Formation of 1,4-diphosphinobenzenes via tele-substitution on fluorobenzenechromium complexes

Article abstract of DOI:10.1016/j.jorganchem.2008.08.030

The meta-tele-substitution of 2-(boranatophosphino)fluorobenzenechromium complexes took place with various lithiated secondary phosphine-boranes as nucleophiles to give para-substituted bis(boranatophosphino)benzenechromiums. It was revealed that the yield of the tele-substitution product was strongly affected by the strength of a proton acid. Isotope labeling experiments indicated that 1,5-hydrogen migration was involved in this transformation.

Full text of DOI:10.1016/j.jorganchem.2008.08.030

Journal of Organometallic Chemistry 693 (2008) 3546–3552
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Formation of 1,4-diphosphinobenzenes via tele-substitution on
fluorobenzenechromium complexes
*
Yoshikazu Yamamoto, Hiroshi Danjo , Kentaro Yamaguchi, Tsuneo Imamoto
Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan
Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 June 2008
Received in revised form 23 August 2008
Accepted 26 August 2008
Available online 31 August 2008
The meta–tele-substitution of 2-(boranatophosphino)fluorobenzenechromium complexes took place with
various lithiated secondary phosphine–boranes as nucleophiles to give para-substituted bis(bor-
anatophosphino)benzenechromiums. It was revealed that the yield of the tele-substitution product was
strongly affected by the strength of a proton acid. Isotope labeling experiments indicated that 1,5-hydro-
gen migration was involved in this transformation.
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
P-chiral phosphines
Arenechromium complexes
meta–tele Substitution
SNAr reation
1. Introduction
by Rose-Munch et al., in which 2-methyl-1,3-dithian-2-yl anion
was introduced at the 3-position of 2,6-dimethylfluorobenzenetri-
Arenechromium complexes are important aryl cation equiva-
lents and utilized in a great number of organic transformations
[1]. In particular, fluoroarenechromium complexes are frequently
employed owing to their unique reactivity and high accessibility.
Recently, we have demonstrated that ortho-difluorobenzenetricar-
bonylchromium (1) could be used as a good intermediate for the
synthesis of optically active P-chiral phosphinobenzenes. In these
studies, a variety of ortho-substituted P-chiral monophosphines
were obtained via stepwise SNAr reaction of 1 with a lithiated sec-
ondary P-chiral boranatophosphine and various nucleophiles (Eq.
(1)) [2]. On the other hand, P-chiral ortho-diphosphinobenzenes
could be prepared by the use of deprotonated bis(phosphine)boro-
nium salts that consisted of two phosphino groups bound to each
other through a boronium linkage [3]. This building block makes
it possible to introduce two sterically hindered phosphino groups
at proximal positions to each other. From these studies, we have
shown that 1 reacted with lithiated (S)-tert-butyl(methyl)phos-
phine–borane (2a) to afford a diastereomixture of 2-(boranato-
tert-butyl(methyl)phosphino)fluorobenzenetricarbonylchromium
((RP,S)-3a and (RP,R)-3a), and no bis(boranatophosphino)benzene
chromium complexes could be detected under these reaction condi-
tions. However, when this reaction was treated with an acid at low
temperature, para-substituted bis(boranatophosphino)benzene
chromium complex (R,R)-4aa was obtained as the main product
(Scheme 1). This type of tele-substitution was previously reported
carbonylchromium [4]. Hong et al. have also studied a similar reac-
tion using phenylacetylide anion as a nucleophile [5]. The attack of
soft nucleophiles on fluoroarenechromium complexes that possess
large substituents close to the fluoro group would tend to occur at
tele-position to avoid the steric repulsion. Herein, we describe some
examples of the meta–tele-substitution reaction of fluorobenzene-
chromium complexes with boranatophosphino nucleophiles, and
discuss the mechanism of the reaction.
BH3
t-Bu
Me
P
Me
F
F
Li
PhMgBr
Ph
P
t-Bu
(OC)3Cr
–Cr(CO)3
–BH3
1
H2
B
t-Bu
Me
Me
t-Bu
P
P
t-Bu
Me
Li
P
P
Me
t-Bu
+
–Cr(CO)3 –BH2
2. Results and discussion
Initially, we examined the substitution reaction using a 2-bor-
anatophosphinofluorobenzenechromium complex with lithiated
* Corresponding author. Tel.: +81 87 894 5111; fax: +81 87 894 0181.
E-mail address: danjo@kph.bunri-u.ac.jp (H. Danjo).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.08.030

Y. Yamamoto et al. / Journal of Organometallic Chemistry 693 (2008) 3546–3552
3547
BH3
t-Bu
Me
(S)-2a
P
F
F
Li
1)
(3 eq), THF, –40 °C, 50 h
2) 1 M HCl (excess), –40 °C to rt, 0.2 h
(OC)3Cr
1
BH3
t-Bu
P
BH3
BH3
t-Bu
t-Bu
Me
P
F
P
F
Me
Me
+
+
(OC)3Cr
t-Bu
(OC)3Cr
(RP,S)-3a: 29% yield
(OC)3Cr
P
Me
H3B
(RP,R)-3a: 18% yield (R,R)-4aa: 53% yield
Scheme 1. The SNAr reaction of 1 with (S)-2a.
BH3
t-Bu
P
F
1) (S)-2a (1.1 eq), THF, –40 °C, 60 h
Me
2) 1M HCl (excess), –40 °C to rt, 0.2 h
BH3
(OC)3Cr
t-Bu
P
36% yield
Me
(RP,S)-3a
(OC)3Cr
t-Bu
P
BH3
Me
t-Bu
H3B
P
F
1) (S)-2a (1.1 eq), THF, –40 °C, 60 h
Me
(OC)3Cr
(RP,R)-3a
Scheme 2. The meta–tele-substitution reaction of (RP,S)-, and (RP,R)-3a with (S)-2a.
(R,R)-4aa
2) 1M HCl (excess), –40 °C to rt, 0.2 h
35% yield
phosphine–borane to confirm the formation of the tele-substitu-
tion product. Compound (RP,S)-3a was treated with 1.1 equiv. of
(S)-2a at ꢀ40 °C, and the reaction was quenched with 1 M HCl at
intact temperature, and para-substituted product (R,R)-4aa was
obtained in 36% yield (Scheme 2). It was also confirmed that the
reactivity of (RP,R)-3a was similar to that of (RP,S)-3a (35% yield).
On the other hand, deboranated (RP)-(2-tert-butylmethylphosphi-
no)fluorobenzenechromium ((RP)-5a) gave no coupling product
under these reaction conditions, probably due to the electron-
donating nature of the free phosphino group (Scheme 3) [2]. The
absolute configurations of (RP,R)-3a and (R,R)-4aa have been
unequivocally determined by single crystal X-ray analysis
(Fig. 1). In each case, the two tert-butyl groups are oriented at
opposite sides of the chromium group owing to their bulkiness.
Especially in (RP,R)-3a, the tert-butyl group shields the ipso-carbon
attached to fluoro group to prevent SNAr at this position. On the
other hand, a nucleophilic attack at the meta-position to the fluoro
group would be advantageous because of the stabilization of the
Meisenheimer-type intermediate by boranatophosphino group,
and would lead to the formation of para-disubstituted product.
Optimization of the reaction conditions was carried out with
lithiated P-chiral secondary phosphine–borane (S)-2a and ortho-
(dicyclohexylboranatophosphino)fluorobenzenetricarbonylchro-
mium (3b, Cy: cyclohexyl). The results are summarized in Table 1.
It is noted that the chemical yield of the coupling reaction was lar-
gely affected by the acid treatment [4]. When the reaction was
quenched by excess amount of 1 M HCl at 0 °C for 30 min, the yield
was suppressed to 22%. The use of 3.0 equiv. of trifluoromethane-
sulfonic acid instead of HCl produced coupling product in 44%
yield. Moreover, further increase of the chemical yield (to 79%)
was realized when the acid treatment was carried out at –78 °C
for 24 h. In each case, tele-substitution product could not be
t-Bu
P
F
Me
1) (S)-2a (1.1 eq), THF, –40 °C, 48 h
(no reaction)
2) 1 M HCl (excess), –40 °C to rt, 0.2 h
(OC)3Cr
(RP)-5a
Scheme 3. The SNAr reaction with (RP)-5a.
detected on TLC before treatment with an acid. When the reaction
was treated with water instead of an acid, only starting material
was recovered.
The meta–tele-substitution reaction of 2-(boranatophosphi-
no)fluorobenzenechromium complexes was then carried out with
various substrates and nucleophiles. The results are summarized
in Table 2. In these reactions, 2-(boranatophosphino)fluoroben-
zenechromium complexes were treated with 3 equiv. of secondary
phosphine–boranes that were previously deprotonated with sec-
butyllithium. The reactions were then quenched with trifluoro-
methanesulfonic acid at –78 °C for 24 h. The products were iso-
lated after removal of the chromium group by UV irradiation in
air. In almost all cases, moderate to high yields of 1,4-bis(bor-
anatophosphino)benzenes were obtained. When dicyclohexyl-
phosphine–borane (2b) and di(tert-butyl)phosphine–borane (2f)
were employed as nucleophiles, coupling products 6ab and 6af
were afforded in 11% and 28% yields, respectively, probably owing
to high steric hindrance of the nucleophiles.
To observe the features of this tele-SNAr process, the reaction
was conducted by treatment of rac-5-D-3b (>95% D) with 2a
(Scheme 4). Deuterated position was determined by 1H NMR after
deboranation and subsequent oxidation of the two phosphino

3548
Y. Yamamoto et al. / Journal of Organometallic Chemistry 693 (2008) 3546–3552
Table 2
tele-Substitution with various substratesa
Entry
3
R1
R2
2
R3
R4
6
Yield (%)b
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3a
3a
3b
3d
3d
3e
3f
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Cy
n-Bu
n-Bu
iPr
Me
Me
Me
Me
Me
Me
Cy
n-Bu
n-Bu
iPr
2a
2b
2c
2d
2f
2h
2a
2a
2a
2a
2a
2a
t-Bu
Cy
Cy
Me
Cy
6aa
6ab
6ac
6ad
6af
6ah
6ab
6ad
6ae
6ae
6af
73
11
70
84
28
59
86
70
79
48
62
83
Fig. 1. ORTEP drawings of (RP,R)-3a (left) and (R,R)-4aa (right). Hydrogens are
omitted for clarity.
Me
n-Bu
t-Bu
Me
Me
Me
Me
Me
Me
Me
n-Bu
t-Bu
1-Ad
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Table 1
tele-Substitution of 3b with (S)-2a under various quenching conditionsa
9
10
11
12
t-Bu
Ph
t-Bu
Ph
3g
6ag
a
All reactions were carried out with 0.1 mmol of 3 and 3.0 equiv. of 2 in 0.7 mL of
THF and then treated with 3.0 equiv. of TfOH.
b
Isolated yield.
Entry
Acid
Temperature (°C)
Time (h)
Yield (%)b
BH3
Cy
1 M HCl aqc
1 M HCl/MeOH
16 M HBF4 aq.
HBF4 ꢁ OEt2
BF3 ꢁ OEt2
TfOH
0
0
0
0
0
0
–40
ꢀ78
0.5
0.5
0.5
0.5
0.5
0.5
3
22
8
18
28
3
44
66
79
BH3
P
D
P
1
2
3
4
5
6
7
8d
Cy
Cy
Cy
P
F
1) (S)-2a (3 eq), THF
–40 °C, 40 h
(OC)3Cr
2) TfOH (3 eq), –78 °C, 24 h
t-Bu
(OC)3Cr
Me
D
H3B
TfOH
TfOH
rac-5-D-3b
>95% D
(SP)-D-4ab: 28% yield
24
>95% D
a
All reactions were carried out with 0.2 mmol of 3b and 3.0 equiv. of 2a in 0.4 mL
of THF and quenched with 3.0 equiv. of acid unless otherwise noted.
O
Cy
P
D
b
Cy
Isolated yield.
Excess amount of HCl was used.
1.4 mL of THF was used.
c
3) 1-methylpyrollidine, rt, 12 h
4) H2O2, EtOH, rt, 10 min
d
(OC)3Cr
t-Bu
P
Me
O
(SP)-3-D-7ab: 46% yield
>95% D (1:1 mixture of diastereomers)
groups. In the coupling product, the deuterium atom was found at
the ortho position to dicyclohexyloxophosphorano group without
decrease of deuteration ratio. This result strongly indicates that
this meta–tele-substitution reaction proceeds via a 1,5-hydrogen
shift [6]. This is also supported by the fact that the chemical yield
of (SP)-D-4ab (28%) was much lower than that obtained from non-
deuterated 3b (86% yield, entry 7 in Table 2). This would indicate
that the shift of hydrogen/deutrium occurs as the rate-determining
step of this transformation. Next, we employed deuterated trifluo-
romethanesulfonic acid in the reaction. Although the para-disub-
stituted product was isolated in 39% yield in its dechromination
form, deuterium was not detected in the product (Scheme 5). This
implies that the proton acid would promote 1,5-hydrogen migra-
tion or elimination of the fluoride anion, rather than protonate
the benzene core.
Scheme 4. A labeling study with rac-5-D-3b.
tively electron-withdrawing nature of the substituent. The
Meisenheimer-type intermediate thus formed undergoes subse-
quent 1,5-hydrogen migration before (path A) or after (path B) pro-
tonation of the fluoro group. In path A, hydrogen migration
proceeds slowly and takes a longer reaction time to obtain the
product in high yield. On the other hand, the reaction via path B
would proceed rapidly because of the acceleration of the hydrogen
migration by protonation of the fluoro group [7]. Treatment of the
Meisenheimer-type intermediate with weak acid might be insuffi-
cient to protonate the fluoro group and allow the elimination of the
phosphorus nucleophile required to regenerate the starting mate-
rials. The direct protonation of the benzene core is also plausible
(path C). In this case, syn-elimination of HF from the later interme-
diate have to be involved because deuterium was not incorporated
in the product after treatment of the reaction with trifluorometh-
anesulfonic acid-D.
Based on the results mentioned above, the mechanism of the
acid-mediated formation of the meta–tele-substitution product
was proposed as depicted in Fig. 2. Nucleophilic attack takes place
at the para-position to the boranatophosphino group on the arene-
chromium complex, due to the steric hindrance and the conjuga-

Y. Yamamoto et al. / Journal of Organometallic Chemistry 693 (2008) 3546–3552
3549
4.2. General procedure for the preparation of 2-(boranatophosphino)
fluorobenzenetricarbonylchromium (3b–g)
BH3
Cy
Cy
BH3
P
Cy
Cy
P
F
1) (S)-2a (3 eq), THF, –40 °C, 5 h
D
To a solution of sec-phosphine–borane (2.2 equiv.) in THF was
added sec-BuLi (1.0 M cyclohexane and n-hexane solution,
2.2 equiv.) at ꢀ78 °C under nitrogen atmosphere, and the reaction
mixture was stirred for 1 h. To the solution was added 1 (1.0 equiv.)
in THF at ꢀ40 °C, and the mixture was stirred for 20 h. The reaction
mixture was diluted with water and extracted with CHCl3. The
combined extracts were dried over Na2SO4, and concentrated under
reduced pressure. The residue was subjected to column chromatog-
raphy on silica gel (n-hexane/EtOAc = 5/1–3/1) to give
2-(boranatophosphino)fluorobenzenetricarbonylchromium.
2) TfOD (3 eq), –78 °C, 20 h
3) hν, air, CHCl3, rt, 3 h
t-Bu
(OC)3Cr
P
Me
H3B
3b
(R)-6ab: 39% yield
0% D
Scheme 5. A labeling study with TfOD.
P
F
F
P
4.2.1. 2-(Boranatodicyclohexylphosphino)
D
+ P' H
Cr
fluorobenzenetricarbonylchromium (3b)
–
–
Yield: 95% as a yellow solid; mp. 202 °C (decomp.); 1H NMR
(CDCl3, 400 MHz) d 6.06 (dt, J = 3.64 Hz, 6.88 Hz, 1H), 5.69 (m,
1H), 5.20 (t, J = 6.40 Hz, 1H), 4.80 (dt, J = 3.20, 5.96 Hz, 1H), 2.35–
2.26 (m, 2H), 2.13–2.05 (m, 1H), 2.00–1.89 (m, 4H), 1.80–1.55
(m, 7H), 1.39–1.10 (m, 8H), 1.0–0.1 (m, 3H); 13C NMR (CDCl3,
100 MHz) d 230, 148 (d, J = 260 Hz), 99.1 (dd, J = 6.67, 124 Hz),
94.2 (d, J = 8.59 Hz), 84.2 (d, J = 7.63 Hz), 78.9 (dd, J = 19.0,
33.4 Hz), 76.9 (dd, J = 23.8, 62.9 Hz), 33.9 (d, J = 27.6 Hz), 32.6 (d,
J = 31.1 Hz), 27.6 (d, J = 5.05 Hz), 27.4, 27.1, 27.0, 26.9, 26.9, 26.8,
D
H+
Cr
path A
H+
P'
+
F
+F
H
D
P
F
P
H
P
P
D
H+
–HF
–HF
–
–
path B
Cr
Cr
Cr
Cr
P'
P'
P'
P'
D
D
D
H+
F
P
F
P
D
path C
H
H
H
26.7, 26.6, 25.9; 31P NMR (CDCl3, 162 MHz)
d 37.2 (d,
H
Cr
Cr
J = 60.4 Hz); IR (KBr) 2937, 3857, 2410, 1970, 1891 cm–1; HRMS
(ESI): m/z Calc. for C21H29BClCrFO3P (M+Cl)ꢀ: 477.1025. Found:
477.1015; Anal. Calc. for: C, 57.03; H, 6.61. Found: C, 57.06; H,
6.67%.
P'
P'
Fig. 2. Proposed mechanism of the acid-mediated meta–tele-substitution.
4.2.2. 2-((S)-Boranatocyclohexylmethylphosphino)
fluorobenzenetricarbonylchromium (3c)
3. Conclusion
Yield: 21% as a yellow solid; mp. 143–145 °C; ½a D24
ꢂ
= 35.5 (c 1.0,
CHCl3); 1H NMR (CDCl3, 400 MHz) d 5.99 (dd, J = 6.88, 10.6 Hz, 1H),
5.70 (m, 1H), 5.22 (t, J = 5.96 Hz, 1H), 4.79 (m, 1H), 2.32 (m, 1H),
2.12 (q, J = 1.24 Hz, 1H), 1.87 (m, 1H), 1.74 (d, J = 11 Hz, 1H), 1.53
(d, J = 9.60 Hz, 3H), 1.48–1.18 (m, 5H), 1.1–0.2 (m, 3H); 13C NMR
The coupling reaction with 2-(boranatophosphino)fluoroben-
zenechromium complexes and various lithiated secondary phos-
phine–boranes afforded para-substituted bis(boranatophosphino)
benzenechromiums in moderate to high yield according to meta–
tele-SNAr manner. It was revealed that this transformation took
place via 1,5-hydrogen migration and subsequent elimination of
HF. Acid treatment is the key step for the effective formation of
the product.
(CDCl3, 100 MHz)
d 230, 149 (d, J = 264 Hz), 98.2, 94.5 (d,
J = 8.00 Hz), 84.0 (d, J = 8.40 Hz), 81.0 (dd, J = 18.4, 39.1 Hz), 76.6
(d, J = 23.0 Hz), 34.6 (d, J = 34.5 Hz), 26.8, 26.6, 26.1, 26.0, 25.6,
9.36 (d, J = 38.0 Hz); 31P NMR (CDCl3, 162 MHz) d 22.6; IR (KBr)
3104, 2931, 2855, 2342, 1972,1885 cm–1; HRMS (ESI): m/z Calc.
for C16H21BClCrFO3P (M+Cl)–: 409.0399. Found: 409.0396.
4. Experimental
4.2.3. Epi-3c
4.1. General
Yield: 24% as a yellow solid; mp. 141–144 °C; ½a D24
= ꢀ65.3 (c
ꢂ
1.0, CHCl3); 1H NMR (CDCl3, 400 MHz) d 6.08 (m, 1H), 5.68 (m,
1H), 5.22 (t, J = 5.96 Hz, 1H), 4.80 (m, 1H), 2.00 (q, J = 1.28 Hz,
1H), 1.9–1.75 (m, 3H), 1.72 (d, J = 10.1 Hz, 4H), 1.53 (s, 1H), 1.41
(m, 2H), 1.3–1.18 (m, 3H), 1.1–0.2 (m, 3H); CDCl3, 100 MHz); 13C
All manipulations were carried out under nitrogen atmosphere.
NMR spectra were recorded on a JEOL JNM-ECX (400 MHz for 1H,
162 MHz for 31P, and 100 MHz for 13C). Chemical shifts were re-
ported in d ppm referenced to an internal tetramethylsilane stan-
dard for 1H NMR, and to an external 85% H3PO4 standard for 31P
NMR. Residual CHCl3 (d 77.0 for 13C) was used as internal reference
for 13C NMR. 1H, 13C, and 31P NMR spectra were recorded in CDCl3
at 25 °C unless otherwise noted. IR spectra were recorded on a JAS-
CO FT/IR-6300. Optical rotations were measured with a JASCO P-
1030 polarimeter with a sodium lamp. MS (ESI) spectra were ob-
tained on JEOL JMS-T100LC spectrometers. HPLC analyses were
performed on a Hitachi L-2130 pump, and L-2450 Diode Array
detector with a chiral column. X-ray crystal structure data were
collected using a Bruker SMART APEX II diffractometer with Mo
NMR (CDCl3, 100 MHz)
d 230, 149 (d, J = 263 Hz), 94.3 (d,
J = 8.00 Hz), 84.0 (d, J = 8.00 Hz), 80.8 (dd, J = 18.4, 40.2 Hz), 76.6
(d, J = 23.0 Hz), 35.1 (d, J = 34.5 Hz), 26.8, 26.6, 26.5, 26.4, 23, 25.6
11.1 (d, J = 44.5 Hz); 31P NMR (CDCl3, 162 MHz)
d 25.7 (d,
J = 60.7 Hz); IR (KBr) 3073, 2941, 2864, 2383, 1975, 1900,
1884 cm–1; HRMS (ESI): m/z Calc. for C16H21BClCrFO3P (M+Cl)–:
409.0399. Found: 409.0396.
4.2.4. 2-(Boranatodi-n-butylphosphino)
fluorobenzenetricarbonylchromium (3d)
Yield: 53% as a yellow oil; 1H NMR (CDCl3, 400 MHz) d 6.11 (dt,
J = 3.68, 6.88 Hz, 1H), 5.69 (m, 1H), 5.23 (t, J = 5.96 Hz, 1H), 4.80 (m,
1H), 2.10–1.79 (m, 5H), 1.59–1.23 (m, 7H), 0.96 (t, J = 7.32 Hz, 3H),
0.87 (t, J = 7.32 Hz, 3H), 1.39–1.10 (m, 8H), 1.1–0.1 (m, 3H); 13C
NMR (CDCl3, 100 MHz) d 150.1, 147.5, 99.1 (d, J = 7.62 Hz), 94.5
Ka radiation. All reagents were obtained from commercial sources
and used without further purification. All solvents were freshly
distilled. Compound 1, (S)-2a, (RP,S)-3a, (RP,R)-3a, and (RP)-5a were
prepared according to the literature procedure [2].

3550
Y. Yamamoto et al. / Journal of Organometallic Chemistry 693 (2008) 3546–3552
(d, J = 7.63 Hz), 84.2 (d, J = 6.67 Hz), 80.6 (dd, J = 18.1, 40.0 Hz), 27.6
(d, J = 36.2 Hz), 25.4 (d, J = 11.4 Hz), 24.5 (d, J = 30.5 Hz), 24.2 (dd,
J = 3.81, 13.4 Hz), 13.6; 31P NMR (CDCl3, 162 MHz) d 24.2 (d,
J = 60.8); HRMS (ESI): m/z Calc. for C17H25B1ClCrO3P (M+Cl)–
425.0712. Found: 425.0702.
irradiation of light for 3 h. After removal of green precipitates by fil-
tration, the filtrate was concentrated under reduced pressure, and
the residue was subjected to column chromatography on silica gel
(n-hexane/EtOAc = 5/1) to give 1,4-bis(boranatophosphino)
benzene.
4.2.5. 2-(Boranatodiisopropylphosphino)
4.3.1. 1,4-Bis(boranato-tert-butylmethylphosphino)benzene (6aa)
fluorobenzenetricarbonylchromium (3e)
Yield: 73% as a A white solid; mp 230 °C (decomp.);
Yield: 79% as a yellow solid; mp. 141–143 °C; 1H NMR (CDCl3,
400 MHz) d 6.08 (m, 1H), 5.69 (m, 1H), 5.21 (t, J = 6.40 Hz, 1H),
4.82 (m, 1H), 2.60 (m, 1H), 2.37 (m, 1H), 1.47 (dd, J = 6.88,
16.5 Hz, 3H), 1.36 (dd, J = 6.88, 16.0 Hz, 3H), 1.17 (dd, J = 6.88,
16.0 Hz, 3H), 1.04 (ddd, J = 1.84, 6.88, 14.2 Hz, 3H), 0.9–0.14 (m,
3H); 13C NMR (CDCl3, 100 MHz) d 149, 147, 98.8 (dd, J = 6.68,
12.4 Hz), 94.3 (d, J = 7.63 Hz), 84.3 (d, J = 6.67 Hz), 78.3 (dd,
J = 19.0, 32.4 Hz), 23.7 (d, J = 4.77 Hz), 23.6, 23.5 (d, J = 4.76 Hz),
23.3, 17.6 (dd, J = 25.8, 25.8 Hz); 31P NMR (CDCl3, 162 MHz) d
½
a 2D3
ꢂ
= ꢀ16.8 (c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.76 (m,
4H), 1.57 (d, J = 9.64 Hz, 6H), 1.09 (d, J = 14.2 Hz, 18H), 1.0–0.2
(m, 6H); 13C NMR (CDCl3, 100 MHz) d 132.6 (t, J = 8.6 Hz), 131.6
(d, J = 45.8 Hz), 28.7 (d, J = 32.4 Hz), 25.3 (d, J = 2.90 Hz), 5.26 (d,
J = 37.2); 31P NMR (CDCl3, 162 MHz) d 33.9 (m); IR (KBr) 2954,
2866, 2370 cm–1; Anal. Calc. for: C, 61.99; H, 11.05. Found: C,
61.75; H, 11.11%.
4.3.2. 1-(Boranato-tert-butylmethylphosphino)-
45.8 (d, J = 65.0 Hz); IR (KBr) 3102, 2979, 2392, 1975, 1930 cm–1
;
4-(boranatodicyclohexylphosphino)benzene (6ab)
HRMS (ESI): m/z Calc. for C15H21BClCrO3P (M+Cl)–: 397.0399.
Found: 397.0412; Anal. Calc. for: C, 49.75; H, 5.85. Found: C,
49.73; H, 5.39%.
Yield: 86% as a white solid; mp 300 °C (decomp.); ½a D24
= ꢀ3.7 (c
ꢂ
1.0, CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.76 (m, 4H), 2.08 (m, 2H),
1.94 (m, 2H), 1.82–1.67 (m, 6H), 1.59 (d, J = 9.60 Hz, 3H), 1.54 (m,
2H), 1.34–1.15 (m, 10H), 1.11 (d, J = 6.80 Hz, 9H), 1.0–0.1 (br,
6H); 13C NMR (CDCl3, 100 MHz) d 133.1 (t, J = 8.58 Hz), 132.7 (t,
J = 8.58 Hz), 131.4 (d, J = 47.7 Hz), 129.6 (d, J = 44.8 Hz), 31.4 (d,
J = 21.9 Hz), 31.1 (d, J = 22.9 Hz), 28.8 (d, J = 32.4 Hz), 26.8, 26.7,
26.6, 26.3 (d, J = 5.72 Hz), 25.91, 25.86, 5.24 (d, J = 37.2 Hz); 31P
4.2.6. 2-(Boranatodi-tert-butylphosphino)
fluorobenzenetricarbonylchromium (3f)
Yield: 85% as a yellow solid; mp. 180–182 °C; 1H NMR (CDCl3,
400 MHz) d 6.44 (dt, J = 3.68, 7.32 Hz, 1H), 5.74 (m, 1H), 5.22 (t,
J = 6.88 Hz, 1H), 4.80 (dt, J = 3.68, 6.44 Hz, 1H), 1.54 (dd, J = 1.84,
14.7 Hz, 2H), 1.24 (d, J = 13.8 Hz, 1H), 1.1–0.3 (m, 3H); 13C NMR
(CDCl3, 100 MHz) d 230 (s), 147.2 (dd, J = 3.21, 263 Hz), 100.2
(dd, J = 7.50, 11.8 Hz), 94.5 (d, J = 7.50 Hz), 80.0 (dd, J = 22.5,
25.7 Hz, 2H), 76.5 (d, J = 25.7 Hz), 35.4 (d, J = 2.10 Hz), 35.2 (d,
J = 4.30 Hz), 29.5 (m), 28.8 (m); 31P NMR (CDCl3, 162 MHz) d 60.0
(d, J = 64.8); IR (KBr) 3080, 2969, 2400, 1976, 1906 cm–1; HRMS
(ESI): m/z Calc. for C17H25BClCrO3P (M+Cl)–: 425.0712. Found
425.0714; Anal. Calc. for: C, 52.33; H, 6.46. Found: C, 52.35; H,
6.39%.
NMR (CDCl3, 162 MHz)
d
27.9 (d, J = 60.7 Hz), 26.8 (d,
J = 65.1 Hz); IR (KBr) 2938, 3855, 2390 cm–1; MS (ESI): m/z 439.3
(M+Cl)–; Anal. Calc. for: C, 67.81; H, 10.90. Found: C, 68.32; H,
11.19%.
4.3.3. 1-(Boranato-tert-butylmethylphosphino)-
4-(boranatocyclohexylmethylphosphino)benzene (6ac)
Yield: 70% as a white solid; mp 179–180 °C; ½a D24
= ꢀ14.7 (c 0.3,
ꢂ
CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.77 (m, 4H), 1.85–1.74 (m,
4H), 1.73–1.61 (m,
2 H), 1.59 (d, J = 9.60 Hz, 3H), 1.54 (d,
J = 10.0 Hz, 3H), 1.29–1.17 (m, 5H), 1.12 (d, J = 14.2 Hz, 9H), 1.1–
0.1 (m, 6H); 13C NMR (CDCl3, 100 MHz) d 132.9 (dd, J = 8.58,
8.58 Hz), 132.7 (d, J = 49.6 Hz), 131.7 (dd, J = 8.58, 8.58 Hz), 131.6
(d, J = 48.6 Hz), 35.7 (d, J = 35.3 Hz), 28.8 (d, J = 32.4 Hz), 26.5,
26.4, 25.7, 25.3, 7.69 (d, J = 38.1 Hz), 5.26 (d, J = 36.9 Hz); 31P
NMR (CDCl3, 162 MHz) d 34.0 (m), 32.5 (m); IR (KBr) 2930, 2857,
4.2.7. 2-(Boranatodiphenylphosphino)
fluorobenzenetricarbonylchromium (3g)
Yield: 69% as a yellow solid; mp 145–147 °C; 1H NMR (CDCl3,
400 MHz) d 7.85 (m, 2H), 7.63–7.40 (m, 8H), 6.19 (t, J = 6.88 Hz,
1H), 5.69 (m, 1H), 5.15 (t, J = 5.96 Hz, 1H), 4.79 (m, 1H), 1.7–0.7
(m, 3H); 13C NMR (CDCl3, 100 MHz)
d
150, 148, 134 (d,
2388 cm–1 HRMS (ESI): m/z Calc. for C18H36B2ClP2 (M+Cl)–:
;
J = 10.5 Hz), 132 (d, J = 9.54 Hz), 132, 131, 129 (d, J = 10.5 Hz),
129 (d, J = 11.4), 128, 98.7 (dd, J = 4.77, 14.3 Hz), 94.4 (d,
J = 7.63 Hz), 83.5 (d, J = 7.63 Hz), 81.9 (dd, J = 17.2, 45.7 Hz), 75.9
371.2167. Found: 371.2168.
4.3.4. 1-(Boranato-tert-butylmethylphosphino)-
(d, J = 21.9 Hz); 31P NMR (CDCl3, 162 MHz)
d
22.86 (d,
4-(boranatodi-n-butylphosphino)benzene (6ad)
J = 24.1 Hz); IR (KBr) 3089, 2384, 1984, 1926 cm–1; HRMS (ESI):
m/z Calc. for C21H17BClCrFO3P (M+Cl)–: 465.0086. Found:
465.0083; Anal. Calc. for: C, 58.64; H, 3.98. Found: C, 58.63; H,
3.80%.
Yield: 84% as a white solid; mp 168 °C; ½a D24
= ꢀ7.3 (c 0.3,
ꢂ
CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.79 (m, 4H), 1.9–1.79 (m,
4H), 1.59 (d, J = 9.60 Hz, 3H), 1.50–1.42 (m, 2H,) 1.38–1.28 (m,
6H), 1.11 (d, J = 13.8 Hz, 9H), 0.87 (t, J = 7.32 Hz, 6H) 0.9–0.2 (m,
6H); 13C NMR (CDCl3, 100 MHz) d 133 (dd, J = 8.60, 8.60 Hz), 133
(d), 132 (dd, J = 8.60, 8.60 Hz), 132 (d, J = 47.7 Hz), 28.8 (d,
J = 32.4 Hz), 25.4, 25.3, 25.2, 24.95, 24.95, 24.9, 24.4, 24.3, 13.6,
5.25 (d, J = 36.2 Hz); 31P NMR (CDCl3, 162 MHz) d 27.0 (d,
4.3. General procedure for the tele-SNAr
To a solution of sec-phosphine–borane (0.3 mmol) in THF
(0.5 mL) was added a solution of sec-BuLi (0.3 mL, 1.0 M cyclohex-
ane solution, 0.3 mmol) at ꢀ78 °C under nitrogen atmosphere,
and the reaction mixture was stirred for 1 h. To the solution was
added 2-boranatophosphinofluorobenzenetricarbonylchromium
(0.1 mmol) in THF (0.2 mL) at ꢀ40 °C, and the mixture was stirred
for 5 h. Trifluoromethanesulfonic acid (0.3 mmol) was then added
slowly to the solution at ꢀ78 °C. After stirring at intact temperature
for 24 h, the mixture was diluted with water and extracted with
CHCl3. The combined extracts were dried over Na2SO4, and concen-
trated under reduced pressure. The resulting yellow solid was dis-
solved in chloroform, and the solution was exposed to air under
J = 65.0 Hz), 16.6 (d, J = 56.4 Hz); IR (KBr) 2957, 2869, 2378 cm–1
;
HRMS (ESI): m/z Calc. for C19H40B2ClP2 (M+Cl)–: 387.2480. Found
387.2474.; Anal. Calc. for: C, 64.81; H, 11.45. Found: C, 64.89; H,
11.26%.
4.3.5. 1-(Boranato-tert-butylmethylphosphino)-
4-(boranatodiisopropylphosphino)benzene (6ae)
Yield: 48% as a white solid; mp 179–180 °C; ½a D24
= ꢀ10.5 (c 0.5,
ꢂ
CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.79 (m, 4H), 2.37 (m, 2H),
1.59 (d, J = 9.64 Hz, 3H), 1.10 (d, J = 14.2 Hz, 9H), 1.20–1.02 (m,
12H), 1.0–0.1 (m, 6H); 13C NMR (CDCl3, 100 MHz) d 133.1 (dd,

Y. Yamamoto et al. / Journal of Organometallic Chemistry 693 (2008) 3546–3552
3551
J = 7.60, 7.60 Hz), 132.7 (dd, J = 8.6, 8.6 Hz), 131.7 (d, J = 46.7 Hz),
129.4 (d, J = 44.8 Hz), 28.7 (d, J = 32.4 Hz), 25.2, 22.0, 16.8, 5.23
(d, J = 36.2 Hz); 31P NMR (CDCl3, 162 MHz) d 35.7 (d, J = 65.0 Hz),
26.9 (d, J = 69.4 Hz); IR (KBr) 2971, 2871, 2380 cm–1; HRMS (ESI):
m/z Calc. for C17H36B2ClP2 (M+Cl)–: 359.2167. Found: 359.2168.;
Anal. Calc. for: C, 63.01; H, 11.20. Found: C, 62.93; H, 10.94%.
J = 6.44 Hz, 1H), 2.18 (t, J = 10.1 Hz, 1H), 2.01 (t, J = 11.0 Hz, 2H),
1.92–1.76 (m, 7H), 1.69 (d, J = 11.9 Hz, 2H), 1.37–1.1 (m, 10H);
13C NMR (CDCl3, 100 MHz)
d 131 (d, J = 269 Hz), 133 (d,
J = 269 Hz), 93.4 (dd, J = 4.76, 21.9 Hz), 90.5 (dd, J = 20.0, 47.7 Hz),
84.9, 81.7 (d, J = 17.1 MHz), 33.4, 33.0, 30.2, 30.0, 29.9, 29.8, 27.3,
27.2, 27.0, 26.9, 26.3, 26.2; 31P NMR (CDCl3, 162 MHz) d 7.92 (d,
J = 13.0 Hz).
4.3.6. 1-(Boranato-tert-butylmethylphosphino)-
4-(boranatodi-tert-butylphosphino)benzene (6af)
4.4.2. 1-Dicyclohexylphosphino-4-duterio-
2,3-difluorobenzenetricarbonylchromium (rac-9)
Yield: 62% as a white solid; mp 167–169 °C; ½a D24
ꢂ
= ꢀ9.0 (c 0.5,
CHCl3); 1H NMR (CDCl3, 400 MHz) d 8.08 (t, J = 8.28 Hz, 2H), 7.79
(t, J = 8.68 Hz, 2H), 1.59 (d, J = 9.64 Hz, 3H), 1.31 (d, J = 13.3 Hz,
18H), 1.10 (d, J = 14.2 Hz, 9H), 1.0–0.1 (m, 6H); 13C NMR (CDCl3,
100 MHz) d 134.7, 132.2 (t, J = 8.58 Hz), 131.4 (d, J = 18.1 Hz),
131.0 (d, J = 7.63 Hz), 33.4 (d, J = 4.77 Hz), 33.1 (d, J = 4.77 Hz),
28.9 (d, J = 2.86 Hz), 28.5, 25.3 (d, J = 2.86 Hz), 5.19 (d,
J = 36.2 Hz); 31P NMR (CDCl3, 162 MHz) d 46.2 (d, J = 82.4 Hz),
26.6 (d, J = 75.8 Hz); IR (KBr) 2971, 2385 cm–1; HRMS (ESI): m/z
Calc. for C19H40B2ClP2 (M+Cl)–: 387.2480. Found: 387.2484. Anal.
Calc. for: C, 64.81; H, 11.45. Found: C, 65.06; H, 11.27%.
To a solution of rac-8 (722 mg, 1.6 mmol) in Et2O (10 mL) was
added n-BuLi (1.2 mL of 1.6 M n-hexane solution, 1.9 mmol) at
ꢀ78 °C under nitrogen atmosphere. After stirring for 0.5 h, the
reaction was quenched with D2O (10 mL), and the mixture was ex-
tracted three times with EtOAc. The combined extracts were
washed with brine. The organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The residue was chromato-
graphed on silica gel (n-hexane/EtOAc = 10/1) to give rac-9 (641
mg, 88% yield, >99% D) as a yellow solid. 1H NMR (CDCl3,
400 MHz) d 5.67 (m, 0.01H), 5.07 (m, 1H), 4.91 (d, J = 6.4 Hz, 1H),
2.15 (t, J = 10.1 Hz, 1H), 2.01 (t, J = 11.0 Hz, 2H), 1.92–1.76 (m,
7H), 1.69 (d, J = 11.9 Hz, 2H), 1.37–1.1 (m, 10H); 31P NMR (CDCl3,
162 MHz) d 7.92 (d, J = 13.0 Hz).
4.3.7. 1-(Boranato-tert-butylmethylphosphino)-
4-(boranatodiphenylphosphino)benzene (6ag)
Yield: 83% as a white solid; mp. 144–145 °C; ½a D24
ꢂ
= 14.8 (c 0.4,
CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.76 (t, J = 6.88 Hz, 2H), 7.66–
7.50 (m, 8H), 7.45 (t, J = 7.32 Hz, 4H), 1.57 (d, J = 9.60 Hz, 3H), 1.10
(d, J = 17.0 Hz, 9H), 1.8–0.2 (br, 6H); 13C NMR (CDCl3, 100 MHz) d
134, 133.3 (d, J = 9.53 Hz), 133.1 (t, J = 9.54 Hz), 132.8 (t,
J = 9.54 Hz), 131.7 (d, J = 44.8 Hz), 131.7, 28.8 (d, J = 32.4 Hz), 25.3
(d, J = 2.86 Hz), 5.26 (d, J = 37.2 Hz); 31P NMR (CDCl3, 162 MHz) d
27.2 (d, J = 45.5 Hz), 21.8 (d, J = 32.1 Hz); IR (KBr) 2963, 2902,
2381, 2341, 2264 cm–1; HRMS (ESI): m/z Calc. for C23H32B2Cl1P2
(M+Cl)–: 427.1854. Found: 427.1850. Anal. Calc. for: C, 70.46; H,
8.23. Found: C, 70.47; H, 7.98%.
4.4.3. 2-Dicyclohexylphosphino-
5-duteriofluorobenzenetricarbonylchromium (rac-10)
A solution of rac-9 (641 mg, 1.43 mmol) in Et2O (30 mL) was
slowly added to a stirred suspension of lithium aluminum hydride
(270 mg, 7.2 mmol) in Et2O (10 mL) at 0 °C, and the mixture was
stirred at intact temperature for 14 h. The reaction mixture was di-
luted with EtOAc, and washed with water, and the aqueous phase
was extracted twice with EtOAc. The combined extracts were
washed with saturated NaHCO3, and brine. The organic layer was
dried over Na2SO4 and concentrated under reduced pressure. The
residue was chromatographed on silica gel (n-hexane/EtOAc = 10/
1) to give rac-10 (162 mg, 26% yield, >95% D) as a yellow solid.
1H NMR (CDCl3, 400 MHz) d 5.54 (m, 1.02H), 5.25 (d, J = 5.04 Hz,
1H), 4.84 (m, 1H), 2.1–1.6 (m, 12H), 1.4–1.1 (m, 10H); 31P NMR
(CDCl3, 162 MHz) d 5.44 (d, J = 26.0 Hz).
4.3.8. 1-(Boranato-tert-butylmethylphosphino)-
4-(boranato-1-adamantylmethylphosphino)benzene (6ah)
Yield: 59% as a white solid; mp 277–279 °C; ½a D24
= ꢀ12.4 (c
ꢂ
0.53, CHCl3); 1H NMR (CDCl3, 400 MHz) d 7.75 (m, 4H), 1.98 (s,
3H), 1.27 (s, 6H), 1.69 (s, 3H), 1.63 (s, 3H), 1.59 (d, J = 9.6 Hz, 3H),
1.53 (d, J = 9.2 Hz, 3H), 1.12 (d, J = 14.2 Hz, 9H), 1.1–0.2 (m, 6H);
13C NMR (CDCl3, 100 MHz) d 132.8 (t, J = 9.53 Hz), 132.5 (t,
J = 8.58 Hz), 131.4 (d, J = 46.7 Hz), 130.7 (d, J = 46.7 Hz), 36.3,
35.9, 31.4 (d, J = 32.4 Hz), 21.8 (d, J = 32.4 Hz), 27.7 (d,
J = 8.58 Hz), 25.3 (d, J = 1.90 Hz), 5.24 (d, J = 37.2 Hz), 3.70 (d,
J = 37.2 Hz); 31P NMR (CDCl3, 162 MHz) d 26.9 (d, J = 60.8 Hz),
23.4 (d, J = 73.8 Hz); IR (KBr) 2905, 2851, 2376 cm–1; HRMS (ESI):
m/z Calc. for C22H40B2ClP2 (M+Cl)–: 409.0399. Found: 409.0396.
4.4.4. rac-5-D-3b
To a solution of rac-10 (161 mg, 0.4 mmol) in THF (1 mL) was
added BH3ꢁTHF complex (0.4 mL of 1.0 M THF solution, 0.4 mmol)
at 0 °C under nitrogen atmosphere. After stirring at room temper-
ature for 2 h, the reaction was quenched with 1 M HCl aq., and the
mixture was extracted three times with EtOAc. The combined ex-
tracts were washed with saturated NaHCO3, and brine. The organic
layer was dried over Na2SO4 and concentrated under reduced pres-
sure. The residue was chromatographed on silica gel (n-hexane/
EtOAc = 10/1) to give rac-5-D-3b (154 mg, 87% yield, >95% D) as
a yellow solid. 1H NMR (CDCl3, 400 MHz) d 6.06 (dt, J = 3.64,
6.88 Hz, 1H), 5.69 (m, 0.05H), 5.20 (d, J = 6.4 Hz, 1H), 4.80 (dd,
J = 3.20, 5.96 Hz, 1H), 2.35–2.26 (m, 2H), 2.13–2.05 (m, 1H), 2.00–
1.89 (m, 4H), 1.80–1.55 (m, 7H), 1.39–1.10 (m, 8H), 1.0–0.1 (m,
3H); 31P NMR (CDCl3, 162 MHz) d 37.2 (d, J = 60.4 Hz).
4.4. Preparation of 2-boranatodicyclohexylphosphino-
5-deuteriofluorobenzenetricarbonylchromium (rac-5-D-3b)
4.4.1. 1-Dicyclohexylphosphino-
2,3-difluorobenzenetricarbonylchromium (rac-8)
To a solution of 1 (707 mg, 2.8 mmol) in Et2O (28 mL) was
added n-BuLi (1.8 mL of 1.6 M n-hexane solution, 2.8 mmol) at
ꢀ78 °C under nitrogen atmosphere. After stirring for 0.5 h, chloro-
4.4.5. Procedure for the labeling studies (Scheme 4)
dicyclohexylphosphine (630
lL, 2.8 mmol) was added at ꢀ78 °C,
To a solution of (S)-tert-butylmethylphosphine–borane (34.9
mg, 0.3 mmol) in THF (0.5 mL) was added sec-BuLi (0.3 mL, 1.0 M
cyclohexane and n-hexane solution, 0.3 mmol) at ꢀ78 °C under
nitrogen atmosphere, and the reaction mixture was stirred for
1 h. To the solution was added rac-5-D-3b (45 mg, 0.1 mmol), and
THF (0.2 mL) at ꢀ40 °C, and the mixture was stirred for 40 h. Tri-
and the mixture was stirred for 3 h at intact temperature. The reac-
tion was quenched with 1 M HCl aq., and the mixture was ex-
tracted three times with EtOAc. The combined extracts were
washed with saturated NaHCO3, and brine. The organic layer was
dried over Na2SO4, and concentrated under reduced pressure. The
residue was chromatographed on silica gel (n-hexane/EtOAc = 10/
1) to give rac-8 (627 mg, 50% yield) as a yellow solid. 1H NMR
fluoromethanesulfonic acid (27 lL, 0.3 mmol) was then added
slowly to the solution at ꢀ78 °C, and the reaction was stirred at in-
(CDCl3, 400 MHz)
d
5.67 (m, 1H), 5.07 (m, 1H), 4.91 (t,
tact temperature. After 24 h, the reaction mixture was diluted with

3552
Y. Yamamoto et al. / Journal of Organometallic Chemistry 693 (2008) 3546–3552
Cy
P
F
F
1) n-BuLi, Et2O
1) n-BuLi, Et2O
Cy
(OC)3Cr
rac-8: 50% yield
–78 °C, 1 h
–78 °C, 1 h
F
F
2) ClPCy2
–78 °C to rt, 3 h
2) D2O
(OC)3Cr
1
BH3
Cy
Cy
Cy
Cy
Cy
Cy
P
F
P
F
P
F
LiAlH4, THF
BH3·THF
F
THF, rt, 2 h
0 °C, 14 h
(OC)3Cr
(OC)3Cr
(OC)3Cr
D
D
D
rac-9: 88% yield
rac-10: 26% yield
rac-5-D-3b: 87% yield
>99% D
>95% D
>95% D
Scheme 6. Preparation of rac-5-D-3b.
water and extracted with CHCl3. The combined extracts were dried
over Na2SO4, and concentrated under reduced pressure. The residue
was subjected to column chromatography on silica gel (n-hexane/
EtOAc = 5/1).
g cm–3, T = 120 K, 3762 unique and 3524 observed [I > 2
r(I)] reflec-
tions, 196 parameters, final [I > 2r(I)] R1 = 0.0249, wR2 = 0.0775.
S = 0.606. Flack parameter = –0.011(15), CCDC-685999.
A mixture of the purified product (27.5 mg) and 1-methylpyr-
rolidine (2 mL) was stirred under nitrogen atmosphere at room
temperature for 12 h. The volatiles were removed under reduced
pressure, and the residue was passed through a column of silica
gel with degassed toluene elution. The eluent was evaporated un-
der reduced pressure to give free phosphine. To a solution of free
phosphine (18 mg) in EtOH (1.0 mL) was added H2O2 at 0 °C and
the mixture was stirred for 10 min at intact temperature. The reac-
tion was quenched with 1 M HCl aq., and the mixture was ex-
tracted three times with EtOAc. The combined extracts were
washed with saturated NaHCO3, and brine. The organic layer was
dried over Na2SO4 and concentrated under reduced pressure. The
residue was chromatographed on silica gel (CHCl3/MeOH = 10/1)
to give a diastereomeric mixture of 3-D-7ab (7.2 mg, 13% yield,
>95% D). 1H NMR (CDCl3, 400 MHz) d 5.74 (t, J = 5.96 Hz, 1H),
5.66 (t, J = 6.40 Hz, 0.48H), 5.59 (t, J = 6.40 Hz, 0.55H), 5.05 (t,
J = 5.96 Hz, 1H), 2.1–1.8 (m, 10H), 1.73 (d, J = 13.6 Hz, 3H), 1.5–
1.2 (m, 12H), 1.18 (d, J = 15.1 Hz, 9H); 31P NMR (CDCl3, 162 MHz)
d 48.4, 43.5.
4.4.8. Crystal data of (R,R)-4aa
Crystal dimensions 0.20 ꢃ 0.20 ꢃ 0.10 mm3; C19H34B2CrO3P2,
Mr = 446.02; orthorhombic space group P212121, a = 8.1336(5),
b = 10.9987(7), c = 26.7003(16) Å, V = 2388.6(3) Å3, Z = 4, Dcalc
=
1.240 g cm–3
[I > 2 (I)] reflections, 276 parameters, final [I > 2
,
T = 120 K, 4673 unique and 4391 observed
(I)] R1 = 0.0267,
r
r
wR2 = 0.0632. S = 1.029. Flack parameter = –0.004(14), CCDC-
686000.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Appendix A. Supplementary material
CCDC 685999 and 686000 contain the supplementary crystallo-
graphic data from this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif.
4.4.6. Procedure for the labeling studies (Scheme 5)
To a solution of (S)-tert-butylmethylphosphine–borane (36 mg,
0.3 mmol) in THF (0.5 mL) was added sec-BuLi (0.3 mL, 1.0 M cyclo-
hexane and n-hexane solution, 0.3 mmol) at ꢀ78 °C under nitrogen
atmosphere, and the reaction mixture was stirred for 1 h. To the
solution was added 3b (44.2 mg, 0.1 mmol) in THF (0.2 mL) at
ꢀ40 °C, and the mixture was stirred for 5 h. Trifluoromethanesulfo-
References
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4.4.7. Crystal data of (RP,R)-3a
Crystal dimensions 0.25 ꢃ 0.40 ꢃ 0.50 mm3; C14H19BCrFO3P,
Mr = 348.08; orthorhombic space group P212121, a = 9.276(5),
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