Chiral aminoborane as a chiral proton source for asymmetric protonation of lithium enolates derived from 2-arylcycloalkanones

Article abstract of DOI:10.1039/a803756f

Reaction of lithium enolates of 2-arylcycloalkanones 2 with (R,R)-aminoborane 1, prepared from (1R,2R)-1,2-diaminocyclohexane 4 and PhBCl2, gives the corresponding optically active ketones 3 with up to 93% ee; this is the first example of enantioselective protonation using a metal-containing chiral proton source.

Full text of DOI:10.1039/a803756f

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Chiral aminoborane as a chiral proton source for asymmetric protonation of
lithium enolates derived from 2-arylcycloalkanones
Akira Yanagisawa, Hiroshi Inanami and Hisashi Yamamoto*†
Graduate School of Engineering, Nagoya University, CREST, Japan Science and Technology Corporation (JST), Chikusa,
Nagoya, 464-8603, Japan
Reaction of lithium enolates of 2-arylcycloalkanones 2 with
(R,R)-aminoborane 1, prepared from (1R,2R)-1,2-diamino-
cyclohexane 4 and PhBCl2, gives the corresponding optically
active ketones 3 with up to 93% ee; this is the first example
of enantioselective protonation using a metal-containing
chiral proton source.
H
N
H
N
Ph
Ph
R
R
S
S
H
N
BR
BPh
N
H
N
H
14
BPh
N
H
1 R = Ph
8 R = 2-MeC6H4
11 R = 9-anthryl
9 R = 3,5-(CF3)2C6H3 12 R = Bun
10 R = 2,4,6-Me3C6H2 13 R = Cl
15
Asymmetric protonation of prochiral metal enolates has proved
to be an efficient method for the synthesis of chiral carbonyl
compounds.1 The success of this process depends on the
structure and acidity of the chiral proton source. Several chiral
acids have been developed so far, and have been applied to
enantioselective protonations.2–4 However, as far as we know,
there are no reports on a proton source containing metal atoms.
We describe here a new enantioselective protonation of lithium
enolates 2 with chiral aminoborane 1 [eqn. (1)].
enantioselectivity, while the chemical yield increased (entry 7).
As a consequence, (R,R)-aminoborane 1 was the most effective
chiral proton source for the protonation of 6.
This asymmetric protonation was applied to a variety of
lithium enolates of ketones 17, and the results with (R,R)-
aminoborane 1 are summarized in Table 2. These reactions have
the following characteristics: (i) all of the reactions proceeded
to give a satisfactory yield at 278 °C for 2 h, except for the
lithium enolate of 2-methylindanone 22, which gave a low yield
due to concomitant side reactions (entry 5); (ii) moderate to high
asymmetric induction occurred in the protonation of lithium
enolates 6, 19–21 and 29, which possess an aryl group at the C-2
position (entries 1–4 and 12). The highest enantioselectivity
(93% ee) was obtained with the enolate of 2-(2-naph-
thyl)cyclohexanone 21 (entry 4). The enolates 22, 23, 27 and 28
derived from 2-methylindanone, 2-methyltetralone and their
derivatives also gave good optical purities (entries 5, 6, 10, and
11). However, the use of simple substrates bearing no aromatic
H
N
R
BPh
OLi
O
N
H
R
Ar
Ar
(R,R)-aminoborane 1
*
(1)
(CH2)n
(CH2)n
2
3
Heteroatom-substituted chiral boron compounds such as
oxazaborolidines and acyloxyboranes are well-known as chiral
Lewis acid catalysts for various asymmetric reactions.5 High
levels of asymmetric induction are obtained in Diels–Alder
reactions or Mukaiyama aldol reactions, and the formation of a
stable complex of a boron catalyst with a carbonyl compound is
regarded as the key to success. We considered that if a chiral
aminoborane could form a rigid cyclic transition state structure
with a lithium enolate, and if the amide proton is acidic enough,
a highly enantioselective protonation might occur.
Table 1 Protonation of the lithium enolate 6 with chiral aminoboranes 1 and
8–15a
OSiMe3
OLi
O
(i) chiral aminoborane
THF, –78 °C, 2 h
Ph
Ph
Ph
*
BunLi
THF, 0 °C
(ii) Me3SiCl
Chiral aminoborane 1 was synthesized from (1R,2R)-
1,2-diaminocyclohexane 4 (2 equiv.) and PhBCl2 (1 equiv.) in
toluene [eqn. (2)].6 The resulting ammonium salt was filtered
5
6
7
Chiral
aminoborane
Entry
Yield (%)b
Ee (%)c Configurationd
H
R
NH2
NH2
N
1
2
3
4
5
6
7
8
9
1
8
9
10
11
12
13
14
15
94
83
65
17
14
74
> 99
20
84
60
47
5
S
S
S
S
R
S
S
R
S
ammonium
salt
(2)
+
+
BPh
PhBCl2
2
toluene
N
H
R
4
1
3
20
44
32
6
off. Treatment of lithium enolate 6, generated from silyl enol
ether 5 and BunLi/hexane (1.1 equiv.) in THF at 0 °C,7 with a
solution of (R,R)-aminoborane 1 (1.5 equiv.) in toluene–THF
(1:1) at 278 °C for 2 h followed by quenching with Me3SiCl (to
remove unreacted 6) at 278 °C gave (S)-enriched 2-phenyl-
cyclohexanone 7 in 94% yield and 84% ee (Table 1, entry 1).‡
Using various chiral aminoboranes, we studied the enantiose-
lectivity of this protonation; yields and enantiomeric excesses of
the product 7 obtained by reactions with other chiral aminobor-
anes 8–15 in THF at 278 °C are shown in Table 1. Substitution
of the phenyl group of 1 by a chlorine atom resulted in a lower
19
a
The lithium enolate 6 was generated from the corresponding silyl enol
ether 5 (1 equiv.) and a solution of BunLi/hexane (1.1 equiv.) in THF at
0 °C for 2 h. The following protonation was carried out using a chiral
aminoborane (1.5 equiv.) in THF at 278 °C for 2 h. The reaction was
quenched by TMSCl at 278 °C to exclude the unreacted enolate 6.
b
c
Isolated yield. Determined by HPLC analysis (Chiralcel OD-H, Daicel
Chemical Industries, Ltd.). d The absolute configuration was determined by
comparison of the [a]D value with reported data [ref. 3(c)].
Chem. Commun., 1998
1573

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Table 2 Enantioselective protonation of various enolates with (R,R)-
aminoborane 1a
2-phenylcyclopentanone or 2-phenylcycloheptanone with re-
spect to enantioselectivity (compare entries 1–3); and (iv)
introduction of an electron-donating group to the aromatic ring
improved the enantiomeric ratios to some extent (entries 11 and
12).
OSiMe3
R
OLi
O
(i) 1, THF
–78 °C, 2 h
BunLi
R
R
THF, 0 °C
(ii) Me3SiCl
(CH2)n
(CH2)n
(CH2)n
Notes and References
16
17
18
† E-mail: j45988a@nucc.cc.nagoya-u.ac.jp
‡ Procedure for protonation of lithium enolate 6 with (R,R)-aminoborane 1:
To a solution of (1R,2R)-1,2-diaminocyclohexane (172 mg, 1.5 mmol) in
dry toluene (4 ml) was added PhBCl2 (97 µl, 0.75 mmol) at 278 °C. The
mixture was warmed to room temperature and again stirred for 2.5 h at this
temperature. The resulting ammonium salt was filtered off under an argon
atmosphere and washed with dry THF (2 ml). To the filtrate was added at
278 °C a solution of lithium enolate 6, prepared from trimethylsilyl enol
Configura-
tione
Entry
Lithium enolateb
Yield (%)c Ee (%)d
OLi
Ph
1
70
94
34f (36)f,g
—
Sh
19 (95:5)
OLi
ether 5 (123 mg, 0.5 mmol) and BunLi (1.67
M hexane solution, 0.33 ml,
Ph
0.55 mmol) in dry THF (2.3 ml) at 0 °C, through a stainless steel cannula
under an argon stream. After being stirred for 2 h at 278 °C, TMSCl (65 µl,
0.5 mmol) was added, and stirring continued for another 30 min at this
temperature. The reaction mixture was treated with saturated aqueous
NH4Cl, extracted with Et2O , dried (Na2SO4), and finally purified by
column chromatography on silica gel to give (S)-enriched 2-phenyl-
cyclohexanone [(S)-7, 94% yield] with 84% ee. The enantiomeric ratio was
determined by HPLC analysis using a chiral column (Chiralcel OD-H,
Daicel Chemical Industries, Ltd.). The absolute configuration was deter-
mined by comparison of its optical rotation with published data; (S)-isomer
2
3
4
84
6 (>99:1)
OLi
Ph
69
84
70f (77)f,g
89 (93)g
—
20 (91:9)
OLi
—
—
29
(87% ee): [a]D 288.9 (c 1.0, CHCl3) [ref. 3(c)]. Observed value of
21 (96:4)
28
(S)-isomer (84% ee): [a]D 294.1 (c 1.1, CHCl3).
OLi
1 Reviews: L. Duhamel, P. Duhamel, J.-C. Launay and J.-C. Plaquevent,
Bull. Soc. Chim. Fr., 1984, II-421; C. Fehr, Chimia, 1991, 45, 253; H.
Waldmann, Nachr. Chem., Tech. Lab., 1991, 39, 413; S. Hünig, in
Houben-Weyl: Methods of Organic Chemistry; ed. G. Helmchen, R. W.
Hoffmann, J. Mulzer and E. Schaumann, Georg Thieme Verlag, Stuttgart,
1995, vol. E 21, p. 3851; C. Fehr, Angew. Chem., Int. Ed. Engl., 1996, 35,
2566.
5
6
26
80
60
70
22
23
OLi
Si
2 Recent reports: Y. Nakamura, S. Takeuchi, A. Ohira and Y. Ohgo,
Tetrahedron Lett., 1996, 37, 2805; J. Muzart, F. He´nin and S. J.
Aboulhoda, Tetrahedron: Asymmetry, 1997, 8, 381; Y. Nakamura, S.
Takeuchi, Y. Ohgo, M. Yamaoka, A. Yoshida and K. Mikami,
Tetrahedron Lett., 1997, 38, 2709; H. Kosugi, M. Abe, R. Hatsuda, H.
Uda and M. Kato, Chem. Commun., 1997, 1857; J. Martin, M.-C. Lasne,
J.-C. Plaquevent and L. Duhamel, Tetrahedron Lett., 1997, 38, 7181.
3 Enantioselective protonation of silyl enol ethers and ketene silyl acetals:
(a) F. Cavelier, S. Gomez, R. Jacquire and J. Verducci, Tetrahedron:
Asymmetry, 1993, 4, 2501; (b) F. Cavelier, S. Gomez, R. Jacquire and J.
Verducci, Tetrahedron Lett., 1994, 35, 2891; (c) K. Ishihara, M. Kaneeda
and H. Yamamoto, J. Am. Chem. Soc., 1994, 116, 11 179; (d) K. Ishihara,
S. Nakamura and H. Yamamoto, Croat. Chem. Acta, 1996, 69, 513; (e) K.
Ishihara, S. Nakamura, M. Kaneeda and H. Yamamoto, J. Am. Chem.
Soc., 1996, 118, 12854; (f) T. Taniguchi and K. Ogasawara, Tetrahedron
Lett., 1997, 38, 6429; (g) M. Takahashi and K. Ogasawara, Tetrahedron:
Asymmetry, 1997, 8, 3125; (h) M. Sugiura and T. Nakai, Angew. Chem.,
Int. Ed. Engl., 1997, 36, 2366.
4 For examples of simple enolates: (a) H. Hogeveen and L. Zwart,
Tetrahedron Lett., 1982, 23, 105; (b) M. B. Eleveld and H. Hogeveen,
Tetrahedron Lett., 1986, 27, 631; (c) K. Matsumoto and H. Ohta,
Tetrahedron Lett., 1991, 32, 4729; (d) K. Fuji, K. Tanaka and H.
Miyamoto, Tetrahedron: Asymmetry, 1993, 4, 247; (e) K. Fuji, T.
Kawabata and A. Kuroda, J. Org. Chem., 1995, 60, 1914; (f) T.
Takahashi, N. Nakao and T. Koizumi, Chem. Lett., 1996, 207; (g) H.
Kosugi, K. Hoshino and H. Uda, Tetrahedron Lett., 1997, 38, 6861; (h)
T. Tsunoda, H. Kaku, M. Nagaku and E. Okuyama, Tetrahedron Lett.,
1997, 38, 7759; (i) P. Riviere and K. Koga, Tetrahedron Lett., 1997, 38,
7589; (j) T. Takahashi, N. Nakao and T. Koizumi, Tetrahedron:
Asymmetry, 1997, 8, 3293.
OLi
7
8
69
>99
93
Si
1j
24 (96:4)
OLi
Sl
16k
25
OLi
9
8
m (10)g,m
Ri
—
—
Ph
26 (84:16)
OLi
10
11
64
88
47
78
Ph
27
OLi
MeO
OLi
28
OMe
81 (86)g
—
12
92
29 (94:6)
a
b
All conditions are the same as in Table 1. Parentheses indicate the
regioisomeric ratio of the starting silyl enol ethers 16. Isolated yield.
c
d
Determined by HPLC analysis (Chiralcel OD-H, Daicel Chemical
5 M. Vaultier and B. Carboni, in Comprehensive Organometallic Chem-
istry II, ed. E. W. Abel, F. G. A. Stone and G. Wilkinson, Pergamon,
Oxford, 1995, vol. 11, p. 247.
6 A review of the preparation of aminoboranes: M. F. Lappert, P. P. Power,
A. R. Sanger and R. C. Srivastava, Metal and Metalloid Amides, Ellis
Horwood, Chichester, 1980, p. 76.
7 BunLi can be used for cleavage of the Si–O bond of silyl enol ether 5
instead of MeLi. Generation of lithium enolates: E. W. Colvin, Silicon in
Organic Synthesis; Butterworth: London, 1981, p. 217.
e
Industries, Ltd.).
The absolute configuration was determined by
f
comparison of the [a]D value with reported data. Determined by HPLC
analysis (Chiralpak AS, Daicel Chemical Industries, Ltd.). Corrected
value based on the regioisomeric ratio of the starting silyl enol ether 16.
Ref. 3(c). Ref. 8. Determined by GC analysis with chiral column
(ChiraldexTM B-TA, astec). Determined by GC analysis with chiral
column (ChiraldexTM G-TA, astec). Ref. 4(b). Determined by HPLC
analysis (Chiralcel OJ, Daicel Chemical Industries, Ltd.).
g
h
i
j
k
l
m
8 A. I. Meyers, D. R. Williams, G. W. Erickson, S. White and M.
Druelinger, J. Am. Chem. Soc., 1981, 103, 3081.
groups gave unsatisfactory results (entries 7 and 8); (iii) a
lithium enolate of 2-phenylcyclohexanone is superior to that of
Received in Cambridge, UK, 19th May 1998; 8/03756F
1574
Chem. Commun., 1998