Absolute configuration and chiroptical properties of an enantiopure [5-chloro-2-(dimethylaminomethyl)phenyl]-phenylborane complex

Article abstract of DOI:10.1246/bcsj.79.796

Enantiomers of the title intramolecular amine-borane complex with a B-pentafluoropropionyloxy ligand were resolved by chiral HPLC. X-ray analysis of the (+)-isomer revealed that the configuration of the chiral boron center was S by the Bijvoet method. Thu

Full text of DOI:10.1246/bcsj.79.796

796 Short Articles
Bull. Chem. Soc. Jpn. Vol. 79, No. 5, 796–798 (2006)
NMe2
Ph
NMe2
Absolute Configuration
R
R
B
B
OCOC2F5
and Chiroptical Properties
of an Enantiopure [5-Chloro-
2-(dimethylaminomethyl)phenyl]-
phenylborane Complex
OCOC2F5
Ph
1 R = H
2 R = Cl
(S)
(R)
Chart 1.
methylaminomethyl)phenyl ligand.7 When a pentafluoropro-
pionyloxy (C2F5COO–) group was introduced at the boron
atom, the configurational stability of the tetrahedral boron
atom was enhanced enough to isolate the enantiomers of 1 at
room temperature (Chart 1). The optical rotation and CD spec-
tra of these enantiomers were measured, but the absolute con-
figuration could not be determined yet because of the experi-
mental restrictions. Therefore, we prepared complex 2 carrying
a heavy atom for the application of the Bijvoet method by
X-ray crystallography. This paper describes the absolute con-
figuration and the chiroptical properties of 2 as an intramolec-
ular amine–borane complex.
ꢀ1
Shinji Toyota, Fumiko Ito,1
Toshiyuki Yamamoto,1 Haruo Akashi,2
and Tetsuo Iwanaga3
1Department of Chemistry, Faculty of Science,
Okayama University of Science,
1-1 Ridaicho, Okayama 700-0005
2Research Institute of Natural Sciences,
Okayama University of Science,
1-1 Ridaicho, Okayama 700-0005
Compound 2 was prepared in a similar manner to 1
(Scheme 1).7 Reaction of 4-chloro-N,N-dimethylbenzylamine
(3) with butyllithium gave the o-lithiated compound, which
was then treated with dichlorophenylborane to form compound
4. The reaction of this chloroborane with a silver acylate re-
agent gave the desired complex 2 in 88% yield. The 11B NMR
signal of 2 was observed at ꢀ 8.6 as a very broad peak, this
chemical shift being typical of tetracoordinated boron atoms.
A racemic sample of 2 was submitted to chiral HPLC with a
Chiralpak AD column with hexane–2-propanol 50:1 eluent.
The enantiomers were isolated with baseline separation. The
3Institute for Materials Chemistry and Engineering,
Kyushu University, 6-10-1 Hakozaki,
Higashi-ku, Fukuoka 812-8581
Received January 12, 2006; E-mail: stoyo@chem.ous.ac.jp
Enantiomers of the title intramolecular amine–borane
complex with a B-pentafluoropropionyloxy ligand were
resolved by chiral HPLC. X-ray analysis of the (þ)-isomer
revealed that the configuration of the chiral boron center
was S by the Bijvoet method. Thus, the absolute configura-
tion of this chiral borane compound was established as (S)-
(þ) or (R)-(ꢁ).
22
specific rotations of the first and second fractions were ½ꢁꢂD
ꢁ158 and þ157, respectively, in acetone. No racemization
was observed as far as the sample solution was treated at room
temperature. The CD spectra of (þ)- and (ꢁ)-2 were measured
in hexane (Fig. 1). The less easily eluted (þ)-isomer exhibits a
small trough at 228 nm and small peaks in the range of 255–
280 nm with a positive strong shoulder in the short wavelength
region (<220 nm). The CD spectrum of the (ꢁ)-isomer was
practically the mirror image of that of the (þ)-isomer.
Optically active compounds with a chiral center at a tetra-
hedral boron atom are stereochemically interesting in relation
to the chemistry of tetrahedral carbon atoms.1 Actually, several
types of borates and coordinated boranes have been enantio-
merically resolved by the diastereomer method or chiral HPLC
as stable entities at room temperature.2–4 For example, enantio-
pure borane complexes with a phosphine or an amine ligand
were applied to elucidate the SN2 mechanism at the boron
atoms.5,6 The absolute configuration of the boron atoms has
been established for some compounds by the X-ray analysis
of their derivatives carrying an internal reference of known
configuration.
The X-ray analysis was carried out with a single crystal of
the less easily eluted (þ)-isomer of 2. An ORTEP drawing
˚
is shown in Fig. 2. The B–N bond distance is 1.652(2) A and
the tetrahedral character (THC) of the boron atom is 56%.8
These structural parameters are comparable to those of 1 (B–N
7
˚
1.668(4) A, THC 56%). The carbonyl carbon atom is nearly
anti relative to the nitrogen atom (torsion angle ꢁ163:7ꢃ),
and the carbonyl oxygen atom and the pentafluoroethyl group
are almost syn and anti relative to the boron atom, respective-
ly. To determine the absolute configuration, structural refine-
ments were carried out for the structure shown in Fig. 2 and
We recently reported the structures and stereochemistry
of the intramolecular amine–borane complexes with a 2-(di-
1) BuLi
2) PhBCl2
NMe2
C2F5COO−Ag+
NMe2
2
Cl
B
Ph
Cl
Cl
3
4
Scheme 1.
Published on the web May 12, 2006; DOI: 10.1246/bcsj.79.796

Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
Ó 2006 The Chemical Society of Japan
797
+40
+2
Experimental
General. Melting points are uncorrected. 1H and 13C NMR
spectra were measured on a Varian Gemini-300 spectrometer at
300 and 75 MHz, respectively. 11B and 19F NMR spectra were
measured on a JEOL Lambda-300 spectrometer at 96 and 282
MHz, respectively. Optical rotations were measured on a JASCO
DIP-1000 digital polarimeter with a 3:5ꢃ ꢄ 100 mm cell. CD
spectra were measured on a JASCO J-810 polarimeter with a
1 mm cell.
+1
0
+20
−1
(+)-2
0
ε
(N–B)-Chloro[5-chloro-2-(dimethylaminomethyl)phenyl]-
phenylborane (4). To a solution of 4-chloro-N,N-dimethylben-
zylamine13 (230 mg, 1.36 mmol) in 10 mL of dry hexane was add-
ed a 1.0 mol Lꢁ1 butyllithium solution in hexane (0.90 mL, 1.5
mmol) at ꢁ78 ꢃC under Ar. This reaction mixture was warmed
to room temperature, and then refluxed for 24 h. This suspension
was slowly added to a solution of dichlorophenylborane (0.20 mL,
1.5 mmol) in 10 mL of dry hexane in an ice bath from a dropping
funnel. After the mixture had been stirred for 3 h at room tem-
perature, the volatile materials were removed by evaporation.
The residue was extracted with dichloromethane, and the organic
solution was washed with aq NaHCO3, dried over MgSO4, and
evaporated. The residue was recrystallized from hexane–dichloro-
methane to give 89 mg (22%) of the desired complex as colorless
(−)-2
−20
−40
200
220
240
260
280
300
λ
/ nm
Fig. 1. CD spectra of enantiomers of 2 in hexane. The
expanded spectra are inset.
1
needles; mp 192–194 ꢃC; H NMR (CDCl3) ꢀ 2.27 (3H, s), 2.95
N
B
(3H, s), 3.92 and 4.49 (2H, ABq, J ¼ 13:8 Hz), 7.18 (1H, d, J ¼
8:0 Hz), 7.24–7.38 (4H, m), 7.52 (1H, d, J ¼ 2:0 Hz), 7.60–7.66
(2H, m); 13C NMR (CDCl3) ꢀ 46.3, 48.5, 67.2, 123.7, 127.4,
127.5, 127.7, 130.7, 133.86, 133.89, 137.0, 140.8 (br), 150.9 (br);
11B NMR (CDCl3) ꢀ 8.8 (half-band width 317 Hz); Anal. Found:
C, 61.95; H, 5.64; N, 4.57%. Calcd for C15H16BCl2N: C, 61.70;
H, 5.52; N, 4.80%.
O(1)
Cl
O(2)
(Æ)-(N–B)-[5-Chloro-2-(dimethylaminomethyl)phenyl](penta-
fluoropropionyloxy)phenylborane (2). To a solution of the
chloride 4 (50 mg, 0.19 mmol) in 4 mL of dry dichloromethane
was added silver pentafluoropropionate (54 mg, 0.19 mmol). The
reaction mixture was stirred for 3 h at room temperature and the
formed precipitate was removed by filtration. The filtrate was
evaporated and the residue was recrystallized from hexane–
dichloromethane to give 119 mg (88%) of the desired compound
as colorless crystals. mp 125–133 ꢃC (dec); 1H NMR (CDCl3) ꢀ
2.23 (3H, s), 2.88 (3H, s), 3.93 and 4.40 (2H, ABq, J ¼ 13:5
Hz), 7.13 (1H, d, J ¼ 7:9 Hz), 7.25–7.41 (6H, m), 7.74 (1H, d,
J ¼ 2:0 Hz); 13C NMR (CDCl3) ꢀ 44.8, 48.2, 67.1, 105.8 (tq,
JCF ¼ 261, 39 Hz), 118.1 (qt, JCF ¼ 285, 35 Hz), 123.6, 127.8,
128.0, 128.1, 132.5, 133.7, 138.0, 138.6 (br), 146.5 (br), 156.5
(t, JCF ¼ 28 Hz); 11B NMR (CDCl3) ꢀ 8.6 (half-band width 259
Hz); 19F NMR (CDCl3) ꢀ ꢁ79:1, ꢁ117:6; Found: C, 51.24; H,
3.98; N, 3.26%. Calcd for C18H16BClF5NO2: C, 51.53; H, 3.84;
N, 3.34%.
Fig. 2. ORTEP drawing of compound (S)-(þ)-2.
its mirror image. While the residual factors R were the same
down to the third decimal place for the two structures, the
Flack parameters ꢂ were 0.00(2) and 1.00(2) for the structures
of the S and R configuration, respectively.9 This result clearly
indicates that the absolute configuration of the (þ)-isomer
should be S. Hence, the absolute configuration of 2 is establish-
ed as (S)-(þ) or (R)-(ꢁ).
To determine the stereochemical relationship between 2 and
1, we attempted dechlorohydrogenation of 2 under various con-
ditions, e.g., Pd-catalyzed hydrogenolysis.10 However, reaction
without affecting the boron moiety was unsuccessful. We also
carried out the theoretical calculations of the CD spectra of
these intramolecular amine–borane complexes by the time-
dependent DFT (TDDFT) method.11 The spectral pattern was
sensitive to the conditions, so that we could not obtain a reliable
conclusion of the correlation between the configuration and the
CD spectra.12 The specific rotation and the CD spectra of (þ)-2
Enantiomeric Resolution by Chiral HPLC. Chiral HPLC
was carried out with a Daicel Chiralpak AD column (1 cmꢃ ꢄ
25 cm) with hexane–2-propanol 50:1 as the eluent. About 10 mg
of the racemic compound of 2 was dissolved in 20 mL of the elu-
ent, and ca 1.5 mL of this solution was injected for each batch.
The enantiomers were eluted at 16.1 and 19.4 min (ꢁ ¼ 1:28) at
a flow rate of 3.0 mL minꢁ1. Each enantiomer was recrystallized
from hexane–dichloromethane to give colorless needles. The
NMR spectra of these enantiomers are identical with that of the
22
and (ꢁ)-2 are quite similar to those of (þ)-1 (½ꢁꢂD þ169) and
22
(ꢁ)-1 (½ꢁꢂD ꢁ167), respectively.7 If this similarity primarily
racemic compound. The first fraction (R)-(ꢁ)-2: mp 153–154 ꢃC;
depends on the configuration at the boron atom regardless of
the presence of the chloro substituent, the absolute configura-
tion of 1 can be assigned as (S)-(þ) or (R)-(ꢁ).
22
½ꢁꢂD ꢁ158 (c 0.10, acetone); CD (hexane, 3:1 ꢄ 10ꢁ4 mol Lꢁ1
)
ꢄðꢀ"Þ 212 (ꢁ28:1, sh), 227 (þ1:5), 272 (ꢁ0:6), 279 (ꢁ0:6);

798 S. Toyota et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 5 (2006)
Found: C, 51.41; H, 3.89; N, 3.30%. Calcd for C18H16BClF5NO2:
C, 51.53; H, 3.84; N, 3.34%. The second fraction (S)-(þ)-2: mp
Org. Chem. 2002, 6, 1469.
a) D. J. Owen, D. VenDerveer, G. B. Schuster, J. Am.
Chem. Soc. 1998, 120, 1705. b) D. J. Owen, G. B. Schuster,
J. Am. Chem. Soc. 1996, 118, 259.
2
22
151–153 ꢃC; ½ꢁꢂD þ157 (c 0.10, acetone); CD (hexane, 3:1 ꢄ
10ꢁ4 mol Lꢁ1) ꢄðꢀ"Þ 211 (þ22:9, sh), 227 (ꢁ1:5), 270 (þ0:4),
278 (þ0:5); Found: C, 51.29; H, 3.90; N, 3.28%. Calcd for
C18H16BClF5NO2: C, 51.53; H, 3.84; N, 3.34%.
X-ray Analysis. A crystal of the (þ)-isomer of 2 was obtained
by crystallization from a hexane–dichloromethane solution. The
diffraction data were collected on a Rigaku RAXIS RAPID imag-
3
a) H. I. Beltran, L. S. Zamudio-Rivera, T. Mancilla,
R. Santillan, N. Farfan, J. Organomet. Chem. 2002, 657, 194.
b) T. Mancilla, R. Contreras, J. Organomet. Chem. 1987, 321,
191.
4
C. S. Shiner, C. M. Garner, R. C. Haltiwanger, J. Am.
Chem. Soc. 1985, 107, 7167.
a) L. Charoy, A. Valleix, T. Le Gall, P. P. van Chuong,
˚
ing plate diffractometer with Mo Kꢁ radiation (ꢄ ¼ 0:71070 A) to
a maximum 2ꢅ value of 55.0ꢃ at ꢁ150 ꢃC. The reflection data were
corrected for the Lorentz-polarization effects. The structure was
solved by the direct method (SIR97)14 and refined by the full-ma-
trix least-squares method. The non-hydrogen atoms were refined
anisotropically. The hydrogen atoms were included but not refined.
(S)-2: Formula C18H16BClF5NO2, FW 419.58, Crystal size 0:33 ꢄ
0:04 ꢄ 0:03 mm3, Monoclinic, Space group P21 (No. 4), a ¼
5
C. Mioskowski, L. Toupet, Chem. Commun. 2000, 2275. b) P.
Vedrenne, V. Le Guen, L. Toupet, T. Le Gall, C. Mioskowski,
J. Am. Chem. Soc. 1999, 121, 1090.
6
6329.
7
T. Imamoto, H. Morishita, J. Am. Chem. Soc. 2000, 122,
a) S. Toyota, T. Hakamata, N. Nitta, F. Ito, Chem. Lett.
ꢃ
˚
10:710ð3Þ, b ¼ 7:1467ð16Þ, c ¼ 12:542ð3Þ A, ꢆ ¼ 102:885ð13Þ ,
2004, 33, 206. b) S. Toyota, F. Ito, N. Nitta, T. Hakamata, Bull.
Chem. Soc. Jpn. 2004, 77, 2081.
V ¼ 935:8ð4Þ A , Z ¼ 2, Dcalcd ¼ 1:489 g cmꢁ3, ꢇ(Mo Kꢁ) =
3
˚
2.654 cmꢁ1, No. of data 13542, R1 (I > 2:00ꢈðIÞÞ ¼ 0:0275,
wR2 ¼ 0:0816, GOF ¼ 0:968, ꢂ ¼ 0:00ð2Þ. Refinement data for
the mirror image structure (R configuration): R1 (I > 2:00ꢈðIÞÞ ¼
0:0275, wR2 ¼ 0:0816, GOF ¼ 0:968, ꢂ ¼ 1:00ð2Þ. Crystallo-
graphic data have been deposited at the Cambridge Crystallo-
graphic Data Centre (12, Union Road, Cambridge, CB2 1EZ, UK;
fax: þ44 1223 336033; deposit@ccdc.cam.ac.uk; http://www.
ccdc.cam.ac.uk/conts/retrieving.html) and copies can be obtained
on request, free of charge, by quoting the publication citation
and the deposition number 294581.
8
9
S. Toyota, M. Oki, Bull. Chem. Soc. Jpn. 1992, 65, 1832.
H. D. Flack, Acta Crystallogr., Sect. A 1983, 39, 876.
¯
10 J. Tsuji, Palladium Reagents and Catalyst, Wiley,
Chichester, 2004, pp. 427–428.
11 Our recent examples of application of the TDDFT meth-
od to the determination of absolute stereochemistry of 9,90-
bianthryl derivatives. a) S. Toyota, T. Shimasaki, N. Tanifuji,
K. Wakamatsu, Tetrahedron: Asymmetry 2003, 14, 1623. b) S.
Toyota, T. Shimasaki, T. Ueda, N. Tanifuji, K. Wakamatsu, Bull.
Chem. Soc. Jpn. 2004, 77, 2065.
12 For (S)-2, a positive shoulder in the short wavelength
region was reasonably reproduced by the TDDFT calculation at
the B3LYP/6-31G basis set. For (S)-1, calculation by the same
method also afforded a positive shoulder in the same region, but
its band shape was delicately influenced by the conformation
and the basis sets.
13 G. Van Koten, A. J. Leusink, J. G. Noltes, J. Organomet.
Chem. 1975, 84, 117.
14 SIR97, Program for the Solution of Crystal Structures:
A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C.
Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori, R.
Spagna, J. Appl. Crystallogr. 1999, 32, 115.
This work was partly supported by ‘‘High-Tech Research
Center’’ Project for Private Universities: matching fund sub-
sidy from MEXT (Ministry of Education, Culture, Sports, Sci-
ence and Technology), 2001–2005. The authors thank Mr. T.
Shimasaki and Prof. T. Shinmyozu of Kyushu University for
their assistance in the X-ray analysis, and Dr. M. Goichi and
Dr. S. Hirano of Okayama University of Science for their tech-
nical assistance.
ꢀ
References
1
T. Murafuji, K. Kurotobi, N. Nakamura, Y. Sugihara, Curr.