Facile synthesis of highly congested 1,2-diphosphinobenzenes from bis(phosphine)boronium salts

Article abstract of DOI:10.1021/ol062717i

(Chemical Equation Presented) Bis(phosphine)boronium salts 3a-c were designed and prepared as key building blocks for the synthesis of highly congested diphosphinobenzenes. The preparation of sterically hindered ortho-phenylene-bridged diphosphines 1a-c was achieved by the reaction of the bis(phosphine)boronium salts 3a-c with difluorobenzenechromium complex 2 and subsequent removal of the BH₂ group. The steric nature of diphosphine 1a was revealed in single-crystal X-ray analysis of its Rh complex.

Full text of DOI:10.1021/ol062717i

ORGANIC
LETTERS
2
006
Vol. 8, No. 26
103-6106
Facile Synthesis of Highly Congested
,2-Diphosphinobenzenes from
Bis(phosphine)boronium Salts
6
1
Yoshikazu Yamamoto, Toru Koizumi, Kosuke Katagiri,†,‡ Yui Furuya,†
†
†,‡
,
†
‡
,†
Hiroshi Danjo,* Tsuneo Imamoto, and Kentaro Yamaguchi*
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences at
Kagawa Campus, Tokushima Bunri UniVersity, and CREST, Japan Science and
Technology Agency (JST), 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan, and
Department of Chemistry, Faculty of Science, Chiba UniVersity, 1-33 Yayoi-cho,
Inage-ku, Chiba 263-8522, Japan
danjo@kph.bunri-u.ac.jp
Received November 7, 2006
ABSTRACT
Bis(phosphine)boronium salts 3a
diphosphinobenzenes. The preparation of sterically hindered ortho-phenylene-bridged diphosphines 1a
bis(phosphine)boronium salts 3a c with difluorobenzenechromium complex 2 and subsequent removal of the BH
diphosphine 1a was revealed in single-crystal X-ray analysis of its Rh complex.
−
c
were designed and prepared as key building blocks for the synthesis of highly congested
c was achieved by the reaction of the
group. The steric nature of
−
−
2
5
The design and synthesis of new phosphine ligands is one
of the most important research subjects in the field of
transition-metal catalyses. Recently, bulky monophosphines
bromides. The utility of bulky diphosphine ligands repre-
sented by 1,3-bis(di-tert-butylphosphino)propane (dtbpp) or
1,2-bis(di-tert-butylphosphinomethyl)benzene (dtbpmb) was
also demonstrated mainly in Pd-catalyzed alkoxycarbonyl-
1
such as tri-tert-butylphosphine and biaryldicyclohexylphos-
6
7
phines were proven to be effective for Pd-catalyzed amina-
ation of olefins or aryl halides, in which high TON and
2
3,4a
tion of aryl halides, R-arylation of carbonyls, and cross-
4
coupling of arylboronic acids with aryl chlorides or alkyl
(3) (a) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,
1
1
1108-11109. (b) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997,
19, 12382-12383. (c) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc.
†
Tokushima Bunri University and CREST.
Chiba University.
1999, 121, 1473-1478.
‡
(4) For reviews, see: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed.
2002, 41, 4176-4211. (b) Miura, M. Angew. Chem., Int. Ed. 2004, 43,
2201-2203.
(
1) For representative reviews of chiral phosphine ligands, see the
following: (a) Tang, W.; Zhang, X. Chem. ReV. 2003, 103, 3029-3069.
b) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 1-110.
c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley &
(
(5) Netherton, M. R.; Dai, C.; Neusch u¨ tz, K.; Fu, G. C. J. Am. Chem.
Soc. 2001, 123, 10099-10100.
(
(6) (a) Koide, Y.; Bott, S. G.; Barron, A. R. Organometallics 1996, 15,
2213-2226. (b) Clegg, W.; Eastham, G. R.; Elsegood, M. R. J.; Tooze, R.
P.; Wang, X. L.; Whiston, K. Chem. Commun. 1999, 1877-1878. (c) Pugh,
R. I.; Drent, E. AdV. Synth. Catal. 2002, 344, 837-840. (d) Rucklidge, A.
J.; Morris, G. E.; Cole-Hamilton, D. J. Chem. Commun. 2005, 1176-1178.
(7) Jimenez-Rodriguez, C.; Eastham, G. R.; Cole-Hamilton, D. J. Dalton
Trans. 2005, 1826-1830.
Sons: New York, 1994. (d) Pietrusiewicz, K. M.; Zabrocka, M. Chem.
ReV. 1994, 94, 1375-1411.
(
2) For reviews, see: (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem.
2
002, 219, 131-209. (b) Hartwig, J. F. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New
York, 2002; p 1051.
1
0.1021/ol062717i CCC: $33.50
© 2006 American Chemical Society
Published on Web 11/23/2006

regioselectivity were observed. However, despite their high
utility, the synthesis of such phosphines is quite difficult
because of their own steric hindrance, and only a limited
number of bulky phosphines have been prepared so far. As
part of our continuing research toward the development of
efficient transition-metal catalyses, we report here a new
approach to a class of sterically hindered diphosphines that
shows promise in various catalytic processes. We focused
on 1,2-diphosphinobenzenes 1 with bulky alkyl substituents
Scheme 2. Preparation of Bis(phosphine)boronium Salts 3
8
on phosphorus atoms. The ortho-phenylene backbone is
rigid and is expected to form a highly regulated reaction
environment. Previously, we tried to prepare a P-chiral
diphosphine, (R,R)-1,2-bis(tert-butylmethylphosphino)ben-
zene ((R,R)-1b), according to the S
N
Ar approach in which
1,2-difluorobenzenetricarbonylchromium (2) and (S)-tert-
butylmethylphosphine-borane were employed as coupling
9
components. Despite numerous attempts to use any order
of events, sequential substitution of the two halogens with
two phosphino groups did not proceed at all (eq 1). The
Di-tert-butylphosphine, generated in situ from di-tert-butyl-
chlorophosphine and lithium aluminum hydride, was treated
with 0.5 equiv of a monobromoborane dimethylsulfide
complex. The reaction proceeded in dichloromethane at room
temperature to afford bis(di-tert-butylphosphine)boronium
bromide (3a‚Br) in 72% yield. Optically active bis(phos-
phine)boronium salts were also prepared from optically pure
secondary phosphine-boranes. Thus, (S)-tert-butylmethyl-
phosphine-borane was converted into the corresponding
phosphine-iodoborane by treatment with 0.5 equiv of
1
2
iodine, which was then coupled with racemic tert-butyl-
methylphosphine to afford bis(tert-butylmethylphosphine)-
boronium iodide (3b‚I) in 70% yield as a mixture of
diastereomers. Diastereomerically enriched (S,S)-3b‚I could
be obtained by recrystallization from THF (96% de).
Boronium salt (S)-3c‚I was also prepared from (S)-tert-
butylmethylphosphine-borane (99% ee) and di-tert-butyl-
phosphine in the same manner.
boranato(dialkyl)phosphino group was too bulky to be
introduced at the ortho position of the phosphinobenzenes.
To avoid steric repulsion between two phosphorus nucleo-
philes, we used bis(phosphine)boronium salts 3, in which
two secondary phosphine compounds are coupled through
the BH
2
linkage (Scheme 1).10
Synthesis of diphosphines 1 was then carried out with the
boronium salts 3a-c as starting materials (Scheme 3). At
first, 3a was subjected to the coupling reaction with 1,2-
difluorobenzenetricarbonylchromium (2) after deprotonation
with 2.0 equiv of n-BuLi at ambient temperature. The
reaction took place in the presence of 5 equiv of HMPA at
Scheme 1. Design of Bis(phosphine)boronium Salts 3
6
5 °C, and diphosphinobenzeneboronium salt 4a‚Br was
1
3
obtained in 62% yield. As the second step, the removal of
the bridging boronium group of the diphosphineboronium
compound was attempted under various reaction conditions.
Boronium salt 4a‚Br was stable against strong acids such as
trifluoromethanesulfonic acid or tetrafluoroboric acid, which
are effective reagents for the deboranation of phosphine-
The preparation of 3 was easily achieved by reacting
11
secondary phosphine with monobromoborane (Scheme 2).
(8) For examples, see: (a) Kyba, E. P.; Liu, S.-T.; Harris, R. L.
Organometallics 1983, 2, 1877-1879. (b) Kyba, E. P.; Kerby, M. C.; Rines,
S. P. Organometallics 1986, 5, 1189-1194. (c) Burk, M. J. Am. Chem.
Soc. 1991, 113, 8518-8519. (d) Gray, M.; Chapell, B. J.; Felding, J.; Taylor,
N. J.; Snieckus, V. Synlett 1998, 422-423. (e) Miura, T.; Imamoto, T.
Tetrahedron Lett. 1999, 40, 4833-4836. (f) Imamoto, T.; Sugita, K.;
Yoshida, K. J. Am. Chem. Soc. 2005, 127, 11934-11935.
1
4
boranes. The boronium group was also intact in 1-methyl-
pyrrolidine at 60 °C. After screening various reaction
15
(12) Imamoto, T.; Hikosaka, T. J. Org. Chem. 1994, 59, 6753-6759.
(13) Cr(CO)3 was removed under these reaction conditions without
irradiation of sunlight.
(14) (a) Mckinstry, L.; Livinghouse, T. Tetrahedron Lett. 1994, 35,
9319-9322. (b) Mckinstry, L.; Livinghouse, T. Tetrahedron 1995, 51,
7655-7666.
(15) Imamoto, T.; Kusumoto, T.; Suzuki, N.; Sato, K. J. Am. Chem. Soc.
1985, 107, 5301-5303.
(
9) Katagiri, K.; Danjo, H.; Yamaguchi, K.; Imamoto, T. Tetrahedron
005, 61, 4701-4707.
10) (a) Schmidtbaur, H. J. Organomet. Chem. 1980, 200, 287-306. (b)
2
(
Westcott, S. A.; Blom, H. P.; Marder, T. B. Inorg. Chem. 1993, 32, 2175-
2
182.
(11) Martin, D. R.; Merkel, C. M.; Ruiz, J. P. Inorg. Chim. Acta 1985,
1
00, 293-297.
6104
Org. Lett., Vol. 8, No. 26, 2006

P
stepwise protocol shown in Scheme 4. Phosphine (R )-5 was
coupled with (S)-tert-butylmethylphosphine-trifluoromethane-
sulfonyloxyborane to form int-A (not isolated). Intramolecu-
Scheme 3. Preparation of Diphosphinobenzenes 1
N
lar S Ar took place after deprotonation of the terminal
phosphino group to give (R,R)-4b‚OTf in 58% yield. The
P-stereogenic centers were completely retained during this
transformation (99% de, <99% ee).
Figure 1. ORTEP drawing of [1a‚Rh(nbd)]PF
and PF are omitted for clarity.
6
. Hydrogen atoms
6
conditions, tetra-n-butylammonium fluoride (TBAF) was
found to be effective for this transformation. Thus, the
reaction took place in the presence of 3.0 equiv of TBAF in
chlorobenzene at 70 °C, and 1a was formed in 89% yield
within 24 h. Optically active P-chiral diphosphines were also
prepared from boronium salts (S,S)-3b‚I and (S)-3c‚I. The
coupling reaction of (S,S)-3b with 2 (1:1 molar ratio)
proceeded at -40 °C, and (R,R)-4b‚I with 97% de was
obtained in 87% yield. The optical purity of (R,R)-4b‚I was
determined to be >99% ee by reverse-phase chiral HPLC
The single-crystal X-ray analysis of [1a‚Rh(nbd)]PF
6
revealed that although the bite angle (P1-Rh-P2) of 82.5°
6a,b
is small in comparison to other diphosphines the four tert-
butyl groups on phosphorus atoms effectively shield the
coordination surface (Figure 1). It is noteworthy that the
norbornadiene ligand is significantly inclined (23°) from the
coordination plane due to steric hindrance of the tert-butyl
groups.
The utility of diphosphine ligand 1a was tested in
palladium-catalyzed hydroesterification of terminal olefins
Table 1). The reaction was conducted in the presence of
1
6
analysis. The reaction of (R,R)-4b‚I with TBAF was also
successful, and free P-chiral diphosphine (R,R)-1b was
obtained in 78% yield. The enantiomeric excess of (R,R)-
(
0
.2 mol % of Pd(OAc) , 0.25 mol % of 1a, and 1.5 mol %
2
1b was determined to be >99% (98% de) in its phosphine
of methanesulfonic acid under 6 atm of CO. In each case,
the reaction proceeded smoothly and gave the corresponding
hydroesterification product mainly in linear form. This
regioselectivity is similar to that obtained by dtbpp rather
sulfide form, indicating that almost no racemization occurred
during the diphosphine synthesis. Unsymmetric P-chiral
diphosphine (R)-1c was prepared in the same manner (57%
yield, 97% ee in two steps). Optically active diphosphine-
boronium salt 4b could also be obtained according to the
Table 1. Pd-Catalyzed Hydroesterification of Olefinsa
Scheme 4. Stepwise Procedure for the Preparation of
Bis(phosphine)boronium Salts 4b
entry
R
yield/%b
n/ic
1
2
3
4
5
Ph
92
94
42
88
73
7.7:1
30:1
7.7:1
5.6:1
5.0:1
2-MeC6H4
4-MeOC6H4
4-ClC6H4
n-Hex
d
a
Reagents and conditions: olefin (2.5 mmol), Pd(OAc)2 (0.2 mol %),
a (0.25 mol %), MsOH (1.5 mol %), EtOH (0.4 mL), toluene (1 mL), CO
1
(
6 atm), 80 °C, 12 h. b Isolated yield. c Determined by H NMR. 4-(1-
1
d
Ethoxyethyl)anisole was formed in 37% yield.
Org. Lett., Vol. 8, No. 26, 2006
6105

than dtbpmb, probably owing to the small bite angle of 1a.17
The hydroesterification did not proceed in the presence of
was demonstrated in Pd-catalyzed hydroesterification of
olefins.
1
c instead of 1a.
Acknowledgment. The authors wish to thank Prof.
Ken Kamikawa at Osaka Prefecture University for
helpful discussions. This work was supported by a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Culture, Sports, Science, and Technology,
Japan.
In conclusion, bis(phosphine)boronium salts 3a-c were
prepared as key building blocks for highly advantageous
diphosphine synthesis. The preparation of sterically hindered
ortho-phenylene-bridged diphosphines 1a-c was achieved
by the reaction of the bis(phosphine)boronium salts 3a-c
with the difluorobenzenechromium complex 2 and subse-
Supporting Information Available: Experimental pro-
quent removal of the BH
2
group. The performance of 1a
cedures and spectroscopic data for all new compounds and
6
X-ray diffraction data for [1a‚Rh(nbd)]PF in the form of a
CIF file. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
16) Decreased enantiomeric excess (97% de, 83% ee) was observed
when the coupling reaction was carried out at room temperature.
17) Ooka, H.; Inoue, T.; Itsuno, S.; Tanaka, M. Chem. Commun. 2005,
173-1175.
(
1
OL062717I
6106
Org. Lett., Vol. 8, No. 26, 2006