Chiral α-amino phosphonates via rhodium-catalyzed asymmetric 1,4-addition reactions

Article abstract of DOI:10.1021/ol402059w

A new approach for the preparation of enantioenriched α-amino phosphonates and derivatives is described. Indeed, the rhodium-catalyzed asymmetric 1,4-addition of potassium organotrifluoroborates to dehydroaminophosphonates afforded α-amino phosphonates in

Full text of DOI:10.1021/ol402059w

ORGANIC
LETTERS
2013
Vol. 15, No. 16
4274–4276
Chiral r‑Amino Phosphonates via
Rhodium-Catalyzed Asymmetric
1,4-Addition Reactions
†
Nicolas Lefevre, Jean-Louis Brayer, Benoıt Folleas, and Sylvain Darses*
‡
‡
,†
ꢀ
ˆ
ꢀ
Ecole Nationale Superieure de Chimie de Paris, Laboratoire Charles Friedel
(UMR 7223, CNRS), 11 rue Pierre et Marie Curie, 75231 Paris cedex 05, France, and
Diverchim, ZAC du Moulin, 6 rue du Noyer, 95700 Roissy-en-France, France
sylvain-darses@chimie-paristech.fr
Received July 22, 2013
ABSTRACT
A new approach for the preparation of enantioenriched R-amino phosphonates and derivatives is described. Indeed, the rhodium-catalyzed
asymmetric 1,4-addition of potassium organotrifluoroborates to dehydroaminophosphonates afforded R-amino phosphonates in good yields and
high enantioselectivities (up to 96%) using Difluorphos as a chiral ligand.
Optically active R-amino phosphonic acids and deriva-
tives are important synthetic intermediates used in the
pharmaceutical and agrochemical industries to prepare
target molecules such as peptides, proteins, or even many
natural products.1 These are analogues of R-amino acids2
in which the carboxylic acid group has been substituted
with a phosphonic acid group. Among the chiral phos-
phonic acids described, some have been isolated from
natural products and possess various biological activities:
antiviral, antifungal, herbicides, or anti-HIV.1,3 In the
synthesis of such compounds, it is important to control
the absolute configuration of the R-stereogenic center
because the biological properties of the products are
correlated: for example (R)-1-phospholeucine is a better
inhibitor of leucine peptidase than the (S)-isomer.1
derivatives.1 Most of the strategies employed involve the
formation of a new carbonꢀhydrogen, carbonꢀphosphorus,
carbonꢀcarbon, or carbonꢀnitrogen bond. While many
reactions using stoichiometric chiral auxiliaries have been
described,4 catalytic approaches are scarcer. Asym-
metric hydrogenation of unsaturated substrates is a first
(4) For some examples: CꢀP bond formation: (a) Gilmore, W. F.;
McBride, H. A. J. Am. Chem. Soc. 1972, 94, 4361. (b) Smith, A. B., III;
Yager, K. M.; Taylor, C. M. J. Am. Chem. Soc. 1995, 117, 10879. (c)
Bongini, A.; Camerini, R.; Panunzio, M. Tetrahedron: Asymmetry 1996,
7, 1467. (d) Lefebvre, I. M.; Evans, S. A. J. Org. Chem. 1997, 62, 7532. (e)
Alonso, E.; Alonso, E.; Solıs, A.; del Pozo, C. Synlett 2000, 698. (f)
Kolodiazhnyi, O. I.; Sheiko, S.; Grishkun, E. V. Heteroat. Chem. 2000,
ꢀ
11, 138. (g) Dejugnat, C.; Etemad-Moghadam, G.; Rico-Lattes, I. Chem.
Commun. 2003, 1858. (h) Kumara Swamy, K. C.; Kumaraswamy, S.;
Senthil Kumar, K.; Muthiah, C. Tetrahedron Lett. 2005, 46, 3347. (i)
Cherenok, S.; Vovk, A.; Muravyova, I.; Shivanyuk, A.; Kukhar, V.;
Lipkowski, J.; Kalchenko, V. Org. Lett. 2006, 8, 549. CꢀC bond
formation: (j) Hanessian, S.; Bennani, Y. L. Tetrahedron Lett. 1990,
31, 6465. (k) Ouazzani, F.; Roumestant, M.-L.; Viallefont, P.;
El Hallaoui, A. Tetrahedron: Asymmetry 1991, 2, 913. (l) Groth, U.;
Several methodshave beendescribed for the preparation
of enantiomerically enriched R-amino phosphonic acids
€
Richter, L.; Schollkopf, U. Tetrahedron 1992, 48, 117. CꢀN bond
†
ꢀ
ꢀ
Ecole Nationale Superieure de Chimie de Paris.
formation: (m) Palacios, F.; Aparicio, D.; Lopez, Y.; de los Santos, J.
ꢀ
‡ Diverchim.
Tetrahedron Lett. 2004, 45, 4345. (n) Palacios, F.; Aparicio, D.; Lopez,
Y.; de los Santos, J. Tetrahedron 2005, 61, 2815.
(5) Schmidt, U.; Krause, H. W.; Oehme, G.; Michalik, M.; Fischer,
C. Chirality 1998, 10, 564.
(1) Reviews: (a) Aminophosphonic and Aminophosphinic Acids: Chem-
istry and Biological Activity; Kukhar, V. P., Hudson, H. R., Eds.; Wiley:
Chichester, 2000. (b) Huang, J.; Chen, R. Heteroat. Chem. 2000, 11, 480. (c)
ꢀ~
€
Ordonez, M.; Rojas-Cabrera, H.; Cativiela, C. Tetrahedron 2009, 65, 17.
(6) Schollkopf, U.; Hoppe, I.; Thiele, A. Liebigs Ann. Chem. 1985, 555.
(d) Ma, J.-A. Chem. Soc. Rev. 2006, 35, 630.
(7) (a) Schmidt, U.; Oehme, G.; Krause, H. W. Synth. Commun. 1996,
26, 777. (b) Burk, M. J.; Stammers, T. A.; Straub, J. A. Org. Lett. 1999, 1,
387. (c) Wang, D.-Y.; Huang, J.-D.; Hu, X.-P.; Deng, J.; Yu, S.-B.;
Duan, Z.-C.; Zheng, Z. J. Org. Chem. 2008, 73, 2011.
(2) Amino acids synthesis: (a) Ma, J.-A. Angew. Chem., Int. Ed. 2003,
42, 4290. (b) Najera, C.; Sansano, J. M. Angew. Chem., Int. Ed. 2007,
107, 4584.
(3) (a) Maier, L.; Diel, P. J. Phosphorus Sulfur Silicon Relat. Elem.
1994, 90, 259. (b) Maier, L.; Diel, P. J. Phosphorus Sulfur Silicon Relat.
Elem. 1991, 57, 57. (c) Natchev, I. A. Liebigs Ann. Chem. 1988, 861.
(8) (a) Kitamuraa, M.; Tokunagaa, M.; Phamb, T.; Lubellb, W. D.;
Noyoria, R. Tetrahedron Lett. 1995, 36, 5769. (b) Kitamura, M.;
Tokunaga, M.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 2931.
r
10.1021/ol402059w
Published on Web 08/01/2013
2013 American Chemical Society

approach for the formation of enantiomerically enriched
R-amino phosphonates.5ꢀ8 Enantioselectivities up to 96%
have been achieved, but the preparation of substrates
is not obvious. Another approach has been described
by Jørgensen and co-workers via the asymmetric cata-
lytic electrophilic amination (CꢀN bond formation) of a
β-ketophosphonate with dibenzyl azodicarboxylate in
the presence of a zinc(II) complex and a chiral
bisoxazoline.9 The addition of nucleophiles to R-imino
phosphonates, in the presence of chiral catalysts, also
provides access to enantiomerically enriched R-amino
phosphonates via CꢀC bond formation.10 However, the
most effective approach is currently the catalytic hydro-
phosphonylation of imines.11 This reaction has been first
described by Shibasaki and co-workers in 1995 and is
catalyzed by chiral lanthanide complexes.12 Other chiral
catalysts have since been developed, mainly Brønsted
acids13 or aluminum and others complexes.14
afforded an access to a variety of protected R-amino esters
with high yields and enantiomeric excesses up to 95%.16
Undertheseconditions, thatisinthepresenceofarhodium
catalyst associated with Difluorphos ligand and using
guaiacol as proton source, moderate conversion (66%)
and enantioselectivity (76%) were observed. The use of
other chiral ligands did not result in any improvement.
After several optimizations, we were pleased to find that
by using [RhCl(CH2CH2)2]2 as a rhodium catalyst pre-
cursor and Difluorphos as a chiral ligand, but with iso-
propanol as solvent and NaHCO3 as base, R-amino
phosphonates were obtained cleanly with improved yields
and high levels of enantioselecivity (Scheme 2).
Scheme 2. Enantioenriched R-Amino Phosphonates via
Rhodium-Catalyzed Addition/Protonation
We report here for the first time a straightforward and
alternative approach for the preparation of enantioen-
riched R-amino phosphonates via the asymmetric rho-
dium-catalyzed addition of organoboron derivatives to
dehydroaminophosphonates (Scheme 1).
Indeed, the addition of potassium phenyltrifluoroborate
(2a) to dehydroaminophosphonate 1a occurred smoothly at
90 °C, providing the enantioenriched R-amino phosphonate
3aa with an enantiomeric excess of 94% (Table 1, entry 1).
The other enantiomer was easily obtained, with the same
level of enantioselectivity, using (R)-Difluorphos as the
ligand (entry 2). In order to determine the absolute config-
uration, the known R-amino phosphonate 3ba was prepared
via the addition of potassium phenyltrifluoroborate to
dehydroaminophosphonate 1b. The 1,4-addition product
Scheme 1. Chiral R-Amino Phosphonates from
Rhodium-Catalyzed Asymmetric 1,4-Addition Reactions
We previously reported that the conjugate addition
of potassium trifluoro(organo)borates15 to dehydroala-
nine derivatives, catalyzed by a chiral rhodium catalyst,
(9) Bernardi, L.; Zhuang, W.; Jørgensen, K. A. J. Am. Chem. Soc.
2005, 127, 5772.
(10) (a) Kobayashi, S.; Kiyohara, H.; Nakamura, Y.; Matsubara, R.
J. Am. Chem. Soc. 2004, 126, 6558. (b) Kiyohara, H.; Nakamura, Y.;
Matsubara, R.; Kobayashi, S. Angew. Chem., Int. Ed. 2006, 45, 1615. (c)
Yamashita, Y.; Guo, X.-X.; Takashita, R.; Kobayashi, S. J. Am. Chem.
Soc. 2010, 132, 3262.
Table 1. Rhodium-Catalyzed Addition of Potassium
Aryltrifluoroborates to Dehydroaminophosphonatesa
yieldb
(%)
eec
ꢀ
ꢀ
(11) Review on hydrophosphonylation: Merino, P.; Marques-Lopez,
E.; Herrera, R. P. Adv. Synth. Catal. 2008, 350, 1195.
entry
1
ArBF3K
(%)
(12) (a) Sasai, H.; Arai, S.; Tahara, Y.; Shibasaki, M. J. Org. Chem.
1995, 60, 6656. (b) Shibasaki, M.; Sasai, H.; Tahara, Y. Patent 1998,
EP0877028.
1
1a
1a
1b
1a
1a
1a
1a
1a
1a
1a
1a
2a
2a
2a
2b
2c
2d
2e
2f
91 (3aa)
65 (3aa)
69 (3ba)
65 (3ab)
72 (3ac)
80 (3ad)
86 (3ae)
84 (3af)
76 (3ag)
51 (3ah)
77 (3ai)
94 (ꢀ)
96 (þ)
92 (R)
92 (ꢀ)
93 (ꢀ)
94 (ꢀ)
94 (ꢀ)
94 (ꢀ)
91 (ꢀ)
94 (ꢀ)
90 (ꢀ)
2d
3
(13) For some recent examples, see: (a) Joly, G. D.; Jacobsen, E. N.
J. Am. Chem. Soc. 2004, 126, 4102. (b) Akiyama, T.; Morita, H.; Itoh, J.;
Fuchibe, K. Org. Lett. 2005, 7, 2583. (c) Pettersen, D.; Marcolini, M.;
Bernardi, L.; Fini, F.; Herrera, R. P.; Sgarzani, V.; Ricci, A. J. Org.
Chem. 2006, 71, 6269. (d) Fini, F.; Micheletti, G.; Bernardi, L.; Pettersen,
D.; Fochi, M.; Ricci, A. Chem. Commun. 2008, 4345. (e) Akiyama, T.;
Morita, H.; Bachu, P.; Mori, K.; Yamanaka, M.; Hirata, T. Tetrahedron
2009, 65, 4950. (f) Fu, X.; Loh, W.-T.; Zhang, Y.; Chen, T.; Ma, T.; Liu,
H.; Wang, J.; Tan, C.-H. Angew. Chem., Int. Ed. 2009, 48, 7387.
(14) (a) Saito, B.; Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2007,
129, 1978. (b) Zhou, X.; Shang, D.; Zhang, Q.; Lin, L.; Liu, X.; Feng, X.
Org. Lett. 2009, 11, 1401.
(15) Reviews: (a) Darses, S.; Genet, J.-P. Eur. J. Org. Chem. 2003,
4313. (b) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49.
(c) Molander, G. A.; Ellis, N. M. Acc. Chem. Res. 2007, 40, 275. (d)
Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623. (e)
Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108, 288.
4
5
6
7
8
9
2g
2h
2i
10
11
a Reactions conducted on 0.34 mmol of 1, 2 equiv of 2, 1 equiv
of NaHCO3, 1.5 mol % of [RhCl(CH2CH2)2]2, and 3.3 mol % of
(S)-Difluorphos, in isopropanol at 90 °C for 20 h. b Isolated yields.
c Determined by chiral HPLC analysis (see Supporting Information).
The sign of the optical rotation or absolute configuration for known
compounds is shown in parentheses. d Using (R)-Difluorphos as a chiral
ligand.
(16) (a) Navarre, L.; Darses, S.; Genet, J.-P. Angew. Chem., Int. Ed.
2004, 43, 719. (b) Navarre, L.; Martinez, R.; Genet, J.-P.; Darses, S.
J. Am. Chem. Soc. 2008, 130, 6159.
Org. Lett., Vol. 15, No. 16, 2013
4275

addition of phenylboronic acid to 1a afforded R-amino
phosphonate 3aa in 92% yield and 93% ee (Scheme 4).
Scheme 3. Preparation of Enantioenriched R-Amino
Phosphinates
Scheme 4. Enantioenriched R-Amino Phosphonates from
Boronic Acids
was obtained in 69% yield and with an enantiomeric excess
of 92% and proved to be in the (R) configuration.5
Diversely substituted enantioenriched R-amino phos-
phonates were readily obtained using this tandem carbo-
metalation/enantioselective protonation process (entries
4ꢀ11) with high levels of enantioselectivities (above
90%) whatever the substitution pattern on the aryltrifluor-
oborate moiety.
These reaction conditions are not limited to the prepara-
tion of enantioenriched R-amino phosphonates. Indeed,
under identical conditions, the addition of potassium
phenyltrifluoroborate (1a) to 1c afforded good yields of
diastereoisomeric R-amino phosphinates 3ca and 3ca0
(Scheme 3) with nearly identical enantiomeric excesses
(94% and 92% respectively). This result suggests that the
chiral center on the phosphorus atom did not influence the
chirality of the newly created chiral carbon center. Single-
crystal X-ray diffraction of 3ca confirmed the (R,R) con-
figuration of this isomer (see Supporting Information).
These conditions were also suitable for the addition of
arylboronic acids, but with a somewhat lower enantio-
selectivity. For example, the rhodium-catalyzed asymmetric
We have developed a new and straightforward method
to access enantioenriched, useful R-amino phosphonate
and phosphinate derivatives using rhodium-catalyzed
asymmetric 1,4-addition of potassium organotrifluorobo-
rates to dehydroaminophosphorous compounds. This
simple procedure would allow the fast generation of libraries
of such compounds with useful levels of enantioselectivity.
Acknowledgment. N.L. thanks Diverchim for a grant.
The authors thanks Lise-Marie Chamoreau (IPCM, Uni-
ꢀ
versite Pierre et Marie Curie) for X-ray diffraction
analysis.
Supporting Information Available. Experimental pro-
cedures, description of the compounds, and X-ray dif-
fraction of 3ca. This material is available free of charge
via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
4276
Org. Lett., Vol. 15, No. 16, 2013