Diamidophosphites with isomeric carborane fragments: a comparison of catalytic activity in asymmetric Pd-catalyzed allylic substitution reactions

Article abstract of DOI:10.1016/j.tetlet.2010.01.084

New chiral diamidophosphite ligands containing electron-donating 9-meta-carborane and electron-withdrawing 1-meta-carborane substituents have been synthesized. The ligand 3a with an electron-donating group demonstrated high enantioselectivity in Pd-cataly

Full text of DOI:10.1016/j.tetlet.2010.01.084

Tetrahedron Letters 51 (2010) 1682–1684
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Diamidophosphites with isomeric carborane fragments: a comparison of
catalytic activity in asymmetric Pd-catalyzed allylic substitution reactions
a
b
b
Sergey E. Lyubimov a, , Vadim A. Davankov , Konstantin N. Gavrilov , Tatiana B. Grishina ,
Eugenie A. Rastorguev b, Andrey A. Tyutyunov a, Tatiana A. Verbitskaya a, Valery N. Kalinin a,
Evamarie Hey-Hawkins c
*
a Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, 119991 Moscow, Russian Federation
b Department of Chemistry, Ryazan State University, 46 Svoboda Street, 390000 Ryazan, Russian Federation
c Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
New chiral diamidophosphite ligands containing electron-donating 9-meta-carborane and electron-with-
drawing 1-meta-carborane substituents have been synthesized. The ligand 3a with an electron-donating
group demonstrated high enantioselectivity in Pd-catalyzed allylic substitution reactions with C-, S- and
N-nucleophiles (up to 98% ee). The isomeric diamidophosphite 3b bearing an electron-withdrawing sub-
stituent showed in all cases, moderate-to-poor conversion and lower enantioselectivity.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 21 October 2009
Revised 23 December 2009
Accepted 22 January 2010
Available online 1 February 2010
Keywords:
Asymmetric allylic alkylation
Palladium
Carboranyldiamidophosphites
Electronic effect
Strategies for controlling the stereoselectivity and activity in
catalytic reactions have usually relied on the design or manipula-
tion of the steric environment of the catalytically active metal,
but the electronic properties of the ligands can also exert a pro-
found influence on the selectivity and rates of fundamental orga-
nometallic processes.1–5 In asymmetric catalysis, variation of the
electronic properties of the ligands has seldom been successfully
exploited. Indeed, changing the donor/acceptor properties of simi-
lar ligands by the introduction of appropriate substituents leads to
a simultaneous change in their steric properties, and this makes
differentiation between the electronic and steric contributions of
ligands to the enantioselectivity and activity of a catalyst difficult
to estimate.3,6–9 Recently, we designed the first examples of chiral
mono- and bidentate phosphite-type ligands containing sterically
congested carborane groups and reported their high efficiency in
Rh-catalyzed asymmetric hydrogenation (up to 99.8% ee) and Pd-
catalyzed allylic alkylation processes (up to 95% ee).10–14 Also, we
have taken advantage of these highly modular ligands to show that
catalyst optimization can be performed easily by variation of the
carbaboranyl substituents attached to the phosphorus atom.12,13
No less important is the fact that even though all dicarba-closo-
dodecaborane isomers (ortho, meta and para) have the same steric
effect, each has very specific electronic properties depending on
the position of the carborane cage substitution,15 and thus, the
influence of the electronic properties of the carborane substituent
in related ligands on the enantioselectivity and conversion may be
clearly studied.12 In a programme aimed at the synthesis and appli-
cation of carborane-containing ligands in asymmetric catalysis, we
also sought to examine the effect of the electron-donating and
electron-withdrawing properties of carborane substituents in
asymmetric allylic substitution reactions.
H
C
H
C
2a
HO
CH
CH
N
O
P
, Et3N, C6H6
N
- Et3N·HCl
3a
(87% yield)
H
C
N
Cl
P
H
C
2b
N
C
HO
, Et3N, C6H6
- Et3N·HCl
1
C
N
O
P
N
3b
(76% yield)
* Corresponding author. Tel.: +7 499 1352548; fax: +7 499 1356471.
E-mail address: lssp452@mail.ru (S.E. Lyubimov).
Scheme 1. Synthesis of carborane-containing diamidophosphite ligands.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.084

S. E. Lyubimov et al. / Tetrahedron Letters 51 (2010) 1682–1684
1683
Table 1
The new monodentate diamidophosphite ligands 3a,b were
synthesized by a convenient one-step phosphorylation of the cor-
responding 9-hydroxy-meta-carborane (2a) and 1-hydroxy-meta-
carborane (2b) (Scheme 1). The ligands 3a,b were characterized
by 31P, 13C and 11B NMR spectroscopy and by elemental analysis.
The ligands are white solids and are air-stable under ambient
conditions.
Allylic alkylation with dimethyl malonate (CH2Cl2, BSA [N,O-bis(trimethylsilyl)acet-
amide], KOAc)a
Entry
Ligand
L/Pd
Conversionb (%)
eeb (%)
1
2
3
4
3a
3a
3b
3b
1/1
2/1
1/1
2/1
98
97
38
49
94 (S)
98 (S)
70 (S)
92 (S)
To examine the catalytic efficiency of these ligands, we first
tested them in the palladium-catalyzed allylic alkylation of 1,3-di-
phenyl-2-propenyl acetate (4) with dimethyl malonate (Scheme 2).
The results summarized in Table 1 show that the conversion and
enantioselectivities proved to be dramatically influenced by the
donor/acceptor character of the carboranyl substituent in the li-
gand structure. The Pd catalyst with ligand 3a based on the donor
9-meta-carborane (di = À0.12)15 exhibited high enantioselectivity
(up to 98% ee) and high conversions (Table 1, entries 1 and 2).
a
All the reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room tem-
perature for 48 h.
b
The conversion of substrate 4 and enantiomeric excess of 5a were determined
by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH = 99:1, 0.6 ml/min, 254 nm).
Table 2
Allylic sulfonylation with sodium para-toluenesulfonate (THF)a
Entry
Ligand
L/Pd
Yield (%)
eeb (%)
The
electron-withdrawing
1-meta-carboranyl
substituent
(di = +0.21)15 in ligand 3b leads to a significant decrease in the con-
version (Table 1, entries 3 and 4), and the enantiomeric excesses
were also lower. It should be noted that in all cases, the best com-
bination of activity and enantioselectivity was achieved with an L/
Pd molar ratio of 2/1.
1
2
3
4
3a
3a
3b
3b
1/1
2/1
1/1
2/1
97
98
30
26
87 (S)
92 (S)
30 (S)
46 (S)
a
All the reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room tem-
perature for 48 h.
b
In the allylic sulfonylation of 1,3-diphenyl-2-propenyl acetate
(4) with p-TolSO2Na as the S-nucleophile, diamidophosphite 3a
again showed excellent activity and very good enantioselectivity
(Scheme 2, Table 2, entries 1 and 2). The ligand 3b bearing a strong
electron-accepting 1-meta-carboranyl group led to a large decrease
in the enantioselectivity and activity of the catalyst (Table 2, en-
tries 3 and 4), compared to ligand 3a containing the electron-
donating 9-meta-carborane substituent.
Enantiomeric excess of 5b was determined by HPLC (Daicel Chiralcel OJ, C6H14
/
i-PrOH = 4:1, 0.5 ml/min, 254 nm).
Nu
*
OAc
Ph
NuX, catalyst
Solvent
Ph
Ph
Ph
Nu = N(nPr)2, X = H, 5c
Nu = N(CH2)4, X = H, 5d
4
5c,d
To expand the utility of these diamidophosphites and to investi-
gate further the influence of the carborane component, we also
examined the Pd-catalyzed enantioselective allylic amination of
1,3-diphenyl-2-propenyl acetate (4) with di-n-propylamine and
pyrrolidine (Scheme 3). The results in Table 3 show again that the
enantioselectivity of the reaction is sensitive to the electronic effect
of the carborane moiety, which further confirms the favourable
influence of the electron-donating carboranyl group. The use of the
9-meta-carborane-derived ligand 3a in the amination of 4 with di-
n-propylamine gave the product 5c in very good enantioselectivity,
and excellent conversion was observed (Table 3, entries 1 and 2). In
contrast, ligand 3b bearing the electron-withdrawing 1-meta-carb-
oranyl group showed very low activity, the enantioselectivities
being moderate: 44 and 55% ee, depending on the L/Pd molar ratio.
We also screened ligands 3a and 3b in the closely related reaction
of 4 with pyrrolidine (Scheme 3, Table 3). In this case, diam-
idophosphite 3a provided high activity, but the enantioselectivity
was lower compared to the amination with di-n-propylamine. It is
interesting that in the amination with pyrrolidine, ligand 3b bearing
the electron-withdrawing substituent gave product 5d with enanti-
oselectivity close to that obtained with diamidophosphite 3a having
the electron-donating carborane group, when a molar ratio L/Pd = 1/
1 was used. Nevertheless, the strong electron-withdrawing 1-meta-
carboranyl group in ligand 3b resulted in low activity, as was
observed in all other cases.
Scheme 3. Pd-catalyzed allylic amination of 1,3-diphenyl-2-propenyl acetate (4).
Table 3
Pd-catalyzed allylic amination of 1,3-diphenyl-2-propenyl acetate (4) with di-n-
propylamine and pyrrolidinea
Entry
Ligand
L/Pd
Conversion (%)
ee (%)
Allylic amination with di-n-propylamine (THF)b
1
2
3
4
3a
3a
3b
3b
1/1
2/1
1/1
2/1
95
100
5
90 (+)
83 (+)
44 (+)
55 (+)
8
Allylic amination with pyrrolidine (THF)c
5
6
7
8
3a
3a
3b
3b
1/1
2/1
1/1
2/1
100
100
21
75 (R)
77 (R)
74 (R)
60 (R)
15
a
All the reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 at room tem-
perature for 48 h.
b
The conversion of substrate
4
was determined by 1H NMR spectroscopy.
Enantiomeric excess of 5c was determined by HPLC (Daicel Chiralcel OD-H, C6H14/i-
PrOH/HNEt2 = 1000:1:1, 0.4 ml/min, 254 nm, t(+) = 8.2 min, t(À) = 9.1 min).
c
The conversion of substrate 4 and enantiomeric excess of 5d were determined
by HPLC (Daicel Chiralcel OD-H, OD-H, C6H14/i-PrOH/HNEt2 = 200:1:0.1, 0.9 ml/min,
254 nm).
In summary, new chiral diamidophosphite ligands containing
isomeric carboranyl substituents have been synthesized. The ligand
3a with the electron-donating 9-meta-carboranyl group demon-
strated high enantioselectivity in the Pd-catalyzed allylic substitu-
tion reactions with C-, S- and N-nucleophiles (up to 98% ee), and
complete-to-very high conversion of 1,3-diphenyl-2-propenyl ace-
tate (4) was observed. The isomeric diamidophosphite 3b bearing
an electron-withdrawing substituent showed, in all cases, moder-
ate-to-poor conversion and lower enantioselectivity.
Nu
*
OAc
Ph
NuX, catalyst
Solvent
Ph
Ph
Ph
4
5a,b
Nu = CH(CO2Me)2, X = H, 5a
Nu = SO2pTol, X = Na, 5b
Scheme 2. Pd-catalyzed allylic sulfonylation and alkylation of 1,3-diphenyl-2-
propenyl acetate (4).

1684
S. E. Lyubimov et al. / Tetrahedron Letters 51 (2010) 1682–1684
All the reactions were carried out under a dry argon atmosphere
C13H25B10N2OP: calcd: C, 42.84, H, 6.91, N, 7.69; found: C, 42.96,
H, 7.08, N, 7.60.
in freshly dried and distilled solvents. Phosphorylating reagent 1
was prepared as described by us earlier.6 9-Hydroxy-meta-cabora-
ne (2a)16 and 1-hydroxy-meta-caborane (2b)17 were prepared as
described. The Pd-catalyzed allylic substitution: sulfonylation of
substrate 4 with sodium para-toluenesulfonate, alkylation with di-
methyl malonate, amination with di-n-propylamine and pyrroli-
dine were performed according to the reported procedures.6,7,18
General procedure for the preparation of ligands 3a,b: A solution
of Et3N (0.27 ml, 1.9 mmol) and the appropriate alcohol (0.291 g,
1.8 mmol) in benzene (8 ml) were added dropwise to a vigorously
stirred solution of phosphorylating reagent 1 (0.433 g, 1.8 mmol)
in benzene (8 ml). The mixture was heated to the boiling point
and then cooled to 20 °C. Solid Et3NÁHCl was removed by filtration.
The resulting solution was filtered through a short plug of silica gel,
the solvent evaporated under reduced pressure (40 Torr) and the
product dried in vacuo (1 Torr) for 1 h.
(2R,5S)-2-(meta-Carboran-9-yloxy)-3-phenyl-1,3-diaza-2-phosp-
habicyclo[3.3.0]octane (3a): White powder; yield 0.57 g (87%); mp
124–126 °C. 31P{H} NMR (162.0 MHz, CDCl3, 25 °C): dP = 128.5.
13C{H} NMR (100.6 MHz, CDCl3, 25 °C): dC = 26.2 [d, 3J = 4.0 Hz,
C(7)], 31.5 [s, C(6)], 47.6 [d, 2J = 35.7 Hz, C(8)], 49.6 (s, 2CHcarb),
53.2 [d, 2J = 6.9 Hz, C(4)], 62.5 [d, 2J = 8.4 Hz, C(5)], 115.1 (d,
3J = 12.8 Hz, CHAr), 118.4 (s, CHAr), 128.8 (s, CHAr), 145.6 (d,
2J = 15.3 Hz, CAr). 11B{H} NMR (128.4 MHz, CDCl3, 25 °C): dB = 6.7
(s, 1B), À7.9 (s, 2B), À11.8 (s, 1B), À14.8 (s, 2B), À16.6 (s, 2B),
À20.3 (s, 1B), À25.9 (s, 1B). MS (EI, 70 eV): m/z (%) = 364 (17)
[M]+, 259 (100). C13H25B10N2OP: calcd: C, 42.84, H, 6.91, N, 7.69;
found: C, 43.03, H, 7.00, N, 7.64.
Acknowledgements
This work was supported by the Russian Foundation for Basic
Research (Grant No. 08-03-00416-a) and DFG-RFBR Grant No. 09-
03-91345.
References and notes
1. Rothenberg, G. Catalysis: Concepts and Green Applications; Wiley-VCH:
Weinheim, 2008.
2. Gavrilov, K. N.; Tsarev, V. N.; Konkin, S. I.; Petrovskii, P. V.; Lubuzh, E. D.;
Davankov, V. A. Russ. J. Coord. Chem. 2007, 33, 383.
3. Pàmies, O.; Claver, C.; Diéguez, M. J. Mol. Catal. A: Chem. 2006, 249, 207.
4. Catalysis: An Integrated Approach to Homogeneous, Heterogeneous and Industrial
Catalysis; Moulijn, J. A., Van Leeuwen, P. W. N. M., Van Santen, R. A., Eds.;
Elsevier BV: The Netherlands, 1993.
5. Phosphorus Ligands in Asymmetric Catalysis; Boerner, A., Ed.; Wiley-VCH:
Weinheim, 2008.
6. Tsarev, V. N.; Lyubimov, S. E.; Shiryaev, A. A.; Zheglov, S. V.; Bondarev, O. G.;
Davankov, V. A.; Kabro, A. A.; Moiseev, S. K.; Kalinin, V. N.; Gavrilov, K. N. Eur. J.
Org. Chem. 2004, 2214.
7. Gavrilov, K. N.; Lyubimov, S. E.; Zheglov, S. V.; Benetsky, E. B.; Davankov, V. A. J.
Mol. Catal. A: Chem. 2005, 231, 255.
8. Lyubimov, S. E.; Davankov, V. A.; Loim, N. M.; Popova, L. N.; Petrovskii, P. V.;
Valetskii, P. M.; Gavrilov, K. N. J. Organomet. Chem. 2006, 691, 5992.
9. Tu, T.; Hou, X.-L.; Dai, L.-X. J. Organomet. Chem. 2004, 689, 3847.
10. Lyubimov, S. E.; Tyutyunov, A. A.; Kalinin, V. N.; Said-Galiev, E. E.; Khokhlov, A.
R.; Petrovskii, P. V.; Davankov, V. A. Tetrahedron Lett. 2007, 48, 8217.
11. Lyubimov, S. E.; Tyutyunov, A. A.; Vologzhanin, P. A.; Safronov, A. S.; Petrovskii,
P. V.; Kalinin, V. N.; Gavrilov, K. N.; Davankov, V. A. J. Organomet. Chem. 2008,
693, 3321.
12. Lyubimov, S. E.; Kalinin, V. N.; Tyutyunov, A. A.; Olshevskaya, V. A.; Dutikova, Y. V.;
Cheong, C. S.; Petrovskii, P. V.; Safronov, A. S.; Davankov, V. A. Chirality 2009, 21, 2.
13. Lyubimov, S. E.; Davankov, V. A.; Petrovskii, P. V.; Hey-Hawkins, E.; Tyutyunov,
A. A.; Rys, E. G.; Kalinin, V. N. J. Organomet. Chem. 2008, 693, 3689.
14. Lyubimov, S. E.; Kuchurov, I. V.; Vasil’ev, A. A.; Tyutyunov, A. A.; Kalinin, V. N.;
Davankov, V. A.; Zlotin, S. G. J. Organomet. Chem. 2009, 694, 3047.
15. Kalinin, V. N.; Ol’shevskaya, V. A. Russ. Chem. Bull. 2008, 57, 815. and references
cited therein.
(2R,5S)-2-(meta-Carboran-1-yloxy)-3-phenyl-1,3-diaza-2-phosp-
habicyclo[3.3.0]octane (3b): White powder; yield 0.50 g (76%); mp
111–114 °C. 31P{H} NMR (162.0 MHz, CDCl3, 25 °C): dP = 133.5.
13C{H} NMR (100.6 MHz, CDCl3, 25 °C): dC = 26.5 [d, 3J = 4.0 Hz,
C(7)], 31.2 [s, C(6)], 46.8 [d, 2J = 40.8 Hz, C(8)], 50.8 (s, 2CHcarb),
53.1 [d, 2J = 6.0 Hz, C(4)], 62.3 [d, 2J = 9.4 Hz, C(5)], 115.1 (d,
3J = 17.4 Hz, CHAr), 119.6 (s, CHAr), 129.0 (s, CHAr), 144.5 (d,
2J = 19.6 Hz, CAr). 11B{H} NMR (128.4 MHz, CDCl3, 25 °C):
dB = À4.7 (s, 1B), À11.4 (s, 2B), À13.2 (s, 2B), À15.5 (s, 3B), À16.2
(s, 2B). MS (EI, 70 eV): m/z (%) = 364 (23) [M]+, 259 (100).
16. Zakharkin, L. I.; Kalinin, V. N.; Podvisotskaya, L. S. Zh. Obshch. Khim. 1966, 36,
1786.
17. Ohta, K.; Goto, T.; Yamazaki, H.; Pichierri, F.; Endo, Y. Inorg. Chem. 2007, 46,
3966.
18. Lyubimov, S. E.; Davankov, V. A.; Gavrilov, K. N. Tetrahedron Lett. 2006, 47,
2721.