Asymmetric hydrogenation of aromatic heterocyclic ketones catalyzed by the MsDPEN-Cp*Ir(III) complex

Article abstract of DOI:10.3987/COM-09-S(S)34

Asymmetric hydrogenation of aromatic heterocyclic ketones catalyzed by Cp^*Ir(OTf)(Msdpen) (MsDPEN = N-(methanesulfonyl)-l,2-diphenylethylenediamine) affords the heterocyclic alcohols in 93% to >99% ee. The reaction is conducted in a methanolic solution with a substrate-to-catalyst molar ratio of 200-5000 under 15 atm of H₂. The heterocyclic rings of substrates are left intact.

Full text of DOI:10.3987/COM-09-S(S)34

HETEROCYCLES, Vol. 80, No. 1, 2010
141
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 141 - 147. © The Japan Institute of Heterocyclic Chemistry
Received, 13th June, 2009, Accepted, 16th July, 2009, Published online, 17th July, 2009
DOI: 10.3987/COM-09-S(S)34
ASYMMETRIC HYDROGENATION OF AROMATIC HETEROCYCLIC
‡
KETONES CATALYZED BY THE MsDPEN–Cp*Ir(III) COMPLEX
b
b
b
Noriyuki Utsumi, Kunihiko Tsutsumi, Masahiko Watanabe, Kunihiko
b
a
a
a,
Murata, Noriyoshi Arai, Nobuhito Kurono, and Takeshi Ohkuma *
a
Division of Chemical Process Engineering, Graduate School of Engineering,
Hokkaido
University,
Sapporo
060-8628,
Japan.
E-mail:
b
ohkuma@eng.hokudai.ac.jp; Central Research Laboratory, Technology and
Development Division, Kanto Chemical Co., Inc., Soka, Saitama 340-0003,
Japan.
‡
th
Dedication to Professor Akira Suzuki on the occasion of his 80 birthday
Abstract – Asymmetric hydrogenation of aromatic heterocyclic ketones
catalyzed by Cp*Ir(OTf)(Msdpen) (MsDPEN
=
N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the heterocyclic
alcohols in 93% to >99% ee. The reaction is conducted in a methanolic solution
with a substrate-to-catalyst molar ratio of 200–5000 under 15 atm of H . The
2
heterocyclic rings of substrates are left intact.
Asymmetric hydrogenation of ketones is a key technology to synthesize optically active secondary
1
alcohols. Selection of appropriate chiral catalysts according to the structure and chemical features of
the ketonic substrates is crucial to achieve high reactivity and enantioselectivity. We have previously
2
,3
4
exploited RuXY(diphosphine)(1,2-diamine) and RuXY(diphosphine)(ꢀ-picolylamine) (X = Y = Cl or
1
X = H, Y = ꢀ -BH ), which act as excellent catalysts for asymmetric hydrogenation of simple ketones in
4
basic or slightly basic alcoholic solutions. However, these catalysts cannot be used for the reaction of
seriously base-labile 3(2H)-benzofuranones, 4-chromanones, and their derivatives. We have recently
6
–
reported that Ru(OTf)(Tsdpen)(ꢀ -p-cymene) (TfO = trifluoromethanesulfonate, TsDPEN =
N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine) without any basic compounds catalyzes
5
,6
hydrogenation of 4-chromanone to give the chiral alcohol in 97% ee quantitatively.
The neutral to
slightly acidic reaction conditions prevent decomposition of the substrate. The isoelectronic Ir(III)

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HETEROCYCLES, Vol. 80, No. 1, 2010
complex, Cp*Ir(OTf)(Msdpen) (3) (Cp*
=
pentamethylcyclopentadienyl, MsDPEN
=
N-(methanesulfonyl)-1,2-diphenylethylenediamine), has been revealed to be an excellent catalyst for
asymmetric hydrogenation of ꢀ-hydroxy ketones, which are another class of base-sensitive ketonic
7
substrates.
We herein describe enantioselective hydrogenation of aromatic heterocyclic ketones
catalyzed by the Ir(III) complex 3. The reaction of 4-chromanone resulted in an optical yield of 99%,
6
even higher than that by Ru(OTf)(Tsdpen)(ꢀ -p-cymene). A series of heterocyclic alcohols was
obtained with high enantioselectivity.
Asymmetric hydrogenation of 3(2H)-benzofuranone (1a) with the Ir complex, (S,S)-3, at a
substrate-to-catalyst molar ratio (S/C) of 500 in CH OH at 60 °C under 15 atm of H was completed in 24
3
2
8
h to afford the desired alcohol, (R)-2a, in 94% ee (Table 1, entry 1). The heterocyclic ring was left
intact. To our knowledge, this is the first example of asymmetric hydrogenation of
(2H)-benzofuranones. The substrate with a CH O group at the C7 position, 1b, was also converted to
3
3
9
(
R)-2b in high enantioselectivity (entry 2). When 1-indanone (1c) was hydrogenated at 30 °C (S/C =
2
00, 15 atm H , 24 h), (S)-1-indanol [(S)-2c] was obtained in 98% ee and 95% yield with some
2
1
0–12
unidentified byproducts, possible due to instability of the substrate (entry 3).
The reaction conducted
at 60 °C was stopped at about 50% conversion. The Ir complex (S,S)-3 exhibited excellent performance
in hydrogenation of 4-chromanone (1d). Thus, the reaction with an S/C of 5000 (15 atm H , 60 °C) for
2
5
,11,13
2
4 h quantitatively gave (S)-2d in 99% ee (entry 4).
The high substrate concentration of 3.5 M is
suitable for practical use. The catalytic activity of 3 for hydrogenation of 1d is comparable to that of an
6
isoelectronic Ru(OTf)(Tsdpen)(ꢀ -p-cymene), but the enantioselective ability is higher than that of the Ru
5
complex (99% vs. 97%). 4-Chromanones with a CH or Cl substituent at the C6 position, 1e and 1f,
3
1
4,15
were also smoothly hydrogenated with 3 in >98% optical yield (entries 5 and 6).
The electronic and
steric properties of these substituents little affected the reactivity and enantioselectivity. The
Ir-catalyzed hydrogenation was applicable to 4-thiochromanone (1g) without loss of thiocyclic skeleton
1
1
16
(entry 7).
The desired alcohol (S)-2g was obtained in >99% ee quantitatively.
A cyclic keto sulfone
1
2
1
9
h, which is hardly soluble in CH OH, was hydrogenated in a 3:2 mixture of CH OH and DMF ([1h] =
3
3
1
8).
7
.0
M)
to
give
(S)-2h
in
98%
ee
(entry
Hydrogenation
of
-tert-butoxycarbonyl-1,2,3,4-tetrahydro-4-quinolinone (1i) afforded 2i in 96% ee and 90% yield (entry
1
).
8
It is noteworthy that hydrogenation of 1-tetralone (1j), a carbocyclic aromatic ketone, gave the
1
1,12,19,20
alcohol 2j in only 93% ee and 88% yield (entry 10: S/C = 500, 15 atm H , 60 °C, 24 h),
suggesting
2
that a heteroatom, especially oxygen, in the aliphatic ring of the substrate plays crucial roles in achieving
high reactivity and enantioselectivity (see for example entry 4).
In summary, we have disclosed enantioselective hydrogenation of aromatic heterocyclic ketones
catalyzed by the MsDPEN–Cp*Ir(III) complex 3. The reaction is conducted with an S/C of 200–5000

HETEROCYCLES, Vol. 80, No. 1, 2010
143
under 15 atm of H to give the heterocyclic alcohols in >99% ee in the best cases. The heterocyclic
2
structures are left intact.
This is the first example of asymmetric hydrogenation of
3
(2H)-benzofuranones, 4-thiochromanone 1,1-dioxides, and 1,2,3,4-tetrahydro-4-quinolinones. Thus,
this method provides an efficient strategy to synthesize chiral heterocyclic alcohols.
a
Table 1. Asymmetric Hydrogenation of Cyclic Ketones (1)
O
OH
Ir
Ms
Y
(S,S)-3
Y
CF SO
N
+
H2
3
3
N
H
X
X
H
Z
Z
1
(R)-2a,b
(
S)-2c–j
(
S,S)-3
b
c
d
e
entry
ketone 1 ([1] , M)
S/C
yield, %
ee, %
94
0
1
2
3
4
5
6
7
8
9
1a: X = O, Y = Z = H (2.0)
500
200
>99 (97)
>99 (99)
95 (83)
1b: X = O, Y = H, Z = OMe (2.0)
93
f
1c: X = CH , Y = Z = H (3.5)
200
98
2
1d: X = OCH , Y = Z = H (3.5)
5000
3000
3000
500
>99 (99)
98 (98)
99
2
1e: X = OCH , Y = CH , Z = H (3.5)
98
2
3
1f: X = OCH , Y = Cl, Z = H (3.5)
>99 (99)
>99 (99)
>99 (97)
90 (90)
>99
>99
98
2
1g: X = SCH , Y = Z = H (3.5)
2
g
1h: X = S(O )CH , Y = Z = H (2.0)
500
2
2
1i: X = N(Boc)CH , Y = Z = H (2.0)
500
96
2
1
0
1j: X = (CH ) , Y = Z = H (3.5)
500
88 (83)
93
2
2
a
Unless otherwise stated, reactions were conducted at 60 °C under 15 atm of H using 1.0–20.0 mmol of
2
b
1
in MeOH containing 2.0–15.0 μmol of (S,S)-3 in a glass autoclave. Reaction time was 24 h.
Initial
c
d
1
concentration of 1.
Substrate/catalyst molar ratio.
Determined by H NMR analysis. Isolated yield
e
f
g
is given in parenthesis.
Determined by chiral HPLC analysis. Reaction at 30 °C.
Reaction in a
3
:2 mixture of MeOH and DMF.
ACKNOWLEDGEMENTS
This work was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS)
Grant No. 21350048).
(

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HETEROCYCLES, Vol. 80, No. 1, 2010
REFERENCES AND NOTES
1.
Reviews on asymmetric hydrogenation of ketones: T. Ohkuma and R. Noyori, ‘Comprehensive
Asymmetric Catalysis,’ Vol. 1, ed. by E. N. Jacobsen, A. Pfaltz, and H. Yamamoto, Springer,
Berlin–Heidelberg, 1999, pp. 199–246; T. Ohkuma, M. Kitamura, and R. Noyori, ‘Catalytic
Asymmetric Synthesis, 2nd ed.,’ ed. by I. Ojima, Wiley-VCH, New York, 2000, pp. 1–110; T.
Ohkuma and R. Noyori, ‘Transition Metals for Organic Synthesis, 2nd ed.,’ Vol. 2, ed. by M. Beller
and C. Bolm, Wiley-VCH, Weinheim, 2004, pp. 29–113; T. Ohkuma and R. Noyori, ‘The Handbook
of Homogeneous Hydrogenation,’ Vol. 3, ed. by J. G. de Vries and C. J. Elsevier, Wiley-VCH,
Weinheim, 2007, pp. 1105–1163.
2
.
See for example: H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E. Katayama, A. F.
England, T. Ikariya, and R. Noyori, Angew. Chem. Int. Ed., 1998, 37, 1703; T. Ohkuma, M. Koizumi,
H. Doucet, T. Pham, M. Kozawa, K. Murata, E. Katayama, T. Yokozawa, T. Ikariya, and R. Noyori,
J. Am. Chem. Soc., 1998, 120, 13529; T. Ohkuma, M. Koizumi, K. Muñiz, G. Hilt, C, Kabuto, and R.
Noyori, J. Am. Chem. Soc., 2002, 124, 6508; N. Arai, H. Ooka, K. Azuma, T. Yabuuchi, N. Kurono,
T. Inoue, and T. Ohkuma, Org. Lett., 2007, 9, 939; N. Arai, K. Azuma, N. Nii, and T. Ohkuma,
Angew. Chem. Int. Ed., 2008, 47, 7457; H. Ooka, N. Arai, K. Azuma, N. Kurono, and T. Ohkuma, J.
Org. Chem., 2008, 73, 9084.
3
4
.
.
Reviews: T. Ohkuma, J. Synth. Org. Chem. Jpn., 2007, 65, 1070; R. Noyori and T. Ohkuma, Angew.
Chem. Int. Ed., 2001, 40, 40.
T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K. Muñiz, and R. Noyori, J. Am. Chem.
Soc., 2005, 127, 8288; N. Arai, K. Suzuki, S. Sugizaki, H. Sorimachi, and T. Ohkuma, Angew. Chem.
Int. Ed., 2008, 47, 1770; K. Tsutsumi, T. Katayama, N. Utsumi, K. Murata, N. Arai, N. Kurono, and
T. Ohkuma, Org. Proc. Res. Dev., 2009, 13, 625.
5
.
.
T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, C. A. Sandoval, and R. Noyori, J. Am. Chem. Soc.,
2
006, 128, 8724; C. A. Sandoval, T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, and R. Noyori,
Chem. Asian J., 2006, 1–2, 102.
6
6
For asymmetric hydrogenation of ꢀ-chloro ketones catalyzed by ꢀ -arene/TsDPEN–Ru(II)
complexes, see: T. Ohkuma, K. Tsutsumi, N. Utsumi, N. Arai, R. Noyori, and K. Murata, Org. Lett.,
2
007, 9, 255.
T. Ohkuma, N. Utsumi, M. Watanabe, K. Tsutsumi, N. Arai, and K. Murata, Org. Lett., 2007, 9,
565.
(R)-2,3-Dihydro-3-benzofuranol (R)-2a: HPLC analytical conditions: column, CHIRALCEL OJ-H
4.6 mm i.d. x 250 mm); eluent, n-hexane/2-propanol = 99/1; flow rate, 1.5 mL/min; temp, 35 °C;
7
.
.
2
8
(
2
5
detection, UV 220 nm; retention time (t ) of (R)-2a, 34.4 min; t of (S)-2a, 31.9 min. [ꢀ] –61.6
R
R
D

HETEROCYCLES, Vol. 80, No. 1, 2010
145
2
5
(
c 1.68, CHCl ) [lit., [ꢀ] +47 (c 1.70, CHCl ), 73% ee, (S)-isomer, D. R. Boyd, N. D. Sharma, R.
3 D 3
1
Boyle, J. F. Malone, J. Chima, and H. Dalton, Tetrahedron: Asymmery, 1993, 4, 1307]. H NMR
(
400 MHz, CDCl ) ꢁ 1.88 (d, 1H, J = 7.3 Hz), 4.45 (dd, 1H, J = 2.7, 11.0 Hz), 4.54 (dd, 1H, J = 6.4,
3
1
3
1
1.0 Hz), 5.36 (m, 1H), 6.88–6.97 (m, 2H), 7.28 (m, 1H), 7.43 (m, 1H).
C NMR (100 MHz,
CDCl ) ꢁ 72.2, 79.1, 110.6, 121.0, 125.4, 128.2, 130.8, 160.2.
3
9
.
(R)-7-Methoxy-2,3-dihydro-3-benzofuranol (R)-2b:
HPLC analytical conditions: column,
CHIRALCEL OJ-H; eluent, n-hexane/2-propanol = 9/1; flow rate, 1.0 mL/min; temp, 35 °C;
2
5
detection, UV 220 nm; t of (R)-2b, 19.9 min; t of (S)-2b, 24.2 min. [ꢀ] –43.2 (c 1.00, CHCl3).
R
R
D
1
H NMR (400 MHz, CDCl ) ꢁ 1.97 (br d, 1H, J = 7.3 Hz), 3.89 (s, 3H), 4.51 (dd, 1H, J = 2.3, 10.5
3
Hz), 4.59 (dd, 1H, J = 6.4, 10.5 Hz), 5.38 (m, 1H), 6.86 (m, 1H), 6.91 (t, 1H, J = 7.8 Hz), 7.04 (m,
1
3
1
H).
C NMR (100 MHz, CDCl ) ꢁ 56.0, 72.8, 79.7, 113.1, 117.2, 121.8, 129.3, 145.1, 148.9.
3
1
The absolute configuration was estimated by H-NMR analysis after conversion to the (R)- and
(S)-MTPA esters as described in the literature, see: I. Ohtani, T. Kusumi, Y. Kashman, and H.
Kakisawa, J. Am. Chem. Soc., 1991, 113, 4092.
1
0. (S)-1-Indanol (S)-2c: HPLC analytical conditions: column, CHIRALCEL OB-H (4.6 mm i.d. x 250
mm); eluent, n-hexane/2-propanol = 9/1; flow rate, 0.5 mL/min; temp, 30 °C; detection, UV 220 nm;
2
5
25
t of (R)-2c, 11.1 min; t of (S)-2c, 16.2 min. [ꢀ] +31.2 (c 1.03, CHCl ) [lit., [ꢀ]D +29.8 (c 2.0,
R
R
D
3
CHCl ), 98% ee, (S)-isomer, J. S. Yadav, S. Nanda, P. T. Reddy, and A. B. Rao, J. Org. Chem., 2002,
3
1
6
7, 3900]. H NMR (400 MHz, CDCl ) ꢁ 1.71 (br s, 1H), 1.95 (m, 1H), 2.50 (m, 1H), 2.83 (m, 1H),
3
3
.06 (ddd, 1H, J = 4.6, 8.2, 15.6 Hz), 5.25 (dd, 1H, J = 6.0, 6.4 Hz), 7.21–7.34 (m, 3H), 7.42 (d, 1H,
1
3
J = 5.5 Hz).
C NMR (100 MHz, CDCl ) ꢁ 29.8, 36.0, 76.5, 124.2, 124.9, 126.7, 128.3, 143.3,
3
1
45.0.
1
1
1
1. For asymmetric hydrogenation of cycloalkanones catalyzed by the BINAP–Ir(I)–aminophosphine
system, see: X. Zhang, T. Taketomi, T. Yoshizumi, H. Kumobayashi, S. Akutagawa, K. Mashima,
and H. Takaya, J. Am. Chem. Soc., 1993, 115, 3318.
2. For asymmetric hydrogenation of aromatic ketones catalyzed by Ru(II) complexes with some
amine-based chiral ligands, see: H. Huang, T. Okuno, K. Tsuda, M. Yoshimura, and M. Kitamura, J.
Am. Chem. Soc., 2006, 128, 8716; M. Ito, Y. Endo, and T. Ikariya, Organometallics, 2008, 27, 6053.
3. Procedure for asymmetric hydrogenation of 4-chromanone (1d) with (S,S)-3: 4-Chromanone (1d)
(
2.97 g, 20.0 mmol) and (S,S)-3 (3.10 mg, 4.0 μmol) were placed in a 100-mL glass autoclave. The
atmosphere was replaced with Ar gas, and MeOH (3.3 mL) was added to this mixture. Hydrogen
was initially introduced into the autoclave at a pressure of 10 atm, before being reduced to 1 atm.
This procedure was repeated five times. Then the autoclave was pressurized with H gas (15 atm),
2
1
and the solution was stirred vigorously at 60 °C for 24 h. The H-NMR and chiral HPLC analysis

146
HETEROCYCLES, Vol. 80, No. 1, 2010
indicate that (S)-4-chromanol [(S)-2d] was obtained in 99% ee and >99% yield. Silica gel
chromatography (silica gel 60N (Kanto Chemical), eluent: Et O) of the crude product gave pure
2
(S)-4-chromanol [(S)-2d] in 99% ee and 99% isolated yield (2.98 g, colorless crystals). The HPLC
analytical conditions were the same as those described in note 8; t of (R)-2d, 30.3 min; t of (S)-2d,
R
R
2
5
5
25
1
2
5.5 min. [ꢀ]D –71.3 (c 0.50, EtOH) [lit., [ꢀ]D –77 (c 0.5, EtOH), 95% ee, (S)-isomer].
H
NMR (400 MHz, CDCl ) ꢁ 1.86 (br s, 1H), 2.00–2.17 (m, 2H), 4.26–4.31 (m, 2H), 4.79 (dd, 1H, J =
3
1
3
3
.7, 4.1 Hz), 6.84–6.94 (m, 2H), 7.19–7.32 (m, 2H).
3.2, 117.1, 120.6, 124.3, 129.6, 129.7, 154.6.
C NMR (100 MHz, CDCl ) ꢁ 30.8, 61.9,
3
6
1
1
1
4. (S)-6-Methyl-4-chromanol (S)-2e: HPLC analytical conditions were the same as those described in
2
5
5
25
note 8; t of (R)-2e, 27.2 min; t of (S)-2e, 22.1 min. [ꢀ] –38.7 (c 1.44, CHCl ) [lit., [ꢀ] –38
R
R
D
3
D
1
(
c 1.0, CHCl ), 98% ee, (S)-isomer]. H NMR (400 MHz, CDCl ) ꢁ 1.81 (br s, 1H), 1.98–2.15 (m,
3
3
2
H), 2.28 (s, 3H), 4.22–4.25 (m, 2H), 4.75 (dd, 1H, J = 3.7, 4.1 Hz), 6.75 (d, 1H, J = 8.2 Hz), 7.01
1
3
(dd, 1H, J = 1.8, 8.2 Hz), 7.11 (d, 1H, J = 1.8 Hz).
C NMR (100 MHz, CDCl ) ꢁ 20.5, 31.0, 61.9,
3
6
3.3, 116.8, 123.9, 129.79, 129.83, 130.4, 152.3.
5. ( S)-6-Chloro-4-chromanol (S)-2f: HPLC analytical conditions were the same as those described in
2
5
5
25
note 8; t of (R)-2f, 33.1 min; t of (S)-2f, 34.8 min. [ꢀ] –26.3 (c 1.00, CHCl ) [lit., [ꢀ] –24 (c
R
R
D
3
D
1
1
2
2
1
.0, CHCl ), 98% ee, (S)-isomer]. H NMR (400 MHz, CDCl ) ꢁ 1.89 (br s, 1H), 1.99–2.16 (m,
3
3
H), 4.23–4.29 (m, 2H), 4.76 (dd, 1H, J = 4.1, 4.6 Hz), 6.78 (d, 1H, J = 9.2 Hz), 7.15 (dd, 1H, J =
1
3
.7, 9.2 Hz), 7.30 (d, 1H, J = 2.7 Hz).
C NMR (100 MHz, CDCl ) ꢁ 30.6, 62.2, 63.1, 118.5, 125.2,
3
25.6, 129.1, 129.6, 153.2.
6. ( S)-4-Thiochromanol (S)-2g: HPLC analytical conditions: column, CHIRALCEL OD (4.6 mm i.d.
x 250 mm); eluent, n-hexane/2-propanol = 98/2; flow rate, 1.0 mL/min; temp, 35 °C; detection, UV
2
5
22
2
20 nm; t of (R)-2g, 27.4 min; t of (S)-2g, 21.0 min. [ꢀ] –136 (c 1.00, CHCl ) [lit., [ꢀ] –136
R R D 3 D
(
c 1.00, CHCl ), 97% ee, (S)-isomer, C. V. Ursini, G. H. M. Dias, and J. A. R. Rodrigues, J.
3
1
Organomet. Chem., 2005, 690, 3176]. H NMR (400 MHz, CDCl ) ꢁ 1.84 (br s, 1H), 2.05 (m, 1H),
3
2
7
1
.35 (m, 1H), 2.86 (ddd, 1H, J = 3.7, 5.5, 12.4 Hz), 3.32 (dt, 1H, J = 12.4, 2.8 Hz), 4.81 (m, 1H),
1
3
.05–7.18 (m, 3H), 7.31 (d, 1H, J = 6.9 Hz).
C NMR (100 MHz, CDCl ) ꢁ 21.5, 30.0, 66.5, 124.3,
3
26.7, 128.4, 130.3, 133.2, 134.6.
1
7. ( S)-4-Thiochromanol 1,1-dioxide (S)-2h: HPLC analytical conditions were the same as those
2
5
1
described in note 9; t of (R)-2h, 34.3 min; t of (S)-2h, 37.8 min. [ꢀ] +5.1 (c 1.00, CHCl3).
H
R
R
D
NMR (400 MHz, CDCl ) ꢁ 2.30 (d, 1H, J = 5.5 Hz), 2.55 (m, 1H), 2.75 (m, 1H), 3.30 (ddd, 1H, J =
3
3
.2, 7.8, 14.2 Hz), 3.72 (ddd, 1H, J = 3.2, 11.0, 14.2 Hz), 4.93 (dd, 1H, J = 5.5, 9.2 Hz), 7.51–7.61
1
3
(m, 3H), 7.90 (d, 1H, J = 8.2 Hz).
C NMR (100 MHz, CDCl ) ꢁ 29.4, 46.5, 65.7, 123.6, 129.1,
3
1
1
29.7, 133.0, 137.7, 137.8. The absolute configuration was estimated by H-NMR analysis after

HETEROCYCLES, Vol. 80, No. 1, 2010
147
9
conversion to the (R)- and (S)-MTPA esters as described in the literature.
1
8. ( S)-1-tert-Butoxycarbonyl-1,2,3,4-tetrahydro-4-quinolinol (S)-2i: HPLC analytical conditions were
2
5
the same as those described in note 8; t of (R)-2i, 21.6 min; t of (S)-2i, 18.6 min. [ꢀ] –27.7 (c
R
R
D
1
1
.04, CHCl3). H NMR (400 MHz, CDCl ) ꢁ 1.53 (s, 9H), 1.85 (br s, 1H), 1.98–2.11 (m, 2H), 3.59
3
(ddd, 1H, J = 3.7, 9.6, 13.3 Hz), 4.05 (ddd, 1H, J = 4.6, 6.0, 13.3 Hz), 4.77 (t, 1H, J = 4.6 Hz), 7.07
1
3
(m, 1H), 7.25 (m, 1H), 7.38 (m, 1H), 7.78 (m, 1H),
C NMR (100 MHz, CDCl ) ꢁ 28.3, 31.9, 40.4,
3
6
5.9, 81.2, 123.4, 123.6, 127.9, 128.2, 130.5, 137.8, 153.6. The absolute configuration was
1
estimated by H-NMR analysis after conversion to the (R)- and (S)-MTPA esters as described in the
9
literature.
1
2
9. For asymmetric hydrogenation of 1-tetralones catalyzed by BINAP/chiral 1,4-diamine–Ru(II)
complexes, see: T. Ohkuma, T. Hattori, H. Ooka, T. Inoue, and R. Noyori, Org. Lett., 2004, 6, 2681.
0. ( S)-1-Tetralol (S)-2j: HPLC analytical conditions were the same as those described in note 8; t of
R
2
5
19
23
(
R)-2j, 14.6 min; t of (S)-2j, 13.3 min. [ꢀ]D +31.1 (c 1.05, CHCl ) [lit., [ꢀ] –33.5 (c 1.01,
R
3
D
1
CHCl ), 99% ee, (R)-isomer]. H NMR (400 MHz, CDCl ) ꢁ 1.65 (br s, 1H), 1.76–2.02 (m, 4H),
3
3
2
.71–2.86 (m, 2H), 4.79 (dd, 1H, J = 3.7, 5.5 Hz), 7.11 (m, 1H), 7.18–7.22 (m, 2H), 7.43 (m, 1H),
1
3
C NMR (100 MHz, CDCl ) ꢁ 18.7, 29.2, 32.2, 68.1, 126.1, 127.5, 128.6, 129.0, 137.1, 138.7.
3