A modular approach to a new class of phosphinohydrazones and their use in asymmetric allylic alkylation reactions

Article abstract of DOI:10.1016/j.tetasy.2010.05.031

A group of five phosphino hydrazones with a pendant binaphthyl unit as a chiral modifier has been synthesized from non-racemic 2,2′- bis(bromomethyl)-1,1′-binaphthyl and 3,3′-diiodo-2,2′- bis(bromomethyl)-1,1′-binaphthyl as the key intermediates. Their efficiency as chiral ligands in palladium-catalyzed allylic alkylation reactions has been investigated showing up to 95% ee under optimized conditions. X-ray diffraction structures of mono- and dimeric Pd complexes are also reported.

Full text of DOI:10.1016/j.tetasy.2010.05.031

Tetrahedron: Asymmetry 21 (2010) 1971–1982
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A modular approach to a new class of phosphinohydrazones and their use
in asymmetric allylic alkylation reactions
a
b
c
c
Michael Widhalm a, , Michael Abraham , Vladimir B. Arion , Siret Saarsalu , Uno Maeorg
*
a Institute of Organic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 38, A-1090 Wien, Austria
b Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 42, A-1090 Wien, Austria
c Institute of Chemistry, University of Tartu, Ravila 14a, 50411, Tartu, Estonia
a r t i c l e i n f o
a b s t r a c t
Article history:
A group of five phosphino hydrazones with a pendant binaphthyl unit as a chiral modifier has been
synthesized from non-racemic 2,20-bis(bromomethyl)-1,10-binaphthyl and 3,30-diiodo-2,20-bis(bromo-
methyl)-1,10-binaphthyl as the key intermediates. Their efficiency as chiral ligands in palladium-cata-
lyzed allylic alkylation reactions has been investigated showing up to 95% ee under optimized
conditions. X-ray diffraction structures of mono- and dimeric Pd complexes are also reported.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 4 May 2010
Accepted 18 May 2010
Available online 16 June 2010
1. Introduction
the chelate concurrently reducing steric strain. The less pro-
nounced chiral interaction in the substrate coordination sphere
It is well known that the selectivity in catalysis is highly depen-
dent on a perfect fit of substrate structure, operating reaction
mechanism, and nature of the catalyst. In order to obtain high ste-
reoselectivity in asymmetric transformations, conditions have to
be empirically developed usually on the basis of trial and error
with modification of reaction conditions and stepwise adaptation
of the ligand structure: with regard to the latter, a modular ap-
proach is highly desired providing an economic access to tailor-
made ligands and the build-up of libraries. Along with popular
bidentate P(III) ligands, P(III)–N(sp3) or P(III)–N(sp2) ligands1 have
also attracted much attention. Among these the family of oxazolin-
phospines 1 is prominent forming kinetically stable chelates and
displaying outstanding enantioselectivity in various reactions par-
ticularly in allylic substitutions.2 On the other hand the 2,20-
bridged binaphthyl moiety 2 forming distorted seven-membered
azepine3 and phosphepine4 motifs with (pseudo) C2 symmetry
has found broad application in mono and bidentate ligands useful
in asymmetric catalysis. Previous investigations have shown that
azepine-based P–N ligands such as 4 and 5 displayed different de-
grees of enantioselectivity in various C–C coupling reactions.
Allylic substitutions have been studied in detail revealing that
the introduction of benzylic substituents in 5 gave, only in few
cases, better ee The NMR investigation indicated that such
crowded ligands are monodentate with coordination via the phos-
phorus. From this we concluded that replacement of the sp3 nitro-
gen with an sp2 nitrogen donor and a chiral modifier more distant
from the coordination sites could increase the kinetic stability of
will eventually be counterbalanced by the introduction of
additional substituents at the 3- and 30-positions. To test this
hypothesis, phosphino hydrazones 6 were chosen where the
binaphthyl-based azepine unit is attached through a (rotatable)
N–N
r
bond to the bidentate sp2-N–P(III) unit. The P,N donors will
form conformatively stable six-membered chelates with only one
degree of conformative freedom coming from the (freely) rotatable
N–N bond. Substrates coordinating trans to the P atom will experi-
ence an interaction with the pending azepine unit. Fine tuning and/
or extension of the chiral sphere can be achieved by further substi-
tution at the 3- and 30-positions with the aim of combining maxi-
mum asymmetric interaction with sufficient reactivity. Chiral
ligands of type 3 have only recently been used in the asymmetric
allylation (Fig. 1).5
2. Results and discussion
2.1. Synthesis of ligands
The synthesis of the parent compound 6 started from enantio-
pure 2,20-bis(bromomethyl)-1,10-binaphthyl 7 accessible either by
various well-established optical resolution procedures of racemic
7,6 from non-racemic 2,20-dihydroxy-1,10-binaphthyl7 or 1,10-
binaphthyl-2,20-dicarboxylic acid8 and subsequent stereoconserva-
tive transformations, or by asymmetric cross coupling.9 (R)-7 was
refluxed with excess of Boc-hydrazine/triethylamine in THF to af-
ford the cyclized product (R)-8 in 75% yield. Deprotection (CF3
COOH, CH2Cl2, rt, 96%) and condensation with 2-diphenylphosph-
inobenzaldehyde (MgSO4, CH2Cl2, rt, 97%) gave hydrazone 6 as a
pale yellow foam, which could be handled under air without
* Corresponding author. Tel.: +43 1 427752111; fax: +43 1 4277 9521.
E-mail address: m.widhalm@univie.ac.at (M. Widhalm).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.05.031

1972
M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
oxide of 18 was isolated (63%); its X-ray structure was determined
R"
R"
(see below). With PhSSPh the desired product (R)-19 was formed
albeit in poor yield (10%). A one-step approach from (R)-16 gave
(R)-17 in lower yield.
R'''
PAr2
N
R
X
N
N
O
R
Ph2P
R'''
MeO
2.2. Asymmetric catalysis
R
X = NR, +NR2, PR
The group of new hydrazone-phosphine ligands was tested in
prototypical asymmetric allylic substitution reactions (Scheme 3).
In order to establish the optimal reaction conditions, ligand (R)-6
was used first in the allylic alkylation of 1,3-diphenylprop-1-en-
3-yl acetate with dimethylmalonate and BSA as base (reaction 1).
Under standard conditions in CH2Cl2 with 1 mol % of ‘Pd’ as [Pd(al-
lyl)Cl]2 with Pd/Lig = 1:1 and a catalytic amount of KOAc the prod-
uct was obtained in 90% yield and 67% ee with an (S)-configuration.
As additives CsOAc and LiOAc proved to be superior. A strong
dependence of ee from the Lig/Pd ratio was observed with an opti-
mum of 0.5 mol % of ligand. Lowering the temperature to ꢁ10 °C
resulted in a significant drop of yield and enantioselectivity.
Among the four solvents tested so far the complexation ability
was paralleled with a decrease of selectivity and an increase of
reactivity giving the best result in toluene. The selection of a proper
Pd precursor did not give an uniform picture; while with Pd(OAc)2
the conversion was extremely slow with poor asymmetric induc-
tion (51%), Pd2(dba)3ꢀCHCl3 was the best choice in CH2Cl2
(1 mol % ligand), while [Pd(allyl)Cl] was superior in toluene
(0.5 mol % ligand, 93% ee). Increasing the temperature to 40 °C re-
sulted in some loss of enantioselectivity.
1
2
3
R
N
N
PPh2
Ph2P
R
4
5
R
R
N
N
Ar2P
6
With optimized conditions in hand (Table 1, entry 15), ligands
10, 17, 27, and 28 were investigated in reaction 1 (Table 2). With
(R)-10 slight improvement was observed (88% yield, 95% ee S)
but with 3,30-substituted ligands products with (R)-configuration
were obtained albeit with low or moderate enantioselectivity
and reactions became slow particularly when 0.5 mol % of ligand
was used.
For this reversal of asymmetric induction several effects may
act together (Scheme 4). Different substituents at the 3- and 30-
positions could prefer different conformations I and II by rotating
the dinaphthoazepine moiety around the N–N bond. This in turn
may shift the equilibrium of the substrate complexes and/or
changing their relative reactivity toward the attacking nucleophile.
In addition, the weak nitrogen coordination to Pd plays a role, par-
ticularly hampered when electron-withdrawing and/or bulky
groups are present at the 3- and 30-positions. We speculate that
as a consequence, the mono- and dicoordinated 1:1 complexes (B
and A) are coexisting in equilibrium. This could explain the detri-
mental effect of coordinating solvents on ee. Moreover, 2:1
complexes (C) with P-mono coordination might be involved partic-
ularly when excess of ligand being present.
Next, the more useful ligands were investigated for reactions
2–5 (Table 3). It turned out that reactions became generally slow
particularly with 0.5 mol % of ligand. 3-Pentenyl-2-acetate showed
a moderate degree of asymmetric induction (70–77% ee) at a low
rate while cyclohexenyl acetate was even found to be almost inert
with (R)-10 and (R)-17. Cyclic substrates yielded largely racemic
products, and only for the cycloheptenyl acetate (reaction 5) good
asymmetric induction was observed.
Finally the allylation of a prochiral Schiff base (reaction 6) was
investigated, a reaction where the new stereogenic center is gener-
ated in the approaching reagent. Having only a transient interac-
tion of the pendant binaphthyl unit with the non-coordinated
nucleophile, the degree of asymmetric induction should be low.
A corresponding trend was indeed observed giving the highest
induction of 15% ee with the most demanding ligand at the slowest
conversion (Table 4).
Figure 1. PN ligands
precautions. The electron-rich phosphine (R)-10 was obtained sim-
ilarly in 78% yield from 2-bis(3-anisyl)phosphinobenzaldehyde
(Scheme 1).10
As an alternative approach a one-pot protocol11 with preceding
preparation of (E)-(2-(diphenylphosphino)benzylidene)hydrazine
followed by cyclization with (R)-7 furnished (R)-6 in low yield
(32%). Attempts to isolate the hydrazine intermediate were ham-
pered from its readiness to form (1E,2E)-1,2-bis(2-(diphenylphos-
phino)benzylidene)hydrazine.
For the preparation of 3,30-substituted binaphthyl units
(Scheme 2) a reactive but stable key intermediate was required
with the option of introducing substituents at a later stage of the
synthesis. The diiodide (R)-15 seemed suitable for this purpose.
Its synthesis was based on the facile and high yielding orthometal-
lation of the unprotected dicarboxylic acid (R)-11 with Li-2,2,6,6-
tetramethylpiperid (Li-TMP) and in situ reaction with Me3SiCl12
giving (R)-1213,14 which was reduced (BH3ꢀTHF, reflux) to afford
(R)-13. Replacement of the Me3Si-group by iodide (ICl)15 and bro-
mination of the dibenzylic alcohol (R)-14 with PBr3 at low temper-
ature yielded (R)-15 as a high-melting crystalline solid in 53%
overall yield [from (R)-11]. (R)-15 was cyclized with Boc-hydra-
zine and deprotected (CF3COOH) to afford N-amino-substituted
dihydroazepine (R)-21 as a moderately stable intermediate which
was treated with 2-diphenylphosphinobenzaldehyde/MgSO4 to
give (R)-22 (72%). A subsequent Suzuki reaction16 was applied to
obtain 3,30-substituted ligands (R)-27 and (R)-28 although in mod-
erate yield. Alternatively, diphenyl- and dinaphthyl-substituted li-
gands were prepared via (R)-23 and (R)-25 or (R)-24 and (R)-26,
respectively, in significantly better overall yield [53% and 35%,
respectively, from (R)-20]. Moreover, the synthesis of (R)-17–(R)-
19 from (R)-22 was attempted. After effective two-fold iodo–lithio
exchange (ꢁ78 °C, 5 min) treatment with Me3SiCl gave (R)-17 in
fair yield (66%); while with Cl3CCCl3 exclusively the phosphine

M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
1973
H2N
N
Br
Ph2P
N N
Ph2P
Br
(R)-6
(R)-7
N
NH
Boc
N NH2
8
9
(R)-
(R)-
N
N
P
OMe
MeO
10
(R)-
Scheme 1. Synthesis of (R)-6 and (R)-10.
2.3. Crystal structure analysis
substituents and two ligand molecules with opposite chirality
(Fig. 2b). Although the kinetic stability of this species and its signif-
icance in a catalytic reaction are hardly to predict the ease of its for-
mation prompted us to search for a non-linear effect of asymmetric
induction.18 Reaction 1 (Scheme 3) was performed using ligand 6
with 30%, 50%, 70%, and 100% enantiomeric purity. No significant
deviation from linearity was observed, and products with 24.5%,
40.8%, 59.2%, and 91.8% ee, respectively, were obtained.
To gain insight into structural peculiarities of this new group of
P–N ligands their solid state structure was of interest. Unfortunately
all attempts to obtain crystals suitable for crystal structure determi-
nation of free ligands failed; only the phosphine oxide of ( )-18 gave
single crystals of sufficient quality. For the sake of comparison,
the structure of the unsubstituted binaphthyl-bridged ben-
zylidenehydrazine ( )-2917 was determined (Fig. 2a). As expected
in both cases the hydrazone functionality showed anti geometry
and phenyl rings and C@N–N units were close to coplanarity [devi-
ation 12.2° and 10.5° for ( )-18 and ( )-29, respectively]. The biaryl
angle is slightly enlarged for ( )-18 (57.4° vs 52.9°) which is attrib-
uted to some repulsion of proximate Cl substituents. Generally, both
structures show similar geometric features irrespective of the pres-
ence of the diphenylphosphinoxy group and chloro substituents.
Next, Pd(II) complexes of 6 were investigated (Scheme 5). Com-
plexes prepared in situ from Pd–allyl precursors and ligand showed
complex mixtures of species in 1H and 31P NMR spectra with pro-
nounced broadening of signals presumably caused by exchange
phenomena and/or restricted rotation of phenyl rings. A neutral
PdCl2 complex of (R)-6 gave suitable crystals and sharp signals in
the NMR spectra, while attempts to obtain also crystals from cat-
ionic complexes with various counteranions failed. In the latter
cases, complex NMR spectra indicated the presence of several slowly
interconverting species. In contrast a complex prepared from race-
mic 6 crystallized readily as cationic dimer having bridging chloro
3. Conclusion
In conclusion, a flexible access to a new class of chiral PN ligands
was developed and the first test reactions have been performed.
While in selected cases, good reactivity and enantioselectivity (with
up to 95% ee) were observed, the insufficient kinetic stability of the
PN chelates limits their general usefulness in Pd-catalyzed allylic
substitutions. Improvement via the introduction of electron-donat-
ing substituents proximate to the sp2-N coordination site and appli-
cation to other asymmetric transformations is currently in progress.
4. Experimental
4.1. General
Melting points: Kofler melting point apparatus, uncorrected.
NMR: Bruker AVIII400 spectrometer at 400.27 MHz (1H), 100.66

1974
M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
SiMe3
SiMe3
I
I
OH
OH
OH
COOH
COOH
COOH
COOH
OH
SiMe3
SiMe3
(R)-12
(R)-13
(R)-14
(R)-11
R
R
SiMe3
I
I
N
N
Br
Br
Br
Ph2P
(R)-14
Br
SiMe3
R = SiMe3
Cl
(R
(R
(R
)-17
*
(R
)-16
(R
)-15
18
)-
SPh
)-19
I
I
I
I
Boc
NH
N
N
NH2
N N
Ph2P
I
I
(R)-20
(R)-21
(R)-22
Ar
Ar
Ar
Ar
Ar
Boc
NH
N
NH2
N N
N
Ph2P
Ar
25
(R)-
(R)-23
24
27
(R)-
Ar = Ph
(R)-28
2-naphthyl
(R)-
(R)-26
Scheme 2. Synthesis of 3,30-disubstituted dinaphthoazepine ligands with hydrazone-phosphine functionalities. * Isolated as phosphine oxide, see text.
MeOOC
R
COOMe
R
COOMe
COOMe
OAc
R
BSA
BSA
R= Ph (1)
Me (2)
+
R
*
OAc
MeOOC
COOMe
COOMe
COOMe
n= 0 (3)
1
2
(4)
(5)
+
*
n
n
COOMe
Ph
*
COOMe
Ph
BSA
OAc
(6)
+
Ph
Ph
Scheme 3. Asymmetric allylation reactions.

M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
1975
Table 1
Optimization of the allylic alkylation of 1,3-diphenylpropenyl acetate with dimethyl malonate (1)a,b using Pd/(R)-6
Entry
Pd precursorc
Lig/Pd
solvent
Additive
T (°C)
t (h)
Yieldd (%)
eee (%)
1
3
2
4
5
6
7
8
9
10
11
12
13
14
15
16
17
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
[Pd(
g
g
g
g
g
g
g
g
g
g
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
3-C3H5)Cl]2
1:1
1:1
1:1
2:1
0.5:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
0.5:1
0.5:1
0.5:1
0.5:1
0.5:1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
KOAc
CsOAc
LiOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
CsOAc
LiOAc
LiOAc
LiOAc
LiOAc
21
21
21
21
21
0
ꢁ10
21
21
21
21
21
21
21
21
40
21
2.5
1
90
92
87
82
93
92
56
90
93
93
80
94
90
93
84
89
93
67
75
87
36
77
65
57
52
62
81
51
74
81
87
93
89
87
1.5
1.5
2.0
20
45
1
THF
3
5
Toluene
CH2Cl2
CH2Cl2
Toluene
Toluene
Toluene
Toluene
Toluene
Pd(OAc)2
96
1.5
3
3.5
16
0.5
3.5
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
Pd2(dba)3ꢀCHCl3
[Pd(
[Pd(
g
g
3-C3H5)Cl]2
3-C3H5)Cl]2
Pd2(dba)3ꢀCHCl3
a
b
c
See Scheme 3.
All reactions were run on a 1-mmol scale with BSA as base.
1 mol %.
Isolated yield.
(S)-Configuration.
d
e
(R)-1,10-binaphthyl-2,20-dicarboxylic acid,8 and 2-diphenylphos-
Table 2
Allylic alkylation of 1,3-diphenylpropenyl acetate with dimethyl malonate (1)a,b and
phinobenzaldehyde.19
Pd/(R)-10, Pd/(R)-17, Pd/(R)-27, and Pd/(R)-28
Entry
Ligand
Lig/Pdc
t (h)
Yieldd (%)
ee (%)
4.2. Synthesis
1
2
3
4
5
6
7
8
9
(R)-10
(R)-17
(R)-17
(R)-17
(R)-27
(R)-27
(R)-27
(R)-28
(R)-28
(R)-28
0.5:1
0.5:1
1:1
2:1
0.5:1
1:1
1:2
0.5:1
1:1
18
44
20
20
69
15
15
89
20
20
88
82
86
88
89
88
91
64
87
85
95 (S)
81 (R)
72 (R)
46 (R)
22 (R)
29 (R)
34 (R)
35 (R)
22 (R)
26 (R)
4.2.1. (R)-tert-Butyl-3,5-dihydro-4H-dinaphtho[2,1-c:10,20-
e]azepin-4-yl carbamate (R)-8
(R)-2,20-Bis(bromomethyl)-1,10-binaphthyl (220 mg, 0.5 mmol)
and N-Boc-hydrazine (198 mg, 1.5 mmol, 3 equiv) were placed in
an oven-dried Schlenk tube filled with argon. Freshly distilled
abs THF (2 mL) was added and the mixture was degassed. Next,
Et3N (0.2 mL, 1.5 mmol, 3 equiv) was added and the mixture was
stirred for 22 h at reflux. When TLC (Et2O/petroleum ether,
50:50) indicated complete consumption of the starting material,
water (2 mL) was added and the mixture was diluted with ethyl
acetate (5 mL). The organic layer was separated, the aqueous layer
was extracted with ethyl acetate (2 ꢂ 5 mL), and the combined or-
ganic phases were dried (MgSO4). After evaporation of solvents, the
crude product was crystallized from CH2Cl2/petroleum ether to
yield 130 mg (63%) of pure (R)-8. Column chromatography (Et2O/
petroleum ether, 50:50) of the mother liquor afforded another
fraction to give a total of 153 mg (75%) of (R)-8 as a white crystal-
10
2:1
a
See Scheme 3.
b
All reactions were run on a 1-mmol scale in toluene at rt with BSA/LiOAc as
base.
1 mol % of ‘Pd’ (as [Pd(g
3-C3H5)Cl]2) was used.
c
d
Isolated yield.
MHz (13C), and 162.02 MHz (31P), respectively; chemical shifts d
are reported in ppm rel. to CHCl3 (7.24 or 77.00 ppm, respectively).
Coupling patterns are designated as s (singlet), d (doublet), t (trip-
let), q (quartet), m (multiplet), p (pseudo), and b (broad). 13C{1H}
NMR spectra are recorded in a J-modulated mode; coupling con-
stants refer to P–C coupling; signals are assigned as C, CH2, and
CH3; undesignated signals refer to CH-resonances. In spectral areas
with extensive signal overlapping multiplets that could not be
identified; these signals of unclear relationship are underlined,
ignoring probable multiplet structures. MS: FINNIGAN MAT 8230
EI (70 eV). HRMS: FINNIGAN MAT 8230. For HPLC determination
of chiral products a HP 1090 chromatograph equipped with a diode
array detector was used. Optical rotations were measured with a
Perkin–Elmer polarimeter 243 equipped with a 1-dm thermostated
cell.
line solid; mp: 117–120 °C. ½a D20
ꢃ
¼ ꢁ246 (c 1.02, CHCl3). 1H NMR
(CDCl3) d: 1.47 (s, 9H); 3.43 (d, J = 12.5 Hz, 2H); 3.95 (d, J =
12.5 Hz, 2H); 5.47 (br s, 1H); 7.25 (ddd, J = 8.3, 5.6, 1.1 Hz, 2H);
7.43 (d, J = 8.6 Hz, 2H); 7.45 (m, 2H); 7.60 (d, J = 8.3 Hz, 2H); 7.94
(d, J = 7.8 Hz, 2H); 7.96 (d, J = 8.2 Hz, 2H) ppm. 13C NMR (CDCl3)
d: 28.36 (CH3); 58.95 (CH2); 80.26 (C); 125.74; 125.97; 127.42;
127.58; 128.31; 128.65; 131.45 (C); 132.28 (C); 133.35 (C);
135.11 (C); 154.35 (C) ppm. MS (150 °C) m/z (rel%): 410 (14, M+).
HRMS (ESI) calcd for C27H27N2O2: 411.2073, found: 411.2075.
4.2.2. (R)-3,5-Dihydro-4H-dinaphtho[2,1-c:10,20-e]azepin-4-
amine (R)-9
Petroleum ether, dichloromethane, and ethyl acetate were dis-
tilled, absolute THF from sodium benzophenone ketyl, Et2O from
LiAlH4; dimethoxyethane (DME), dichloromethane, and trimethyl-
amine from CaH2; n-BuLi was used as 1.6 M solution in n-hexane
(Aldrich). All the other chemicals were analytical grade and used
without further purification. Column chromatography was per-
In a round-bottomed flask, (R)-8 (1.20 g, 2.92 mmol) was dis-
solved in CH2Cl2 (4 mL) and a solution of TFA (4 mL) in CH2Cl2
(4 mL) was added. After stirring at rt. for 2 h, the reaction was
quenched with saturated NaHCO3 solution (8 mL) and the reaction
mixture was extracted with CH2Cl2 (6 mL). The organic phase was
washed with H2O (8 mL) and brine (8 mL), dried over MgSO4, and
concentrated to give (R)-9 as a white solid (989 mg, 99%, 92% pur-
ity by NMR); attempted purification by chromatography resulted
formed on SiO2, 40–63
lm. Reported procedures have been
followed to obtain (R)-2,20-bis(bromomethyl)-1,10-binaphthyl,8b

1976
M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
R
N
N
PPh2
Pd
I
R
R
N
N
PPh2
Pd
II
R
+
Pd
Pd
N
P
N
P
N
N
N
N
P
P
P
P
Pd
Pd
C
B
A
N-coordination
ability
good
high
poor
poor
low
e.e.
moderate?
high
reactivity
moderate
low
Scheme 4. Tentative interpretation of observed enantioselectivity.
Table 3
Table 4
Allylic alkylations 2–5a with Pd/(R)-6, Pd/(R)-10, and Pd/(R)-17 as catalyst
Allylic alkylation 6a with Pd/(R)-6, Pd/(R)-27, Pd/(R)-28, and Pd/(R)-17 as catalyst
Entry
Reactionb
Ligand
Lig/Pdc
t (h)
Yieldd (%)
ee (%)
Entry
Reactionb
Ligand
Lig/Pdc
t (h)
Yieldd (%)
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2e
2
2
2e
2
2
3
3
3
4
4
4
5
5
5
(R)-6
(R)-6
(R)-6
0.5:1
0.5:1
1:1
0.5:1
1:1
48
21
22
21
22
22
48
84
48
48
84
48
48
84
48
83
61
25
24
48
3
13
82
74
19
n.r.
n.r
63
48
13
73 (S)
72 (S)
74 (S)
77 (S)
70 (S)
—
4 (R)
4 (R)
20 (R)
2 (S)
—
1
2
3
4
6
6
6
6
(R)-6
1:1
1:1
1:1
1:1
72
72
72
72
47
32
40
23
2 (S)
11 (S)
11 (S)
15 (S)
(R)-27
(R)-28
(R)-17
(R)-10
(R)-10
(R)-17
(R)-6
(R)-10
(R)-17
(R)-6
(R)-10
(R)-17
(R)-6
(R)-10
(R)-17
a
All reactions were run on a 1-mmol scale in toluene at rt with BSA/LiOAc as
base.
1:1
0.5:1
0.5:1
1:1
0.5:1
0.5:1
1:1
0.5:1
0.5:1
1:1
b
See Scheme 3.
With 1 mol % of ‘Pd’ (as [Pd(
Isolated yield.
g
3-C3H5)Cl]2).
c
d
—
J = 8.1, 6.7, 1.4 Hz, 2H); 7.75 (d, J = 8.3 Hz, 2H); 8.07 (d, J = 8.4 Hz,
2 H); 8.16 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR (CDCl3) d: 58.87
(CH2); 126.95; 127.16; 127.38; 127.42 (C); 127.44; 128.63;
130.11; 131.28 (C); 134.32 (C); 135.70 (C); ppm. MS (50 °C) m/z
(rel%): 310 (70, M+). HRMS for C22H18N2 calc. 310.1470, found
310.1467.
20 (R)
14 (R)
52 (R)
a
All reactions were run on a 1-mmol scale in toluene at rt with BSA/LiOAc as
base.
b
see Scheme 3.
With 1 mol % of ‘Pd’ (as [Pd(
Isolated yield.
g
3-C3H5)Cl]2).
c
d
e
4.2.3. (R)-(E)-N-(2-(Diphenylphosphino)benzylidene)-3H-
dinaphtho[2,1-c:10,20-e]azepin-4(5H)-amine (R)-6
The corresponding carbonate was used as substrate.
(R)-N-Aminodinaphthoazepine 9 (300 mg, 0.968 mmol, 1.68
equiv) was dissolved in CH2Cl2 (6 mL). The solution was degassed
and 2-diphenylphosphinobenzaldehyde (167 mg, 0.576 mmol)
and MgSO4 (132 mg, 1.1 mmol) were added. After stirring the mix-
ture for 7 h at rt under argon, the suspension was filtered and the
filtrate was extracted with water (6 mL). The organic layer was
in significant decomposition. (An analytical sample of ( )-9 was
crystallized from CH2Cl2/petroleum ether; mp: 161–165 °C.)
½
a 2D0
ꢃ
¼ ꢁ505 (c 1.01, CHCl3). 1H NMR (CD3OD) d: 3.77 (d, J =
12.9 Hz, 2H); 4.36 (d, J = 13.0 Hz, 2H); 4.85 (br s, 2H); 7.32 (ddd,
J = 8.5, 6.6, 1.2 Hz, 2H); 7.38 (br d, J = 8.5 Hz, 2H); 7.56 (ddd,

M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
1977
Figure 2a. Crystal structure of the phosphine oxide of ( )-18 (left) and ( )-29 (right). Co-crystallized solvent molecules are omitted for the sake of clarity. Selected bond
distances (Å) and angles (°) for ( )-18: P1–O1 1.4919(18), N1–N2 1.380(3), C1–N1 1.483(3), C22–N1 1.488(3), C23–N2 1.287(3), HC2–C11–C12–C21 57.4(3); for ( )-29: N1–N2
1.3840(13), N1–C8 1.4766(15), N1–C29 1.4799(14), N2–C1 1.2839(15), HC28–C19–C18–C9 52.90(15).
gradient 0?50%) yielded 326 mg (97%) of phosphinohydrazone
(R)-6 as a yellowish foam. (The racemic compound was obtained
(R)-6 (RS)-6
as a white solid; mp: 114–117 °C.) ½a D20
¼ þ106 (c 1.00, CHCl3).
ꢃ
Pd(MeCN)2Cl2
AgPF6
Pd(MeCN)2Cl2
1H NMR (CD2Cl2) d: 3.49 (d, J = 12.0 Hz, 2H); 4.39 (d, J = 12.0 Hz,
2H); 6.80 (ddd, J = 7.7, 5.0, 1.1 Hz, 1H); 6.85 (m, 1H); 7.03 (m,
2H); 7.11 (m, 1H); 7.14 (m, 2H); 7.28 (m, 4H); 7.35 (m, 4H);7.41
(d, J = 8.6 Hz, 2H); 7.43 (d, J = 8.3 Hz, 2H); 7.49 (ddd, J = 8.1, 6.7,
1.1 Hz, 2H); 7.75 (d, J = 4.5 Hz, 1H); 7.85 (ddd, J = 7.8, 3.9, 1.1 Hz,
1H); 7.93 (d, J = 8.3 Hz, 2H); 7.97 (d, J = 8.2 Hz, 2H) ppm. 13C
NMR (CDCl3) d: 56.08 (CH2); 125.60; 125.77; 125.81; 127.24;
127.44; 127.48; 128.12; 128.19; 128.25; 128.33; 128.51; 128.58;
131.45 (C); 133.20 (C); 133.31 (C); 133.43; 133.49; 133.50;
133.62; 133.84; 133.89; 134.03; 134.09; 134.21 (C); 134.62 (C);
136.83 (C, d, J = 10.5 Hz); 137.14 (C, d, J = 8.7 Hz); 139.92 (C, d,
J = 17.3 Hz) ppm. 31P NMR (CDCl3) d: ꢁ11.78 ppm. MS (ESI) 583.2
(M+1+). HRMS for C41H32N2P calc. 583.2303, found 583.2315.
N
N
PPh2
PF6
Pd
Cl
N
N
Cl
PPh2
Pd
PF6
Ph2P
Pd
N
Cl
Cl
N
6
(R)- ·PdCl2
(RS)-6·Pd-dimer
4.2.4. (R)-(E)-N-(2-(Bis(3-methoxyphenyl)phosphino)benzyli-
dene)-3H-dinaphtho[2,1-c:10,20-e]azepin-4(5H)-amine (R)-10
(R)-N-Aminodinaphthoazepine 9 (165 mg, 0.532 mmol, 1.34
equiv) was dissolved in CH2Cl2 (2.5 mL). The mixture was degassed
and 2-bis(3-methoxyphenyl)phosphinobenzaldehyde (139 mg,
0.397 mmol) and MgSO4 (55 mg, 0.46 mmol) were added. After
stirring for 20 h at rt under argon, the suspension was filtered
and the filtrate was extracted with water (4 mL). The organic layer
Scheme 5. Synthesis of crystalline Pd(II) complexes of ligand 6.
washed with brine (6 mL), dried over MgSO4, and concentrated.
Purification of the remaining residue by flash chromatography
(4 g silica gel, 254 nm, 10 mL/min, petroleum ether/2-propanol,
Figure 2b. X-ray diffraction structures of [((R)-6-(S)-6)Pd2Cl2]2+ (left) and (R)-6PdCl2 (right). Anions and solvent molecules are omitted for the sake of clarity. Selected bond
distances (Å) and angles (°) for [((R)-6-(S)-6)Pd2Cl2]2+: Pd1–N1 2.075(6), Pd1–P1 2.2315(18), Pd1–Cl1 2.3138(17), Pd–Cl1i 2.4304(16), N1–N2 1.412(8), N1–C23 1.277(9),
HC2–C11–C12–C21 –55.1(9); for (R)-6PdCl2: Pd1–N1 2.099(5), Pd1–P1 2.2191(18), Pd1–Cl1 2.2819(17), Pd–Cl2 2.3893(17), N1–N2 1.391(7), N1–C23 1.278(7), HC2–C11–C12–C21
–
54.2(8).

1978
M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
was washed with brine (4 mL) and dried over MgSO4. Concentra-
tion of the filtrate gave a semisolid residue, which was purified
by column chromatography (petroleum ether/2-propanol, 90:10)
to yield 200 mg (78%) of (R)-10 as a white solid; mp: 94–98 °C.
0.47 (s, 18H); 2.79 (br s, 2H); 4.18 (d, J = 11.6 Hz, 2H); 4.55 (d,
J = 11.6 Hz, 2H); 6.93 (d, J = 8.4 Hz, 2H); 7.21 (ddd, J = 8.3, 7.0,
1.2 Hz, 2H); 7.43 (ddd, J = 7.9, 6.9, 1.0 Hz, 2H); 7.90 (d, J = 8.0 Hz,
2H); 8.20 (s, 2H) ppm. 13C NMR (CDCl3) d: 0.91 (CH3); 62.33
(CH2); 126.03; 126.12, 127.04; 128.21; 132.33 (C); 133.51 (C);
135.76 (C); 136.42; 138.61 (C); 141.08 (C) ppm. MS (160 °C) m/z
(rel%): 458 (8, M+), 440 (3, Mꢁ18+), 425 (59, Mꢁ18ꢁ15+). HRMS
(ESI) calcd for C28H33O2Si2: 457.2019, found: 457.2045.
½
a 2D0
ꢃ
¼ þ100 (c 0.984, CH2Cl2). 1H NMR (CDCl3) d: 3.57 (s, 3H);
3.57 (d, J = 12.2 Hz, 2H); 3.70 (s, 3H); 4.39 (d, J = 12.3 Hz, 2H);
6.53 (ddd, J = 8.2, 2.6, 1.0 Hz, 1H); 6.73 (m, 2H); 6.85 (m, 4H);
6.98 (m, 1H); 7.19 (ptd, J = 7.3, 1.0 Hz, 1H); 7.25 (m, 3H); 7.31
(ptd, J = 7.6, 1.0 Hz, 1H); 7.37 (d, J = 8.3 Hz, 2H); 7.43 (d,
J = 8.7 Hz, 2H); 7.45 (m, 2H); 7.77 (d, J = 4.4 Hz, 1H); 7.81 (ddd,
J = 7.9, 4.0, 1.3 Hz, 1H); 7.87 (d, J = 8.3 Hz, 2H); 7.92 (d, J = 8.3 Hz,
2H) ppm. 13C NMR (CDCl3) d: 55.03 (CH3); 55.15 (CH3); 56.10
(CH2); 114.29 (d, J = 8.8 Hz); 118.91; 119.09; 119.11; 119.32;
125.60; 125.83; 125.91 (d, J = 4.5 Hz); 126.15; 126.26; 126.34;
126.45; 127.26; 127.45; 127.50; 128.28; 128.61); 128.70; 129.23
(d, J = 7.6 Hz); 129.54 (d, J = 8.0 Hz); 131.44 (C); 133.20 (C);
133.30; 133.34 (C); 133.49; 133.72; 133.92 (C); 134.64 (C);
138.47 (C); 138.58 (C); 138.73 (C); 138.82 (C); 140.07 (C, d,
J = 18.0 Hz); 159.28 (C); 159.36 (C); 159.59 (C); 159.68 (C) ppm.
31P NMR (CDCl3) d: ꢁ10.39 ppm. MS (ESI) m/e: 673 (M+MeOH+);
HRMS calcd for C43H36N2O2P: 643.2514, found: 643.2508.
4.2.7. (R)-2,20-Bis(hydroxymethyl)-3,30-diiodo-1,10-binaphthyl
(R)-14
A solution of ICl (487 mg, 3 mmol) in CH2Cl2 (10 mL) was added
dropwise at –40 °C (15–30 min) to a solution of diol (R)-13
(459 mg, 1 mmol) in CH2Cl2 (15 mL). After stirring for 2 h at the
same temperature, NaHSO3 solution (30 mL, 10%) was slowly
added. During warm up a voluminous precipitate of product was
formed. At rt this was filtered off and the organic phase was sepa-
rated. The aqueous phase was extracted with CH2Cl2 (2 ꢂ 20 mL)
and the combined organic phases were dried (MgSO4) and evapo-
rated. The solid residue was washed with little Et2O and dried in
vacuo. Both fractions were found to be pure by 1H NMR, total yield:
481–510 mg (85–90%); mp: 259–263 °C. ½a D20
¼ þ72:3 (c 1.01,
ꢃ
4.2.5. (R)-3,30-Bis(trimethylsilyl)-1,10-binaphthyl-2,20-
dicarboxylic acid (R)-12
CHCl3). 1H NMR (CDCl3) d: 3.41 (br s, 2H); 4.16 (d, J = 12.2 Hz,
2H); 4.59 (d, J = 12.2 Hz, 2H); 6.88 (br d, J = 8.4 Hz, 2H); 7.25
(ddd, J = 8.4, 6.9, 1.3 Hz, 2H); 7.47 (ddd, J = 8.1, 6.9, 1.1 Hz, 2H);
7.80 (br d, J = 8.4 Hz, 2H); 8.59 (s, 2H) ppm. 13C NMR (CDCl3) d:
65.96 (CH2); 98.16 (C); 126.72; 126.97; 127.32; 127.49; 132.52
(C); 134.29 (C); 136.27 (C); 137.86 (C); 139.99 ppm. MS (210 °C)
m/z (rel%): 566 (25, M+). HRMS (ESI) calcd for C22H16O2I2Na:
588.9137, found: 588.9134.
A solution of 2,2,6,6-tetramethylpiperidine (847 mg, 6 mmol,
1.01 mL) in dry THF (10 mL) was degassed and n-BuLi (3.75 mL,
6 mmol) was added dropwise at 0 °C under argon. After stirring
for 20 min at the same temperature the solution was cooled to
ꢁ78 °C and Me3SiCl (1.09 g, 10 mmol, 1.27 mL) was added and
stirring was continued for further 20 min. A degassed solution of
(R)-11 (342 mg, 1 mmol) in THF was added dropwise using a Teflon
cannula. The reaction mixture was allowed to reach rt within 6–
8 h. Hydrochloric acid (10 mL, 4 N) and Et2O (20 mL) were added
with stirring and the organic phase was separated. The aqueous
phase was extracted with a second portion of Et2O (10 mL) and
the combined extracts were stirred with NaOH (20 mL, 1 M) for
15 min. The alkaline layer was separated and the procedure was
repeated. The combined aqueous extracts were washed with Et2O
(20 mL) and acidified with HCl (6 M). The obtained mixture was
extracted with Et2O (2 ꢂ 50 mL) and the extracts were washed
with water and brine and dried (MgSO4). Removal of the solvent
left 410 mg (84%) of (R)-12 sufficiently pure for the next step.
4.2.8. (R)-2,20-Bis(bromomethyl)-3,30-diiodo-1,10-binaphthyl
(R)-15
At ꢁ40 °C, a solution of PBr3 (700 mg, 2.59 mmol, 0.6 equiv
242 lL) in CH2Cl2 (5 mL) was added dropwise for 30 min to a solu-
tion of diol (R)-14 (1.224 g, 2.16 mmol) in abs. THF (40 mL). Over
18 h the temperature was slowly raised to +10 °C. Water (3 mL)
was added and the bulk of solvent was evaporated. The residue
was partitioned between water (50 mL) and CHCl3 (100 mL). Occa-
sional gentle warming was necessary to ensure complete dissolu-
tion. The organic phase was separated, washed with brine, and
dried (Na2SO4). Removal of solvent left a white solid which was
dissolved in THF/CHCl3 (40 + 40 mL) with heating. Partial evapora-
tion of the solvent overnight yielded a first crop of crystalline prod-
uct. The mother liquor was filtered over SiO2 (2 ꢂ 10 cm) in CH2Cl2.
Slow concentration gave a second crop of product. Additional
amounts of the dibromide were obtained by column chromatogra-
phy to yield a total of 1.17 g (78%) of (R)-15 as a white powder. Mp:
½
a 2D0
ꢃ
¼ þ204 (c 1.00, CHCl3). 1H NMR (CDCl3) d: 0.41 (s, 18H);
7.02 (d, J = 8.3 Hz, 2H); 7.19 (m, 2H); 7.36 (m, 2H); 7.80 (d,
J = 8.1 Hz, 2H); 8.11 (s, 2H); ꢄ12.2 (br s, ꢄ2H) ppm. 13C NMR
(CDCl3) d: 0.11 (CH3); 125.98; 126.84; 127.21; 127.67; 131.17
(C); 132.30 (C); 132.91 (C); 134.29 (C); 135.70; 141.15 (C);
175.22 (C) ppm. MS (ESI) m/z: 485.3 (MꢁH+); HRMS calcd for
C
28H29O4Si2: 485.1604, found: 485.1611.
281–283 °C. ½a 2D0
ꢃ
¼ þ74:7 (c 1.01, THF). 1H NMR (CDCl3) d: 4.30 (d,
J = 10.1 Hz, 2H); 4.40 (d, J = 10.1 Hz, 2H); 6.96 (br d, J = 8.5 Hz, 2H);
7.27 (ddd, J = 8.3, 6.8, 1.2 Hz, 2H); 7.49 (ddd, J = 8.1, 6.8, 1.1 Hz,
2H); 7.80 (br d, J = 8.2 Hz, 2H); 8.64 (s, 2H) ppm. 13C NMR (CDCl3)
d: 38.44 (CH2); 97.70 (C); 126.85; 127.36; 127.42; 127.89; 131.73
(C); 134.31 (C); 134.55 (C); 136.38 (C); 140.88 ppm. MS (250 °C)
m/z (rel%): 694 (3.4)/692 (5.1)/690 (2.6) (isotopic pattern for M+).
4.2.6. (R)-2,20-Bis(hydroxymethyl)-3,30-bis(trimethylsilyl)-1,10-
binaphthyl (R)-13
A solution of diacid (R)-12 (972 mg, 2 mmol) in dry THF was de-
gassed. Through a septum, BH3ꢀTHF complex (8 mmol, 8 mL, 1 M in
THF) was added and the reaction was refluxed under argon until
TLC showed complete conversion (usually 20–24 h). Hydrochloric
acid (2 mL, 2 M) was carefully added with external cooling to
decompose the excess of borane. After evaporating the bulk of
THF the residue was partitioned between CH2Cl2 (100 mL) and
HCl (40 mL, 2 M). The organic phase was separated and the aque-
ous phase was extracted with CH2Cl2 (2 ꢂ 20 mL). The combined
extracts were washed with water (50 mL) and brine and dried
(MgSO4). Evaporation and drying at an oil pump left 771 mg
(84%) of (R)-13. Small amounts of an adhesive yellow impurity
could be removed by washing with some cold petroleum ether;
4.2.9. (R)-2,20-Bis(bromomethyl)-3,30-bis(trimethylsilyl)-1,10-
binaphthyl (R)-16
To a solution of diol (R)-13 (1.078 g, 2.35 mmol) in abs. THF
(70 mL) was added dropwise at ꢁ40 °C, PBr3 (1.40 g, 5.17 mmol,
486 lL) dissolved in THF (12 mL). The orange-colored solution
was slowly warmed up overnight and water (2 mL) was added at
0 °C. The bulk of solvent was evaporated and the residue was dis-
solved in CH2Cl2 (100 mL). The mixture was neutralized with suffi-
cient sat. NaHCO3 and the organic layer was separated. The
aqueous layer was extracted once with CH2Cl2 (50 mL) and the
mp: 102–105 °C. ½a D20
ꢃ
¼ þ123 (c 1.03, CHCl3). 1H NMR (CDCl3) d:

M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
1979
combined extracts were washed with water and brine and dried
with MgSO4. Evaporation yielded 925 mg (67%) of almost pure
(R)-16 as a colorless foam, which could not be crystallized (note:
126.34; 126.16 (d, J = 12.8 Hz); 126.96; 127.38 (2 ꢂ CH); 128.16
(d, J = 11.9 Hz); 128.44; 128.59 (d, J = 12.3 Hz); 128.78 (C);
129.78 (C); 130.02 (C); 131.09 (C); 131.30 (d, J = 2.8 Hz); 131.74
(d, J = 2.6 Hz); 131.82 (2 ꢂ d, J = 9.5 Hz); 132.15 (d, J = 22.8 Hz, C);
132.16 (d, J = 2.8 Hz); 132.98 (d, J = 11.9 Hz); 133.19 (d,
J = 21.8 Hz, C); 133.42 (C); 134.04 (d, J = 7.1 Hz); 136.69 (C);
140.63 (d, J = 6.6 Hz, C) ppm. 31P NMR (CDCl3) d: 30.74 (s) ppm.
MS (ESI) m/z: 667.2 (M+). HRMS calcd for C41H30OCl2N2P:
667.1467, found: 667.1475.
for ( )-16, mp: 162–165 °C). ½a D20
ꢃ
¼ þ98:3 (c 1.00, CHCl3). 1H
NMR (CDCl3) d: 0.53 (s, 18H); 4.33 (d, J = 10.3 Hz, 2H); 4.43 (d,
J = 10.3 Hz, 2H); 7.00 (br d, J = 8.5 Hz, 2H); 7.22 (ddd, J = 8.2, 6.8,
1.2 Hz, 2H); 7.46 (ddd, J = 8.1, 6.8, 1.1 Hz, 2H); 7.89 (br d,
J = 8.2 Hz, 2H); 8.22 (s, 2H) ppm. 13C NMR (CDCl3) d: 1.22 (CH3);
34.64 (CH2); 126.76; 126.83; 127.33; 127.99; 132.54 (C); 132.89
(C); 136.13 (C); 137.44; 137.63 (C); 138.26 (C) ppm. MS (140 °C)
m/z (rel%): 584 (28, M+). HRMS (EI) calcd for C28H32Br2Si2:
584.0392, found: 584.0385.
4.2.12. (R)-tert-Butyl 2,6-diiodo-3H-dinaphtho[2,1-c:10,20-
e]azepin-4(5H)-yl carbamate (R)-20
Dibromide (R)-15 (692 mg, 1 mmol), Boc-hydrazine (396 mg,
4.2.10. (R)(E)-N-(2-(Diphenylphosphino)benzylidene)-2,6-
bis(trimethylsilyl)-3H-dinaphtho[2,1-c:10,20-e]azepin-4(5H)-
amine (R)-17
Method A: A suspension of 2-diphenylphosphinobenzaldehyde
(61 mg, 0.21 mmol) and freshly dried MgSO4 (26 mg, 0.22 mmol)
was prepared in toluene (0.2 mL). Hydrazine monohydrate (10
3 mmol) and Et3N (303 mg, 3 mmol, 419 lL) were dissolved in abs.
THF (10 mL) and abs. DMF (2 mL). After degassing, the mixture
was stirred under argon at 60 °C (bath) for 72 h. After this time
TLC (ethyl acetate/petroleum ether 20:80) showed >90% conversion.
The reaction mixture was diluted with ethyl acetate (30 mL) and
water was added (30 mL). After separation the organic phase was
washed with water and brine and dried (MgSO4). Removal of the sol-
vent left 615 mg of crude (R)-20 which was found to be pure enough
l
L, 0.2 mmol) in ethanol (0.3 mL) was added and the degassed
mixture was stirred at 20 °C for 1 h. A solution of dibromide (R)-
16 (58 mg, 0.1 mmol) and triethylamine (35 L, 0.25 mmol) in tol-
l
for the next step (90–95% purity, corr. yield: 88%). ½a D20
¼ ꢁ232 (c
ꢃ
uene (0.3 mL) was added and after degassing (2ꢂ), the reaction
mixture was immersed into an oil bath (80–90 °C) and stirred for
48 h. For work-up CH2Cl2 (10 mL) and water (5 mL) were added.
The aqueous phase was extracted with CH2Cl2 (5 mL) and the com-
bined organic phases were washed with water and brine and dried
(MgSO4). After evaporation of solvents the residue was chromato-
graphed on SiO2 (1 ꢂ 40 cm) in CH2Cl2 (10?15%)/petroleum ether
1.02, CHCl3). 1H NMR (CDCl3) d: 1.49 (s, 9H); 3.45 (d, J = 12.9 Hz,
2H); 4.51 (d, J = 13.0 Hz, 2H); 5.59 (br s, 1H); 7.19 (br d, J = 8.6 Hz,
2H); 7.24 (ddd, J = 7.9, 6.5, 1.3 Hz, 2H); 7.45 (ddd, J = 8.0, 6.5,
1.4 Hz, 2H); 7.80 (d, J = 8.2 Hz, 2H); 8.57 (s, 2H) ppm. 13C NMR
(CDCl3) d: 28.56 (CH3); 61.37 (CH2); 98.31 (C); 126.81 (2 ꢂ CH);
127.17; 127.41; 130.96 (C); 134.06 (C); 134.38 (C); 135.79 (C);
139.74 ppm (Cquart., CO not observed). MS (ESI) m/z: 663.0 (M+1+),
HRMS: calcd for C27H25I2N2O2: 663.0005, found: 662.9997.
to give (R)-17 as a colorless oil; yield: 25 mg (34%). ½a D20
¼ ꢁ21:4 (c
ꢃ
1.00, CHCl3). 1H NMR (CDCl3) d: 0.39 (s, 18H); 3.52 (d, J = 12.7 Hz,
2H); 4.75 (d, J = 12.7 Hz, 2H); 6.70 (m, 1H); 6.75 (m, 1H); 6.94
(m, 2H); 7.07 (m, 1H); 7.10 (m, 2H); 7.14–7.26 (m, 9H); 7.30 (bptd,
J = 7.4, 1.0 Hz, 1H); 7.44 (m, 2H); 7.77 (d, J = 5.7 Hz, 1H); 7.92 (d,
J = 8.3 Hz, 2H); 8.07 (ddd, J = 8.0, 4.1, 1.0 Hz, 1H); 8.09 (s, 2H)
ppm. 13C NMR (CDCl3) d: 0.68 (CH3); 54.07 (CH2); 124.65 (d,
J = 3.5 Hz); 125.54; 126.19; 127.16 (d, J = 2.3 Hz); 127.38; 128.09;
128.17; 128.29; 128.46; 128.51; 128.53; 131.04 (d, J = 26.9 Hz);
132.10 (C); 133.08 (d, J = 3.8 Hz); 133.65 (d, J = 19.6 Hz); 133.77
(d, J = 15.4 Hz, C); 134.09 (d, J = 20.6 Hz); 135.11 (C); 135.87 (d,
J = 9.6 Hz, C); 135.95; 136.25 (d, J = 10.8 Hz, C); 136.91 (C);
137.32 (C); 139.59 (d, J = 15.4 Hz, C) ppm. 31P NMR (CDCl3) d:
ꢁ12.26 (s) ppm. MS (ESI) m/z: 727.2 (M+1+). HRMS calcd for
4.2.13. (R)-2,6-Diiodo-3H-dinaphtho[2,1-c:10,20-e]azepin-4(5H)-
amine (R)-21
Boc-hydrazine (R)-20 (331 mg, 0.5 mmol) was dissolved in
CHCl3 (3 mL) and TFA (1 mL) was added. The solution was stirred
at rt for 3 h after which TLC indicated complete conversion. The
reaction mixture was carefully neutralized with sat. NaHCO3, di-
luted with CH2Cl2 (25 mL), washed with water (30 mL) and brine,
and dried (K2CO3). Removal of the solvent left 281 mg of crude
(R)-21 which was found to be pure enough for the next step
(>97% purity by 1H NMR; corr. yield: 97%). Chromatographic puri-
fication resulted in considerable loss of product due to pronounced
sensitivity of the compound. (An analytical sample of the racemic
compound crystallized from CH2Cl2, mp: 198–200 °C.) 1H NMR
(CDCl3) d: 3.33 (d, J = 12.8 Hz, 2H); 3.36 (br s, 2H); 4.45 (d,
J = 12.8 Hz, 2H); 7.21 (m, 2H); 7.24 (m, 2H); 7.45 (ddd, J = 8.0,
6.1, 1.9 Hz, 2H); 7.80 (br d, J = 8.3 Hz, 2H); 8.57 (s, 2H) ppm. 13C
NMR (CDCl3) d: 63.74 (CH2); 98.58 (C); 126.70; 126.77; 127.18;
127.43; 131.03 (C); 134.34 (C); 134.51 (C); 135.74 (C);
139.52 ppm. MS (EI, 150 °C) m/z (rel%): 562.1 (M +, 12); 532.1
(62); HRMS: calcd for C22H16I2N2: 561.9403, found: 561.9385.
C47H48N2PSi2: 727.3004, found: 727.3076.
Method B: To a degassed solution of (R)-22 (84 mg, 0.1 mmol)
was added n-BuLi solution (0.32 mL, 0.5 mmol) at ꢁ78 °C. After
5 min Me3SiCl (108 mg, 1 mmol, 126 L) was added to the orange
l
solution and the reaction mixture was kept at this temperature for
1 h. After quenching with few drops of water and usual work-up
with ethyl acetate the crude material was purified by column chro-
matography (SiO2, 40 ꢂ 1.5 cm, in CH2Cl2/petroleum ether, 15:85)
to give 48 mg (66%) of (R)-17.
4.2.14. (R)(E)-N-(2-(Diphenylphosphino)benzylidene)-2,6-
diiodo-3H-dinaphtho[2,1-c:10,20-e]azepin-4(5H)-amine (R)-22
To a degassed solution of diiodo hydrazine (R)-21 (281 mg,
0.5 mmol) in CH2Cl2 (2 mL) were added aldehyde (145 mg,
0.5 mmol) and MgSO4 (120 mg, 1 mmol) and the mixture was stir-
red under argon at rt for 5 h. Extractive work-up with CH2Cl2/water
left 378 mg of crude product which contained 11% of aldehyde.
Chromatography on SiO2 in CH2Cl2/petroleum ether (1:1), column
20 ꢂ 2 cm resulted in some decomposition and afforded 299 mg
(72%) of (R)-22 as a foam. 1H NMR (CDCl3) d: 3.41 (d, J = 12.7 Hz,
2H); 5.00 (d, J = 12.7 Hz, 2H); 6.74 (ddd, J = 7.5, 5.2, 1.3 Hz, 1H);
6.91 (m, 1H); 7.06 (m, 2H); 7.11 (bpt, J ꢄ7.4 Hz, 1H); 7.15 (bpt, J
ꢄ7.9 Hz, 2H); 7.20 (br d, J ꢄ 8.5 Hz, 2H); 7.22–7.30 (m, ꢄ7H);
7.35 (bpt, J ꢄ7.3 Hz, 1H); 7.45 (ddd, J = 8.0, 6.4, 1.6 Hz, 2H); 7.79
4.2.11. ( )(E)-2,6-Dichloro-N-(2-
(diphenylphosphoryl)benzylidene)-3H-dinaphtho[2,1-c:10,20-
e]azepin-4(5H)-amine ( )-18
A similar procedure as given for the synthesis of (R)-17 (Method
B) was applied except that Cl3C–CCl3 (1.25 equiv) was used as the
electrophile. After chromatographic purification (SiO2, 30 ꢂ 2 cm,
CH2Cl2/petroleum ether, 15:85) phosphine oxide (R)-18 was iso-
lated in 63% yield, mp: >250 °C (dec.). 1H NMR (CDCl3) d: 3.17 (d,
J = 12.7 Hz, 2H): 5.05 (d, J = 12.8 Hz, 2H); 6.94 (tm, J = 7.5 Hz, 1H);
7.02 (ddd, J = 14.0, 7.6, 1.1 Hz, 1H); 7.11 (m, 2H); 7.15 (m, 1H);
7.24 (m, 4H); 7.36–7.54 (m, 8H); 7.60–7.66 (m, 2H); 7.83 (br d,
J = 8.3 Hz, 2H); 8.00 (2 ꢂ s, 3H); 8.24 (ddd, J = 8.0, 4.0, 0.9 Hz, 1H)
ppm. 13C NMR (CDCl3) d: 51.30 (CH2); 126.01 (d, J = 9.5 Hz);

1980
M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
(d, J = 8.6 Hz, 2H); 7.91 (d, J = 5.8 Hz, 1H); 8.22 (ddd, J = 8.0, 4.0,
1.2 Hz, 1H); 8.52 (s, 2H) ppm. 13C NMR (CDCl3) d: 59.19 (CH2);
98.07 (C); 125.13 (d, J = 4.0 Hz); 126.70 (2 ꢂ CH); 127.14; 127.39;
127.70 (d, J = 2.0 Hz); 128.27; 128.34; 128.52; 128.63; 128.70;
128.80; 130.98 (C); 132.67 (d, J = 3.1 Hz); 134.00; 134.13; 134.20,
134.29 (C); 134.39; 134.41 (C); 134.57 (C); 134.63 (C); 134.75
(C); 135.45 (C); 135.84 (C); 135.93 (C); 136.01 (C); 136.10 (C);
139.31 (C, d, J = 16.7 Hz); 139.66 ppm. 31P NMR (CDCl3) d: ꢁ12.36
(s) ppm. MS (ESI) m/z: 835.0. HRMS calcd for C41H30I2N2P:
835.0236, found: 835,0227.
2H); 7.42–7.50 (m, 8H); 7.58 (br d, J ꢄ7.3 Hz, 4H); 7.94 (br d,
J = 8.3 Hz, 2H); 7.94 (s, 2H) ppm. 13C NMR (CDCl3) d: 56.51 (CH2);
125.88; 126.06; 127.21; 127.55; 128.29; 128.31; 129.17; 129.96;
130.91 (C); 130.93 (C); 132.69 (C); 136.35 (C); 140.46 (C); 141.15
(C) ppm. MS (ESI) m/z: 463.1 (M+1+); HRMS calcd for C34H27N2:
463.2174, found: 463.2192.
4.2.18. (R)-2,6-Di(naphthalen-2-yl)-3H-dinaphtho[2,1-c:10,20-
e]azepin-4(5H)-amine (R)-26
An analogous procedure as given for the synthesis of (R)-25 was
applied yielding 75% of (R)-26 as an off-white powder (purity
>95%). 1H NMR (CDCl3) d: 2.75 (br s, 2H); 3.31 (br d, J = 12.6 Hz,
2H); 4.16 (d, J = 12.7 Hz, 2H); 7.31 (m, 2H); 7.47–7.53 (m, 8H);
7.73 (br d, J ꢄ8.4 Hz, 2H); 7.88 (m, 4H); 7.92 (d, J = 8.5 Hz, 2H);
7.98 (m, 2H); 8.05 (s, 2H); 8.06 (br s, 2H) ppm. 13C NMR (CDCl3)
d: 56.77 (CH2); 125.98; 126.08; 126.12, 126.32; 127.60; 127.72;
127.78; 128.16; 128.34; 128.37; 128.71; 129.49; 131.04 (C);
131.19 (C); 132.50 (C); 132.76 (C); 133.36 (C); 136.44 (C); 138.75
(C); 140.41 (C) ppm. MS (ESI) m/z: 563.2 (M+1+); HRMS calcd for
4.2.15. (R)-tert-Butyl 2,6-diphenyl-3H-dinaphtho[2,1-c:10,20-
e]azepin-4(5H)-yl carbamate (R)-23
Diiodide (R)-20 (132 mg, 0.2 mmol) and benzene boronic acid
(73 mg, 0.6 mmol) were mixed in DME (3 mL) and Cs2CO3
(147 mg, 0.45 mmol, in 0.2 mL of water) was added. After degas-
sing Pd(PPh3)4 (24 mg, 10 mol %) was added and the reaction mix-
ture was heated under argon. After about 20 h the color changed to
brown and TLC indicated complete conversion. Work-up with ethyl
acetate/water (20 + 20 mL), washing the organic phase with water
and satd NaCl, drying with MgSO4, and evaporation of solvent were
followed by column chromatography (8 ꢂ 2 cm) in CH2Cl2/petro-
leum ether (50:50) to remove the catalyst. Elution with ethyl ace-
tate/petroleum ether (20:80) gave 93 mg (84%) of (R)-23 as a foam.
(The racemic compound ( )-23 crystallized; mp: 224–227 °C.)
C42H31N2: 563.2487, found: 563.2506.
4.2.19. (R)(E)-N-(2-(Diphenylphosphino)benzylidene)-2,6-
diphenyl-3H-dinaphtho[2,1-c:10,20-e]azepin-4(5H)-amine (R)-27
Method A: N-Aminodinaphthoazepine (R)-25 (58 mg, 0.126
mmol) was dissolved in CHCl3 (1 mL), the solution was degassed,
and 2-diphenylphosphinobenzaldehyde (36 mg, 0.126 mmol) and
MgSO4 (30 mg, 0.25 mmol) were added. After stirring the mixture
overnight at rt under argon the suspension was worked up with
CH2Cl2 (10 mL) and water (10 mL). The organic layer was separated,
washed with brine, and dried over MgSO4. The filtrate was concen-
trated and the remaining residue was purified by column chroma-
tography (SiO2, CH2Cl2/petroleum ether, 30:70?50:50) to yield
76 mg (81%) of phosphinohydrazone (R)-27 as a solid (>98% pure
½
a 2D0
ꢃ
¼ ꢁ121 (c 0.64, CHCl3). 1H NMR (CDCl3) d: 1.27 (s, 9H); 3.33
(br d, J = 12.5 Hz, 2H); 4.13 (d, J = 12.5 Hz, 2H); 5.10 (br s, 1H);
7.27 (m, 2H); 7.38 (m, 2H); 7.42–7.51 (m, 8 H); 7.65 (bm, 4H);
7.94 (br d, J ꢄ7.9 Hz, 2H); 7.97 (s, 2H) ppm. 13C NMR (CDCl3) d:
28.17 (CH3); 54.48 (CH2); 79.60 (C); 126.00; 126.24; 127.27;
127.52; 128.35 (2 ꢂ CH); 129.52; 130.08; 130.17 (C); 130.84 (C);
132.83 (C); 136.39 (C); 140.23 (C); 140.69 (C) ppm. MS (EI, 50 °C)
m/z (rel%): 562 (1, M+). HRMS calcd for C39H34N2O2: 562.2620,
found: 562.2609.
by NMR). ½a 2D0
ꢃ
¼ þ44:3 (c 0.526, CHCl3). 1H NMR (CDCl3) d: 3.33 (d,
J = 12.6 Hz, 2H); 4.63 (d, J = 12.6 Hz, 2H); 6.62 (bpt, J = 7.4 Hz, 1H);
6.72 (ddd, J = 6.8, 5.4, 1.0 Hz, 1H); 6.84 (m, 2H); 6.99 (m, 2H); 7.09
(m, 3H); 7.17 (m, 3H); 7.25–7.44 (m, 15H); 7.49 (m, 3H); 7.70
(ddd, J = 7.8, 4.0, 1.0 Hz, 1H); 7.87 (s, 2H); 7.93 (d, J = 8.0 Hz, 2H)
ppm. 13C NMR (CDCl3) d: 51.81 (CH2); 124.94 (d, J = 4.0 Hz);
125.80; 126.07; 127.19; 127.37 (d, J = 2.0 Hz); 127.61; 128.00;
128.07; 128.11 (2 ꢂ CH); 128.28; 128.35; 128.39; 128.44; 128.46;
128.65; 129.47; 129.85; 130.91 (C); 131.40 (C); 132.72 (C);
132.74; 132.78; 132.83; 133.09; 133.63; 133.77; 133.83; 133.96;
134.30 (C, d, J = 15.5 Hz); 135.65 (C); 135.70 (C); 135.74 (C);
135.80 (C); 135.95 (C); 139.36 (C, d, J = 16.2 Hz); 140.15 (C);
140.76 (C) ppm. 31P NMR (CDCl3) d: ꢁ12.85 (s) ppm. MS (ESI) m/z:
735.3 (M+1+). HRMS calcd for C53H40N2P: 735.2929, found:
735.2933.
Method B: Diiodide (R)-22 (83 mg, 0.1 mmol) and benzene boro-
nic acid (37 mg, 0.3 mmol) were mixed in DME (2 mL) and Cs2CO3
(82 mg, 0.25 mmol, in 0.15 mL water) was added. After degassing
Pd(PPh3)4 (12 mg, 10 mol %) was added and the reaction mixture
was heated under argon for 24 h. Since the reaction was still heter-
ogeneous and TLC showed only partial conversion another 12 mg
(10 mol %) of Pd(PPh3)4 and 37 mg (0.3 mmol) of benzene boronic
acid were added and heating was continued for further 48 h
obtaining a clear yellow solution. Work-up with CH2Cl2/water
(15 + 15 mL), washing with brine, and drying (MgSO4) were fol-
lowed by column chromatography (see above) to give 41 mg
(56%) of (R)-27.
4.2.16. (R)-tert-Butyl 2,6-di(naphthalen-2-yl)-3H-
dinaphtho[2,1-c:10,20-e]azepin-4(5H)-yl carbamate (R)-24
An analogous procedure as given for the synthesis of (R)-23 was
applied yielding 68% of (R)-24 as a crystalline powder, mp: 165–
166 °C. ½a 2D0
ꢃ
¼ ꢁ60:0 (c 1.00, CHCl3). 1H NMR (CDCl3) d: 0.99 (s,
9H); 3.44 (br d, d, J = 12.5 Hz, 2H); 4.25 (br d, J = 12.6 Hz, 2H);
5.19 (br s, 1H); 7.31 (ddd, J = 8.4, 6.7, 1.3 Hz, 2H); 7.46–7.54 (m,
8H); 7.78 (bm, 2H); 7.88 (m, 2H); 7.93 (d, J = 8.5 Hz, 2H); 7.96
(m, 2H); 7.99 (br d, J = 8.7 Hz, 2H); 8.10 (s, 2H); 8.24 (br s, 2H)
ppm. 13C NMR (CDCl3) d: 27.78 (CH3); 54.56 (CH2); 126.08
(2 ꢂ CH); 126.21; 126.26; 127.56; 127.60; 127.84; 128.26 (b);
128.44; 128.49 (b); 129.11(b); 129.75; 130.65 (C); 130.91 (C);
132.52 (C); 132.91 (C); 133.43 (C); 136.48 (C); 138.17 (C); 140.12
(C) ppm. MS (ESI) m/z: 663.2 (M+1+). HRMS: calcd for
C49H39N2O2: 663.3012, found: 663.3019.
4.2.17. (R)-2,6-Diphenyl-3H-dinaphtho[2,1-c:10,20-e]azepin-
4(5H)-amine (R)-25
Boc-hydrazine (R)-23 (90 mg, 0.16 mmol) was dissolved in
CHCl3 (1 mL) and TFA (0.25 mL) was added. The solution was stir-
red at rt for 2 h after which TLC (ethyl acetate/petroleum ether,
20:80) indicated complete conversion. The reaction mixture was
carefully neutralized with sat. NaHCO3, diluted with of CH2Cl2
(15 mL), washed with water (10 mL) and brine, and dried
(K2CO3). Removal of the solvent left 58 mg of crude (R)-25 which
was found to be pure enough for the next step (>98% purity; corr.
yield: 78%); (note: Attempted chromatographic purification
resulted in considerable loss of product due to pronounced sensi-
tivity of the compound. ( )-25 was obtained crystalline; mp:
226–229 °C.) 1H NMR (CDCl3) d: 2.73 (br s, 2H); 3.21 (d,
J = 12.5 Hz, 2H); 4.08 (d, J = 12.5 Hz, 2H); 7.27 (m, 2H); 7.38 (m,
4.2.20. (R)(E)-N-(2-(Diphenylphosphino)benzylidene)-2,6-
di(naphthalen-2-yl)-3H-dinaphtho[2,1-c:10,20-e]azepin-4(5H)-
amine (R)-28
An analog procedure as applied for the synthesis of (R)-27 was
used yielding 69% of (R)-26 as an off-white powder (purity >98%).

M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
1981
½
a 2D0
ꢃ
¼ þ62:8 (c 0.53, CHCl3). 1H NMR (CDCl3) d: 3.43 (br s, 2H);
4.3. Catalytic experiments
4.69 (br d, J = 12.5 Hz, 2H); 6.60 (pt, J = 7.3 Hz, 1H); 6.73 (ddd,
J = 7.2, 5.9, 1.2 Hz, 1H); 6.79 (m, 2H); 6.88–7.01 (m, 7H); 7.09 (pt,
J = 7.4 Hz, 1H); 7.14 (m, 1H); 7.31 (ddd, J = 8.2, 6.8, 1.2 Hz, 2H);
7.41 (d, J = 5.0 Hz, 1H); 7.45–7.58 (m, 11H); 7.79 (bm, 4H); 7.90
(m, 4H); 7.97 (d, J = 7.9 Hz, 2H); 7.97 (s, 2H) ppm. 13C NMR (CDCl3)
d: 51.95 (CH2); 125.11 (d, J = 3.6 Hz); 125.92 (d, J = 3.2 Hz); 126.13
(d, J = 3.6 Hz); 127.27 (d, J = 2.2 Hz); 127.59; 127.64; 127.70;
127.96; 128.03; 128.16; 128.23; 128.33; 128.49; 128.59; 128.66;
129.84; 131.00 (C); 131.55 (C); 132.55 (C); 132.71; 132.77 (C);
133.25; 133.34 (C); 133.47; 133.58; 133.78; 134.44 (C, d,
J = 15.2 Hz); 135.46 (C); 135.51 (C); 135.55 (C); 135.60 (C);
135.99 (C, br); 138.41 (C); 139.19 (C, d, J = 15.6 Hz); 140.09 (C)
ppm. 31P NMR (CDCl3) d: ꢁ12.37 (s) ppm. MS (ESI) m/z: 835.3
(M+1+). HRMS calcd for C61H44N2P: 835.3242, found: 835.3217.
For performing reactions 1–6 standard procedures were ap-
plied.20 The enantiomeric purity of products was determined by
HPLC (Chiralcel-ODH, 2-PrOH/n-hexane for reaction 1 and 6) or
by 1H NMR using a chiral shift reagent (Eu(hfc)3 in CDCl3 for reac-
tion 2, 3, and 5).
4.4. Synthesis of Pd complexes
4.4.1. (RS)-6.Pd-dimer
To a degassed solution of Pd(MeCN)2Cl2 (14.1 mg, 0.0545 mmol)
in CH2Cl2 (0.5 mL) was added rac-6 (35 mg, 0.0545 mmol) at rt un-
der argon. After 30 min, AgPF6 (13.8 mg 0.0545 mmol) was added
and stirring was continued for 1.5 h. Silver chloride was filtered
off and the solvent was removed. The crude product was crystal-
lized from CH2Cl2/benzene or CDCl3 in orange prisms. Mp: 207–
208 °C (dec.). 1H NMR (CD2Cl2) d: 3.70 (d, J = 12.3 Hz, 2H); 4.89
(br d, J = 12.3 Hz, 2H); 6.70 (br d, J = 7.7 Hz, 2H); 6.84 (dd,
J = 12.1, 7.8 Hz, 1H); 7.22 (ddd, J = 8.0, 6.7, 1.2 Hz, 2H); 7.33 (br d,
J = 8.7 Hz, 2H); 7.44 (ddd, J = 8.0, 6.7, 1.2 Hz, 2H); 6.30–7.47 (bm,
ca. 6H); 7.55 (br s, 1H); 7.66 (d, J = 8.3 Hz, 2H); 7.57–7.77 (bm,
ca. 6H); 7.87 (d, J = 8.3 Hz, 2H); 7.96 (bpt, J ꢄ7.5 Hz, 1H) ppm. 31P
NMR (CD2Cl2) d: 35.9 (br s) ppm.
4.2.21. (2-(1,3-Dioxolan-2-yl)phenyl)bis(3-
methoxyphenyl)phosphine
Magnesium (174 mg, 7.14 mmol, 1.07 equiv) was added to THF
(1.2 mL) in an oven-dried Schlenk tube and the mixture was de-
gassed. A single crystal of iodine was added, followed by the drop-
wise addition of a solution of 3-bromoanisole (1.25 g, 6.67 mmol)
in THF (1.4 mL). After the addition was complete, the reaction mix-
ture was stirred at reflux for 2 h. The solution of the Grignard re-
agent was allowed to cool to rt and added via a cannula to
phosphorous trichloride (366 mg, 2.67 mmol, 0.4 equiv) in de-
gassed THF (7.2 mL) at 0 °C. The reaction mixture was warmed to
rt and stirred overnight. This solution of chlorobis(3-methoxy-
phenyl) phosphine was used directly in the following reaction.
Magnesium (146 mg, 6 mmol, 1.5 equiv) and THF (2.3 mL) were
placed in an oven-dried Schlenk tube and the mixture was de-
gassed. A single crystal of iodine was added, followed by the drop-
wise addition of 2-(2-bromophenyl)-1,3-dioxolane (916 mg,
4 mmol) dissolved in THF (4 mL). After the addition was complete,
the reaction mixture was refluxed for 2 h. The solution of the Grig-
nard reagent was cooled to rt and added via a cannula to the solu-
tion of chlorobis(3-methoxyphenyl)phosphine in degassed THF
(9.8 mL) at 0 °C. The mixture was slowly warmed up and stirred
overnight at 50 °C. The reaction mixture was concentrated, diluted
with ethyl acetate (25 mL), and washed with water (2 ꢂ 20 mL)
and saturated NH4Cl (20 mL). After drying (MgSO4) and evapora-
tion, the crude product was purified by chromatography (ethyl
acetate/petroleum ether, 10:90) to afford 190 mg (18%) of (2-
(1,3-dioxolan-2-yl)phenyl)bis(3-methoxyphenyl)phosphine as an
oil. 1H NMR (CDCl3) d: 4.10 (s, 6H); 4.34 (m, 2H); 4.48 (m, 2H);
6.84 (d, J = 4.9 Hz, 1H); 7.23–7.27 (m, 6H); 7.42 (ddd, J = 7.7, 4.5,
1.4 Hz, 1H); 7.62–7.68 (m, 3H); 7.79 (ptd, J = 7.5, 1.4 Hz, 1H);
8.10 (ddd, J = 7.8, 4.1, 1.5 Hz, 1H) ppm. 31P NMR (CDCl3) d:
ꢁ14.66 (s) ppm.
4.4.2. (R)-6.PdCl2
A
solution of equimolar amounts of (R)-6 with and
Pd(MeCN)2Cl2 in CHCl3 was layered with EtOH. After a few hours
pale yellow needles formed which were completely converted into
orange prisms within several days. Mp: 211–213 °C ½a D20
¼ þ618 (c
ꢃ
0.0676 CHCl3). 1H NMR (CD2Cl2) d: 3.67 (d, J = 12.7 Hz, 2H); 5.27 (d,
J = 12.7 Hz, 2H); 6.78 (ddd, J = 11.0, 7.9, 1.0 Hz; 1H); 7.11 (d,
J = 8.3 Hz, 2H); 7.19 (ddd, J = 8.3, 6.7, 1.3 Hz, 2H);7.19–7.33 (m,
8H); 7.40 (ddd, J = 8.0, 6.6, 1.0 Hz, 2H); 7.44 (br s, 1H); 7.46–7.57
(m, 6H); 7.68 (d, J = 8.3 Hz, 2H); 7.74 (m, 1H); 7.85 (d, J = 8.3 Hz,
2H) ppm. 13C NMR (CD2Cl2) d: 58.16 (CH2); 119.07 (d, J = 50.2 Hz,
C); 126.00 (d, J = 21.6 Hz, C); 126.58 (d, J = 32.4 Hz, C); 126.68
(2 ꢂ CH); 127.69; 127.90; 128.87; 128.88 (d, J = 12.0 Hz); 129.53;
130.22 (d, J = 11.6 Hz); 131.77 (d, J = 8.6 Hz); 131.84 (C); 131.86
(C); 132.36 (d, J = 3.0 Hz); 133.09 (d, J = 3.0 Hz); 133.67 (d,
J = 2.5 Hz); 134.04 (C); 134.22 (d, J = 10.7 Hz); 134.61; 134.71;
134.74; 134.77; 134.88; 135.54 (C); 138.62 (d, J = 15.7 Hz, C);
141.63 (d, J = 8.7 Hz) ppm. 31P NMR (CD2Cl2) d: 29.56 (s) ppm.
4.5. Crystallographic structure determination
X-ray diffraction measurements were performed on X8 APEXII
CCD diffractometer with graphite-monochromated MoK
a radia-
tion, k = 0.71073 Å at 100(2) K. Single crystals were positioned at
35, 40, 40, and 35 mm from the detector and 1776, 2557, 1868,
and 1055 frames were measured, each for 50, 20, 30, and 30 s over
1° scan width for ( )-18ꢀC4H8O2, ( )-29, ½ððRÞ-6-ðSÞ-6ÞPd2Cl2ꢃ2þꢀ
2PF6þ ꢀ 8CH2Cl2 and [((R)-6Pd2Cl2]ꢀCHCl3, correspondingly. The
data were processed using SAINT Plus software.21 The structure
was solved by direct methods and refined by full-matrix least-
squares techniques. Non-hydrogen atoms were refined with
anisotropic displacement parameters. H atoms were placed in geo-
metrically calculated positions and refined as riding atoms in the
subsequent least squares model refinements. The isotropic thermal
parameters were estimated to be 1.2 times the values of the equiv-
alent isotropic thermal parameters of the atoms to which hydro-
gens were bonded. The following software programs, computer,
and tables were used: structure solution, SHELXS-97,22 refinement,
SHELXL-97,23 molecular diagrams, ORTEP,24 computer: Pentium IV;
Tables 4.2.6.8 and 6.1.1.4 for scattering factors were taken from
4.2.22. 2-(Bis(3-methoxyphenyl)phosphino)benzaldehyde
(2-(1,3-Dioxolan-2-yl)phenyl)bis(3-methoxyphenyl)phosphine
(176 mg, 0.447 mmol) was dissolved in acetone (4 mL) and the
mixture was degassed. p-Toluenesulfonic acid monohydrate
(5 mg) was added and the solution was refluxed for 3 h under ar-
gon. During this time, the yellow color of the final product devel-
oped. The product mixture was filtered through a short pad of
SiO2 (CH2Cl2) giving 139 mg (ꢄ80%) of a yellow oil (purity 95%
by NMR). 1H NMR (CDCl3) d: 3.73 (s, 6H); 6.82 (m, 2H); 6.84 (m,
2H); 6.98 (ddd, J = 8.3, 2.8, 1.0 Hz, 2H); 6.99 (m, 1H); 7.25 (m,
2H); 7.46 (m, 2H); 7.95 (m, 1H); 10.48 (d, J = 5.4 Hz, 1H) ppm.
13C NMR (CDCl3) d: 55.16 (CH2); 114.69 (2 ꢂ CH); 119.08;
119.30; 126.24; 126.44; 128.92; 129.68; 129.76; 130.59 (d,
J = 3.9 Hz); 133.66; 133.91; 137.50 (d, J = 10.2 Hz, C); 138.49 (d,
J = 14.7 Hz, C); 140.88 (d, J = 26.2 Hz, C); 159.67 (d, J = 9.2 Hz, C);
191.65 (d, J = 19.2 Hz) ppm. 31P NMR (CDCl3) d: ꢁ10.03 ppm.

1982
M. Widhalm et al. / Tetrahedron: Asymmetry 21 (2010) 1971–1982
the literature.25 Details of crystal data, data collection, and refine-
ment are as follows:26
Spannenberg, A.; Marras, F.; Gladiali, S.; Beller, M. Tetrahedron: Asymmetry
2007, 18, 1288–1298; (c) Kasak, P.; Arion, V. B.; Widhalm, M. Tetrahedron:
Asymmetry 2006, 17, 3084–3090; (d) Kasak, P.; Mereiter, K.; Widhalm, M.
Tetrahedron: Asymmetry 2005, 16, 3416–3426; (e) Junge, K.; Hagemann, B.;
Enthaler, S.; Spannenberg, A.; Michalik, M.; Oehme, G.; Monsees, A.; Riermeier,
T.; Beller, M. Tetrahedron: Asymmetry 2004, 15, 2621–2631; (f) Tang, W.; Wang,
W.; Chi, Y.; Zhang, X. Angew. Chem., Int. Ed. 2003, 42, 3509–3511; (g) Junge, K.;
Oehme, G.; Monsees, A.; Riermeier, T.; Dingerdissen, U.; Beller, M. Tetrahedron
Lett. 2002, 43, 4977–4980; (h) Xiao, D.; Zhang, Z.; Zhang, X. Org. Lett. 1999, 1,
1679–1681.
( )-18ꢀC4H8O2: C45H37Cl2N2O3P, Mr = 755.64, monoclinic, space
group P21/n (no. 14), a = 13.8470(9), b = 10.0712(7), c =
27.1684(16) Å, V = 3754.3(4) Å3, Z = 4,
q l =
calc = 1.337 g/cm3,
0.260 mmꢁ1. Of 130,810 reflections collected up to hmax = 25.5°,
6982 were independent, Rint = 0.162; final R indices: R1 = 0.0480,
wR2 = 0.1045 (all data).
5. (a) Mino, T.; Komatsumoto, E.; Nakadai, S.; Toyoda, H.; Sakamoto, M.; Fujita, T.
Journal. Mol. Cat. A: Chem. 2003, 196, 13–20; (b) Mino, T.; Shiotsuki, M.;
Yamamoto, N.; Suenaga, T.; Sakamoto, M.; Fujita, T.; Yamashita, M. Journal. Org.
Chem. 2001, 66, 1795–1797; (c) Enders, D.; Peters, R.; Lochtman, R.; Runsink, J.
Eur. Journal. Org. Chem. 2000, 2839–2850.
6. Maigrot, N.; Mazaleyrat, J.-P. Chem. Commun. 1985, 317–320.
7. (a) Sun, X.; Li, W.; Zhou, L.; Zhang, X. Chem. Eur. Journal. 2009, 15, 7302–7305;
(b) Ikunaka, M.; Maruoka, K.; Okuda, Y.; Ooi, T. Org. Proc. Res. Dev. 2003, 7, 644–
648; (c) Cai, D.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Tetrahedron Lett.
1995, 36, 7991–7994; (d) Hu, Q.-S.; Vitharana, D.; Pu, L. Tetrahedron: Asymmetry
1995, 6, 2123–2126.
8. (a) Seki, M.; Yamada, S.; Kuroda, T.; Imashiro, R.; Shimizu, T. Synthesis 2000,
1677–1680; (b) Mazaleyrat, J.-P. Tetrahedron: Asymmetry 1997, 8, 2709–2721;
(c) Kanoh, S.; Hongoh, Y.; Motoi, M.; Suda, H. Bull. Chem. Soc. Jpn. 1988, 61,
1032–1034.
9. (a) Putala, M. Enantiomer 1999, 4, 243–262; (b) Hayashi, T.; Hayashizaki, K.;
Kiyoi, T.; Ito, Y. Journal. Am. Chem. Soc. 1988, 110, 8153–8156.
10. See: (a) Hou, J.; Sun, W.; Zhang, S.; Ma, H.; Deng, Y.; Lu, X. Organometallics 2006,
25, 236–244; (b) Schenkel, L. B.; Ellman, J. A. Org. Lett. 2003, 5, 545–548; (c)
Clark, P. W.; Mulraney, B. J. Journal. Organomet. Chem 1981, 217, 51–59.
11. Arai, T.; Endo, Y.; Yanagisawa, A. Tetrahedron: Asymmetry 2007, 18, 165–
169.
12. (a) Nguyen, T.; Castanet, A.-S.; Mortier, J. Org. Lett. 2006, 8, 765–768; (b) Krizan,
T. D.; Martin, J. C. Journal. Am. Chem. Soc. 1983, 105, 6155–6157.
13. Yang, D.; Wong, M.-K.; Yip, Y.-C.; Wang, X.-C.; Tang, M.-W.; Zheng, J.-H.;
Cheung, K.-K. Journal. Am. Chem. Soc. 1998, 120, 5943–5952.
14. For the ortho metallation of corresponding esters see: (a) Hashimoto, T.;
Maruoka, K. Synthesis 2008, 1, 3703–3706; (b) Ooi, T.; Uematsu, Y.; Maruoka, K.
Journal. Am. Chem. Soc. 2006, 128, 2548–2549; (c) Ooi, T.; Uematsu, Y.;
Maruoka, K. Journal. Org. Chem. 2003, 68, 4576–4578.
15. Cf. Lehmann, U.; Schlüter, A. D. Eur. Journal. Org. Chem. 2000, 3483–3487.
16. For recent reviews see: Alonso, F.; Beletskaya, I. P.; Yus, M. Tetrahedron 2008,
64, 3047–3101. and references concerning further reviews given there.
17. Saarsalu, S.; Widhalm, M. Unpublished.
18. Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. 1998, 37, 2922–2959.
19. (a) Schiemenz, G. P.; Kaack, H. Justus Liebigs Ann. 1973, 1480–1493; (b) Hoots, J.
E.; Rauchfuss, T. B.; Wrobleski, D. A.; Knachel, H. C. Inorg. Synth. 1982, 21, 175.
20. (a) Widhalm, M.; Wimmer, P.; Klintschar, G. Journal. Organomet. Chem. 1996,
523, 167–178; (b) Wimmer, P.; Widhalm, M. Monatsh. Chem. 1996, 127, 669–
681.
( )-29: C29H22N2, Mr = 398.49, monoclinic, space group C2/c
(no. 15), a = 11.1143(6), b = 16.3817(6), c = 22.9158(10) Å, V =
4086.7(3) Å3, Z = 8,
q l
calc = 1.295 g/cm3, = 0.076 mmꢁ1. Of 59,223
reflections collected up to hmax = 30.1°, 6001 were independent,
Rint = 0.055; final R indices: R1 = 0.0447, wR2 = 0.1114 (all data).
½ððRÞ-6-ðSÞ-6ÞPd2Cl2ꢃ2þ ꢀ 2PF6þ ꢀ 8CH2Cl2: C90H76Cl18F12N4P4Pd2,
Mr = 2416.33, triclinic, space group P-1 (no. 2), a = 14.6409(11),
b = 14.6437(11), c = 15.0967(12) Å,
a
= 113.405(5), b = 93.507(5),
c
= 119.019(4)°, V = 2464.1(3) Å3, Z = 1,
q
calc = 1.628 g/cm3,
l =
0.988 mmꢁ1. Of 60,424 reflections collected up to hmax = 25.5°,
9019 were independent, Rint = 0.102; final R indices: R1 = 0.0687,
wR2 = 0.2310 (all data).
[((R)-6Pd2Cl2]ꢀCHCl3: C42H32Cl5N2PPd, Mr = 879.32, monoclinic,
space group P21 (no. 4), a = 11.1254(12), b = 10.9705(13), c =
15.8822(19) Å, V = 1874.3(4) Å3, Z = 2,
q l =
calc = 1.558 g/cm3,
0.929 mmꢁ1. Of 36,163 reflections collected up to hmax = 27.0°,
7893 were independent, Rint = 0.127; final R indices: R1 = 0.0564,
wR2 = 0.0972 (all data).
Acknowledgments
We thank Alexander Roller for the collection of X-ray data and
Mirjana Pacar for technical assistance. Two grants of the Estonian
Science Foundation are gratefully acknowledged: 6706 and 8031.
References
1. Guiry, P. J.; Saunders, C. P. Adv. Synth. Catal. 2004, 346, 497–537.
2. Hargaden, G. C.; Guiry, P. J. Chem. Rev. 2009, 2505–2550.
3. Dinaphthoazepines (selection): (a) Pisani, L.; Superchi, S. Tetrahedron:
Asymmetry 2008, 19, 1784–1789; (b) Aillaud, I.; Wright, K.; Collin, J.; Schulz,
E.; Mazaleyrat, J.-P. Tetrahedron: Asymmetry 2008, 19, 82–92; (c) Vasse, J.-L.;
Stranne, R.; Zalubovskis, R.; Gayet, C.; Moberg, C. Journal. Org. Chem. 2003, 68,
3258–3270; (d) Widhalm, M.; Nettekoven, U.; Kalchhauser, H.; Mereiter, K.;
Calhorda, M. J.; Felix, V. Organometallics 2002, 21, 315–325; (e) Mecca, T.;
Superchi, S.; Giorgio, E.; Rosini, C. Tetrahedron: Asymmetry 2001, 12, 1225–
1233; (f) Arroyo, N.; Haslinger, U.; Mereiter, K.; Widhalm, M. Tetrahedron:
Asymmetry 2000, 11, 4207–4219; (g) Bourghida, M.; Widhalm, M. Tetrahedron:
Asymmetry 1998, 9, 1073–1083; (h) Widhalm, M.; Mereiter, K.; Bourghida, M.
Tetrahedron: Asymmetry 1998, 9, 2983–2986; (i) Kubota, H.; Koga, K.
Heterocycles 1996, 42, 543–547; (j) Wimmer, P.; Widhalm, M. Tetrahedron:
Asymmetry 1995, 6, 657–660; (k) Kubota, H.; Koga, K. Tetrahedron Lett. 1994, 35,
6689–6692.
21. Bruker SAINT-Plus, version 7.56a; Bruker AXS: Madison, WI, USA, 2008.
22. Sheldrick, G. M. SHELXS97: Program for Crystal Structure Solution; University of
Göttingen: Germany, 1997.
23. Sheldrick, G. M. SHELXL97: Program for Crystal Structure Refinement; University
of Göttingen: Germany, 1997.
24. Johnson, G. K. Report ORNL-5138. OAK Ridge National Laboratory, Oak Ridge,
Tennessee, 1976.
25. International Tables for X-ray Crystallography; Wilson, A. J. C., Ed.; Kluwer
Academic Press: Dodrecht, The Netherlands, 1992; Vol. C,.
26. CCDC 773202–773205 contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/
conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge CB2 1EZ, UK; fax: (internet) +44 1223/336 033; E-mail:
deposit@ccdc.cam.ac.uk].
4. Dinaphthophosphepines (selection): (a) Dai, Q.; Li, W.; Zhang, X. Tetrahedron
2008, 64, 6943–6948; (b) Enthaler, S.; Erre, G.; Junge, K.; Michalik, D.;