Enantiomeric resolution of intramolecular amine-borane complex with a chiral boron center

Article abstract of DOI:10.1246/cl.2004.206

The enantiomers of [2-(dimethylaminomethyl)phenyl]- (pentafluoropropionyloxy)phenylborane were successfully resolved by chiral HPLC as a new type of intramolecular amine-borane complex with a chiral center at the tetrahedral boron atom. The X-ray structur

Full text of DOI:10.1246/cl.2004.206

206
Chemistry Letters Vol.33, No.3 (2004)
Enantiomeric Resolution of Intramolecular Amine–Borane Complex
with a Chiral Boron Center
Shinji Toyota,ꢀ Tomohiro Hakamata, Naoya Nitta, and Fumiko Ito
Department of Chemistry, Faculty of Science, Okayama University of Science, 1-1 Ridaicho, Okayama 700-0005
(Received November 5, 2003; CL-031056)
The enantiomers of [2-(dimethylaminomethyl)phenyl]-
atoms.12
The X-ray structure of rac-1a is shown in Figure 1.13 The
boron atom is tetrahedral because of intramolecular coordination
of the amino nitrogen atom, where the N–B bond length is
ꢀ
1.668(4) A. The tetrahedral character (THC) of the boron atom
is 56% for 1a, this value being smaller than those of the 9-
BBN complex (9-DMP-9-borabicyclo[3.3.1]nonane 4)2c and
other intramolecular amine–diphenylborinate adducts (70–
80%).14
(pentafluoropropionyloxy)phenylborane were successfully re-
solved by chiral HPLC as a new type of intramolecular
amine–borane complex with a chiral center at the tetrahedral
boron atom. The X-ray structure, the barrier to racemization,
and the chiroptical properties are reported.
We have been studying the molecular structures and dynam-
ics of intramolecular amine–borane complexes with a 2-(di-
methylaminomethyl)phenyl (DMP) ligand.1,2 In most of these
complexes, the boron atoms are configurationally labile in solu-
tion because of racemization via N–B bond dissociation, even
though the tetrahedral boron atom is bonded to four different li-
gands. In general, several enantiopure borates and coordinated
boranes are known,3–8 some of which have been used in organic
syntheses.4,5 In most cases, however, the configuration at a boron
atom is generated by other chiral elements in an identical mole-
cule. Recently, enantiopure compounds with a chiral boron atom
as the sole stereogenic center have been focused on, and com-
plexes with phosphine9 and amine10 ligands have been used in
stereochemical studies in relation to the isoelectronic species
of tetrahedral carbons. We explored such compounds by using
the DMP ligand and found that the introduction of a pentafluoro-
propionyloxy (–OCOC2F5) group at the boron atom enhances
the configurational stability sufficiently to enable isolation of
enantiomers at room temperature. We report herein the enantio-
meric resolution and structure of 1a as a novel optically active
intramolecular amine–borane complex (Scheme 1).
N
C(1)
B
C(10)
O(1)
F
F
F
F
F
Figure 1. ORTEP diagram of rac-1a with thermal ellipsoids at
ꢀ
50% probability. B–N 1.668(4) A, C(1)–B–O(1) 110.4(2),
C(10)–B–O(1) 111.8(2), C(1)–B–C(10) 120.2(2)ꢄ.
NMe2
The enantiomers of 1a were resolved by chiral HPLC with a
Daicel Chiralpak AD column (eluent: hexane/2-propanol, 50:1).
Two fractions were eluted at 21.0 and 27.7 min with the base-
line separation (ꢁ ¼ 1:49). This resolution was much higher
than the case of 1b, which showed only partial separation by chi-
ral HPLC (ꢁ ¼ 1:12) and underwent significant decomposition
during the separation. The specific rotations of the first and sec-
NMe2
NMe2
*
*
B
B
B
X
Ph
X
X
Ph
(R)-1
Ph
(S)-1
a X = OCOC2F5
b X = OCOCF3
27
ond eluted isomers were ½ꢁꢁD þ 169 and ꢂ167 (c 0.10, ace-
Scheme 1.
tone), respectively. As regards the CD spectra, the (+)-isomer
showed a weak trough at 224 nm with a positive broad shoulder
extending to the shorter wavelength region, whereas the spec-
trum of the (ꢂ)-isomer was practically its mirror image
(Figure 2).
(DMP)lithium prepared in a conventional manner was treat-
ed with dichlorophenylborane to give the chlorophenylborane
complex 3 in 66% yield. The reaction of 3 with a silver carbox-
ylate afforded the corresponding acyloxyborane (boric carboxyl-
ic anhydride) in good yield.11 11B NMR signals of 1a and 1b
were observed at ca. ꢀ 10, typical of tetracoordinated boron
Complex 1a slowly undergoes racemization in solution
upon heating. The barrier to racemization was determined by
¼
classical kinetic measurement to be ꢁG 116 kJ molꢂ1 (k 7:2 ꢃ
1) BuLi
2) PhBCl2
NMe2
10ꢂ5 sꢂ1) in heptane at 83 ꢄC, where the enantiomeric ratios were
determined by chiral HPLC. The course of racemization was al-
so monitored from the CD spectra (Figure 2). The racemization
of 1b is faster than that of 1a, its barrier being 105 kJ molꢂ1 as
estimated by saturation transfer experiments of the 1H NMR sig-
Ag+X–
NMe2
B
1
Ph
2
3
Cl
Scheme 2.
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.3 (2004)
207
¯
1554 (1991). c) S. Toyota and M. Oki, Bull. Chem. Soc.
Jpn., 65, 1832 (1992). d) S. Toyota, T. Futawaka, M.
¯
Asakura, H. Ikeda, and M. Oki, Organometallics, 17, 4155
+40
(1998).
T. Murafuji, K. Kurotobi, N. Nakamura, and Y. Sugihara,
Curr. Org. Chem., 6, 1469 (2002) and references therein.
(+)-1a
3
4
+20
0
a) E. Vedejs, R. W. Chapman, M. Muller, and D. R. Powell, J.
¨
Am. Chem. Soc., 122, 3047 (2000). b) E. Vedejs, S. C. Fields,
R. Hayashi, S. R. Hitchcock, D. R. Powell, and M. R.
Schrimpf, J. Am. Chem. Soc., 121, 2460 (1999).
a) H. I. Beltran, L. S. Zamudio-Rivera, T. Mancilla, R.
Santillan, and N. Farfan, J. Organomet. Chem., 657, 194
(2002). b) A. R. Rico, M. Tlahuextl, A. Flores-Parra, and
R. Contreras, J. Organomet. Chem., 581, 122 (1999).
P. Vedrenne, V. Le Guen, L. Toupet, T. Le Gall, and C.
Mioskowski, J. Am. Chem. Soc., 121, 1090 (1999).
C. S. Shiner, C. M. Garner, and R. C. Haltiwanger, J. Am.
Chem. Soc., 107, 7167 (1985).
ε
0
5
–20
(–)-1a
-10
–40
6
7
8
9
210
220
260
230
200
220
240
λ
/ nm
D. J. Owen, D. VenDerveer, and G. B. Schuster, J. Am. Chem.
Soc., 120, 1705 (1998).
T. Imamoto and H. Morishita, J. Am. Chem. Soc., 122, 6329
(2000).
Figure 2. CD spectra of (+)- and (ꢂ)-1a in hexane. Inset spec-
tra are changes during the racemization of (ꢂ)-1a upon heating
for 0, 70, 300, 600, and 1080 min at 69 ꢄC.
nals.
10 L. Charoy, A. Valleix, L. Toupet, T. Le Gall, P. P. van
Chuong, and C. Mioskowski, Chem. Commun., 2000, 2275.
11 1a: Yield 66%; mp 140–142 ꢄC; Found: C, 55.89; H, 4.78; N,
3.97% (Calcd for C18H17BF5NO2: C, 56.13; H, 4.45; N,
3.64%); 1H NMR (CDCl3) ꢀ ¼ 2:22 (3H, s), 2.89 (3H, s),
3.95 and 4.46 (2H, ABq, JAB ¼ 13:2 Hz), 7.19 (1H, d, J ¼
7:2 Hz), 7.28–7.32 (5H, m), 7.41 (2H, m), 7.78 (1H, d, J ¼
7:2 Hz); 11B NMR (CDCl3) ꢀ ¼ 8:8 (half-band width,
240 Hz). Enantiomers were resolved by chiral HPLC (Daicel,
Chiralpak AD) with hexane:2-propanol (50:1) as eluent.
As proposed for other borane–amine complexes,2a,b the
mechanism of racemization can be deduced from the dissocia-
tion of the N–B bond, the rotation about the C–B bond by
180ꢄ, and the recombination of the coordination bond, where
the first step is rate-determining (Scheme 1). Thus, the rates of
racemization mainly depend on the strength of the N–B coordi-
nation bonds. The above kinetic measurements revealed that the
coordination bonds in 1 are stronger than those in 4 (ca.
75 kJ molꢂ1), contrary to the small THC in the former; namely,
perfluoroacyloxy groups as well as phenyl groups tend to en-
hance the Lewis acidity of boron atoms with a small structural
change from trigonal to tetrahedral geometry. The difference
in barrier heights between 1a and 1b is attributed to the inductive
effect of extra fluorine atoms in the former, which increases the
Lewis acidity of the boron atom.15 The use of a –OCOC2F5
group not only enhances the barrier to racemization but also in-
creases the chemical stability and the solubility, greatly facilitat-
ing the enantiomeric resolution.
In summary, we have successfully resolved enantiomers
of the intramolecular amine–borane complexes with a chiral
boron center by taking advantage of the DMP system with a
–OCOC2F5 ligand. To the best of our knowledge, this compound
is the first example of an enantiopure borane complex with four
nonhydrogen ligands, and the racemization process is isoelec-
tronically related to the SN1 reaction at a tertiary carbon atom.
Further studies on the effects of substituents at the boron atom
on the barrier to racemization and the determination of absolute
configuration are in progress.
27
Easily eluted isomer: mp 141–142 ꢄC, ½ꢁꢁD þ 169 (c 0.10,
acetone), less easily eluted isomer: mp 141–143 ꢄC,
27
½ꢁꢁD ꢂ 167 (c 0.10, acetone). 1b: Yield 79%; mp 134–
136 ꢄC; Found: C, 60.57; H, 4.89; N, 4.42% (Calcd for
C17H17BF3
1
NO2: C, 60.93; H, 5.11; N, 4.18%); H NMR (CDCl3) ꢀ ¼
2:23 (3H, s), 2.90 (3H, s), 3.96 and 4.48 (2H, ABq, JAB
13:5 Hz), 7.20 (1H, m), 7.31–7.44 (7H, m), 7.80 (1H, m);
11B NMR (CDCl3) ꢀ ¼ 11:3 (half-band width, 81 Hz).
¼
12 11B NMR signals of similar borane complexes are observed at
ꢀ 4–12: for example, (N–B)-Bu(AcO)B(CH2)3NMe2 ꢀ 8.3. H.
Noth and B. Wrackmeyer, ‘‘Nuclear Magnetic Resonance
¨
Spectroscopy of Boron Compounds,’’ Springer Verlag, Berlin
(1978).
13 Crystal data for 1a: C18H17BF5NO2, Mr ¼ 385:14, ortho-
rhombic, space group P212121 (#19), a ¼ 7:7168ð2Þ, b ¼
ꢀ
ꢀ 3
14:1933ð5Þ, c ¼ 17:0483ð5Þ A, V ¼ 1867:2ð1Þ A , Z ¼ 4,
Dcalcd ¼ 1:370 g cmꢂ3, ꢂ(Mo Kꢁ) = 1.21 cmꢂ1, T ¼ 93 K,
Rigaku RAXIS diffractometer, 2170 reflections, R1 ¼
0:049, Rw ¼ 0:138. CCDC deposition number: 227362.
14 For example, the N–B bond length and the THC of (N–B)-
This work was partly supported by the Japan Private School
Promotion Foundation.
ꢀ
Ph2BO(CH2)2NMe2 are 1.691 A and 80%, respectively.
S. J. Rettig and J. Trotter, Can. J. Chem., 61, 2334 (1983);
See also H. Hopfl, J. Organomet. Chem., 581, 129 (1999).
References and Notes
¨
1
2
a) I. Omae, Coord. Chem. Rev., 83, 137 (1988). b) I. Omae,
‘‘Organometallic Intramolecular Coordination Compounds,’’
Elsevier, Amsterdam (1986), p 35.
15 The pKa values of trifluoroacetic acid and pentafluoropro-
pionic acid are 0.52 and ꢂ0:41, respectively. ‘‘Ionisation
Constants of Organic Acids in Aqueous Solutions,’’ ed. by
E. P. Serjeant and B. Dempsey, Pergamon Press, Oxford
(1979).
¯
a) S. Toyota and M. Oki, Bull. Chem. Soc. Jpn., 63, 1168
¯
(1990). b) S. Toyota and M. Oki, Bull. Chem. Soc. Jpn., 64,
Published on the web (Advance View) January 26, 2004; DOI 10.1246/cl.2004.206