Exploring the utility of a new chiral phosphoramidite P,N-ligand derived from (R)-binol and 7-azaindole in asymmetric catalysis

Article abstract of DOI:10.1139/V08-092

Lithiation of 7-azaindole, followed by quenching with [(R)-(1,1′- binaphthalene-2,2′-diyl)]chlorophosphite afforded the new chiral phosphoramidite 1 in 92% isolated yield. Treatment of 0.5 equiv. of [(COD)MCl]₂ (M = Rh, Ir; COD = η⁴-1,5-cyclooctadiene) with 2 equiv. of 1 afforded the corresponding [(κ¹-P,N-1) (κ²-P,N-1)MCl] complexes in 68% (2a, Rh) and 72% (2b, Ir) yield, while treatment of (PPh₃)₃RhCl with 1 equiv. of 1 afforded [(PPh₃)(κ²-P,N-1)RhCl] (3) as an analytically pure solid in 74% isolated yield. In examining the reaction of 1 with a mixture of 0.5 equiv. of [(COD)RhCl]₂ and 1 equiv. of AgBF₄, an inseparable mixture of [(κ²-P,N-1) ₂Rh]⁺BF₊- (4a) and [(COD)(κ²- P,N-1)Rh]⁺BF₄- (5a) was generated. Under analogous conditions employing [(COD)IrCl]₂, the complex [(COD) (κ²-P,N-1)Ir]+BF₄- (5b) was obtained in 86% isolated yield. Treatment of 0.5 equiv. of [(η³-allyl)PdCl]₂ with 1 afforded [(η³-allyl)(κ²-P,N-1)Pd] ⁺Cl^- (6) in 86% isolated yield. The application of 1 in platinum group metal-mediated asymmetric chemical transformations, including alkene hydrogenation and hydroboration, ketone hydrosilylation, and allylic alkylation, was examined.

Full text of DOI:10.1139/V08-092

Pagination not final/Pagination non finale
1
Exploring the utility of a new chiral
phosphoramidite P,N-ligand derived from (R)-
BINOL and 7-azaindole in asymmetric catalysis1
Dominik Wechsler and Mark Stradiotto
Abstract: Lithiation of 7-azaindole, followed by quenching with [(R)-(1,1′-binaphthalene-2,2′-diyl)]chlorophosphite af-
forded the new chiral phosphoramidite 1 in 92% isolated yield. Treatment of 0.5 equiv. of [(COD)MCl]2 (M = Rh, Ir;
4
COD = η -1,5-cyclooctadiene) with 2 equiv. of 1 afforded the corresponding [(κ1-P,N-1)(κ2-P,N-1)MCl] complexes in
68% (2a, Rh) and 72% (2b, Ir) yield, while treatment of (PPh3)3RhCl with 1 equiv. of 1 afforded [(PPh3)(κ2-P,N-
1)RhCl] (3) as an analytically pure solid in 74% isolated yield. In examining the reaction of 1 with a mixture of 0.5
equiv. of [(COD)RhCl]2 and 1 equiv. of AgBF4, an inseparable mixture of [(κ2-P,N-1)2Rh]+BF4 (4a) and [(COD)(κ2-
–
P,N-1)Rh]+BF4 (5a) was generated. Under analogous conditions employing [(COD)IrCl]2, the complex [(COD)(κ2-P,N-
–
1)Ir]+BF4 (5b) was obtained in 86% isolated yield. Treatment of 0.5 equiv. of [(η -allyl)PdCl]2 with 1 afforded [(η -
allyl)(κ2-P,N-1)Pd]+Cl– (6) in 86% isolated yield. The application of 1 in platinum group metal-mediated asymmetric
chemical transformations, including alkene hydrogenation and hydroboration, ketone hydrosilylation, and allylic
alkylation, was examined.
–
3
3
Key words: chiral, ligand, phosphoramidite, asymmetric catalysis.
Résumé : La lithiation du 7-azaindole, suivie d’un piégeage avec du chlorophosphite de [(R)-(1,1′-binaphtalène-2,2′-
diyle) conduit à la formation du nouveau phospharamidite chiral, 1, avec un rendement de 92% en produit isolé. Le
4
traitement de 0,5 équiv. de [(COD)MCl]2 (M= Rh, Ir; COD = η -cycloocta-1,5-diène) avec deux équiv. de 1 conduit à
la formation des complexes correspondants [κ1-P,N-1)(κ2-P,N-1)MCl avec des rendements de 68% (2a, Rh) et de 72%
(2b, Ir) alors que le traitement de (PPh3)3RhCl avec 1 équiv. de 1 conduit à la formation du [(PPh3)(κ2-P,N-1)(RhCl]
(3) qui a été isolé avec un rendement de 74% sous la forme d’un solide analytiquement pur. La réaction du produit 1
avec un mélange de 0,5 équiv. de [(COD)RhCl]2 et un équiv. de AgBF4 conduit à un mélange inextricable de [(κ2-P,N-
1)2Rh]+BF4 et de [(COD)(κ2-P,N-1)Rh]+BF4 (5a); dans des conditions impliquant l’utilisation du [(COD)IrCl]2, on ob-
–
–
tient le complexe [(COD)(κ2-P,N-1)Ir]+BF4 (5b) avec un rendement isolé de 86%. Le traitement de 0,5 équiv. de [(η -
–
3
3
allyl)PdCl]2 avec le produit 1 conduit à la formation du produit [(η -allyl)(κ2-P,N-1)Pd]+Cl– (6) avec un rendement d
86% en produit isolé. On a examiné l’application du composé 1 dans les transformations chimiques asymétriques cata-
lysées par un métal du groupe du platine, y compris les réactions d’hydrogénation et d’hydroboration des alcènes,
d’hydrosilylation de cétones et d’alkylation allylique.
Mots-clés : chiral, ligand, phosphoramidite, catalyse asymétrique.
[Traduit par la Rédaction] Wechsler and Stradiotto
8
Introduction
industrial scales (1). Platinum-group metal (PGM) com-
plexes supported by chiral, heterobidentate P,N-ligands have
proven particularly effective in mediating important trans-
formations of this type, including the asymmetric addition of
E–H bonds to unsaturated substrates (E = H, B, Si, etc.) and
the enantioselective formation of C–C linkages (2). As a re-
sult, the pursuit of chiral P,N-ligands that can enable new
and (or) improved asymmetric substrate transformations rep-
resents an important theme of modern catalysis research.
Transition metal-catalyzed asymmetric synthesis repre-
sents one of the most effective approaches for the prepara-
tion of chiral non-racemic molecules on both benchtop and
Received 3 April 2008. Accepted 23 April 2008. Published
on the NRC Research Press Web site at canjchem.nrc.ca on
16 July 2008.
One facet of our research program focuses on the develop-
ment of novel P,N-ligands for use in metal-mediated cata-
lytic applications (3). In building upon this theme and
encouraged by the utility of monodentate phosphoramidite
(MonoPhos) ligands (4) as well as rigid κ2-P,N phosphino-
oxazoline (PHOX) ligands (5) in PGM catalysis, we identi-
fied potentially bidentate chiral phosphoramidite ligands
derived from 7-azaindole as attractive and readily prepared
synthetic targets. Notably, while two reports by Woolins and
We dedicate this article to Professor Richard Puddephatt, in
recognition of his widespread contributions to chemical
research in Canada.
D. Wechsler and M. Stradiotto.2 Department of Chemistry,
Dalhousie University, Halifax, NS B3H 4J3, Canada.
1This article is part of a Special Issue dedicated to Professor
Richard J. Puddephatt.
2Corresponding author (e-mail: mark.stradiotto@dal.ca).
Can. J. Chem. 87: 1–8 (2009)
doi:10.1139/V08-092
© 2008 NRC Canada

Pagination not final/Pagination non finale
2
Can. J. Chem. Vol. 87, 2009
co-workers (6) and Burrows et al. (7) document the PGM
coordination chemistry of achiral κ2-P,N-(7-aza-N-
indolyl)phosphines, the preparation and application in asym-
metric catalysis of chiral variants of such ligands has not
been reported. Herein we report on the synthesis and charac-
terization of a new chiral phosphoramidite ligand 1, a pre-
liminary account of the Rh, Ir, and Pd coordination
chemistry of this ligand, and the application of 1 in PGM-
mediated asymmetric chemical transformations including
alkene hydrogenation and hydroboration, ketone hydro-
silylation, and allylic alkylation.
formed by Canadian Microanalytical Service Ltd., Delta,
British Columbia, Canada.
Synthesis of 1
A 1.6 mol/L hexanes solution (pre-cooled to –35 °C) of n-
BuLi (0.51 mL, 0.82 mmol) was added dropwise to a vial
containing a magnetically stirred solution (pre-cooled to
–35 °C) of 7-azaindole (0.097 g, 0.82 mmol) in THF (4 mL),
producing a colorless solution. The reaction mixture was
stirred for 0.75 h at ambient temperature, followed by cool-
ing to –35 °C. A pre-cooled (–35 °C) mixture of [(R)-(1,1′-
binaphthalene-2,2′-diyl)]chlorophosphite (0.29 g, 0.82 mmol)
and THF (5 mL) was then transferred slowly to the reaction
mixture via Pasteur pipette. Upon completion of transfer, the
resulting mixture was stirred for 2 h, after which the THF
and other volatile materials were removed in vacuo. The res-
idue was dissolved in a mixture of diethyl ether (4 mL) and
benzene (2 mL) and filtered through Celite. The filtrate was
dried in vacuo yielding 1 as an analytically pure, white solid
Experimental
General Considerations
All manipulations were conducted in the absence of oxy-
gen and water under an atmosphere of dinitrogen, either by
use of standard Schlenk methods or within an mBraun
glovebox apparatus, utilizing glassware that was oven-dried
(130 °C) and evacuated while hot prior to use. Celite was
oven-dried for 5 d and then evacuated for 24 h prior to use.
The non-deuterated solvents tetrahydrofuran, diethyl ether,
benzene, toluene, hexanes, and pentane were deoxygenated
and dried by sparging with dinitrogen gas, followed by pas-
sage through a double-column solvent purification system
purchased from mBraun Inc. Tetrahydrofuran and diethyl
ether were purified over two alumina-packed columns, while
benzene, toluene, hexanes, and pentane were purified over
one alumina-packed column and one column packed with
copper-Q5 reactant. All solvents used within the glovebox
were stored over activated 4 Å molecular sieves. CD2Cl2
(Cambridge Isotopes) was degassed by using three repeated
freeze–pump–thaw cycles, dried over CaH2 for 7 days, dis-
tilled in vacuo, and stored over 4 Å molecular sieves for
24 h prior to use. C6D6 (Cambridge Isotopes) was degassed
by using three repeated freeze–pump–thaw cycles and then
dried over 4 Å molecular sieves for 24 h prior to use; styrene
(Sigma-Aldrich, containing 10–15 ppm 4-tert-butylcatechol
as inhibitor) was degassed in a similar manner, but was not
stored over molecular sieves. Ph2SiH2 (Gelest, shipped under
argon) was not degassed and was dried over 4 Å molecular
sieves for 24 h prior to use. Hydrogen (99.999%, UHP
Grade) gas was obtained from Air Liquide and was used as
received. [(R)-(1,1′-binaphthalene-2,2′-diyl)]chlorophosphite
(8) and ( )-(E)-1,3-diphenylprop-2-enyl acetate (9) were
prepared by the use of literature procedures, while the transi-
tion metal reagents and silver salts were purchased from
Strem Chemicals Inc. All purchased and prepared solid re-
agents were dried in vacuo for 24 h prior to use. Otherwise,
1
(0.33 g, 0.76 mmol, 92%). H NMR (C6D6) δ: 8.42 (d of d,
3JHH = 4.5 Hz, J = 1.5 Hz, 1H, C4-H or C6-H Aza.), 7.61 (d,
3
3JHH = 8.5 Hz, 1H, C-H Naph.), 7.57 (d, JHH = 9.0 Hz, 1H,
3
C-H Naph.), 7.55 (d, JHH = 4.0 Hz, 1H, C-H Naph.), 7.53
3
3
(d, JHH = 4.5 Hz, 1H, C-H Naph.), 7.45 (d, JHH = 7.5 Hz,
3
1H, C6-H or C4-H Aza.), 7.41 (d, JHH = 8.5 Hz, 1H, C-H
3
Naph.), 7.32 (d, JHH = 2.0 Hz, 1H, C-H Naph.), 7.30 (d,
3JHH = 2.5 Hz, 1H, C-H Naph.), 7.17–7.10 (m, 2H, C-H
Naph.), 6.97 (m, 1H, C-H Naph.), 6.93 (m, 1H, C-H Naph.),
3
3
6.81 (d of d, JHH = 5.0 Hz, JHH = 8.0 Hz, 1H, C5-H Aza.),
3
6.76 (d, JHH = 4.0 Hz, 1H, C2-H or C3-H Aza.), 6.65 (d,
3JHH = 9.0 Hz, 1H, C-H Naph.), 5.92 (d of d, JHH = 4.0 Hz,
3
J = 1.0 Hz, C3-H or C2-H Aza.). 13C{1H} NMR (C6D6) δ:
152.8 (d, J = 16.0 Hz, quat Aza.), 148.4 (quat Naph.), 148.0
(d, J = 4.2 Hz, quat Naph.), 143.7 (C4 or C6 Aza.), 133.0
(quat Naph.), 132.6 (quat Naph.), 131.7 (quat Naph.), 131.4
(quat Naph.), 131.1 (C-H Naph.), 130.1 (C-H Naph.), 128.5
(C-H Naph.), 128.4 (C-H Naph.), 128.2 (C6 or C4 Aza.),
127.0 (C-H Naph.), 126.9 (C-H Naph.), 126.5 (C-H Naph.),
126.4 (C-H Naph.), 126.2 (d, J = 4.3 Hz, C2 or C3 Aza.),
125.2 (C-H Naph.), 125.1 (C-H Naph.), 124.5 (d, J = 5.4 Hz,
quat Aza.), 123.6 (quat Naph.), 122.3 (quat Naph.), 121.5
(C-H Naph.), 121.3 (C-H Naph.), 117.7 (C5 Aza.), 104.2
(C3 or C2 Aza.). 31P{1H} NMR (C6D6) δ: 133.8. Anal.
calcd. for C27H17P1N2O2: C 74.98; H 3.97; N 6.48. Found: C
74.58; H 3.93; N 6.26.
Synthesis of 2a
To a vial containing a magnetically stirred solution of 1
(0.056 g, 0.13 mmol) in THF (2 mL) was added dropwise a
solution of [(COD)RhCl]2 (0.016 g, 0.032 mmol) in THF
(2 mL). The reaction mixture was stirred for 1 h, after which
the solvent and other volatiles were removed in vacuo. The
residue was washed with pentane (2 mL) and dried in vacuo,
yielding 2a as a pale yellow solid (0.044 g, 0.044 mmol,
all other commercial reagents were obtained from Sigma-
1
Aldrich or Fluka and were used as received. H, 13C, and 31
P
NMR characterization data were collected at 300 K on a
Bruker AV-500 spectrometer operating at 500.1, 125.8, and
202.5 MHz (respectively) with chemical shifts reported in
1
1
parts per million downfield of SiMe4 (for H and 13C) or
68%). H NMR (C6D6) δ: 9.34 (1H, C-H), 8.50–8.45 (m,
1
3
85% H3PO4 in D2O (for 31P). H and 13C NMR chemical
2H, C-Hs), 8.40 (d, JHH = 8.8 Hz, 1H, C-H), 7.68–7.63 (m,
shift assignments are made on the basis of data obtained
2H, C-Hs), 7.60 (d, J = 8.75 Hz, 1H, C-H), 7.55–7.45 (m,
from 13C-DEPT, H-1H COSY, H-13C HSQC, and H-13C
HMBC NMR experiments. In some cases, fewer than ex-
pected unique 13C NMR resonances were observed, despite
prolonged acquisition times. Elemental analyses were per-
3H, C-Hs), 7.41 (d, 3JHH = 8.1 Hz, 1H, C-H), 7.35 (d, 3JHH
=
=
1
1
1
3
8.2 Hz, 1H, C-H), 7.30–7.26 (m, 2H, C-Hs), 7.23 (d, JHH
8.6 Hz, 1H, C-H), 7.13 (m, 1H, C-H), 7.07–6.98 (m, 3H, C-
Hs), 6.97–6.82 (m, 4H, C-Hs), 6.81–6.75 (m, 2H, C-Hs),
© 2008 NRC Canada

Pagination not final/Pagination non finale
Wechsler and Stradiotto
3
6.71 (m, 1H, C-H), 6.57–6.50 (m, 2H, C-Hs), 6.41 (m, 1H,
3JHH = 5.3 Hz, 1H, C-H), 7.99–7.91 (m, 6H, C-Hs), 7.79
3
3
3
C-H), 6.21 (d, JHH = 8.8 Hz, 1H, C-H), 6.11 (d, JHH
=
(br s, 1H, C-H), 7.57 (d, JHH = 8.2 Hz, 1H, C-H), 7.44 (d,
3
3.5 Hz, 1H, C-H), 5.96 (d, JHH = 8.7 Hz, 1H, C-H), 5.80–
5.75 (m, 2H, C-H). 13C{1H} NMR (C6D6) δ: 151.8 (quat),
148.8 (quat), 148.4 (quat), 147.9 (quat), 143.1 (C-H), 142.9
(C-H), 132.8 (quat), 132.2 (quat), 132.1 (quat), 132.1 (quat),
131.9 (quat), 131.8 (quat), 131.0 (quat), 130.7 (quat), 130.6
(C-H), 130.2 (C-H), 129.8 (C-H), 129.4 (C-H), 129.3 (C-H),
129.0 (C-H), 128.8 (C-H), 128.2 (C-H), 128.2 (C-H), 128.1
(C-H), 128.0 (C-H), 127.2 (C-H), 127.0 (C-H), 126.9 (C-H),
126.8 (C-H), 126.3 (C-H), 125.8 (C-H), 125.8 (C-H), 125.4
(C-H), 125.3 (C-H), 124.7 (C-H), 124.5 (C-H), 123.6 (C-H),
123.6 (quat), 123.1 (quat), 122.3 (quat), 121.9 (quat), 121.3
(quat), 120.8 (C-H), 120.3 (C-H), 118.5 (quat), 117.5 (C-H),
117.3 (C-H), 108.0 (C-H), 103.6 (C-H). 31P{1H} NMR
3JHH = 8.85 Hz, 1H, C-H), 7.42 (d, 3JHH = 8.2 Hz, 1H, C-H),
3
3
7.31 (d, JHH = 8.6 Hz, 1H, C-H), 7.26 (d, JHH = 8.8 Hz,
1H, C-H), 7.08–7.20 (m, 3H, C-Hs), 7.03 (m, 1H C-H), 6.93
3
(d, JHH = 8.8 Hz, 1H, C-H), 6.91–6.83 (m, 3H, C-Hs),
6.80–6.76 (m, 8H, C-Hs), 6.58 (m, 1H, C-H), 5.91 (d, 3JHH
=
3
3.7 Hz, 1H, C-H), 5.80 (d, JHH = 3.6 Hz, 1H, C-H).
13C{1H} NMR (C6D6) δ: 154.3 (d, J = 24.3 Hz, quat), 148.5
(d, J = 14.6 Hz, quat), 147.8 (d, J = 7.2 Hz, quat), 143.7 (C-
H), 136.1 (quat), 135.7 (quat), 135.3 (C-H), 135.2 (C-H),
132.7 (m), 131.6 (quat), 131.3 (quat), 130.4 (C-H), 130.2
(C-H), 129.5 (C-H), 128.9 (C-H), 128.4 (C-H), 128.2 (C-H),
127.4 (C-H), 126.9 (m), 126.5 (C-H), 125.8 (C-H), 125.4
(C-H), 124.9 (C-H), 124.8 (m), 122.3 (m), 122.1 (C-H),
1
2
(C6D6) δ: 146.6 (d of d, JPRh = 275.2 Hz, JPP = 64.5 Hz),
121.8 (C-H), 118.2 (d, J = 6.3 Hz, quat), 117.4 (C-H), 107.8
1
2
1
140.0 (d of d, JPRh = 309.3 Hz, JPP = 64.2 Hz). Anal.
calcd. for C54H34Cl1P2N4O4Rh1: C 64.64; H 3.41; N 5.59.
Found: C 64.55; H 3.74; N 5.48.
(C-H). 31P{1H} NMR (C6D6) δ: 135.4 (d of d, JPRh
=
=
2
1
322.0 Hz, JPP = 64.7 Hz, 1P, PN), 43.4 (d of d, JPRh
2
159.8 Hz, JPP = 64.7 Hz, PPh3). Anal. calcd. for
C45H32Cl1P2N2O2Rh1: C 64.86; H 3.87; N 3.36. Found:
64.99; H 4.13; N 3.01.
Synthesis of 2b
A procedure analogous to that described for the synthesis
of 2a was employed, using [(COD)IrCl]2 (0.048 g,
0.072 mmol) in THF (2 mL). Complex 2b was isolated as a
light brown solid (0.11 g, 0.10 mmol, 72%). 1H NMR
(C6D6) δ: 9.51 (br s, 1H, C-H), 8.42 (d, JHH = 8.7 Hz, 1H,
C-H), 8.37–8.34 (m, 2H, C-H), 7.89 (br s, 1H, C-H), 7.67 (d,
Synthesis of 5b
To a vial containing a magnetically stirred suspension of
[(COD)IrCl]2 (0.074 g, 0.11 mmol) in THF (2 mL) was
added a suspension of AgBF4 (0.043 g, 0.22 mmol) in THF
(2 mL). An orange solution was generated immediately
along with a white precipitate. The supernatant solution was
separated from the precipitate by filtration through Celite,
and the solution was transferred to a vial containing a mag-
netically stirred solution of 1 (0.095 g, 0.22 mmol) in THF
(2 mL). The reaction mixture was stirred for an additional
3 h at ambient temperature, during which the solution devel-
oped a red-orange coloration. The reaction mixture was then
filtered through a plug of Celite, followed by removal of the
solvent and other volatiles in vacuo to yield 5b as a bright
red-orange solid (0.16 g, 0.19 mmol, 86%). 1H NMR
3
J = 8.75 Hz, 1H, C-H), 7.62 (d, J = 8.75 Hz, 1H, C-H),
3
7.55–7.49 (m, 3H, C-H), 7.42 (d, JHH = 8.1 Hz, 1H, C-H),
3
7.36 (d, JHH = 8.2 Hz, 1H, C-H), 7.32–7.28 (m, 2H, C-H),
3
7.25 (d, JHH = 8.6 Hz, 1H, C-H), 7.06–7.02 (m, 2H, C-H),
6.98–6.89 (m, 4H, C-H), 6.88–6.83 (m, 2H, C-H), 6.82–6.78
(m, 2H, C-H), 6.71 (m, 1H, C-H), 6.59–6.52 (m, 2H, C-H),
3
6.39 (m, 1H, C-H), 6.27 (d, JHH = 8.8 Hz, 1H, C-H), 6.15
3
3
(d, JHH = 3.3 Hz, 1H, C-H), 5.96 (d, JHH = 8.8 Hz, 1H, C-
3
3
H), 5.93 (d, JHH = 3.5 Hz, 1H, C-H), 5.75 (d, JHH
=
2.9 Hz, 1H, C-H). 13C{1H} NMR (C6D6) δ: 151.4 (quat),
148.7 (quat), 148.5 (quat), 147.7 (quat), 142.8 (C-H), 141.0
(C-H), 132.8 (quat), 132.3 (quat), 132.2 (quat), 132.0 (quat),
131.7 (quat), 130.9 (quat), 130.6 (C-H), 130.4 (C-H), 129.9
(C-H), 129.4 (C-H), 128.7 (C-H), 128.1 (C-H), 128.1 (C-H),
127.3 (C-H), 127.1 (C-H), 127.0 (C-H), 126.9 (C-H), 126.3
(C-H), 125.7 (C-H), 125.4 (C-H), 125.2 (C-H), 125.1 (C-H),
124.6 (C-H), 124.5 (C-H), 124.3 (quat), 123.6 (C-H), 123.1
(quat), 122.2 (quat), 121.8 (quat), 121.2 (quat), 120.9 (C-H),
120.6 (C-H), 118.6 (quat), 117.4 (C-H), 117.1 (C-H), 107.8
(C-H), 103.3 (C-H). 31P{1H} NMR (C6D6) δ: 107.6 (d,
3
(CD2Cl2) δ: 8.43 (d, JHH = 8.0 Hz, 1H, C-H), 8.31 (d,
3JHH = 5.5 Hz, 1H, C-H), 8.24 (d, JHH = 9.0 Hz, 1H, C-H),
3
3
8.21 (d, JHH = 8.5 Hz, 1H, C-H), 8.15–8.10 (m, 2H, C-Hs),
3
7.76 (d, JHH = 9.0 Hz, 1H, C-H), 7.68–7.60 (m, 3H, C-Hs),
3
7.47–7.39 (m, 5H, C-Hs), 7.14 (d, JHH = 4.0 Hz, 1H, C-H),
6.43 (d of d, J = 2.0 Hz, J = 3.5 Hz, 1H, C-H), 6.04 (br s,
1H, COD), 5.98 (br s, 1H, COD), 4.19 (br s, 1H, COD),
4.13 (br s, 1H, COD), 2.52–2.18 (m, 8H, COD). 13C{1H}
NMR (CD2Cl2) δ: 156.9 (quat), 146.8 (d, J = 13.7 Hz, quat),
145.8 (d, J = 7.0 Hz, quat), 142.4 (C-H), 135.1 (C-H), 132.4
(quaJune 24, 2008t), 132.2 (quat), 132.1 (C-H), 132.0 (C-H),
128.8 (C-H), 128.8 (C-H), 127.5 (2 C-Hs), 127.0 (C-H),
127.0 (C-H), 126.7 (C-H), 126.6 (C-H), 124.6 (d, J =
6.0 Hz, C-H), 122.3 (quat), 122.0 (quat), 121.1 (d, J =
8.3 Hz, quat), 120.0 (C-H), 119.8 (C-H), 119.7 (C-H), 111.9
(C-H), 70.3 (m, C-H), 62.2 (C-H), 33.2 (CH2), 33.0 (CH2),
29.0 (CH2), 28.8 (CH2). 31P{1H} NMR (CD2Cl2) δ: 115.3.
Anal. calcd. for C35H29P1N2O2B1F4Ir1: C 51.26; H 3.57; N
3.42. Found: 51.24; H 3.78; N 2.99.
2
2JPP = 63.4 Hz), 104.3 (d, JPP = 63.5 Hz). Anal. calcd. for
C54H34Cl1P2N4O4Ir1: C 59.36; H 3.14; N 5.13. Found:
59.79; H 3.46; N 4.91.
Synthesis of 3
To a vial containing a magnetically stirred solution of 1
(0.047 g, 0.11 mmol) in THF (2 mL) was added dropwise a
solution of (PPh3)3RhCl (0.10 g, 0.11 mmol) in THF (2 mL),
and the reaction mixture was stirred for 2 h. Pentane
(10 mL) was added to the reaction mixture, causing the
product to precipitate. The supernatant was decanted away
and the precipitate washed with pentane (2 mL). The solid
was dried in vacuo, yielding 3 as a yellow-brown solid
Synthesis of 6
To a vial containing a magnetically stirred solution of
1(0.078 g, 0.18 mmol) in THF (1 mL) was added dropwise a
1
3
(0.065 g, 0.081 mmol, 74%). H NMR (C6D6) δ: 9.97 (d,
solution of [(η -allyl)PdCl]2 (0.033 g, 0.090 mmol) in THF
© 2008 NRC Canada

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4
Can. J. Chem. Vol. 87, 2009
(2 mL). The reaction mixture was stirred for 0.5 h, and the
solvent and other volatiles were removed in vacuo yielding
solvent were combined to give a 0.030 mol/L solution of the
catalyst (based on the metal). The solution was allowed to
equilibrate for 0.75 h, at which point the ketone (0.90 mmol)
was added by use of an Eppendorf pipette. The vial was then
sealed, shaken vigorously, and cooled to –35 °C. Subse-
quently, pre-cooled (–35 °C) Ph2SiH2 (1.6 mmol) was added
dropwise by use of an Eppendorf pipette to the reaction mix-
ture, and the vial was then sealed and the reaction mixture
was magnetically stirred for 18 h at ambient temperature.
The reaction mixture was then cooled to 0 °C, and 1 mol/L
HCl (5 mL) and acetone (5 mL) were added. The mixture
was stirred for 1.5 h at 0 °C followed by 0.5 h at ambient
temperature. A solution of saturated sodium bicarbonate was
added, and the reaction mixture was stirred until no more
gas evolution was observed (approx. 0.25 h). The reaction
mixture was extracted with diethyl ether (2 × 5 mL). The
combined organic layers were dried over Na2SO4, and the
catalyst was removed by passing the solution through a plug
of alumina (0.6 cm × 2 cm) from which a clear, colorless so-
lution eluted. This solution was transferred to a GC vial and
sealed. Products were identified by use of GC-MS while
quantitative data were obtained from chiral GC-FID analysis
by using a Supelco BETA-DEX 120 column.
1
6 as a yellow solid (0.092 g, 0.15 mmol, 86%). H NMR
(CD2Cl2) δ: 8.60 (d of d, 3JHH = 5.0 Hz, J = 1.4 Hz, 1H, C4-
3
H or C6-H Aza.), 8.19 (d, JHH = 8.9 Hz, 1H, C-H), 8.09 (d,
3JHH = 8.3 Hz, 1H, C-H), 8.06–8.03 (m, 2H, C-Hs), 7.98 (d,
3JHH = 8.9 Hz, 2H, C-Hs), 7.62–7.57 (m, 2H, C-Hs), 7.51–
7.45 (m, 2H, C-Hs), 7.44–7.39 (m, 2H, C-Hs), 7.34 (d of d,
3
3
1H, JHH = 5.0 Hz, JHH = 7.9 Hz, C5-H Aza.), 7.15 (d of d,
1H, 3JHH = 8.80 Hz, J = 0.7 Hz, C-H), 6.71 (d of d, 1H, 3JHH
= 3.8 Hz, J = 1.6 Hz, C2-H or C3-H Aza.), 6.55 (d, JHH
3
=
3.8 Hz, 1H, C3-H or C2-H Aza.), 5.83 (m, 1H, allyl), 3.94
(br s, 4H, allyl). 13C{1H} NMR (CD2Cl2) δ: 152.5 (C3a or
C7a Aza.), 152.3 (C7a or C3a Aza.), 147.5 (m, quat), 146.9
(d, J = 4.9 Hz, quat), 143.3 (C4 or C6 Aza.), 132.4–131.9
(m, quat), 131.5 (C-H), 131.1 (C-H), 130.4 (C-H), 128.7–
128.6 (m, aryl C-H and allyl C-H), 127.0 (m, C-Hs), 126.9
(C-H), 126.1 (m, C-Hs), 123.0 (quat), 122.6 (quat), 121.7 (d,
J = 2.0 Hz, C-H), 120.3 (C-H), 118.8 (C5 Aza.), 107.5 (C3
or C2 Aza.). 31P{1H} NMR (CD2Cl2) δ: 133.1. Anal. calcd.
for C30H22Cl1P1N2O2Pd1: C 58.53; H 3.61; N 4.55. Found:
58.11; H 3.63; N 4.03.
General protocol for the metal-catalyzed hydrogenation
experiments
Representative protocol for the metal-catalyzed allylic
alkylation experiments
A solution of metal (M = Rh or Ir) precursor (0.025 mmol
in 0.5 mL) and 1 (1.2 equiv. relative to M; 0.030 mmol in
0.5 mL) in the desired solvent were combined to give a
0.025 mol/L solution of the catalyst (based on M). The solu-
tion was allowed to equilibrate for 0.75 h, at which point
methyl 2-acetamidoacrylate (0.50 mmol in 0.5 mL) was
added by use of an Eppendorf pipette. The mixture was
placed in glass reactor cell, which was equipped with a mag-
netic stir bar and sealed under nitrogen with a PTFE valve.
The cell was transferred to a Schlenk line, and the mixture
was degassed by use of three freeze–pump–thaw cycles, fol-
lowed by the addition of ca. 1 atm of H2 (1 atm =
101.325 kPa), while magnetically stirring the solution. At
the desired sampling time, the reaction mixture was concen-
trated in vacuo and extracted with diethyl ether (2 mL). The
catalyst was removed by passing the diethyl ether extract
through a plug of silica (0.6 cm × 2 cm) from which a clear,
colorless solution eluted. This solution was transferred to a
GC vial and sealed. Quantitative data were obtained from
chiral GC-FID analysis using a Varian CHIRAL-L-VAL col-
umn.
A 0.020 mol/L stock solution of catalyst was prepared by
3
adding [(η -allyl)PdCl]2 (0.0073 g, 0.020 mmol) in THF
(1 mL) to ligand 1 (0.017 g, 0.040 mmol) in THF (1 mL),
followed by stirring for 0.5 h. A 0.40 mol/L stock solution
of the substrate was prepared by dissolving ( )-(E)-1,3-
diphenylprop-2-enyl acetate (0.27 g, 1.1 mmol) in THF
(2.7 mL). A 0.12 mL aliquot was taken from each of the two
stock solutions and combined; this reaction mixture was
stirred for 0.25 h and was then diluted with THF to a total
volume of 12 mL to produce a final substrate concentration
of 0.004 mol/L. Dimethyl malonate (6.6 µL, 0.058 mmol,
1.1 equiv.), N,O-bis(trimethylsilyl)acetamide (14.1 µL,
0.058 mmol, 1.1 equiv.), and KOAc (catalytic amount) were
added to the reaction mixture, and the resulting suspension
was stirred at 24 °C for 72–100 h. The reaction mixture was
then concentrated in vacuo, passed through a short silica gel
column (0.6 cm × 5 cm), and eluted with diethyl ether/hex-
anes (2:1). A portion of the eluent was transferred to a GC
vial and sealed, while the remaining eluent was concentrated
in vacuo. The reaction products were identified by use of
GC-MS, while quantitative data were obtained from GC-FID
analysis using a Supelco DB200 column. The enantiomeric
General protocol for the metal-catalyzed hydroboration
experiments
1
excess of 11 was determined by use of H NMR methods
through the addition of Eu(hfc)3 (8–10 mg) in CDCl3
(0.6 mL) to the reaction sample. Isomer assignments are
given on the basis of literature data (11).
The general protocol employed herein for the
hydroboration of styrene with HBpin has been described
elsewhere (10). For reactions in which HBcat was employed,
pinacol (2.1 equiv.) was added to the reaction mixture after
24 h followed by stirring for an additional 24 h. The subse-
quent work up procedure employed was the same as that un-
dertaken for reactions involving HBpin.
Results and discussion
Ligand synthesis and coordination chemistry
The new chiral phosphoramidite 1 was prepared in 92%
isolated yield (Scheme 1) via lithiation of 7-azaindole, fol-
lowed by quenching with [(R)-(1,1′-binaphthalene-2,2′-
diyl)]chlorophosphite prepared from the commercially avail-
able reagents R-BINOL and PCl3. Prior to evaluating the
General protocol for the metal-catalyzed hydrosilylation
experiments
A solution of metal precursor (0.045 mmol in 0.75 mL)
and 1 (1.2 equiv.; 0.054 mmol in 0.75 mL) in the desired
© 2008 NRC Canada

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Wechsler and Stradiotto
5
Scheme 1. Synthesis of the new chiral P,N-ligand 1.
Scheme 3. Reactivity of 1 with [(COD)MCl]2/AgBF4 (M = Rh,
Ir; COD = η -1,5-cyclooctadiene) and [(η -allyl)PdCl]2.
4
3
containing product in such reactions when the 1/Rh ratio
was reduced to 0.5:1. Conversely, reactions employing 1:Ir
Scheme 2. Reactivity of 1 with [(COD)MCl]2 or (PPh3)3RhCl
(M = Rh, Ir; COD = η -1,5-cyclooctadiene).
4
–
in a 1:1 ratio afforded [(COD)(κ2-P,N-1)Ir]+BF4 5b as the
major product, thereby allowing for the isolation of this spe-
cies in 86% yield.
The ability of 1 to form 1:1 complexes with Pd was con-
3
firmed upon treatment of 0.5 equiv. of [(η -allyl)PdCl]2 with
3
1; the corresponding salt [(η -allyl)(κ2-P,N-1)Pd]+Cl– 6 was
obtained as an analytically pure solid in 86% isolated yield
(Scheme 3). While shortly following dissolution the 31P
NMR spectrum of 6 exhibits a single resonance at
133.1 ppm, a new signal at 129.4 ppm was observed to grow
in over the course of 3 h. Although we are presently unable
to comment definitively regarding the relationship between
these two phosphorus-containing species, the propensity of
3
utility of 1 as a chiral ancillary ligand in PGM-mediated ca-
talysis, we sought to examine the coordination chemistry of
this new ligand. Treatment of 0.5 equiv. of [(COD)MCl]2
[(η -allyl)(κ2-P,N)Pd]+X– complexes to exhibit complicated
dynamic behavior is well-established (13). Having briefly
explored the coordination chemistry of 1 with Rh, Ir, and Pd,
the utility of this new chiral P,N-ligand in PGM-mediated
asymmetric synthesis was surveyed. For convenience, cata-
lyst complexes were prepared in situ by using an appropriate
metal precursor in combination with 1 (except where noted).
4
(M = Rh, Ir; COD = η -1,5-cyclooctadiene) with 1 equiv. of
1 did not afford [(COD)(κ1-1)MCl]; instead, a clean mixture
of 0.5 equiv. of [(κ1-P,N-1)(κ2-P,N-1)MCl] 2a and 2b and
0.25 equiv. of unreacted [(COD)MCl]2 was observed by use
of NMR spectroscopic methods (Scheme 2). Compounds 2a
and 2b are observed as the only phosphorus-containing
product when a 1/M ratio of 2:1 is employed, thereby allow-
ing for the convenient isolation of 2a and 2b as analytically
pure solids in 68% (2a, Rh) and 72% (2b, Ir) yields, respec-
tively. The observation of 31P-31P coupling between the
magnetically non-equivalent phosphorus centers in the 31P
NMR spectra of 2a and 2b (as well as the clearly
discernable 103Rh coupling in the case of 2a) is consistent
with the existence of P-M-P′ linkages in 2a and 2b. More-
over, the cis-disposition of the phosphorus fragments in 2a
and 2b as depicted in Scheme 2 is in keeping with the mag-
Asymmetric hydrogenation
The Rh- and Ir-mediated asymmetric hydrogenation of
methyl-2-acetamidoacrylate 7 to afford 8 (eq. [1]) under
mild conditions (24 °C, ca. 1 atm H2, 5.0 mol% Rh or Ir)
was selected as a preliminary catalytic test reaction to use in
benchmarking the performance of 1 (14); key results of
these hydrogenation studies are collected in Table 1. Control
experiments confirmed the ability of catalyst mixtures de-
rived from 0.5 [(COD)RhCl]2 and AgBF4 in THF (without
added 1) to mediate the reduction of 7 (Table 1, entry 1–1).
Under analogous conditions employing 6.0 mol% of 1 (1.2
equiv. relative to Rh), the quantitative reduction of 7 was
also achieved, affording 8 in 65% ee (Table 1, entry 1–2).
However, increasing the amount of 1 to 12.0 mol% (Table 1,
entry 1–3) in such transformations was found to diminish
both the conversion (78%) and the enantioselectivity (50%
ee), possibly because of the preferential formation of less
effective catalytic intermediates derived from [(κ2-P,N-
1)2Rh]+BF4– 4a. On the basis of this postulate and in light of
the established preference of 1 to form 4a (and not
2
nitude of the observed JPP value (ca. 64 Hz) for these com-
plexes. Whereas 2a is also formed upon treatment of
(PPh3)3RhCl with 2 equiv. of 1, the use of only 1 equiv. of 1
under similar conditions afforded [(PPh3)(κ2-P,N-1)RhCl] 3
as an analytically pure solid in 74% isolated yield.
In the pursuit of [(COD)(κ2-P,N-1)M]+X– complexes (M =
Rh, Ir), the reaction of 1 with mixtures of 0.5 equiv. of
[(COD)MCl]2 and 1 equiv. of AgBF4 in THF was examined.
For M = Rh, NMR analysis revealed the formation of an in-
–
–
separable mixture of [(κ2-P,N-1)2Rh]+BF4
4a and
[(COD)(κ2-P,N-1)Rh]+BF4 5a) when combined with
–
–
[(COD)(κ2-P,N-1)Rh]+BF4 5a (12) as depicted in Scheme 3.
Compound 4a was also observed as a major phosphorus-
[(COD)Rh(THF)2]+BF4 (vide supra), it is likely that the re-
sults featured in entry 1–2 (Table 1) do not truly reflect the
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6
Can. J. Chem. Vol. 87, 2009
Table 1. Hydrogenation of methyl 2-acetamidoacrylate.
Table 2. Rhodium-catalyzed addition of HBpin and HBcat to
styrene.
Metal precursor
Entry (5.0 mol%)
Mol% of
1 added
a
Solvent
%
% eeb
Substrate
conc. (mol/L)
Branched:
[(COD)Rh(THF)2]+BF4
[(COD)Rh(THF)2]+BF4 6.0
0
THF
THF
THF
>99 <1
>99 65
78 50
–
–
Entry
Boranea
linearb (9a:9b)
1–1
1–2
1–3
1–4
2–1
2–2
2–3
2–4
HBpin
HBpin
HBcat
HBcat
0.19
0.046
0.19
73:27
68:32
60:40
61:39
–
[(COD)Rh(THF)2]+BF4 12.0
–
[(COD)Ir(THF)2]+BF4
0
CH2Cl2 >99 <1
–
0.046
Note: Conditions: 24 °C, 1 atm H2. [(COD)M(THF)2]+BF4 prepared in
situ from 0.5 [(COD)MCl]2 and AgBF4 in THF (M = Rh, Ir and COD =
η4-1,5-cyclooctadiene).
–
Note: Conditions: –30 °C for 24 h; 5.0 mol% [(COD)2Rh]+BF4 ; 5.5
mol% 1; borane-to-styrene ratio of 1.2:1; THF. For all experiments >95%
conversion of styrene was achieved.
aPercent conversion based on the consumption of methyl-2-
acetamidoacrylate (7) at 24 h.
aHBpin = pinacolborane; HBcat = catecholborane.
bProduct ratio on the basis of GC-FID data, rounded to the nearest per-
cent. In all cases, other boron-containing products represented <3% of the
total product distribution. No enantioselectivity was achieved in these re-
actions, on the basis of chiral GC-FID data.
bEnantiomeric excess of 8 determined on the basis of chiral GC-FID
data.
performance of the target pre-catalyst complex 5a alone;
Table 3. Addition of diphenylsilane to acetophenone.
rather, the previously discussed coordination chemistry stud-
–
ies indicate that each of [(COD)Rh(THF)2]+BF4 , 4a, and 5a
Metal precursor
Mol% of
a
% eeb
are likely to be present as pre-catalysts under these experi-
mental conditions. In this regard, the inherent enantio-
selectivity of 5a is likely underestimated, owing to the
Entry (5.0 mol% Rh)
1 added
Solvent
%
3–1
3–2
3–3
3–4
[(COD)RhCl]2
6.0
THF
THF
THF
50 32
<1 N/D
69 28
24 19
[(COD)RhCl]2
12.0
6.0
significant
background
reactivity
associated
with
[(COD)Rh(THF)2]+BF4
[(COD)Rh(THF)2]+BF4
–
–
–
[(COD)Rh(THF)2]+BF4 (Table 1, entry 1–1) and the gener-
ally inferior performance of 4a, as based on entry 1–3. In an
effort to possibly promote the formation of 5a, the reaction
solvent was changed to CH2Cl2; however, all such reactions
12.0
THF
–
Note: Conditions: 24 °C. [(COD)Rh(THF)2]+BF4 prepared in situ from
0.5 [(COD)RhCl]2 and AgBF4 in THF (COD = η4-1,5-cyclooctadiene).
aPercent conversion based on the consumption of ketone at 18 h.
bEnantiomeric excess of 10 determined on the basis of chiral GC-FID
data, rounded to the nearest percent (N/D = not determined).
–
employing [(COD)Rh(THF)2]+BF4 (pre-formed in THF) in
combination with 0, 1.2, or 2.4 equiv. of 1 relative to Rh
afforded no conversion of the alkene substrate (15).
Similarly, the pre-formed Rh complex 3 proved to be
catalytically inactive in either THF or CH2Cl2. While
–
[(COD)2Ir]+BF4 and 5.5 mol% 1 afforded exclusively the
–
[(COD)Ir(THF)2]+BF4 mediated the quantitative conversion
linear product 9b.
of 7 to 8 in CH2Cl2 (Table 1, entry 1–4), the activity of Ir in
this chemistry was completely inhibited by the addition of
1.2 equiv. of 1 for reactions carried out in CH2Cl2 or THF.
[2]
[1]
Asymmetric hydrosilylation
Asymmetric hydroboration
The asymmetric hydrosilylation of ketones represents an
appealing synthetic route to chiral secondary alcohols. While
highly effective PGM catalysts for this challenging
enantioselective transformation are relatively few, a report
by Tao and Fu (17) highlights the utility of appropriately de-
signed chiral P,N-ligands in Rh-catalyzed transformations of
this type. Key results of our investigation of asymmetric
hydrosilylation of acetophenone with Ph2SiH2 (eq. [3]) in
THF are collected in Table 3. In preliminary experiments
The asymmetric hydroboration of styrene (16) employing
either pinacolborane (HBpin) or catecholborane (HBcat) was
selected as an alternative E–H addition reaction with which
to evaluate the ability of 1 to promote chemo-, regio-, and
enantioselectivity in PGM-mediated catalysis (eq. [2] and
Table 2). For reactions employing HBpin, catalyst mixtures
–
derived from 5.0 mol% [(COD)2Rh]+BF4 and 5.5 mol% 1
were found to exhibit modest selectivity towards the desired
branched isomer 9a over the linear isomer 9b at substrate
concentrations of 0.19 mol/L (Table 2, entry 2–1) and
0.046 mol/L (Table 2, entry 2–2); inferior selectivity was
noted for analogous reactions in which HBcat was used (Ta-
ble 2, entries 2–3 and 2–4). Unfortunately, no enantioselectivity
(in 9a) was achieved in the aforementioned hydroboration
reactions, and analogous reactions employing 5.0 mol%
using
a catalyst mixture comprised of 0.25 mol%
[(COD)RhCl]2 and 6.0 mol% 1, 50% conversion of the
ketone was achieved; however, the derived secondary alco-
hol formed upon acidic workup was obtained in only 32% ee
(Table 3, entry 3–1). When employing catalyst mixtures
featuring 1/Rh in a 2:1 ratio, no conversion was achieved
(Table 3, entry 3–2), thereby indirectly suggesting that 2a is
© 2008 NRC Canada

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Wechsler and Stradiotto
7
Table 4. Palladium-catalyzed allylic alkylation.
Substrate
conc. (mol/L)
Mol% of
1 added
Time
(h)
b
Entry
Solvent
Ratioa
%
% eec
5.0
5.0
5.0
5.0
24
24
24
24
4–1
4–2
4–3
4–4
0.2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1:1.1
1:1.1
1:3
>99
85
24 (R)
43 (R)
22 (R)
40 (R)
0.04
0.2
>99
>99
0.04
1:3
4–5
4–6
4–7
4–8
0.2
0.04
0.2
0.04
0.004
0.004
0.004
0.004
5.0
5.0
5.0
5.0
2.5
5.0
10.0
15.0
THF
THF
THF
THF
THF
THF
THF
THF
1:1.1
1:1.1
1:3
24
24
24
96
93
>99
81
49
>99
61
40 (R)
57 (R)
15 (R)
38 (R)
70 (R)
66 (R)
17 (S)
7 (S)
1:3
24
4–9
1:1.1
1:1.1
1:1.1
1:1.1
100
100
100
100
4–10
4–11
4–12
10
Note: Conditions: 24 °C; 2.5 mol% [(η3-allyl)PdCl]2 and stated amount of 1.
aRatio of ( )-(E)-1,3-diphenylprop-2-enyl acetate to dimethyl malonate.
bPercent conversion to 11 based on the consumption of ( )-(E)-1,3-diphenylprop-2-enyl acetate.
1
cProduct distribution determined on the basis of H NMR integration of the product mixture after the addition of the
chiral shift reagent Eu(hfc)3, rounded to the nearest percent (error 5%); the major isomer is indicated in parentheses.
an ineffective pre-catalyst for this transformation. While the
the amount of added 1 was varied (0.5, 1.0, 2.0, and 3.0
equiv. relative to Pd; Table 4, entries 4–9 to 4–12). While a
1:1 ratio of 1/Pd (Table 4, entry 4–10) produced the most ef-
fective catalyst system, resulting in >99% conversion (after
100 h) and affording R-11 in 66% ee, it is noteworthy that
the catalyst system obtained, when employing 2.0 or 3.0
equiv. of 1 relative to Pd, exhibits a modest preference for
the formation of the opposite enantiomer S-11 (Table 4, en-
tries 4–11 and 4–12). Although these preliminary results are
somewhat promising, it is important to recognize that the
overall performance of 1 in the Pd-mediated enantioselective
synthesis of 11 is not competitive with the best chiral P,N-
ligands, including PHOX (5) and alternative phosphor-
amidite ligands (20), which offer >99% conversion and
>95% ee for this enantioselective transformation (18a).
–
use of 5.0 mol% [(COD)Rh(THF)2]+BF4 in combination
with 1 (6.0 or 12.0 mol%) afforded a correspondingly more
active catalyst system (Table 3, entries 3–3 and 3–4), only
modest enantioselectivities (<30% ee) were achieved.
[3]
Asymmetric allylic alkylation
The Pd-mediated asymmetric allylic alkylation of ( )-(E)-
1,3-diphenylprop-2-enyl acetate with dimethyl malonate
(eq. [4]) is a well-established C–C bond forming reaction
that is used commonly as a means of benchmarking the util-
ity of chiral P,N-ligands in enantioselective catalysis (13,
18). Table 4 summarizes some key results of our catalytic
studies employing catalyst mixtures of derived from
[4]
3
2.5 mol% [(η -allyl)PdCl]2 and 1 under standard conditions
(18a) employing N,O-bis(trimethylsilyl)acetamide (BSA)
and a catalytic amount of potassium acetate as base. In a
preliminary catalytic survey (5.0 mol% 1, 24 h), the influ-
ence of solvent (CH2Cl2, THF), substrate concentration
(0.2 mol/L, 0.04 mol/L), and the ratio of ( )-(E)-1,3-
diphenylprop-2-enyl acetate to dimethyl malonate (1:1.1,
1:3) on conversion and enantioselectivity was examined (Ta-
ble 4, entries 4–1 to 4–8). Whereas a number of experimen-
tal conditions were identified that could provide >99%
conversion to 11, reactions employing 0.04 mol/L ( )-(E)-
1,3-diphenylprop-2-enyl acetate and 1.1 equiv. of dimethyl
malonate in THF (Table 4, entry 4–6) afforded what we
viewed as the best balance between conversion (93%)
and enantioselectivity (57%). Schenkel and Ellman (19)
have reported that improved enantioselectivity in Pd-
catalyzed asymmetric allylic alkylation can be achieved by
conducting the reaction under dilute conditions. In this con-
text, a series of catalytic reactions were carried out employ-
ing a substrate concentration of 0.004 mol/L and in which
Summary and conclusions
In conclusion, we have reported herein on the synthesis
and characterization of
a new chiral heterobidentate
phosphoramidite ligand 1, which is easily prepared in high
yield from the commercially available reagents 7-azaindole,
R-BINOL, and PCl3. Preliminary coordination chemistry
studies confirm the ability of 1 to form isolable κ2-P,N com-
plexes with Rh, Ir, and Pd. However, in the course of such
synthetic studies, Rh (and in some cases Ir) exhibited a
marked propensity to form M(1)2 complexes; such behavior
may contribute in part to the generally lacklustre catalytic
performance exhibited by mixtures of 1 and Rh precursor
complexes in the asymmetric addition of E–H fragments
(E = H, B, Si) to unsaturated substrates. While under certain
3
conditions, mixtures of 1 and [(η -allyl)PdCl]2 proved
capable of mediating the addition of dimethyl malonate to
© 2008 NRC Canada

Pagination not final/Pagination non finale
8
Can. J. Chem. Vol. 87, 2009
McDonald, S.A. Westcott, and M. Stradiotto. Organometallics,
25, 5965 (2006).
4. (a) A.J. Minnaard, B.L. Feringa, L. Lefort, and J.G. de Vries.
Acc. Chem. Res. 40, 1267 (2007); (b) J.G. de Vries and L.
Lefort. Chem. Eur. J. 12, 4722 (2006).
5. G. Helmchen and A. Pfaltz. Acc. Chem. Res. 33, 336 (2000).
6. H.L. Milton, M.V. Wheatley, A.M.Z. Slawin, and J. D. Woolins.
Inorg. Chem. Commun. 7, 1106 (2004).
( )-(E)-1,3-diphenylprop-2-enyl acetate with >99% conver-
sion and
a maximum ee of 66%, the rather low
enantioselectivity achieved suggests that 1 is not competitive
with more well-established chiral P,N-ligands for such
asymmetric transformations.
Acknowledgement
7. A.D. Burrows, M.F. Mahon, and M.Varrone. Dalton Trans.
4718 (2003).
Acknowledgment is made to Dalhousie University (in-
cluding the Department of Chemistry and the Industry Liai-
son and Innovation Office for a Research Innovation Award
for MS), the Natural Sciences and Engineering Research
Council of Canada (for a postgraduate scholarship for DW),
and the Springboard Atlantic Network for their generous
support of this work. We also thank Drs. Michael Lumsden
and Katherine Robertson (Atlantic Region Magnetic Reso-
nance Center, Dalhousie) for assistance in the acquisition of
NMR data.
8. R. Sablong, C. Newton, P. Dierkes, and J.A. Osborn. Tetrahe-
dron Lett. 37, 4933 (1996).
9. I.D.G. Watson and A.K. Yudin. J. Am. Chem. Soc. 127, 17516
(2005).
10. D. Wechsler, M.A. Rankin, R. McDonald, M.J. Ferguson,
G. Schatte, and M. Stradiotto. Organometallics, 26, 6418
(2007).
11. G. Brenchley, M. Fedouloff, M.F. Mahon, K.C. Molloy, and
M. Wills. Tetrahedron, 51, 10581 (1995).
12. 31P{1H} NMR (CD2Cl2) δ: 148.6 (d, JRhP = 280.0 Hz, 4a),
1
1
130.7 (d, JRhP = 270.4 Hz, 5a).
13. P.S. Pregosin and R. Salzmann. Coord. Chem. Rev. 155, 35
(1996).
References
14. For an overview of the Rh-mediated asymmetric hydrogena-
tion of alkenes bearing polar functional groups, see: I.D.
Gridnev and T. Imamoto. Acc. Chem. Res. 37, 633 (2004).
15. By comparison, a recently reported phosphine-phosphoramidite
ligand afforded >99% conversion and >99% ee in the Rh-
catalyzed asymmetric hydrogenation of dehydroamino acid es-
ters in CH2Cl2: J.-D. Huang, X.-P. Hu, Z.-C. Duan, Q.-H.
Zeng, S.-B. Yu, J. Deng, D.-Y. Wang, and Z. Zheng. Org. Lett.
8, 4367 (2006).
16. For reviews on metal-mediated asymmetric hydroboration, see:
(a) A.-M. Carroll, T.P. O’Sullivan, and P.J. Guiry. Adv. Synth.
Catal. 347, 609 (2005); (b) C.M. Crudden and D. Edwards.
Eur. J. Org. Chem. 4695 (2003).
1. (a) N.B. Johnson, I.C. Lennon, P.H. Moran, and J.A. Ramsden.
Acc. Chem. Res. 40, 1291 (2007); (b) V. Farina, J.T. Reeves,
C.H. Senanayake, and J.J. Song. Chem. Rev. 106, 2734
(2006); (c) H.-U. Blaser, B. Pugin, and F. Spindler. J. Mol.
Cat. A, 231, 1 (2005); (d) H.-U. Blaser, F. Spindler, and M.
Studer. Appl. Cat. A, 221, 119 (2001).
2. For selected reviews, see: (a) K. Källström, I. Munslow, and
P. G. Andersson. Chem. Eur. J. 12, 3194 (2006); (b) P.J. Guiry
and C.P. Saunders. Adv. Synth. Catal. 346, 497 (2004); (c) G.
Chelucci, G. Orrù, and G.A. Pinna. Tetrahedron, 59, 9471
(2003); (d) K.N. Gavrilov and A.I. Polosukhin. Russ. Chem.
Rev. 69, 661 (2000).
3. For selected references to catalysts supported by P,N-indene
and related ligands, see: (a) R.J. Lundgren, M.A. Rankin, R.
McDonald, and M. Stradiotto. Organometallics, 27, 254
(2008); (b) R.J. Lundgren, M.A. Rankin, R. McDonald, G.
Schatte, and M. Stradiotto. Angew. Chem. Int. Ed. 46, 4732
(2007); (c) B.M. Wile, R. McDonald, M.J. Ferguson, and M.
Stradiotto. Organometallics, 26, 1069 (2007); (d) J. Cipot, R.
McDonald, M.J. Ferguson, G. Schatte, and M. Stradiotto.
Organometallics, 26, 594 (2007); (e) J. Cipot, C.M. Vogels, R.
17. B. Tao and G.C. Fu. Angew. Chem. Int. Ed. 41, 3892 (2002).
18. (a) B.M. Trost and D.L. Van Vranken. Chem. Rev. 96, 395
(1996); (b) P. von Matt, G.C. Lloyd-Jones, A.B.E. Minidis, A.
Pfaltz, L. Macko, M. Neuburger, M. Zehnder, H. Rüegger, and
P.S. Pregosin. Helv. Chim. Acta, 78, 265 (1995).
19. L.B. Schenkel and J.A. Ellman. Org. Lett. 5, 545 (2003).
20. For a recent example, see: O. Pàmies, M. Diéguez, and
C. Claver. Adv. Synth. Catal. 349, 836 (2007).
© 2008 NRC Canada