. Am.
Chem. Soc. 1999, 121, 5091-5092.
(entry 5) alkyl-substituted propargylic alcohols cleanly
afforded the corresponding R,â-enones 2a-e in almost
quantitative yield with complete trans:cis selectivity (100:
0). The electronic nature of the aromatic substituent did not
affect the yield or the trans:cis ratio of R,â-enones 2f,g
(entries 6 and 7), but a sterically demanding substituent on
the phenyl decreased the trans:cis ratio of R,â-enone 2h
(entry 8). Although the isomerization of aryl-ethynyl/alkyl
carbinols proceeded cleanly, that of alkyl-ethynyl/alkyl9 or
alkynyl/aryl10 carbinols did not proceed cleanly due to
significant side reactions.
(14) For a recent example of an enzymatic kinetic resolution of
propargylic alcohols, see: Raminelli, C.; Comasseto, J. V.; Andrade, L.
H.; Porto, A. L. M. Tetrahedron: Asymmetry 2004, 15, 3117-3122 and
references therein.
Next, a kinetic resolution of secondary propargylic alcohol
1a was investigated using chiral rhodium(I) or iridium(I)/
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Org. Lett., Vol. 7, No. 16, 2005

messy reactions, and the selectivity factors were very low
(entries 5 and 6). Changing the counterion from BF4 to OTf
improved the selectivity factor (entry 8).15
A series of secondary propargylic alcohols 1a-h can be
resolved using Rh(I)+/(R)-BINAP as a catalyst (Table 4).
Table 4. Cationic Rhodium(I)/(R)-BINAP Complex-Catalyzed
Kinetic Resolution of Secondary Propargylic Alcohols
% ee of
s
unreacted alcohol (selectivity
entry alcohol
Ar
R
(% conversiona)
factor)
1
2
3
4
5b
6
7
8
1b
1a
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Me
42 (58)
76 (59)
82 (60)
58 (51)
62 (58)
62 (55)
78 (60)
80 (55)
2.8
7.3
Et
rhodium(I) catalyst. The isomerization to thermodynamically
stable trans-R,â-enone 2 may occur through heating in the
presence of the cationic rhodium(I) catalyst.
n-Bu
i-Pr
t-Bu
8.2
6.1
4.7
4-MeOC6H4 Et
4-CF3C6H4 Et
2-MeC6H4
5.8
1g
1h
7.2
Et
11.5
Scheme 1
a Determined by 1H NMR. b Performed with 5% [Rh((R)-BINAP)]BF4.
The length and steric demand of the alkyl groups affected
the enantioselectivity of the isomerization (entries 1-5).
Good selectivity factors were observed in Et-, n-Bu-, and
i-Pr-substituted propargylic alcohols (entries 2-4). Although
the electronic nature of the aromatic substituent appeared to
have a modest impact on the selectivity factor (entries 6 and
7), sterically demanding substituents on the aryl ring
improved the selectivity factor (entry 8).
The reaction of a deuterated propargylic alcohol was
investigated to gain mechanistic insight into this reaction.
Deuterium from the propargylic alcohol 1b-d was incorpo-
rated into the R-position (25% D) and â-position (75% D)
of the R,â-enone 2b-d (eq 1). Furthermore, we have
established that the migration is an intramolecular process.
Treatment of a 1:1 mixture of deuterated propargylic alcohol
1b-d and nondeuterated propargylic alcohol 1c with [Rh-
(rac-BINAP)]BF4 furnishes deuterated 2b-d and nondeuter-
ated 2c (eq 2).16
Scheme 1 depicts a plausible mechanism for this reaction.
We believe that reaction of a rhodium(I) catalyst with a
propargylic alcohol 1 furnishes rhodium hydride complex
A. Addition of rhodium hydride to alkyne furnishes π-oxallyl
rhodium intermediate B or alkenyl rhodium intermediate C,
which is protonated to give an R,â-enone and regenerate the
In conclusion, we have developed a cationic rhodium(I)/
BINAP complex-catalyzed isomerization of secondary pro-
pargylic alcohols to R,â-enones. The asymmetric variant of
this reaction, a kinetic resolution of secondary propargylic
alcohols, was also developed with good selectivity. Further-
more, we have determined that the isomerization proceeds
through intramolecular 1,3- and 1,2-hydrogen migration
pathways. Expansion of the scope and a detailed mechanistic
study of this reaction are underway in our laboratory.
Acknowledgment. We thank Takasago International
Corporation for the gift of modified BINAP ligands.
(15) A similar counterion effect was observed in the enantioselective
isomerization of geraniol with Rh(I)+/BINAP; see ref 11d.
(16) Deuterium labeling studies revealed that the isomerization of allylic
alcohols proceeds through 1,3-hydrogen migration pathway, see: (a)
McGrath, D. V.; Grubbs, R. H. Organometallics 1994, 13, 224-235. (b)
Trost, B. M.; Kuliawec, R. J. J. Am. Chem. Soc. 1993, 115, 2027-2036.
(c) Bergens, S. H.; Bosnich, B. J. Am. Chem. Soc. 1991, 113, 958-967.
Also, see ref 11b.
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
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