Efficient Stereoselective Synthesis of o -Functionalized P-Chirogenic Phosphines Applied to Asymmetric Catalysis

Article abstract of DOI:10.1080/10426507.2014.993760

The stereoselective synthesis of P-chirogenic o-halogenophenylphosphines and their use for the preparation of o-functionalized derivatives are reported. The key step of this synthesis is based on the reaction of a P-chirogenic secondary phosphine borane,

Full text of DOI:10.1080/10426507.2014.993760

This article was downloaded by: [University of Nebraska, Lincoln]
On: 07 September 2015, At: 23:21
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: 5 Howick Place, London, SW1P 1WG
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Efficient Stereoselective Synthesis of o-
Functionalized P-Chirogenic Phosphines
Applied to Asymmetric Catalysis
Jérôme Bayardona & Sylvain Jugéa
a Institut de Chimie Moléculaire de l’Université de Bourgogne
(ICMUB-StéréochIM), UMR CNRS 6302, 9 avenue A. Savary, Dijon
Cedex, 21078, France
Published online: 01 Jul 2015.
Click for updates
To cite this article: Jérôme Bayardon & Sylvain Jugé (2015) Efficient Stereoselective Synthesis of
o-Functionalized P-Chirogenic Phosphines Applied to Asymmetric Catalysis, Phosphorus, Sulfur, and
Silicon and the Related Elements, 190:5-6, 700-705, DOI: 10.1080/10426507.2014.993760
To link to this article: http://dx.doi.org/10.1080/10426507.2014.993760
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 190:700–705, 2015
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2014.993760
EFFICIENT STEREOSELECTIVE SYNTHESIS OF
o-FUNCTIONALIZED P-CHIROGENIC PHOSPHINES
APPLIED TO ASYMMETRIC CATALYSIS
Je´roˆme Bayardon and Sylvain Juge´
Institut de Chimie Mole´culaire de l’Universite´ de Bourgogne
(ICMUB-Ste´re´ochIM), UMR CNRS 6302, 9 avenue A. Savary 21078, Dijon Cedex,
France
GRAPHICAL ABSTRACT
Abstract The stereoselective synthesis of P-chirogenic o-halogenophenylphosphines and their
use for the preparation of o-functionalized derivatives are reported. The key step of this synthesis
is based on the reaction of a P-chirogenic secondary phosphine borane, previously prepared
using ephedrine methodology, with n-butyllithium (1.2 equiv.) and 1,2-dihalogenobenzene.
The reaction proceeds by addition of the phosphide borane to the benzyne generated in situ
from 1,2-dihalogenobenzene by metal-halide exchange with the intermediate carbanion. The
o-halogenophenylphosphine boranes were obtained with retention of configuration at the P-
center and with enantioselectivities up to 99% ee. The free o-halogenophenylphosphines were
applied for the preparation of various kinds of o-functionalized P-chirogenic phosphines useful
in asymmetric catalyzed reactions.
Keywords P-chirogenic phosphines; secondary phosphine boranes; o-halogenoarylphosp-
hines; aryne chemistry; asymmetric catalysis
INTRODUCTION
Chiral tertiary phosphines are an important class of compounds with wide applica-
tions as ligands in asymmetric transition metal catalysis1, as precursors for phosphonium
Received 15 October 2013; accepted 20 November 2014.
Address correspondence to Je´roˆme Bayardon, Institut de Chimie Mole´culaire de l’Universite´ de Bour-
gogne (ICMUB-Ste´re´ochIM), UMR CNRS 6302, 9 Avenue A. Savary 21078, Dijon Cedex, France. E-mail:
Jerome.bayardon@u-bourgogne.fr
700

o-FUNCTIONALIZED P-CHIROGENIC PHOSPHINES
701
Figure 1 Representative o-substituted or o-functionalized chiral phosphines.
salts2 or Wittig reagents,3 and also as Lewis bases in organocatalysis.4 During the last
decade, functionalized phosphines have attracted a growing interest due to the devel-
opment of new building blocks such as 1a–e, useful for the preparation of hybrid or
dissymmetric chiral ligands 1f–k (Figure 4).1,5–11 On the other hand, it was shown that
o-halogenophenylphosphines 1d,e or their oxide derivatives, are useful for the preparation
of biaryl mono- or diphosphines ligands,12,13 or still ambiphilic P-B compounds with Lewis
acid-base properties.14
Although most chiral o-functionalized phosphines 1f–k are derived from 1a–e and
their asymmetric centers are beared by the carbon backbone, few examples with the chirality
on the phosphorus center (P-chirogenic) are reported.15 This is because the stereoselective
synthesis of these compounds is demanding of strategies and few P-chirogenic building
blocks are easily usable in the presence of functional groups.1e,g In connection with our
ongoing investigation on chiral organophosphorus chemistry, we are interested to the stere-
oselective synthesis of P-chirogenic o-halogenoarylphosphines as building blocks useful
for the preparation of o-functionalized derivatives.
We recently described an efficient stereoselective synthesis of P-chirogenic phos-
phonium triflates, by quaternization of phosphines with an aryne generated in situ.2c In
these conditions, the diphenylphosphine Ph2PH reacts with benzyne to afford the corre-
sponding tetraphenylphosphonium salt.2c We now report the use of P-chirogenic secondary
phosphine borane complexes 2 in aryne chemistry, for the stereoselective synthesis of o-
halogenophenylphosphines 3 and 4, and their applications for the preparation of various
o-substituted or o-functionalized chiral phosphines 4 and 5.
RESULTS AND DISCUSSION
P-chirogenic o-bromo- or o-iodo-phenylphosphine boranes 3 were stereoselectively
synthesized by reaction of the secondary phosphine boranes 2 with n-BuLi and the 1,2-
dibromo or 1,2-diiodobenzene 6a (or 6b) (Scheme 1).16 In these conditions, the P-chirogenic
secondary phosphide boranes 7 obtained by deprotonation of 2, react with the benzyne 8,
in situ formed from 1,2-dihalogenobenzene 5 by elimination, to afford an intermediate
carbanion and then the corresponding o-halogenophenylphosphine boranes 3 by metal-
halide exchange (Scheme 1). The compounds 3a-d are isolated in 45–53% yield and
with ee up to 99% (Table 1, entries 1–4). In the same conditions, the reaction of the
secondary phosphine boranes 2 with 1,2-diiodobenzene 6b led to the corresponding o-
iodophenylphosphine boranes 3e–f in 42–55% yields and with 95–99% ee (entries 5,6).
The stereoselectivity of the reaction which proceeds with retention of configuration at the
phosphorus center, has been established by X-ray structure of borane complexes 3.16 The
decomplexation of the o-halogenophenylphosphine boranes 3 was achieved using DABCO
to afford the free P-chirogenic o-halogenophenylphosphines 4 in excellent yields and with
enantiomeric excesses up to 99% (Scheme 1, Table 1).

´
702
J. BAYARDON AND S. JUGE
Scheme 1
The P-chirogenic o-halogenophenylphosphines 4 were useful to prepare various hy-
brid or dissymmetric P-chirogenic phosphines 5, by substitution in ortho position of the
P-center (Scheme 2). Thus the reaction of o-halogenophenylphosphine 4 with n-BuLi
at −78◦C affords the anions in ortho position by metal-halide exchange, which were
trapped with various electrophilic reagents 9 to afford stereoselectively the corresponding
o-functionalized P-chirogenic phosphines 5 in moderate to good yields (Scheme 2).16a
Scheme 2
A selection of o-functionalized P-chirogenic phosphines prepared from the o-
bromophenylphosphine (R)-4a with electrophilic reagents 9 such as borate,16c acid chloride,
chlorosilane or chlorophosphine . . . are reported in the Table 2.
As representative substitution, metal-halide exchange of o-bromophenylphosphine
(R)-4a with n-BuLi at −78◦C in THF, followed by the addition of 2-isopropoxy-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane 9a or pivaloyl chloride 9b, led to the corresponding o-
boronatophenylphosphine (S)-5a or ketophosphine (S)-5b in 58 and 87% yields, respec-
tively, and with ee up to 99% (Table 2, entries 1,2). When two equivalents of anion
prepared from (R)-4a were trapped with the dichlorodimethylsilane 9d, the C2-symmetric
(R,R)-diphosphine 9d with a silano bridge was obtained in 61% yield and with 99% ee
(entry 4). In the case of the 1-cyano-3,4-dimethylphosphole 9c, the reaction with the anion
Table 1 Synthesis of borane complexes 3 and P-chirogenic o-halogenophenylphosphines 4
sec-Phosphine borane 2
Borane complex 3
yield (%)a ee (%)b
P-chirogenic phosphine 4
yield (%)a ee (%)b
Entry
R1
R2
X
1
2
3
4
5
6
(R)-2a
(R)-2b
(S)-2c
(S)-2d
(R)-2e
(R)-2f
o-An
Fc
i-Pr
c-Hex
o-An
Fc
Ph
Ph
Ph
Ph
Ph
Ph
Br
Br
Br
Br
I
(R)-3a
(R)-3b
(S)-3c
(S)-3d
(R)-3e
(R)-3f
53
47
48
47
–
95
99
95
95
–
(R)-4a
90
75
82
–
42 c
–
99
(R)-4b
(S)-4c
–
(R)-4e
–
99
95
–
95
–
I
55
99
aIsolated yields.
bDetermined by HPLC on chiral column.
cOverall yield from 2e.

o-FUNCTIONALIZED P-CHIROGENIC PHOSPHINES
703
Table 2 Selection of o-substituted P-chirogenic phosphines 5 prepared from (R)-4a
Entry
1
Electrophilic reagent 9
o-Substituted P-chirogenic phosphine 5 yield (%)a ee (%)b
9a
9b
(S)-5a
58
99
99
2
3
t-BuCOCl
(S)-5b
87
9c
(R)-5c
39
99
4
5
9d
9e
(CH3)2SiCl2
(R,R)-5d
(R)-5e
61
70
99
99
Ph2PCl
aIsolated yields.
bDetermined by HPLC on chiral column.
derived from (R)-4a led to the P-chirogenic phosphine-phosphole (R)-5c in 39% and with
99% ee (entry 3). Finally, the 1,2-diphosphinobenzene (R)-9e was obtained by reaction of
the anion derived from (R)-4a with the chlorodiphenylphosphine 9e, in 70% yield and with
ee up to 99% (entry 5).
On the other hand, some of the P-chirogenic phosphines 9 were tested as chiral
ligands in asymmetric catalyzed reactions with transition–metal complexes. As example, P-
chirogenic phosphines 9c–e were used in palladium-catalyzed asymmetric allylic alkylation
of 1,3-diphenylprop-2-en-1-yl acetate with dimethyl malonate. The reactions were carried
out in CH2Cl2 in the presence of a (π-allyl)-palladium complex, generated in situ from 0.5%
mol of [Pd(η3-C3H5)Cl]2 and 1.2% mol of the chiral ligands 9. The nucleophilic reagent
was then generated from dimethyl malonate using N,O-bis(trimethylsilyl)acetamide (BSA)
and a catalytic amount of KOAc. In these conditions, the allylic product was obtained in
(S) absolute configuration and with enantioselectivities of 34%, 30%, and 24% ee, using
the P-chirogenic phosphine ligands 9c, 9d, and 9e, respectively.16a In addition, when the
P-chirogenic diphosphinobenzene ligand (R)-9e was used as chiral ligand in asymmetric
hydrogenation of α-methyl acetamidocinnamate catalyzed by 1% of rhodium complex in
methanol, the D-α-phenylalanine derivative was obtained with 63% ee.16a

´
J. BAYARDON AND S. JUGE
704
CONCLUSION
An efficient synthesis of P-chirogenic o-halogenoarylphosphines has been developed.
The synthesis is based on the reaction between a secondary P-chirogenic phosphine bo-
rane with an aryne, generated in situ from 1,2-dihalogenobenzene and n-butyllithium as
a base. Under these conditions, the reaction proceeds without racemization and retention
of the configuration at the P-center, and the o-halogenated phosphines were obtained with
enantioselectivities up to 99%. These compounds are promising chiral building blocks for
the modular synthesis of various classes of o-substituted P-chirogenic phosphines useful as
hybrid or dissymmetric ligands or functionalized organocatalysts in asymmetric-catalyzed
reactions.16,17
ACKNOWLEDGMENTS
The authors would like to thank Dr. M. Gouygou (LCC-Toulouse) for the gift of
phosphole derivative.
FUNDING
This work was supported by the French Ministry of Research, the CNRS, the Bur-
gundy Country Council (grant Pari-Smt8) and the Agence Nationale de la Recherche (ANR
grant 07BLAN292-01).
REFERENCES
1. (a) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029-3070. (b) Shimidzu, H.; Nagasaki, I.; Saito,
T. Tetrahedron 2005, 61, 5405-5432. (c) Arrayas, R.; Adrio, J.; Carretero, J. C. Angew. Chem.,
Int. Ed. 2006, 45, 7674-7715. (d) Zhang, W.; Chi, Y.; Zhang, X. Acc. Chem. Res. 2007, 40,
1278-1290. (e) Phosphorous Ligands in Asymmetric Catalysis, Bo¨rner, A., Ed.; Wiley-VCH:
Weinheim, Germany, 2008; Vol. 3. (f) Hargarden, G. C.; Guiry, P. J. Chem. Rev. 2009, 109,
2505-2550. (g) Phosphorus (III) Ligands in Homogeneous Catalysis: Design and Synthesis, P.
C. J. Kamer, P. C. J.; van Leeuwen, P. W. N. M. (Eds); Wiley, 2012.
2. (a) Horner, L.; Winkler, H.; Rapp, A.; Mentrup, A.; Hoffmann, H.; Beck, P. Tetrahedron Lett.
1961, 2, 161-166. (b) Leglaye, P.; Donadieu, B.; Brunet, J.-J.; Chauvin, R. Tetrahedron Lett.
1998, 39, 9179-9182. (c) Re´mond, E.; Tessier, A.; Leroux, F. R.; Bayardon, J.; Juge´, S. Org. Lett.
2010, 12, 1568-1571.
3. Rein, T.; Pedersen, T. M. Synthesis 2002, 5, 579-594.
4. (a) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726-3748. (b) Shi, M.; Chen,
L.-H.; Li, C.-Q.; J. Am. Chem. Soc. 2005, 127, 3790-3800. (c) He, R.; Wang, X.; Hashimoto, T.;
Maruoka, K. Angew. Chem., Int. Ed. 2008, 47, 9466-9468. (d) He, R.; Ding, C.; Maruoka, K.
Angew. Chem., Int. Ed. 2009, 48, 4559-4561.
5. (a) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921-2944. (b) Breit, B.; Laungani,
A. C. Tetrahedron: Asymmetry 2003, 14, 3823-3826. (c) Hird, A. W.; Hoveyda, A. H. Angew.
Chem. Int. Ed. 2003, 42, 1276-1279. (d) Johannesen, S. A.; Glegola, K.; Sinou, D.; Framery,
E.; Skrydstrup, T. Tetrahedron Lett. 2007, 48, 3569-3573. (e) Marhino, V. R.; Rodrigues, A. I.;
Burke, A. J. Tetrahedron: Asymmetry 2008, 19, 454-458.
6. (a) Brunner, H.; Ittner, K.-P.; Lunz, D.; Schmatloch, S.; Schmidt, T.; Zabel, M. Eur J. Org.
Chem. 2003, 855-862. (b) Schenkel, L. B.; Ellman, J. A. J. Org. Chem. 2004, 69, 1800-1802.
(c) Birabar, D. B.; Gau, H.-M. Tetrahedron: Asymmetry 2008, 19, 733-738. (d) Wencel, J.;

o-FUNCTIONALIZED P-CHIROGENIC PHOSPHINES
705
Rix, D.; Jennequin, T.; Labat, S.; Cre´visy, C.; Mauduit, M. Tetrahedron: Asymmetry 2008, 19,
1804-1809.
7. (a) Peer, M.; de Jong, J. C.; Kiefer, M.; Langer, T.; Rieck, H.; Schell, H.; Sennhenn, P.; Sprinz,
J.; Steinhagen, H.; Wiese, B.; Helmchen, G. Tetrahedron 1996, 52, 7547-7583. (b) Pfaltz, A.;
Blankenstein, J.; Hilgraf, R.; Ho¨rmann, E.; McIntyre, S.; Menges, F.; Scho¨nleber, M.; Smidt, S.
P.; Wu¨stenberg, B.; Zimmermann, N. Adv. Synth. Catal. 2003, 345, 33-43. (c) Garcia-Yebra, C.;
Janssen, J. P.; Rominger, F., Helmchen, G. Organometallics 2004, 23, 5459-5470. (d) Smidt, S.
P.; Zimmermann, N.; Studer, M.; Pfaltz, A. Chem. Eur. J. 2004, 10, 4685-4693. (e) Fro¨lander,
A.; Moberg, C. Org. Lett. 2007, 9, 1371-1374. (f) Lu, Z.-L.; Neumann, E.; Pfaltz, A. Eur. J.
Org. Chem. 2007, 4189-4192. (g) Be´langer, E.; Pouliot, M. F.; Paquin, J. F. Org. Lett. 2009, 11,
2201-2204.
8. (a) Kim, G.-J.; Kim, S.-H.; Chong, P.-H.; Kwon, M.-A. Tetrahedron Lett. 2002, 43, 8059-8062.
(b) Zhang, A.; Rajanbabu, T. V. Org. Lett. 2004, 6, 1515-1517. (c) Nakano, H.; Takahashi, K.;
Okuyama, Y.; Senoo, C.; Tsugawa, N.; Suzuki, Y.; Fujita, K.; Sasaki, K.; Kabuto, C. J. Org.
Chem. 2004, 69, 7092-7100. (d) Desrosiers, J. N.; Charette, A. B. Angew. Chem. Int. Ed. 2007,
46, 5955-5957.
9. (a) Vargas, S.; Rubio, M.; Suarez, A.; Pizzano, A. Tetrahedron Lett. 2005, 46, 2049-2052.
(b) Chavez, M. A.; Vargas, S.; Suarez, A.; Alvarez, E.; Pizzano, A. Adv. Synth. Catal. 2011, 353,
2775-2794.
10. (a) Hiroi, K.; Watanabe, K. Tetrahedron: Asymmetry 2001, 12, 3067-3071. (b) Moessner, C.;
Bolm, C. Angew. Chem. Int. Ed. 2005, 44, 7564-7567. (c) Mino, T.; Tanaka, Y.; Hattori, Y.;
Yabusaki, T.; Saotome, H.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2006, 71, 7346-7353. (d) Val-
lianatou, K. A.; Kostas, I. D.; Holz, J.; Bo¨rner, A. Tetrahedron Lett. 2006, 47, 7947-7950.
(e) Eggenstein, M.; Thomas, A.; Theurerkauf, J.; Francio, G.; Leitner, W. Adv. Synth. Catal.
2009, 351, 725-732.
11. (a) Jiang, Q.; Jiang, Q.; Xia, D.; Cao, P.; Zhang, X. Angew. Chem. Int. Ed. 1998, 37, 1100-1103.
(b) Schull, T. L.; Knight, D. A. Tetrahedron: Asymmetry 1999, 10, 207-211. (c) Reetz, M. T.;
Gosberg, A. Tetrahedron: Asymmetry 1999, 10, 2129-2137. (d) Burk, M. J. Acc. Chem. Res.
2000, 33, 363-372. (e) Kottsieper, K. W.; Ku¨hner, U.; Selzer, O. Tetrahedron: Asymmetry 2001,
12, 1159-1169. (f) Matsumura, K.; Shimizu, H.; Saito, T.; Kumobayashi, H. Adv. Synth. Catal.
2003, 345, 180-184. (g) Bonnaventure, I.; Charette, A. B. J. Org. Chem. 2008, 73, 6330-6340.
12. (a) Joshaghami, M.; Daryanavard, M.; Raffiee, E.; Xiao, J.; Baillie, C. Tetrahedron Lett. 2007,
48, 2025-2027. (b) Baillie, C.; Xiao, J. Tetrahedron 2004, 60, 4159-4168.
13. (a) Hingst, M.; Tepper, M.; Stelzer, O. Eur. J. Inorg. Chem. 1998, 73-82. (b) Quintard, D.; Keller,
M.; Breit, B. Synthesis 2004, 6, 905-908. (c) Zhong, J.; Xie, J. H.; Wang, A. E.; Zhang, W.; Zhou,
Q. L. Synlett 2006, 8, 1193-1196. (d) Seipel, K. R.; Platt, Z. H.; Nguyen, M.; Holland, A. W. J.
Org. Chem. 2008, 73, 4291-4294.
14. Malacea, R.; Saffon, N.; Gomez, M.; Bourissou, D. Chem. Comm. 2011, 47, 8163-8165.
15. (a) Moulin, D.; Bago, S.; Bauduin, C.; Darcel, C.; Juge´, S. Tetrahedron: Asymmetry 2000,
11, 3939-3956. (b) Popovici, C.; Ona-Burgos, P.; Fernandez, I.; Roces, L.; Garcia-Granda, S.;
Iglesias, M. J.; Ortiz, F. L. Org. Lett. 2010, 12, 428-431. (c) Stephan, M.; Modec, B.; Mohar,
B. Tetrahedron Lett. 2011, 52, 1086-1089. (d) Zhang, Z.; Tamura, K.; Mayama, D.; Sugiya, M.;
Imamoto, T. J. Org. Chem. 2012, 77, 4184-4188. (e) Nakamura, A.; Kageyama, T.; Goto, H.;
Carrow, B. P.; Ito, S.; Nozaki, K. J. Am. Chem. Soc. 2012, 134, 12366-12369.
16. (a) Juge´, S.; Bayardon, J.; Laure´ano, H.; Henry, J. C.; Colobert, F.; Leroux, F.; Re´mond, E. Intern.
Patent 2011 US 61/506,291; Fr 11 56686; PCT/EP2012/063489. (b) Bayardon, J.; Laureano, H.;
Diemer, V.; Dutartre, M.; Das, U.; Rousselin, Y.; Henry, J.-C.; Colobert, F.; Leroux, F. R.; Juge´,
S. J. Org. Chem. 2012, 77, 5759-5769. (c) Bayardon, J.; Bernard, J.; Remond, E.; Rousselin, Y.;
Malacea-Kaballa, R.; Juge´, S. Org. Lett. 2015, doi: 10.1021/acs.Olglett 5b00167.
17. (a) Re´mond, E.; Bayardon, J.; Takizawa, S.; Rousselin, Y.; Sasai, H.; Juge´, S. Org. Lett. 2013, 15,
1870-1873. (b) Takizawa, S.; Re´mond, E.; Arteaga, F.; Yoshida, Y.; Vellaisamy, S.; Bayardon,
J.; S. Juge´, S.; Sasai, H. Chem. Commun. 2013, 49, 8392-8394.