Scandium triflate-promoted addition of organozinc reagents to benzaldiminetricarbonylchromium derivatives

Article abstract of DOI:10.1080/00397910701490147

The reaction of benzaldiminetricarbonylchromium derivatives with organozinc reagents in the presence of scandium triflate afforded a single diastereomer of the corresponding amine complex exclusively. Even in the case of benzaldiminetricarbonylchromium ha

Full text of DOI:10.1080/00397910701490147

Synthetic Communicationsw, 37: 3351–3358, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701490147
Scandium Triflate–Promoted Addition of
Organozinc Reagents to
Benzaldiminetricarbonylchromium
Derivatives
Kaori Ishimaru, Kyoko Ohe, and Takakazu Kojima
Department of Chemistry, National Defense Academy, Hashirimizu,
Yokosuka, Japan
Abstract: The reaction of benzaldiminetricarbonylchromium derivatives with
organozinc reagents in the presence of scandium triflate afforded a single diastereomer
of the corresponding amine complex exclusively. Even in the case of benzaldiminetri-
carbonylchromium having an m-substituent of the aromatic ring, one diastereomer was
obtained using the o-TMS-protected chromium complex. The TMS group and the
chromium moiety were easily removed and the benzyl group was deprotected using
HOOH and Pd to afford the corresponding amine.
Keywords: imines, organozinc reagents, stereocontrol
Stereoselective nucleophilic addition to benzaldiminetricarbonylchromium
derivatives that have a planar chiral moiety[1–3] is an important transformation
for constitiution of chiral amines, because the bulkiness of the tricarbonyl-
chromium moiety plays an important role promoting the reaction with quite
high facial selectivities, and the tricarbonylchromium moiety is easily
removed by air and sunlight. Recently, we reported diastereoselective
addition of organozinc reagents to the benzaldiminetricarbonylchromium
[4]
derivatives in the presence of BF3 Et2O. Though the reaction of the
.
Received October 26, 2006
Address correspondence to Kaori Ishimaru, Department of Chemistry, National
Defense Academy, Hashirimizu 1-10-20, Yokosuka 239–8686, Japan. E-mail:
kaoriisi@nda.ac.jp
3351

3352
K. Ishimaru, K. Ohe, and T. Kojima
chromium complex having a m-substituted aromatic ring at the a-position of
the benzaldimine moiety gave both diastereomers (62% de), single diastereo-
mers were observed in the case of the complexes having an o-substituted
aromatic ring. Herein, we describe the diastereoselective reaction of the ben-
zaldiminetricarbonylchromium derivatives having an N-benzyl group with
organozinc reagents in the presence of Sc(OTf)3 to give one diastereomer of
the corresponding chromium complex, even in the case of the chromium
complex having an m-substituted aromatic ring. Deprotection of the tricarbo-
nylchromium moiety and the N-benzyl group of the products afforded the cor-
responding amines, which would be useful for synthesis of natural products.[5]
We first examined the reaction of benzaldiminetricarbonylchromium
derivatives[6] with benzylzinc bromide using various Lewis acids
(Scheme 1). Many examples using the chromium complexes having an
N-aryl group have been reported;[7] however, there are few reports on the
reactions of the complexes having N-alkyl or other functional groups. We
tried the reactions of the complexes (1a–1c) having an N-TMS, N-tosyl, or
1
N-methyl group, but no product was detected by H NMR under the various
reaction conditions. Fortunately, the use of an N-benzyl group gave the corre-
sponding chromium complex in the presence of SnCl4 or Sc(OTf)3 (Table 1,
entries 2–7). Removal of the tricarbonylchromium moiety of the complex by
using air and sunlight led to the secondary amine. Using Sc(OTf)3 (2 equiv. to
the chromium complex) afforded excellent de of the product in 99% yield
(entry 3). A catalytic amount of Sc(OTf)3 (0.5 equiv. to the chromium
complex) produced 50% yield of the product (entry 4). We also examined
the reaction of o- or m-substituted benzaldiminetricarbonylchromium deriva-
tives in the presence of Sc(OTf)3 (entries 5–7). A single diastereomer was
obtained using the chromium complex having an o-substituted aromatic
Scheme 1. Addition of benzylzinc bromide to benzaldiminetricarbonylchromium
derivatives.

Organozinc Reagents with Scandium Triflate
3353
Table 1. Reaction of the Chromium complexes in the presence of Lewis acids
Chromium
complex
Lewis acid (equiv to
complex)
Isolated yield
of 3 (%)b
Entry
De (%) of 2a
.
BF3 Et2O (2 equiv)
SnCl4 (2 equiv)
1
2
3
4
5
6
7
1d
1d
1d
1d
1e
1f
—
—
0
,30
99
Sc (OTf)3 (2 equiv)
Sc (OTf)3(0.5 equiv)
Sc (OTf)3 (2 equiv)
Sc (OTf)3 (2 equiv)
Sc (OTf)3 (2 equiv)
.95
.95
.95
.95
48
50
88
90
72
1g
1
aDetermined by H NMR of the crude product.
bYields after column chromatography.
ring; however, two diastereomers were observed in the case of the chromium
complex 1 g having an m-tolyl group (48% de, entry 7) where rotation
between the carbon atom of the C55N bond and the a-carbon of the
aldimine might decrease the diastereoselectivities.
To circumvent the problem, we used the TMS group at the ortho position
of the aromatic ring of the chromium complex,[8] which would lead to a
dramatic increase in diastereoselectivities. The chromium complex 1h was
prepared as shown in Scheme 2, starting from o-tolualdehyde.[9] As
expected, the reaction using the complex 1h selectively gave single diastereo-
mer 2h. The result indicated that using benzaldiminetricarbonylchromium
derivatives with an o-TMS-protected aromatic ring afforded one diastereomer
exclusively even though the complexes have m-substituents. After removal of
the chromium moiety, deprotection of the TMS group of the corresponding
product using tetrabutylammonium (TBAF) or aqueous HCl solution under
Scheme 2. Preparation of benzaldiminetricarbonylchromium derivative 1 h and its
reaction.

3354
K. Ishimaru, K. Ohe, and T. Kojima
Scheme 3. Deprotection of the benzyl group in 3d.
various conditions resulted in recovery of the starting materials. However,
TMS deprotection of the complex 2h and then removal of the tricarbonylchro-
mium moiety gave 82% yield of the product 3g.[8b] Deprotection of the
N-benzyl group in 3d was carried out using Pd and HCOOH in MeOH[10]
to give the corresponding amine in quantitative yield (Scheme 3).
In conclusion, we have developed diastereoselective reaction of benzaldi-
minetricarbonylchromium derivatives having o- and m-substituents of the
aromatic ring with organozinc reagents. Further studies to investigate the
chiral reactions and applications are now in progress.
EXPERIMENTAL
Typical Experimental Procedure for Reaction of
Benzaldiminetricarbonylchromium Derivatives
To a stirred solution of benzaldiminetricarbonylchromium derivatives
(0.24mmol) and scandium trifluoromethanesulfonate (0.47 g, 0.48 mmol) in
dry THF (5 mL), 1.5 ml (0.75 mmol) of benzylzinc bromide (0.5 M THF
solution) were added at room temperature. The solution was stirred at rt for
18 h, and the mixture was quenched with water. The mixture was extracted
with ether (20 mL ꢀ 3), and the combined organic layers were dried over
NaSO4. The precipitates were filtered off, and the solvent was evaporated to
give the crude chromium product. The diastereomeric ratio was determined
by 1H NMR. To the crude chromium product, dichloromethane (60 mL)
was added, and the mixture was exposed to air and sunlight for 1 h. The
solvent was evaporated, and ether was added to the mixture. The precipitates
were filtered off, and the solvent was evaporated to give the crude amine,
which was purified by flash-column chromatography on SiO2 (n-hexane/
EtOAc ¼ 3/1). Isolated yields were measured after the chromatography.
Deprotection of N-Benzyl Group in 3d[11]
To a stirred solution of 3d (1.5 g, 0.5 mmol) and Pd (0.8 g, 7.7 mmol) in dry
MeOH (5 mL), 0.22 mL of HCOOH was added. The mixture was stirred at rt
for 2 h, then monitored by thin-layer chromatography (TLC). Pd (0.8 g,
7.7 mmol) and HCOOH (0.22 mL) were further added to the solution and

Organozinc Reagents with Scandium Triflate
3355
stirred for 1 h. The mixture was quenched with sat. NaHCO3 solution and
extracted with ether. The combined organic layers were dried over Na2SO4,
and the mixture was filtered off. The solvent was evaporated to give 1.08 g
(100%) of the corresponding product 4d.
The products were identified by the following data.
Data
1
3d: H NMR (500 MHz, CDCl3); d 2.11 (s, 3H), 2.80–2.84 (m, 1H), 2.91
(m, 1H), 3.43 (d, 1H, J ¼ 13.4 Hz), 3.65 (d, 1H, J ¼ 13.4 Hz), 4.14–4.16
(m, 1H), 7.08–7.28 (m, 13H), 7.66–7.67 (m, 1H). HRMS-FAB(Mþ): Obsd.
m/z 301.1843. Calcd. for C22H23 N: 301.1830.
3e: 1H NMR (300 MHz, CDCl3); d 2.79–2.92 (m, 2H), 3.40 (d, 1H,
J ¼ 13.5 Hz), 3.60 (d, 1H, J ¼ 13.5 Hz), 3.70 (s, 3H), 3.77–3.82 (m, 1H),
6.98–7.22 (m, 14H). HRMS-FAB(M þ H)þ: Obsd. m/z 318.1874. Calcd.
for C22H24NO: 318.1858.
1
3f: H NMR (300 MHz, CDCl3); d 0.36 (s, 9H), 2.81 (dd, 1H, J ¼ 13.8,
9.8 Hz), 3.08 (dd, 1H, J ¼ 13.8, 3.7 Hz), 3.50–3.53 (m, 2H), 4.34 (dd, 1H,
J ¼ 9.8, 3.7 Hz), 7.01–7.31 (m, 14H). HRMS-FAB(Mþ): Obsd. m/z
359.2059. Calcd. for C24H29NSi: 359.2069.
1
3g: H NMR (500 MHz, CDCl3); d 2.28 (s, 3H), 2.76–2.90 (m, 2H), 3.37
(d, 1H, J ¼ 13.6 Hz), 3.58 (d, 1H, J ¼ 13.6 Hz), 3.74–3.79 (m, 1H), 6.99–
8.28 (m, 14H). HRMS-FAB(Mþ): Obsd. m/z 301.1815. Calcd. for
C22H23 N: 301.1830.
1
3h: H NMR (500 MHz, CDCl3); d 0.26 (s, 9H), 2.31 (s, 3H), 2.73 (dd, 1H,
J ¼ 14.0, 9.9 Hz), 3.00 (dd, 1H, J ¼ 14.0, 3.9 Hz), 3.46–3.51 (m, 2H), 4.24
(dd, 1H, J ¼ 9.9, 3.9 Hz), 7.09–7.60 (m, 13H). HRMS-FAB(Mþ): Obsd.
m/z 373.2216. Calcd. for C25H31NSi: 373.2226.
1
4d: H NMR (500 MHz, CDCl3); d 2.20 (s, 3H), 2.65 (dd, 1H, J ¼ 13.3,
8.9 Hz), 2.89 (dd, 1H, J ¼ 13.3, 4.5 Hz), 4.33 (dd, 1H, J ¼ 8.9, 4.5 Hz),
7.06–7.21 (m, 9H). HRMS-FAB(Mþ): Obsd. m/z 211.1365. Calcd. for
C15H17 N: 211.1361.
ACKNOWLEDGMENT
We thank Shinji Ohta and Mihoko Yanai, the Instrument Center for Chemical
Analysis, Hiroshima University, for help with the measurement of HRMS.

3356
K. Ishimaru, K. Ohe, and T. Kojima
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