Induction of axially chiral N-C bonds in N-aryl acridane and related complexes by chromium tricarbonyl migration reactions

Article abstract of DOI:10.1039/c0cc00836b

The thermal chromium tricarbonyl migration reaction induced axially chiral N-C bonds of N-aryl acridane and related complexes in good yield with outstanding enantiomeric excess.

Full text of DOI:10.1039/c0cc00836b

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Induction of axially chiral N–C bonds in N-aryl acridane and related
complexes by chromium tricarbonyl migration reactionsw
Akiyoshi Mori,a Shunsuke Kinoshita,a Masaru Furusyob and Ken Kamikawa*a
Received 9th April 2010, Accepted 30th July 2010
DOI: 10.1039/c0cc00836b
The thermal chromium tricarbonyl migration reaction induced
axially chiral N–C bonds of N-aryl acridane and related com-
plexes in good yield with outstanding enantiomeric excess.
The stereoselective synthesis of axially chiral N–C bonds is
gaining increasing attention1 because of their potential use in
asymmetric reactions2 and as intermediates for the synthesis of
biologically active natural products,3 agricultural herbicides,
and fungicides.4 Among the compounds with axially chiral
Scheme 2 Induction of axially chiral N–C bond utilizing N-aryl
N–C bonds, the stereoselective synthesis of axially chiral
anilide has been intensively studied and some outstanding
carbazole chromium complex.
methods involving catalytic and enantioselective syntheses
have been reported.5 On the other hand, we previously reported
the diastereoselective synthesis of N-aryl indoles, another class
of compounds with axially chiral N–C bonds.6 During the
course of our study, we found that the chromium tricarbonyl
(Cr(CO)3) group migrates7 to the benzene ring of indole in a
diastereoselective manner. This result prompted us to investi-
gate the possibility of exploring novel types of axially chiral
induction involving Cr(CO)3 migration. The concept of this
research is shown in Scheme 1.
obtained in 30% yield in the diastereomerically pure form. The
stereochemistry of 4 was judged from 1H-NMR that the
Cr(CO)3 group oriented toward the same side as the dioxolane
group, since the chemical shift of the methine proton in a
dioxolanyl group shifted 0.46 ppm lower field than that of 3
due to the anisotropic effect of the Cr(CO)3 group.9 However,
it was found that the enantiomeric excess (ee) of 4, which
indicates not only the ee of the planar chirality but also that of
the N–C axial chirality induced by desymmetrization, was only
17% (Scheme 2). On the other hand, when this migration
reaction was stopped at 30 min, the ee of 4 was improved to
70%. The results indicate that the racemization proceeds from
the enantiomerically enriched migrated complex during reflux
for a long time.10 This would be caused by the slippage of the
Cr(CO)3 group through the conjugated aromatic system of
carbazoles (Scheme 3).11
If the Cr(CO)3 group in complex 1 that has a prochiral N–C
bond axis could stereoselectively migrate to the neighboring
arene ring while avoiding steric hindrance, not only planar
chirality but also N–C axial chirality would be simultaneously
induced by the desymmetrization in complex 2.
In line with this idea, the induction of an axially chiral N–C
bond utilizing an N-aryl carbazole chromium complex was
initially investigated.
First, optically active complex 38 was refluxed in toluene
When the slippage occurred from one benzene ring to
the other benzene ring of carbazole, both axial and planar
chiralities were simultaneously inverted to form the corres-
ponding enantiomer. Thus, this process is presumed to cause
racemization of the newly formed Cr(CO)3 migrated complex.
Therefore, if this p-conjugated system of carbazoles was
changed to a non-conjugated one, such as acridane, the racemi-
zation via slippage of the Cr(CO)3 group would be suppressed.
To confirm this hypothesis, we next examined the Cr(CO)3
migration reaction utilizing symmetrical non-conjugated N-aryl
complexes (Table 1). To our delight, the migration reaction of
N-aryl acridane chromium complex 5a proceeded smoothly to
give product 6a in 78% yield with 99% ee without any loss of
enantiomeric purity of the planar chirality of 5a. Therefore,
solution for two hours. As a result, migrated complex 4 was
Scheme 1 Concept for induction of axially chiral N–C bond by
chromium tricarbonyl migration reaction.
a Department of Chemistry, Graduate School of Science,
Osaka Prefecture University Sakai, Osaka 599-8531, Japan.
E-mail: kamikawa@c.s.osakafu-u.ac.jp; Fax: +81 72-254-9931;
Tel: +81 72-254-9721
b Analysis Technology Research Center, Sumitomo Electric Industries
Ltd., 1-1-1, Koyakita, Itami, Hyogo, 664-0016, Japan
w Electronic supplementary information (ESI) available: Details of
synthetic methods, analyses. CCDC 768398 (7). For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/
c0cc00836b
Scheme 3 Racemization via slippage.
c
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Table 1 Induction of axially chiral N–C bonds in acridane and
related chromium complexes
both planar and N–C axial chiralities were induced with high
stereoselectivity.12 The stereochemistry of the migrated
chromium complex 6a was confirmed by the X-ray analysis
of hydrolyzing complex 7.z It was revealed that the Cr(CO)3
group oriented toward the same side as the aldehyde group,
and therefore, the Cr(CO)3 group was directed toward the
acetal group in complex 6a. This result is in good agreement
with our previous studies (Fig. 1).6
These migration reactions required the acetal group as a
directing group. When the acetal group was changed to a 1,3-
dioxane group, the ee of the product was decreased to 89%.
Other functional groups, such as MOMOCH2 or ethyl groups,
are not effective for the migration reaction (entries 3 and 4).
When 2,7-dimethylacridane complex 5e was used, the migration
reaction proceeded slowly and required a longer time (4.5 h).
As a result, the ee of the migrated product was slightly
decreased to 98% (entry 5). Phenoxazine complex 5f gave
the product with 94% ee (entry 6). Then, ortho-trisubstituted
complexes were also examined. When N-arylacridane complex
5g was refluxed, the migrated product was formed in 61%
yield with 99% ee along with an inseparable diastereomer
based on the planar chirality and the axial one (entry 7).13 In
the case of phenoxazine complexes 5h and 5i, the ee of the
product was slightly decreased to 95% (entries 8 and 9). When
phenothiazine complex 5j was used, ee dropped markedly to
85% (entry 10).
Yield
(%)
ee
(%)
Entry Substrate
Product
dr
1
2
3
4
5a
5b
5c
5d
78
70
>99 : o1 99
>99 : o1 89
a
—
—
—
—
—
—
—
We also conducted the diastereoselective transformation of
6a utilizing a newly formed planar chirality of the complex
(Scheme 4). Thus, complex 6a was treated with nBuLi and
subsequent trapping with MeI from the exo side of the
Cr(CO)3 group to give complex 8 as a single diastereomer.
Therefore, the central chirality was also introduced from a
single mobile chiral auxiliary.
a
—
5b
5e
42
>99 : o1 98
>99 : o1 94
Interestingly, identical 8 was also synthesized via a nucleo-
philic reaction with 9-methylacridane and a subsequent dia-
stereoselective Cr(CO)3 migration in one pot. Thus, planar,
axial, and central chiralities were newly formed at the same
time in a stereoselective manner (Scheme 5). The stereoselective
formation of complex 8 would be caused by a structural
difference between complexes 10 and 11 which were formed in
the course of the reaction as an inseparable mixture. The
chromium tricarbonyl migration would preferentially occur
from diastereomer 11 whose methyl group in an acridane
fragment oriented toward the opposite side as the directing
group.
6
7
8
9
5f
5g
5h
5i
60
61
73
60
71
87 : 13
85 : 15
99
95
We have succeeded in the induction of axially chiral N–C
bonds of N-aryl acridane and related chromium complexes by
>99 : o1 95
>99 : o1 85
10
5j
a
b
Starting material was recovered. The reaction was carried out for 4.5 h.
Fig. 1 ORTEP drawing of complex 7.
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Scheme 4 Diastereoselective transformation utilizing the migrated
planar chirality of complex 6a.
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Scheme 5 Synthesis of complex 8 by nucleophilic substitution and
chromium tricarbonyl migration reaction in one pot.
diastereoselective Cr(CO)3 migration. Further applications are
under investigation in our laboratory.
Notes and references
8 The absolute stereochemistry of the planar chirality in the complex
3 was determined as (1R, 2S). See ESIw for details.
ꢀ
z Crystal data for 7: C27.5H23CrNO4, M = 483.48, triclinic, P1,
a = 10.867(4), b = 14.490(7), c = 14.911(4), V = 2293.2(1) A3,
9 (a) M. Uemura, H. Nishimura, K. Kamikawa and M. Shiro, Inorg.
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10 Isolated complex 4 was refluxed in toluene for further 2 h, however
formation of complex 3 was not observed.
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12 Direct chromium complexation with Cr(CO)6 in non-chromium
coordinated N-arylacridane 5a gave complex mixture of mono-
and dichromium coordinated complexes.
Z = 4, Dc = 1.4000 g cmꢀ3, m(MoKa) = 0.71075 mmꢀ1, F(000) =
1004.00, T = 296 K, 22 335 reflections collected, 10 174 unique (Rint =
0.024), R1 = 0.047 (I > 3s(I)), wR2 = 0.145 (I > 3s(I)), S = 1.03.
Data collection was carried out using the RIGAKU RAXIS RAPID,
and SHELXL97 programs were used for the structure solution and
refinement.
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See ESIw for details.
c
6848 Chem. Commun., 2010, 46, 6846–6848
This journal is The Royal Society of Chemistry 2010