Enantioselective hydrogenation of itaconate using rhodium bihelicenol phosphite complex. Matched/mismatched phenomena between helical and axial chirality

Article abstract of DOI:10.1016/S0040-4039(03)01183-3

Phosphites prepared from bihelicenol, menthol (or 1-phenylethanol), and PCl₃ are effective ligands for the rhodium-catalyzed enantioselective hydrogenation of dimethyl itaconate. Stereochemistry of the helicene moiety plays an important role in

Full text of DOI:10.1016/S0040-4039(03)01183-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4969–4971
Enantioselective hydrogenation of itaconate using rhodium
bihelicenol phosphite complex. Matched/mismatched phenomena
between helical and axial chirality
Daisuke Nakano and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578,
Japan
Received 14 April 2003; revised 8 May 2003; accepted 9 May 2003
Abstract—Phosphites prepared from bihelicenol, menthol (or 1-phenylethanol), and PCl3 are effective ligands for the rhodium-cat-
alyzed enantioselective hydrogenation of dimethyl itaconate. Stereochemistry of the helicene moiety plays an important role in the
asymmetric induction, and matched/mismatched phenomena are observed between helical and axial chirality. © 2003 Elsevier
Science Ltd. All rights reserved.
Helicenes are a group of aromatic compounds with
helical structures. In spite of their unique chiral struc-
ture, they were rarely employed for ligands in asymmet-
ric catalysis.1 In view of successful achievement of
2,2%-binaphthol (binol) in asymmetric catalysis, we were
interested in bihelicenols 1, which are dimeric helicenols
possessing helical and axial chirality. It was wondered
whether 1 would be even a better ligand, because it
should form a larger chiral pocket at the catalyst metal
center. Also wondered was that 1 might exhibit differ-
ent stereoselectivity between diastereomers. We previ-
ously reported the synthesis of all six isomers of
optically pure organic compounds. Rhodium-catalyzed
asymmetric hydrogenation of prochiral olefins has gen-
erally been conducted using bidentate phosphines.
Monodentate phosphites,3 however, have recently been
shown to be excellent ligands by Pringle,4 Reetz,5
Feringa,6 and Xiao.7 They employed ligands derived
from binol and an alcohol including chiral menthol or
1-phenylethanol, and showed that the enantiodiscrimi-
nation is controlled by the biaryl moiety and not the
alcohol moiety.5,7 Based on the studies, we started to
investigate asymmetric hydrogenation of dimethyl ita-
conate 4 using phosphites 2 and 3 derived from 1. A
high selectivity was attained using (M,M,S,l)-2 pre-
pared from (M,M,S)-1 and l-menthol, and matched/
mismatched phenomena were observed between helical
and axial chirality.
bihelicenols
(M,M,S)-1,
(M,M,R)-1,
(P,P,S)-1,
(P,P,R)-1, (P,M,S)-1, and (P,M,R)-1.2
Phosphites 2 were conveniently synthesized from 1 and
menthols (Table 1).5,7,8 For example, the reaction of
PCl3 with 1 equiv. of l-(1R,2S,5R)-menthol in THF
yielded l-menthyl phosphorodichloride, and the addi-
tion of the solution to (M,M,S)-1 and triethylamine in
THF at −78°C followed by warming to −20°C for 1 h
afforded the phosphite (M,M,S,l)-2 in 81% yield. 1-
Phenylethanol derivatives 3 were also synthesized
analogously.
Transition metal-catalyzed asymmetric hydrogenation
is a highly efficient and practical way of producing
The ligands thus obtained were used in the rhodium-
catalyzed asymmetric hydrogenation of 4 (Table 2). The
catalyst was formed in situ by treating [Rh(cod)2]BF4
(cod=1,5-cyclooctadiene) (1 mol%) and (M,M,S,l)-2 (3
mol%) in CH2Cl2, and 4 was hydrogenated with 90 atm
* Corresponding author. Tel.: +81-22-217-6812; fax: +81-22-217-6811;
e-mail: yama@mail.pharm.tohoku.ac.jp
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01183-3

4970
D. Nakano, M. Yamaguchi / Tetrahedron Letters 44 (2003) 4969–4971
Table 1. Synthesis of bihelicenol phosphites 2 and 3
lectivity, and that the chirality of menthol is unimpor-
tant. In contrast, (R)-5 was obtained in very low ee,
when (M,M,R,l)-2 or (M,M,R,d)-2 was used (entries 6
and 7). The combination of (M)-helicene and (S)-axis
of 2 represents the matched pair for this reaction.
Phosphite
Yield (%)
[h]2D5 a
31P NMRb
(M,M,S,l)-2
(M,M,S,d)-2
(M,M,R,l)-2
(M,M,R,d)-2
81
82
82
75
+603
+1014
+150
139.6
153.4
162.5
157.7
Hydrogenation employing (M,M,S,S)-3 under 90 atm
hydrogen at 20°C gave (S)-5 in 77% ee (entry 8).
Enantioselectivity in this case lowered to 49% ee, when
the reaction was conducted by warming from −78 to
20°C (entry 9). The higher pressure was again required
for the higher ee (entry 10). Since use of (M,M,S,R)-3
gave (S)-5 in 73% ee (entry 11), the asymmetric induc-
tion is controlled by the (M,M,S)-bihelicenol moiety as
was (M,M,S)-2. (M,M,R,S)-3 and (M,M,R,R)-3 gave 5
with lower ee (entries 12 and 13) exhibiting that (M)-
helical and (S)-axial chirality of 3 are again the
matched pair. It might be interesting to note that the
diastereomers with larger [h]D and higher field 31P
NMR chemical shifts exhibit higher selectivity for both
2 and 3 (Table 1). The mismatched case showed an
interesting behavior: (M,M,R,S)-3 and (M,M,R,R)-3
gave enantiomeric 5, in which the chirality of 1-
phenylethanol moiety is important. Such phenomenon
was not observed in the reactions using binol
phosphites.
+160c
(M,M,S,S)-3
(M,M,S,R)-3
(M,M,R,S)-3
(M,M,R,R)-3
77
83
78
76
+1070
+958
+83
139.6
141.2
153.7
150.9
+95
a Optical rotation in CHCl3 at the concentration of c 0.5.
b Chemical shift in CDCl3 employing triphenylphosphate as external
standard l −18.0.
c At the concentration of c 0.25.
Table 2. Rh-catalyzed asymmetric hydrogenation of 4a
Entry
Ligand
Temp. (°C)
Ee (%)b
Config.c
1
2
3
4e
5
6
7
(M,M,S,l)-2
−78 to 20d
−78 to 20
20
96
90
77
37
85
10
1
S
S
S
S
S
R
R
Catalytic hydrogenation of dimethyl itaconate 4 using
[Rh(cod)2]BF4 and (M,M,S,l)-2 results in full conver-
sion and high ee. The stereochemistry at the helicene
moiety plays an important role in the asymmetric
induction, and (M)/(S) combination turned out to be
the matched pair. It should be noted that the substitu-
tion of achiral naphthalene moiety of binol with the
chiral helicene provides a method to fine-tune chiral
environment of metal center for asymmetric catalysis.
20
(M,M,S,d)-2
(M,M,R,l)-2
(M,M,R,d)-2
−78 to 20
−78 to 20
−78 to 20
8
9
(M,M,S,S)-3
20
77
49
53
73
37
54
S
S
S
S
R
S
−78 to 20
10e
11
12
13
20
20
20
20
(M,M,S,R)-3
(M,M,R,S)-3
(M,M,R,R)-3
Acknowledgements
a See Ref. 9 for experimental procedures. 5 was obtained in a quanti-
tative yield.
b Ee was determined by GC using a chiraldex G-TA (30 m×0.25 mm)
column.
This work was supported by grants from the Japan
Society of Promotion of Science.
c The absolute configuration was determined by the sign of optical
rotation.
d Reacted at −78°C for 6 h, and then warmed to 20°C.
e Reacted with 40 atm of hydrogen.
References
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hydrogen at −78°C for 6 h, which was followed by
warming to 20°C for 18 h. Methylsuccinate (S)-5 was
obtained in a quantitative yield with 96% ee (entry 1).
The selectivity compares favorably with those obtained
with binol phosphites, and the same absolute configura-
tion of 5 was obtained in regard to the axial chirality.
The reaction was slower probably due to the narrower
pocket of the rhodium complex with (M,M,S,l)-2 than
binol phosphite. When the mixture was immediately
warmed from −78°C to 20°C, ee slightly lowered (entry
2). Enantioselectivity was reduced to 77% ee when
reacted at 20°C (entry 3), and to 37% ee under 40 atm
hydrogen (entry 4). Switching the ligand to (M,M,S,d)-
2 gave (S)-5 in 85% ee (entry 5) indicating that
(M,M,S)-bihelicenyl moiety is decisive for the stereose-

D. Nakano, M. Yamaguchi / Tetrahedron Letters 44 (2003) 4969–4971
4971
7. Chen, W.; Xiao, J. Tetrahedron Lett. 2001, 42, 2897.
8. Brunel, J.-M.; Buono, G. J. Org. Chem. 1993, 58, 7313.
9. Under an argon atmosphere, [Rh(cod)2]BF4 (4.0 mg, 0.01
mmol) and (M,M,S,l)-2 (24 mg, 0.03 mmol) were added to
degassed dichloromethane (5 mL), and the orange solution
was stirred at room temperature for 5 min. In a stainless
autoclave (50 mL) was added dimethyl itaconate 4 (158
mg, 1 mmol). An argon atmosphere was applied, and
degassed dichloromethane (5 mL) was added. The
rhodium complex solution was then added to the substrate
solution in the autoclave, and the mixture was stirred for
1 min. Then, the solution was cooled to −78°C, and 90
atm of hydrogen was applied. The mixture was stirred for
6 h, and warmed to room temperature for 18 h. The gas
was removed, and the solvents were evaporated under
reduced pressure. After short silica gel column chromatog-
raphy, bulb-to-bulb distillation gave (S)-5 (158 mg, quant.,
96% ee) as colorless oil.