Asymmetric transfer hydrogenation of α,β-acetylenic ketones

Full text of DOI:10.1021/ja971570a

8738
J. Am. Chem. Soc. 1997, 119, 8738-8739
Asymmetric Transfer Hydrogenation of
r, â-Acetylenic Ketones
the first asymmetric transfer hydrogenation of acetylenic ketones
using chiral Ru(II) catalysts and 2-propanol as the hydrogen
9
donor. This method allows highly selective reduction of
structurally diverse acetylenic ketones to propargylic alcohols
of high enantiomeric purity leaving the CtC bond intact (eq
Kazuhiko Matsumura, Shohei Hashiguchi,
Takao Ikariya, and Ryoji Noyori*
,
†
1
).
ERATO Molecular Catalysis Project
Japan Science and Technology Corporation
247 Yachigusa, Yakusa-cho, Toyota 470-03, Japan
1
ReceiVed May 15, 1997
Chiral propargylic alcohols are useful building blocks for the
1
synthesis of various biologically active and structurally interest-
2
ing compounds. Compounds of this important class had been
prepared by stoichiometric asymmetric reduction of acetylenic
3
ketones with chirally modified metal hydrides, reductive
4
cleavage of chiral acetylenic acetals, enantioselective alkyny-
5
6
lation of aldehydes, or enzymatic transformations until Corey
and Parker developed the catalytic asymmetric hydroboration
of R,â-ynones with chiral oxazaborolidines.7 Although asym-
metric hydrogenation would be the most straightforward ap-
proach, none of the currently available catalyst systems can
convert R,â-acetylenic ketones to propargylic alcohols in a
chemoselective and enantioselective manner.8 Here, we describe
†
Author to whom correspondence should be addressed at the follow-
ing: Department of Chemistry, Nagoya University, Chikusa, Nagoya 464-
0
1, Japan.
(1) For selected examples, see: [pheromones] (a) Mori, K.; Akao, H.
Tetrahedron Lett. 1978, 43, 4127-4130. (b) Vigneron, J. P.; Bloy, V.
Tetrahedron Lett. 1980, 21, 1735-1738. [prostaglandins] (c) Fried, J.; Sih,
J. C. Tetrahedron Lett. 1973, 40, 3899-3902. (d) Kluge, A. F.; Kertesz,
D. J.; O-Yang, C.; Wu, H. Y. J. Org. Chem. 1987, 52, 2860-2868. [steroids]
A search for the appropriate conditions using 1a, known as
1
0
(e) Johnson, W. S.; Brinkmeyer, R. S.; Kapoor, V. M.; Yarnell, T. M. J.
a difficult substrate, revealed that the chiral 16-electron Ru
Am. Chem. Soc. 1977, 99, 8341-8343. [alkaloids] (f) Overman, L. E.; Bell,
K. L. J. Am. Chem. Soc. 1981, 103, 1851-1853. [palytoxins] (g) Leder, J.;
Fujioka, H.; Kishi, Y. Tetrahedron Lett. 1983, 24, 1463-1466. (h) Cheon,
S. H.; Christ, W. J.; Hawkins, L. D.; Jin, H.; Kishi, Y.; Taniguchi, M.
Tetrahedron Lett. 1986, 27, 4759-4762. [vitamins E and K] (i) Cohen,
N.; Lopresti, R. J.; Neukom, C.; Saucy, G. J. Org. Chem. 1980, 45, 582-
11
complexes 3 are excellent catalysts for the carbonyl-selective
asymmetric reduction with 2-propanol (method A). The asym-
metric reaction, normally with a 0.1 to 1 M 2-propanol solution
of the ketone, proceeds under neutral conditions at room
temperature with a substrate/catalyst molar ratio (S/C) of 100-
200, or even 1000 in certain cases, giving 2a in up to 98% ee
588. [roridins and trichoverrins] (j) Roush, W. R.; Spada, A. P. Tetrahedron
Lett. 1982, 23, 3773-3776. [cytochalasins] (k) Stork, G.; Nakamura, E. J.
Am. Chem. Soc. 1983, 105, 5510-5512. [sterpurene] (l) Gibbs, R. A.;
Okamura, W. H. J. Am. Chem. Soc. 1988, 110, 4062-4063. [microcystins]
(
enantiomeric excess) and in >99% yield. The Ru catalysts 3
can be conveniently generated in situ by mixing the 18-electron
(
m) Kim, H. Y.; Stein, K.; Toogood, P. L. J. Chem. Soc., Chem. Commun.
12
1
996, 1683-1684. [methylenolactocin] (n) Zhu, G.; Lu, X. J. Org. Chem.
precursors 4 and KOH in a 1:1.2 molar ratio (method B) or
6
1
995, 60, 1087-1089.
simply [RuCl2(η -arene)]2 (5), (1S,2S)- or (1R,2R)-N-(p-toluene-
(
2) (a) Colas, Y.; Cazes, B.; Gore, J. Tetrahedron Lett. 1984, 25, 845-
sulfonyl)-1,2-diphenylethylenediamine, and KOH in 2-propanol
8
3
4
48. (b) Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1984, 25, 3055-
058. (c) Henderson, M. A.; Heathcock, C. H. J. Org. Chem. 1988, 53,
736-4745. (d) Burger, A.; Hetru, C.; Luu, B. Synthesis 1989, 2, 93-97.
(
Ru:diamine:KOH ) 1:1:2.5) (method C), only if a ketonic
substrate is insensitive to the KOH treatment. The mesitylene
and p-cymene complexes 3a and 3b worked equally well, while
the former was somewhat more reactive. A combined catalyst
(e) Elsevier, C. J.; Vermeer, P. J. Org. Chem. 1989, 54, 3726-3730. (f)
Marshall, J. A.; Wang, X.-j. J. Org. Chem. 1992, 57, 1242-1252. (g) Myers,
A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492-4493. (h) Mukai, C.;
Kataoka, O.; Hanaoka, M. J. Org. Chem. 1993, 58, 2946-2952. (i) Botta,
M.; Summa, V.; Corelli, F.; Pietro, G. D.; Lombardi, P. Tetrahedron:
Asymmetry 1996, 7, 1263-1266.
6
system consisting of [RuCl2(η -C6(CH3)6)]2, (1S,2S)-2-(methyl-
amino)-1,2-diphenylethanol, and KOH (Ru:amino alcohol:KOH
1
3
)
1:1:2.5) is also usable (method D).
(
3) (a) Brinkmeyer, R. S.; Kapoor, V. M. J. Am. Chem. Soc. 1977, 95,
8
339-8341. (b) Noyori, R.; Tomino, I.; Yamada, M.; Nishizawa, M. J.
Various achiral acetylenic ketones 1 can be reduced to chiral
Am. Chem. Soc. 1984, 106, 6717-6725. (c) Midland, M. M.; Tramontano,
14
propargylic alcohols 2 in good yields. Table 1 lists some
A.; Kazubski, A.; Graham, R. S.; Tsai, D. J. S.; Cardin, D. B. Tetrahedron
examples. The ee values are consistently high regardless of
1
984, 40, 1371-1380. (d) Ramachandran, P. V.; Teodorovi c´ , A. V.;
2
10
Rangaishenvi, M. V.; Brown, H. C. J. Org. Chem. 1992, 57, 2379-2386.
e) Bach, J.; Berenguer, R.; Garcia, J.; Loscertales, T.; Vilarrasa, J. J. Org.
Chem. 1996, 61, 9021-9025.
the bulkiness of R substituents from methyl to tert-butyl. Both
(
(8) The RuCl2(phosphine)n/1,2-diamine/KOH system cannot be used:
Ohkuma, T.; Ooka, H.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995,
117, 10417-10418.
(
4) Ishihara, K.; Mori, A.; Arai, I.; Yamamoto, H. Tetrahedron Lett. 1986,
6, 983-986.
5) (a) Mukaiyama, T.; Suzuki, K.; Soai, K.; Sato, T. Chem. Lett. 1979,
2
(
(9) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97-102.
(10) The methyl ketone was converted to the alcohol in 96% ee and in
80% yield only with neat B-(iso-2-n-propylapopinocampheyl)-9-borabicyclo-
[3.3.1]nonane (Prapine-Borane) (Brown, H. C.; Ramachandran, P. V.;
Weissman, S. A.; Swaminathan, S. J. Org. Chem. 1990, 55, 6328-6333),
4
47-448. (b) Mukaiyama, T.; Suzuki, K. Chem. Lett. 1980, 255-256. (c)
Tombo, G. M. R.; Didier, E.; Loubinoux, B. Synlett 1990, 547-548. (d)
Niwa, S.; Soai, K. J. Chem. Soc., Perkin Trans. 1 1990, 937-943. (e) Corey,
E. J.; Cimprich, K. A. J. Am. Chem. Soc. 1994, 116, 3151-3152.
7b
(
6) (a) Bradshaw, C. W.; Hummel, W.; Wong, C.-H. J. Org. Chem. 1992,
whereas the Corey method afforded quantitatively the product in 87% ee.
5
7, 1532-1536. (b) Ansari, M. H.; Kusumoto, T.; Hiyama, T. Tetrahedron
(11) (a) Haack, K.-J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R.
Angew. Chem., Int. Ed. Engl. 1997, 36, 285-288. (b) Hashiguchi, S.; Fujii,
A.; Haack, K.-J.; Matsumura, K.; Ikariya, T.; Noyori, R. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 288-290.
Lett. 1993, 34, 8271-8274. (c) Burgess, K.; Jennings, L. D. J. Am. Chem.
Soc. 1991, 113, 6129-6139. (d) Jeromin, G. E.; Scheidt, A. Tetrahedron
Lett. 1991, 32, 7021-7024. Also see ref 1a.
(
7) (a) Corey, E. J.; Helal, C. J. Tetrahedron Lett. 1995, 36, 9153-9156.
(12) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1995, 117, 7562-7563.
(
b) Helal, C. J.; Magriotis, P. A.; Corey, E. J. J. Am. Chem. Soc. 1996,
1
18, 10938-10939. (c) Parker, K. A.; Ledeboer, M. W. J. Org. Chem.
996, 61, 3214-3217.
(13) Takehara, J.; Hashiguchi, S.; Fujii, A.; Inoue, S.; Ikariya, T.; Noyori,
R. J. Chem. Soc., Chem. Commun. 1996, 233-234.
1
S0002-7863(97)01570-9 CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 37, 1997 8739
Table 1. Asymmetric Transfer Hydrogenation of R,â-Acetylenic
(3R,4S)-7 in >99% ee and >97% yield. Thus, the carbonyl
diastereofaces in (S)-6 are efficiently differentiated by the
chirality of the Ru template, while the adjacent nitrogen-
substituted stereogenic center does not play any significant role.
The reaction of racemic 6 in 2-propanol containing (R,R)-3b
a
Ketones Catalyzed by Chiral Ruthenium(II) Complexes
Ru catalyst
product 2
substrate complex methodb time (h) yield (%)c ee (%)d confige
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
a
a
(S,S)-3a
(S,S)-3b
A
A
A
A
B
B
B
C
C
D
B
B
B
20
20
20
41
4
63
18
18
18
18
12
5
87
>99
94
58
>99
99
94
>99
90
93
97
98
>99
84
70
90
85
>99
86
>99
99
98
98
97
96
94
97
95
96
98
97
90
97
99
98
98
98
>99
99
98
98
97
94
99
99
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
(
S/C ) 100) indicated that the S enantiomer is four times more
reactive than the R isomer.
-Propanol is the best hydrogen donor. Attempted reduction
using a 2 M solution of 1a in a 1:1 formic acid/triethylamine
a (1 M) (S,S)-3b
a (5 M) (S,S)-3b
a
2
(S,S)-4a
1
6
mixture containing (S,S)-4b (S/C ) 200, THF, 28 °C, 20 h)
gave (S)-2a in 91% ee but only 55% yield. Similarly, reaction
of 1g (S/C ) 100) afforded (S)-2g in 97% ee and 60% yield.
The success of the asymmetric reaction in 2-propanol relies
on the appropriate chiral structures of the Ru complexes,
a (1 M) (S,S)-4a
a
a
a
a
b
c
d
e
f
(S,S)-4b
f
5
5
5
g
h
(S,S)-4a
(S,S)-4a
(S,S)-4a
(S,S)-4a
(S,S)-4a
(S,S)-4a
11a
mechanism-based functional group discrimination allowing
i
j
the selective saturation of the carbonyl group, and suitable
thermodynamic and kinetic parameters. Hydrogen transfer
between secondary alcohols and ketones is reversible. Fortu-
13
13
6
k
B
B
B
B
l
l
12
g
6
nately, in comparison to the reduction of aromatic ketones,
k
l
g (1 M) (S,S)-4a
13
12
27
12
12
15
12
the ynone/ynol thermodynamic balance that limits the product
yield favors the reduced form more. Thus, the reaction using
a 1 M (not 0.1 M) 2-propanol solution of 1a catalyzed by (S,S)-
m
m
o
o
o
q
h
h
i
(S,S)-3b
(S,S)-3b
(S,S)-3b
A
A
A
A
A
A
n
4
a (method B, S/C ) 200) gave 2a in up to 99% yield.
k
p
j (1 M) (S,S)-3b
j
k
p
Furthermore, reduction of 1a catalyzed by (S,S)-3b afforded (S)-
2a in 94% ee, even when the reaction was conducted with a
substrate concentration as high as 5 M (S/C ) 200). This ee
value is lower than 97% obtained with a 0.1 M solution but is
still synthetically useful.
(R,R)-3b
(S,S)-3b
R
i
>99
S
a
Unless otherwise specified, the reaction was carried out at 28 °C
using a 0.1 M solution of the ketone in 2-propanol with S/C ) 200.
b
Method A, 1:3 ) 200:1; method B, 1:4:KOH ) 200:1:1.2; method
A separate structural study revealed the cause of the catalyst
deactivation. Treatment of (S,S)-3b with a 1 M solution of 1a
in 2-propanol (ketone/Ru ) 10, 28 °C, 12 h) produced the
orange-yellow complex (S,S)-8, mp 160-162 °C dec, in 88%
isolated yield. The structure of (S,S)-8 posessing the R
C, 1:5:(1S,2S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine:KOH
)
200:0.5:1:2.5; method D, 1:5:(1S,2S)-2-(methylamino)-1,2-diphen-
c
ylethanol:KOH ) 200:0.5:1:2.5. Isolated yield after flash chroma-
d
tography on silica gel. HPLC analysis using a Daicel Chiralcel OD
column unless otherwise specified. Determined by the sign of rotation
e
f
6
g
6
of the isolated product. η -arene ) mesitylene. η -arene ) p-cymene.
h
6
i
η -arene ) hexamethylbenzene. Determined after conversion to the
j
methyl (S)-2-(benzoyloxy)-3-methylbutyrate. Determined after conver-
k
sion to the methyl (S)-O-benzoylhexahydromandelate. S/C ) 100.
l
Capillary GLC using a Chrompack Cp-Cyclodextrin-â-236-M-19
column. m HPLC analysis of the corresponding 3,5-dinitrobenzoate
n
o
using a Chiralcel OD-H column. S/C ) 1000. HPLC analysis of
the corresponding benzoate using a Chiralcel OJ-R column. Deter-
mined after hydrolysis to (S)- or (R)-1-octyn-3-ol. HPLC using two
p
q
Chiralpak AD columns.
configuration at Ru was confirmed by X-ray crystallographic
aryl- and alkylethynyl ketones serve as good substrates.
Although unsubstituted ethynyl ketones are not usable, the
silylated compounds are reduced easily under neutral conditions
1
1a
analysis. The 16-electron complex (S,S)-3b dehydrogenates
-propanol, giving the 18-electron Ru hydride intermediate (S,S)-
2
11
9, which is responsible for carbonyl reduction of the ynone.
The hydride complex, however, partly undergoes irreversible
addition across the triple bond to result in the catalytically
inactive alkenyl complex (S,S)-8. This side reaction becomes
serious with a high substrate concentration. Overall, the high
catalytic efficiency, enantioselectivity, and operational conven-
ience are obtained with 0.1 (S/C ) 200) to 1 M (S/C ) 100)
concentrations of an ynone in 2-propanol.
with the preformed catalysts 3. The precursor of the lower
side chain unit of prostaglandins, (S)- or (R)-2j,15 of high
enantiomeric purity can be prepared by this method. However,
the starting materials should be carefully purified, because
terminal acetylenes are strong inhibitors of this catalytic reaction.
The asymmetric transfer hydrogenation of acetylenic ketones
with a preexisting stereogenic center leads to diastereomeric
propargylic alcohols. When the chiral ketone (S)-6 with 98%
ee was reduced with 2-propanol containing (R,R)-3b (S/C )
Acknowledgment. We thank Professors Shin-ichi Inoue (Aichi
Institute of Technology), Toshio Fuchigami (Tokyo Institute of
Technology), and Shun-ichi Fukuzumi (Osaka University) for valuable
discussions and Miss Mieko Kunieda (JST) and Mr. Toshihiro Kiho
(Nagoya University) for skillful experimental assistance.
1
00, [ketone] ) 0.1 M, 28 °C, 2 h), (3S,4S)-7 with >99% ee
was produced in >97% yield together with small amounts of
other stereoisomers. In a similar manner, reduction of (S)-6
with the enantiomeric catalyst (S,S)-3b (S/C ) 50, 5 h) gave
(
14) A mixture of 1a (721 mg, 5 mmol) and (S,S)-3b11a (15 mg, 0.025
Supporting Information Available: Experimental procedures for
the transfer hydrogenation, HPLC or GLC behavior, and [R] values
D
of the products and data of single-crystal X-ray analysis of (S,S)-8 (34
pages). See any current masthead page for ordering and Internet access
instructions.
mmol) in 2-propanol (50 mL) was stirred under argon at 28 °C for 20 h.
The reaction mixture was then concentrated under reduced pressure. The
residue was subjected to flash chromatography on silica gel (3:1 hexane/
23
ethyl acetate) to afford (S)-2b (731 mg, 100% yield) in 97% ee. [R]D
25
-
50.0 (c 1.50, ether) (lit.6c [R]D -50.6 (c 1.475, ether), >95% ee (S)).
The ee value was determined by HPLC analysis (Chiralcel OD, 20%
2
1
-propanol in hexane, 0.5 mL/min, λ ) 254 nm, tR ) 19.5 min, S isomer,
JA971570A
1.8 min, R isomer).
(
15) (a) Noyori, R.; Suzuki, M. Angew. Chem., Int. Ed. Engl. 1984, 23,
(16) (a) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1996, 118, 2521-2522. (b) Uematsu, N.; Fujii, A.;
Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118, 4916-
4917.
8
47-876. (b) Suzuki, M.; Kato, K.; Noyori, R.; Watanabe, Y.; Takechi,
H.; Matsumura, K.; Långstr o¨ m, B.; Watanabe, Y. Angew. Chem., Int. Ed.
Engl. 1996, 35, 334-336.