Enantioselective Friedel-Crafts alkylations catalysed by well-defined iridium and rhodium half-sandwich complexes

Article abstract of DOI:10.1016/j.tetasy.2011.05.003

Aqua-complexes (S_M,R_C)-[CpM{(R)-prophos}(H ₂O)][SbF₆]₂ (M = Rh 1, Ir 2) catalysed the alkylation of α,β-unsaturated aldehydes with aromatics and heteroaromatics but in some cases, mixtures of products

Full text of DOI:10.1016/j.tetasy.2011.05.003

Tetrahedron: Asymmetry 22 (2011) 893–906
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective Friedel–Crafts alkylations catalysed by well-defined
iridium and rhodium half-sandwich complexes
⇑
Daniel Carmona , María Pilar Lamata, Antonio Sánchez, Fernando Viguri, Luis A. Oro
Departamento de Química Inorgánica, Instituto Universitario de Catálisis Homogénea, Instituto de Ciencia de Materiales de Aragón,
Universidad de Zaragoza-Consejo Superior de Investigaciones Científicas, 50009 Zaragoza, Spain
a r t i c l e i n f o
a b s t r a c t
Aqua-complexes (SM,RC)-[Cp⁄M{(R)-prophos}(H2O)][SbF6]2 (M = Rh 1, Ir 2) catalysed the alkylation of
a,b-
Article history:
Received 14 April 2011
Accepted 13 May 2011
Available online 15 June 2011
unsaturated aldehydes with aromatics and heteroaromatics but in some cases, mixtures of products were
obtained. Complexes 1 and 2 were also used to activate nitroalkenes for the Friedel–Crafts alkylation of a
variety of aromatics and heteroaromatics, in particular, 1,3,5-trimethoxybenzene. For this substrate, the
monoalkylated adduct was obtained in quantitative yield with enantioselectivities of up to 73% ee being
achieved. The intermediate catalyst/nitroalkene was isolated and characterized and the complex catalyst/
adduct was detected spectroscopically. From these data a plausible catalytic cycle is proposed.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
2+
The catalytic enantioselective Friedel–Crafts reaction of elec-
tron-rich aromatic or heteroaromatic substrates with electron-
deficient alkenes is one of the most direct methods for introducing
a new stereogenic centre on an aromatic or heteroaromatic com-
pound.1–9 Asymmetric protocols based on both metal-1–6 and
organocatalysed1–4,6–9 alkylations have been developed.
M*
Ph2P
*
PPh2
M = Rh, Ir
Figure 1. The chiral cations Cp⁄M{(R)-prophos)}.
In particular, the asymmetric alkylation of activated alkenes,
carbonyl compounds or imines was shown to take place for a num-
ber of (hetero)aromatic compounds and, although the first report
of asymmetric Friedel–Crafts reactions involved the alkylation of
phenols10 and naphthols,11 indoles are by far the most widely
employed nucleophiles.3,4,6,7,9
2. Results and discussion
2.1. Enals as electrophiles
Wehaverecentlyisolatedandcharacterizedchiral half-sandwich
rhodium or iridium compounds (SM,RC)-[Cp⁄M{(R)-prophos}(H2O)]
[SbF6]2 [Cp⁄ = C5Me5; M = Rh, Ir; prophos = propane-1,2-diyl-
bis(diphenylphosphane)].12,13 These complexes easily lose water
and the resulting unsaturated Lewis-acid cations (Fig. 1) efficiently
We first examined the homogeneous asymmetric Friedel–Crafts
alkylation of a series of activated arenes, pyrroles and indoles
(Scheme 1) with enals in the presence of 5 mol % of the catalyst
precursors (SM,RC)-[Cp⁄M{(R)-prophos}(H2O)][SbF6]2 (M = Rh 1, Ir
2). Although 2,3-dimethylacrolein 7c and trans-cinnamaldehyde
7d were tested as enals, most of the reactions were carried out
with methacrolein 7a or trans-crotonaldehyde 7b (Scheme 2).
Dichloromethane was used as solvent and reactions were carried
out at ꢀ10 °C, in the presence of 4 Å molecular sieves (MS). A
1:20:60, catalyst/aromatic/enal molar ratio was employed. Accord-
ing to the NMR data, after 72 h of treatment under these condi-
tions, no reaction was observed between monosubstituted arenes
3a–c and trans-crotonaldehyde nor between 3b,c and methacro-
lein. Under the same conditions, more activated arenes such as
1,3-dimethoxy- or 1,3,5-trimethoxy-benzene do not react either.
However, the iridium complex 2 catalysed the reaction between
m-N,N-dimethyl anisidine 4a and trans-crotonaldehyde 7b. After
activate organic substrates, such as enals or a,b-unsaturated nitriles,
for Diels–Alder14–16 or 1,3-dipolar cycloadditions.12,13,17–19 Quanti-
tative yields and excellent enantioselectivities have been achieved
for both types of processes.
Taking into account these results, we envisaged the possibility
of applying this metallic fragment as a catalyst for the Friedel–
Crafts alkylation of aromatic and heteroaromatic substrates with
activated alkenes. Herein we report our results.
⇑
Corresponding author. Tel.: +34 976762027; fax: +34 976761187.
E-mail address: dcarmona@unizar.es (D. Carmona).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.05.003

894
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
R1
R
R3
R2
N
R
N
R1
R2
OMe
R
1 = NMe2, R2 = H 4a
R = Me 5a,
Bn 5b
R = OMe 3a,
NMe2 3b,
R1 = H, R2 = H, R3 = H 6a, 4-Me,5-MeO, 6b
R1 = OMe, R2 = H 4b
1 = OMe, R2 = OMe 4c
R1 = H, R2 = Me, R3 = H 6c
SiMe3 3c
R1 = Me, R2 = H, R3 = H 6d, 5-Br 6e
R1 = Me, R2 = Me, R3 = H 6f
R
Scheme 1. Aromatics and heteroaromatics investigated.
[Cp⁄Rh{(R)-prophos}(H2O)][SbF6]2 1 did not catalyse the reaction
between anisidine 4a and enals 7a and 7b.
Although poor results were obtained, to the best of our knowl-
edge, this is the first example of the alkylation of activated arenes
with enals using metal-based catalysts. In this context, an organo-
O
O
O
O
Me
Me
H
H
H
H
Me
Me
Ph
7a
7b
7c
7d
catalysed reaction of anilines and methoxyanilines with a,b-unsat-
urated aldehydes was recently reported by MacMillan and Paras.20
Next, we examined the Friedel–Crafts reaction of pyrroles and
indoles with enals. At ꢀ10 °C, N-methyl pyrrole 5a reacted with
trans-crotonaldehyde 7b to give the corresponding 2-substituted
Friedel–Crafts adduct 8f, with 8% or 12% ee when the rhodium
complex 1 or the iridium complex 2 were used as the catalyst pre-
cursor, respectively (Scheme 5). No reaction was observed between
N-benzyl pyrrole 5b and enals 7a,b in the presence of complexes 1
or 2.
Scheme 2. Enals employed.
72 h of reaction, the monosubstituted Friedel–Crafts product at the
para-position with respect to the amine was obtained in 49% iso-
lated yield and in 26% ee, measured on the alcohol obtained by
reduction with NaBH4 (Scheme 3). Analogously, complex 2 cata-
lysed the reaction between anisidine 4a and methacrolein, but a
mixture of three compounds was obtained. After reduction with
NaBH4, the major product was characterized as alcohol 8c. The
NMR data indicated that the two remaining products were the
other two possible monosubstituted Friedel–Crafts adducts 8d
The reaction of a series of indoles with methacrolein and trans-
crotonaldehyde was then examined, using iridium complex 2 as a
catalyst precursor (Scheme 6). The indole was alkylated at the 3-
NMe2
NMe2
NMe2
O
NaBH4
EtOH
Cat.* 5 mol %
OMe
OMe
H
+
*
*
CH2Cl2, 4Å MS
OMe
Yield : 49%
E.e.: 26%
CH2OH
H
O
4a
Cat.* = [Cp*Ir{(R)-profos}(H2O)](SbF6)2
Scheme 3. Catalytic reaction between m-N,N-dimethylanisidine and trans-crotonaldehyde.
7b
8a
8b
2
OMe
NMe2
OMe
Me
*
CH2OH
CH2OH
CH2OH
*
*
Me
Me
Me2N
MeO
NMe2
8d
8c
8e
Yield : 67%
E.e.: 65%
22%
60%
11%
73%
Scheme 4. Products distribution of the reaction between m-N,N-dimethylanisidine and methacrolein.
and 8e. Quantitative conversion was achieved after 72 h of reaction
with the product distribution and enantioselectivity, measured on
the alcohol derivatives, depicted in Scheme 4.
No reaction was observed between 4a and the enals 2,3-
dimethylacrolein 7c and trans-cinnamaldehyde 7d. Under the
aforementioned conditions, the rhodium complex (SM,RC)-
When, under similar conditions, rhodium compound
1 was employed as a
catalyst precursor instead of iridium compound 2, for the reactions between
N-methylindole 6d and methacrolein or trans-crotonaldehyde, the corresponding
Friedel–Crafts adducts 8k and 8l were obtained in similar yields and enantioselec-
tivities: 8k, 22% yield, 23% ee; 8l, 49% yield, 16% ee (yield and ee measured after
reduction to the alcohol).

D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
895
O
R1
2.2. trans-b-Nitrostyrenes as electrophiles
R1
R2
O
Cat.* 5 mol %
H
Examples of homogeneous catalytic enantioselective additions
of aromatic and heteroaromatic C–H bonds to nitroolefins have
only appeared recently. In 2005, Bandini et al. reported the enan-
tioselective condensation of indole with nitroalkenes catalysed
by [AlCl(salen)] (salen = (R,R)-(ꢀ)-N,N0-bis(3,5-di-t-butylsalicylid-
ene)-1,2-cyclohexanediamine).21 In the same year, Jørgensen
et al. developed hydrogen-bond-based organocatalysts for this
reaction.22 Since then, a handful of metal-catalysed,23–37 and a
few organocatalysed,38–45 examples have been reported.
Copper25,26,31,33,37 and zinc23,24,27–30,32,34–36 are the only metals
that have been employed with nitrogen and/or oxygen donor li-
gands as the chiral source. The organocatalysts tested were based
on thioureas,38–40,45 phosphoric acids42–44 or quinolinium ami-
do(thio)amides.41 Indole alkylation with nitroolefins is by far the
most investigated reaction.21–26,28,29,31–39,41,42 Pyrroles,28,30,33,43
4,7-dihydroindoles,44 phenol45 and naphthols40,45 are much less
studied, and only one example of the addition of nitroolefins to
2-methoxyfuran27 has been recently published.
Taking all of the above into account, we decided to investigate
the Friedel–Crafts alkylation of nitroolefins, specifically trans-
b-nitrostyrenes, by introducing catalysts based on two new metals,
rhodium and iridium, with a chiral diphosphane ligand namely,
(R)-prophos, as a chiral source.
First, we examined the reaction of trans-b-nitrostyrene as an al-
kene model, with a series of activated arenes 3c, 4a–c, N-methyl
pyrrole 5a and indole 6a using the iridium complex 2 as a catalyst
precursor (Scheme 7). Dichloromethane was used as solvent and
reactions were carried out at ꢀ10 °C, in the presence of 4 Å MS. A
1:20:20, catalyst/aromatic/trans-b-nitrostyrene molar ratio was
employed. According to spectroscopic and chromatographic data,
a quantitative yield was obtained in all cases, except for phenyltri-
+
N
R
N
R
CH2Cl2, 4Å MS
H
R2
R1 = Me, R2 = H 7a
R = Me 5a
Bn 5b
R = Me, R1 = H, R2 = Me 8f
R1 = H, R2 = Me 7b
Cat.* = [Cp*M{(R)-profos}(H2O)][SbF6]2 (M = Rh 1, Ir 2)
Scheme 5. Catalytic reaction between pyrroles and enals.
position in all the cases attempted. After 24–48 of reaction at ꢀ10 °C,
the isolated yield of the alcohol obtained by subsequent reduction of
the Friedel–Crafts product, ranged from 15% to 58%. Enantiomeric
excesses from 7% to 33% ee were achieved. The low yield was
accompanied by the formation of several by-products we were
unable to completely characterize. However, when trans-
crotonaldehyde 7b was used as the electrophile, together with the
expected alkylated indole 8h, 8j or 8l, we detected in the 1H NMR
spectra of the crude of the reaction an ABX spin system consistent
with the presence of a –C(Me)H–C(H)@C(H) connectivity in one of
the by-products in all the three cases. Figure 2 shows the 1H NMR
peaks encountered in the crude spectra of compound 8h and Table 1
collects the chemical shifts and coupling constants detected in the
three experiments. It is likely that the formation of this common
fragment involves the reaction of both unsaturated enal groups,
namely the C@C and C@O double bonds. This fact, along with the
generally poor results obtained in the alkylation reaction of enals,
prompted us to try the nitrostyrenes as electrophiles. We expected
that the nitro group on the one side would provide the substrate
with a binding capability and on the other would activate the C@C
double bond without interfering in its Friedel–Crafts reactivity.
H
O
R4
O
R5
R5
2, 5-10 mol %
R3
R2
R3
R2
H
+
N
+
CH2Cl2, 4Å MS
by-products
N
R4
R1
R1
R1 = H, R2 = H, R3 = H 6a,
4-Me,5-MeO 6b
R1= H, R2= H, R3= H, R4= H, R5= Me 8g
R1= H, R2= H, R3= H, R4= Me, R5= H 8h
R1= H, R2= H, R3= 4-Me,5-MeO, R4= H, R5= Me 8i
R1= H, R2= Me, R3= H, R4= Me, R5= H 8j
R1= Me, R2= H, R3= H, R4= H, R5= Me 8k
R1= Me, R2= H, R3= H, R4= Me, R5= H 8l
R1= Me, R2= H, R3= 5-Br, R4= H, R5= Me 8m
R1= Me, R2= Me, R3= H, R4= H, R5= Me 8n
R4= H, R5= Me 7a
R4= Me, R5= H 7b
R1 = H, R2 = Me, R3 = H 6c
R1 = Me, R2 = H, R3 = H 6d, 5-Br 6e
R1 = Me, R2 = Me, R3 = H 6f
Scheme 6. Catalytic reaction between indoles and enals.
Figure 2. Selected fragments of the 1H NMR spectrum of the crude of the reaction between 6a and 7b.

896
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
methylsilane 3c and 1,3-dimethoxybenzene 4b. No reaction was
observed for the monosubstituted arene 3c after 72 h of treatment
while a yield of 17%, with 2% ee, was measured, after the same time
of reaction, for 4b. Reactions were completely regioselective. Only
monosubstituted Friedel–Crafts adducts were detected: the arene
substituted at the para-position with respect to amine 10a, for
m-N,N-dimethyl anisidine 4a and the 2-substituted pyrrol 10d or
3-substituted indole 10e for the heteroaromatic substrates.à Enan-
tiomeric excesses ranging from 3% to 40% ee were achieved.
Since the best results were obtained for 1,3,5-trimethoxyben-
zene 4c (quantitative yield after 6 h of reaction, 40% ee) and this
substrate had not been previously investigated in this type of Fri-
edel–Crafts reaction, we next studied the reactivity between 4c
and a family of trans-b-nitrostyrenes. Table 2 lists the results ob-
tained when the catalytic reactions were carried out with complex
2 as a catalyst precursor, under the conditions reported above for
unsubstituted trans-b-nitrostyrene. The collected results are the
average of at least two comparable reaction runs. Reactions are
clean: only the monoalkylated adduct was spectroscopically and
chromatographically detected.§ Catalyst precursors have to be
treated with the corresponding nitroolefin in the presence of 4 Å
MS before the addition of the arene. Under these conditions,
[Cp⁄M{(R)-prophos}(nitroolefin)]2+ were the only metallic com-
plexes present in solution (see below).
similar trend by plotting the obtained ee’s versus the reported
Hammet parameter values for a series of nitroalkenes (Fig. 3).
r
2.3. Isolation and characterization of the catalyst/electrophile
intermediate
In spite of the fact that several metal-based catalytic systems
have already been applied to the Friedel–Crafts reaction between
aromatic or heteroaromatic substrates and nitroalkenes,21,23–37 to
the best of our knowledge, no experimental data regarding the
metallic intermediates involved in the catalytic reaction have been
reported to date. In some cases, the stereochemical outcome of the
catalytic reactions has been explained by assuming that activation
of the nitroalkene occurs through monodentate35,37 or biden-
tate23,24,28,31 coordination to copper31,37 or zinc23,24,28,35 accompa-
nied24,28,35,37 or not23,28,31 by additional interactions between the
catalyst and the nucleophilic partner.
To gain an insight into the catalytic mechanism, we studied the
reaction between the catalyst precursors (SM,RC)-[Cp⁄M{(R)-pro-
phos}(H2O)][SbF6]2 (M = Rh 1, Ir 2) and nitroalkene 9m, as a model.
When 3 equiv of 9m were added to dichloromethane solutions of
complexes 1 or 2, in the presence of 4 Å MS, the complex cations
[Cp⁄M{(R)-prophos}(9m)]2+ are instantaneously and quantitatively
formed. From the solution solids of formula [Cp⁄M{(R)-pro-
phos}(9m)][SbF6]2 (M = Rh 11, Ir 12) can be isolated in around
80% yield (Eq. 1).
In general, high yields were obtained after a few hours of reac-
tion at ꢀ10 °C. Enantiomeric excesses of up to 73% were achieved.
NO2
CH2Cl2, 4Å MS
[Cp*M{(R)-profos}(9m)][SbF6]2
(SM,RC)-[Cp*M{(R)-profos}(H2O)][SbF6]2
M = Rh 1, Ir 2
+
-H2O
OMe
OMe
ð1Þ
M = Rh 11, Ir 12
9m
Both, electron donating and electron withdrawing groups generate
less active systems (compare, e.g., entry 1 with entries 3 and 6 or
with entries 17 and 18). Only the 3-methoxy and the 2-fluoro
substituted substrates (entries 4 and 16, respectively) gave a cata-
lytic rate comparable to that of the unsubstituted nitroolefin. In
this line, the lowest rates corresponded to nitroolefins with two
substituents on the aromatic ring. This trend is probably caused
by the increase in steric hindrance of the alkylation reagent.
Electronic factors strongly affect the enantioselectivity of the
system. Thus, while electron donating substituents located at the
2- or 4-positions of the aromatic ring improve ee (compare entry
1 with entries 3 and 5 or 6 and 8), it decreases when substituents
of this type are placed at the 3-position (compare entry 1 with en-
tries 4 or 7). However, two donor substituents situated at 2- and
4-positions do not produce further improvement on the ee
(compare entries 3 and 5 with entry 10). Conversely, lower ee’s were
obtained with electron withdrawing substituents. The 2,6-disubsti-
tuted nitroolefin 9ac, which gives a 47% ee (entry 24), is the only
exception to this trend. In this context, Bandini et al. found a good
degree of correlation between the enantiomeric excess of the prod-
ucts and the Hammet parameter46 associated with the nitroalkene
substituent, for the Friedel–Crafts reaction between indoles and
nitroalkenes, catalysed by aluminium–salen complexes.21 With re-
gard to the influence of the electronic factors on the ee, we found a
Complexes 11 and 12 were characterized by microanalysis and
by IR, 1H, 13C and 31P NMR spectroscopies (see Section 4). The
reaction is completely diastereoselective; from ꢀ50 °C to rt only
one set of sharp signals was observed in the NMR spectra of
the three nuclei investigated. The assignment of the NMR peaks
was carried out by a combination of mono- and bi-dimensional,
homo- and hetero-nuclear experiments. The 1H NMR spectrum
showed the presence of the Cp⁄, (R)-prophos and 9m ligands in
a 1:1:1 molar ratio. This technique unambiguously establishes
the presence of coordinated 9m. Thus, for example for complex
11, two doublets centred at 7.31 (Hb, see Fig. 4) and 7.47 (Ha)
ppm, with a coupling constant of 13.9 Hz, could be attributed to
the olefinic protons of the nitroalkene and the two methoxy
substituents of the aromatic ring resonate as singlets at 3.87
(OMea) and 3.89 (OMeb) ppm.
The 31P NMR spectrum of the rhodium complex 11 consisted of
two double doublets centred at 75.99 (J(Rh,P1) = 130.8 Hz,
J(P2,P1) = 38.3 Hz) and at 51.52 ppm (J(Rh,P2) = 133.1 Hz) while
that of the iridium compound 12 comprised of two doublets cen-
tred at 49.04 (P1) and 27.71 (P2) ppm with a coupling of 10.7 Hz.
Important stereochemical conclusions can be drawn from the
NMR experiments (Fig. 4). Notably, the strong NOE relationship be-
tween the protons H21 and H11 and the methyl protons of one of
the methoxy groups (OMea) support the (S)-configuration at the
metal for both complexes. Thus, the reaction depicted in Eq. 1 takes
place with retention of the configuration at the metal atom. Fur-
thermore, from the assignment of the resonances for the ortho pro-
tons of the phenyl rings of the (R)-prophos ligand, a k conformation
can be inferred for the M–P1–C–C–P2 five-membered metallacycle.
à
The low yield did not allow the complete NMR characterization of adduct 10b.
The low yield did not allow the complete NMR characterization of adducts 10ab
§
and 10ad.

D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
897
Table 1
Chemical shifts and coupling constants for the detected –C(Me)H–C(H)@C(H) moieties
Indole
HA
HB
HX
Me
d (ppm)
JXA (Hz)
d (ppm)
JAB (Hz)
d (ppm)
JMeX (Hz)
d (ppm)
6a
6c
6d
6.48
6.55
6.44
6.9
5.6
6.9
6.71
6.64
6.69
16.0
16.4
15.9
3.98
4.01
3.97
7.0
7.1
6.5
1.62
1.64
1.73
Table 2
Reactions between 1,3,5-trimethoxybenzene and trans-b-nitrostyrenes
NO2
OMe
NO2
OMe
*
Cat.* 5 mol %
CH2Cl2, 4Å MS
+
H
R
R
OMe
MeO
OMe
10
MeO
4c
9
Entry
R
t (h)
Yield (%)
ee (%)
Adduct
1
2
3
4
5
6
7
8
H 9c
4-Me 9f
6
14
16
7
>99
>99
94
>99
>99
69
83
98
89
22
95
92
96
>99
97
>99
92
89
>99
>99
95
40
54
73
18
51
69
15
43
70
51
40
67
20
9
35
22
31
21
9
9
0
0
3
10c
10f
10g
10h
10i
10j
10k
10l
2-OMe 9g
3-OMe 9h
4-OMe 9i
2-OBn 9j
3-OBn 9k
4-OBn 9l
2,3-(OMe)2 9m
2,4-(OMe)2 9n
2,5-(OMe)2 9o
3,4-(OMe)2 9p
3,4-(OBn)2 9q
3,5-(OBn)2 9r
3-OBn,4-OMe 9s
2-F 9t
2-Cl 9u
2-Br 9v
4-Cl 9w
4-Br 9x
2,3-(Cl)2 9y
2,4-(Cl)2 9z
2,6-(Cl)2 9ab
2-Cl,6-F 9ac
2-CF3 9ad
15
17
21
17
24
22
24
22
25
18
18
4
22
25
22
16
40
17
49
118
96
9
10ma
10n
10o
10p
10q
10r
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
10s
10t
10u
10v
10w
10x
10y
10z
10ab
10ac
10ad
60
2.5
50
22
47
9
a
Enantiopure samples (>99.9% ee) of 10m can be obtained by crystallization from CH2Cl2/n-hexane.
Figure 3. Plot of the ee obtained in the reaction of the nitroolefins 9c, 9f, 9h, 9i, 9w, and 9x, versus the Hammet parameter r.
2.4. The catalyst/electrophile/1,3,5-trimethoxybenzene system
benzene 4c. For this reason, we monitored, by NMR, the system
generated by the addition of 4c to the rhodium complex 11.
Figure 5 shows the evolution of the region of the 31P NMR spectra
where the double doublets corresponding to the P2 nucleus appear
(see Fig. 4). Each double doublet in this zone is related to one
After the formation of the diastereopure electrophile containing
species (SM,RC)-[Cp⁄M{(R)-prophos}(9m)][SbF6]2 (M = Rh 11, Ir 12),
the next step of the catalytic process most likely should involve
their interaction with the nucleophilic species 1,3,5-trimethoxy-
Rh{(R)-prophos} containing complex. Trace
A corresponds to

898
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
R3
NO2
R3
Ph
H
R1
R2
R1
R2
R1 = OMe, R2 = NMe2, R3 = H 4a
R1 = OMe, R2 = NMe2, R3 = H 10a
R1 = OMe, R2 = OMe, R3 = H 4b
R
R
1 = OMe, R2 = OMe, R3 = H 10b
1 = OMe, R2 = OMe, R3 = OMe 10c
R
1 = OMe, R2 = OMe, R3 = OMe 4c
NO2
*
NO2
N
+
Ph
N
9c
H
Ph
Me
Me
5a
10d
NO2
*
Ph
H
N
N
H
6a
Cat.* = [Cp*Ir{(R)-profos}(H2O)](SbF6)2
2
10e
H
Scheme 7. Reaction of several aromatics and heteroaromatics with trans-b-nitrostyrene.
MebO
2+
MeaO
Hb
Ha
O
N
N
O
Ha
OMea
H11
*
Ph1
*
3
OMeb
Ph3
Ph4
M
Ph1
Ph2
O
Ph2
Me
P1
O
P1
*
Ph3
P2
H21
M
P2
H21
Hb
*
H11
Me
1
2
Ph4
H22
H22
A
B
Figure 4. (A) Cation of the complexes 11 (M = Rh) and 12 (M = Ir) showing the NMR labelling scheme. (B) NOE pattern measured for these cations.
complex 11, formed in situ by the addition of 2 equiv of nitroalkene
9m to a CD2Cl2 solution of the aqua complex (SRh,RC)-[Cp⁄Rh{(R)-
prophos}(H2O)][SbF6]2, in the presence of 4 Å MS, according to
Eq. 1. At ꢀ50 °C, two double doublets (labelled as complexes I
and II, trace B) emerged when one equivalent of arene 4c was
added. These doublets correlate with two Cp⁄ proton peaks at
1.30, (I) and 1.32 (II) ppm. At this temperature, the concentration
of I and II increases with time at the expense of complex 11 (trace
C) while the formation of Friedel–Crafts adduct was not detected
by 1H NMR spectroscopy. Heating up to ꢀ25 °C produces a de-
crease in the concentration of II and also the slow formation of
the Friedel–Crafts adduct (trace D). Finally, at ꢀ10 °C, the Fri-
[M] OH2
nitroalkene
4 Å MS
[M] nitroalkene
1,3,5-trimethoxybenzene
adduct
complex
type I
nitroalkene
[M] adduct
[M] = Cp*M{(R)-Prophos}
M = Rh, Ir
Figure 5. Fragment of the 31P NMR spectra for the reaction between the rhodium
complex 11 and 1,3,5,-trimethoxybenzene (see text).
Figure 6. Proposed catalytic cycle.

D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
899
edel–Crafts alkylation was quickly completed with concomitant
decrease of the concentrations of I and II (trace E).
4. Experimental
4.1. General
To obtain more information on the nature of the species I and II,
in an independent experiment, we added 1 equivalent of enantio-
pure Friedel–Crafts adduct 10m (see footnote, in Table 2) to a
CD2Cl2 solution of the aqua complex (SRh,RC)-[Cp⁄Rh{(R)-
prophos}(H2O)][SbF6]2, in the presence of 4 Å MS (Eq. 2). At
ꢀ50 °C, a new compound was formed, which was characterized
as II by comparison of its 1H and 31P NMR spectra with those re-
corded in the preceding experiment.
All solvents were treated in a PS-400-6 Innovative Technologies
Solvent Purification System (SPS) and degassed prior to use. All
preparations were carried out under argon. Infrared spectra were
obtained as KBr pellets with a Perkin–Elmer 1330 spectrophotom-
eter. Carbon, hydrogen and nitrogen analyses were performed
using a Perkin–Elmer 2400 CHNS/O microanalyser. NMR spectra
NO2
OMe
OMe
OMe
CD2Cl2, 4Å MS
[Cp*Rh{(R)-profos}(10m)]2+
(SM,RC)-[Cp*Rh{(R)-profos}(H2O)]2+
+
ð2Þ
-H2O
H
OMe
1
II
MeO
10m
Similarly, the reaction between the aqua complex 1 and a sam-
ple of 10m of 70% ee was also monitored. As expected, two new
complexes appeared. The major one was complex II and the minor,
complex III, presented a P2 double doublet centred at 51.11 ppm
that in the spectra of Figure 5 could be overlapped by the corre-
sponding signal of complex 11. Thus, complex III has to be the iso-
mer of complex II in which the less abundant enantiomer of the
Friedel–Crafts adduct 10m is coordinated to the [Cp⁄Rh{(R)-
prophos} moiety and the structure of the intermediate I remains
unclear. We currently do not have data enough to propose a struc-
ture for it. However, from the evolution of the spectra shown in
Figure 5, it seems that complex I is an intermediate formed by
the interaction between 11 and the nucleophile 1,3,5-trimethoxy-
benzene 4c before the catalyst/adduct complexes II and III are
formed.
were recorded on Brucker Avance-300, 400 or 500 MHz spectrom-
eters; unless otherwise stated all NMR measurements were carried
at rt. 1H (300.13, 400.16, 500.13 MHz), 31P{1H} (161.96 MHz) and
13C{1H} (75.48, 100.61, 125.77 MHz) NMR chemical shifts are re-
ported in ppm relative to tetramethylsilane and referenced to par-
tially deuterated solvent resonances for 1H and 13C and H3PO4
(85%) for 31P. Coupling constants (J) are given in Hertz. NOEDIFF
and 1H correlation spectra were obtained using standard proce-
dures. Analytical high performance liquid chromatography (HPLC)
was performed on an Alliance Waters (Waters 2996 PDA detector)
instrument using the chiral columns Chiralcel OD-H (0.46 ꢁ 25 cm)
and OD-H guard (0.46 ꢁ 5 cm) or Chiralpak AD-H (0.46 ꢁ 25 cm) or
AS-H (0.46 ꢁ 25 cm).
The
(M = Rh 1, Ir 2) were prepared using literature procedures13 with
the following small modifications: to suspension of
[(Cp⁄MCl)2(
-Cl)2] (0.400 mmol) in acetone (20 mL) 549.9 mg
complexes
(SM,RC)-[Cp⁄M{(R)-Prophos}(H2O)](SbF6)2
a
l
2.5. Proposed catalytic cycle
(1.6 mmol) of AgSbF6 were added. The resulting suspension was stir-
red for 15 h and the precipitate was filtered off and washed with ace-
tone (3 ꢁ 1 mL). The filtrate was vacuum-concentrated until ca.
5 mL and cooled down to ꢀ25 °C (Rh) or ꢀ50 °C (Ir). Under argon,
at the corresponding temperature, 330.4 mg (0.800 mmol) of
(R)-prophos was added and the solution was stirred for 30 min.
The addition of n-hexane (20 mL) and subsequent stirring gave or-
ange (Rh) or yellow (Ir) solids. The solution was poured off and the
solid washed with n-hexane (3 ꢁ 20 mL) and then vacuum-dried.
The solids were recrystallized three times at ꢀ25 °C (Rh) or ꢀ50 °C
(Ir) from CH2Cl2/n-hexane, 1:5, v/v. Yield: 92.3% (Rh), 88.7% (Ir).
Taking into account all of the above observations, we proposed
the catalytic cycle shown in Figure 6. Nitroalkenes displace the
coordinated molecule of water from the catalysts precursors
(SM,RC)-[Cp⁄M{(R)-prophos}(H2O)][SbF6]2 (M = Rh 1, Ir 2), in the
presence of 4 Å MS, affording the corresponding nitroalkene com-
plex, which is the true catalyst. These complexes reacted with free
1,3,5-trimethoxybenzene to give catalyst-adduct complexes prob-
ably via intermediates of the type I, which we have not been able
to characterize. The adduct is dissociated by a new molecule of
nitroalkene with concomitant regeneration of the metal-nitroalk-
ene complex which restarts a new catalytic cycle.
4.2. General procedure for the reaction between aromatics or
heteroaromatics and enals
3. Conclusions
At ꢀ10 °C, in a thermostatic bath, a Schlenk flask equipped with
a magnetic stirrer was introduced. Under argon, 0.03 mmol of
(SM,RC)-[Cp⁄M{(R)-Prophos}(H2O)](SbF6)2, CH2Cl2 (4 mL), the corre-
sponding enal (0.60 mmol) and approximately 100 mg of 4 Å MS
were added. The mixture was stirred for 15 min and then the cor-
responding aromatic or heteroaromatic reagent (1.80 mmol) was
added. The reaction was monitored by TLC. After the appropriate
reaction time, the suspension was vacuum-concentrated until dry-
ness. The residue was extracted with Et2O (3 ꢁ 5 mL) and the solu-
tion vacuum-evaporated until dryness. In some cases, the resulting
oils were analysed and characterized by NMR and HPLC tech-
niques. The residue was dissolved in ethanol (4 mL) and 68.1 mg
(1.80 mmol) of NaBH4 were added. After 15 min of reaction, 1 mL
of a saturated solution of Na2CO3 in water was added. The mixture
The chiral fragments Cp⁄M{(R)-prophos} (M = Rh, Ir) efficiently
activate
a,b-unsaturated aldehydes and nitroalkenes for the
Friedel–Crafts alkylation of a variety of aromatics and heteroaro-
matics. Clean reactions to the monoalkylated Friedel–Crafts prod-
uct were observed in most of the cases investigated. In
particular, quantitative and regioselective conversion to the
monoalkylated adduct was obtained in the reaction between
1,3,5-trimethoxybenzene and nitroalkenes. The intermediates
(SM,RC)-[Cp⁄M{(R)-prophos}(9m)][SbF6]2 (M = Rh 11, Ir 12) have
been isolated and characterized. The catalyst/adduct complexes
formed by the reaction of complex 11 with 1,3,5-trimethoxyben-
zene have been spectroscopically detected. A catalytic cycle that
includes these two types of intermediates is proposed.

900
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
AS-H (97:3, n-hexane/ethanol, 1.0 mL/min); tR, min: 19.57 (minor),
20.63 (major). Yield: 11%. Ee: 73%.
was extracted with CH2Cl2 (3 ꢁ 10 mL) and the organic phase was
dried over MgSO4. The resulting solution was vacuum-evaporated
to dryness and purified by column chromatography (SiO2;
AcEt/n-hexane, 40:60). Evaporation of the solvent gives pale oils
that were analysed and characterized by NMR and HPLC
techniques.
4.2.5. 3-(1-Methyl-1H-pyrrol-2-yl)butanal 8f
*
4.2.1. 3-(4-(Dimethylamino)-2-methoxyphenyl)butanal 8a
CHO
N
Me
Me
Me
This compound was characterized by comparison of its spectro-
scopic data with those reported in the literature.47 (Cat.⁄ 1: Yield:
82%, Ee: 8% (S). Cat.⁄ 2: Yield: 50%, Ee: 12% (S).
*
CHO
OMe
Me2N
4.2.6. Characterization of the alcohol derived from 8g
This compound was characterized by comparison of its spectro-
scopic data with those reported in the literature.20 Yield: 49%. Ee:
26% (S).
Me
Hd
2
Hf
He
OH
Ha
*
1
3
Hg
Hh
6
Hc
4
4.2.2. 3-(4-(Dimethylamino)-2-methoxyphenyl)-2-
methylpropan-1-ol 8c
5
7
8
Hb
Hj
11
10
9
N
H
Hi
Hf
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.96 (br s, 1H, NH), 7.55 (d,
J = 7.8 Hz, 1H, Hf), 7.29 (d, J = 8.1 Hz, 1H, Hi), 7.12 (pt, 1H, Hh),
7.04 (pt, 1H, Hg), 6.93 (d, J = 2.3 Hz, 1H, Hj), 3.52, 3.45 (dd,
J = 10.5, 5.9 Hz, 2H, Ha + Hb), 2.80, 2.56 (dd, J = 14.4, 6.6 Hz, 2H,
Hd + He), 2.01 (oc, 1H, J = 6.8 Hz, Hc), 1.29 (br s, 1H, OH), 0.91 (d,
J = 6.8 Hz, 3H, Me). 13C NMR (100.61 MHz, CDCl3) d, ppm: 137.00
(C10), 128.23, 113.50 (C4, C5), 126.98 (C11), 121.44 (C7), 119.13
(C9), 118.62 (C8), 111.09 (C6), 68.06 (C1), 36.87 (C2), 28.84 (C3),
17.05 (Me). HPLC: Chiralpak AS-H (97:3, n-hexane/etha-
nol, 1.0 mL/min); tR, min: 53.8 (minor), 64.5 (major). Yield: 26%.
Ee: 22%.
He Hd
Me
2
Hg
5
3
4
6
*
1
7
Hc
9
CH2OH
8
OMe
Me2N
Hh
1H NMR (300.13 MHz, CDCl3) d, ppm: 6.98 (pt, 1H, Hf), 6.34 (br d,
1H, Hg), 6.33 (s, 1H, Hh), 3.86 (s, 3H, OMe), 3.40, 3.45 (m, 2H,
CH2OH), 2.96 (s, 6H, NMe2), 2.61, 2.50 (dd, J = 21.2, 7.3 Hz, 2H,
Hd + He), 1.92 (m, 1H, Hc), 0.97 (d, J = 7.3 Hz, 3H, Me). 13C NMR
(75.48 MHz, CDCl3) d, ppm: 158.16 (C9), 150.51 (C7), 133.14 (C5),
117.09 (C4), 105.25, 96.61 (C6, C8), 66.88 (C1), 55.39 (OMe), 40.99
(NMe2), 36.87 (C2), 28.84 (C3), 17.05 (Me). HPLC: Chiralpak AS-H
(97:3, n-hexane/ethanol; 1.0 mL/min); tR, min: 10.9 (minor), 12.7
(major). Yield: 67%. Ee: 65%.
4.2.7. 3-(1H-Indole-3-yl)butanal 8h
Me
*
O
4.2.3. 3-(2-(Dimethylamino)-4-methoxyphenyl-2-
methylpropan-1-ol 8d
N
H
This compound was characterized by comparison of its spectro-
scopic data with those reported in the literature.48 Yield: 15%. Ee:
7%.
NMe2
Me
*
CH2OH
MeO
4.2.8. Characterization of the alcohol derived from 8i
1H NMR (300.13 MHz, CDCl3) d, ppm: 3.88 (s, 3H, OMe), 2.98 (s, 6H,
NMe2), 0.99 (br d, 3H, Me). 13C NMR (75.48 MHz, CDCl3) d, ppm:
55.60 (OMe), 40.81 (NMe2), 20.43 ppm (Me). HPLC: Chiralpak AS-
H (97:3, n-hexane/ethanol, 1.0 mL/min); tR, min: 15.25 (minor),
16.31 (major). Yield: 22%. Ee: 60%.
Me13
Hd
2
Me12
He
OH
Ha
*
1
3
MeO
Hf
6
Hc
4
5
7
8
Hb
Hh
11
10
9
N
H
Hg
4.2.4. 3-(2-(Dimethylamino)-5-methoxyphenyl-2-
methylpropan-1-ol 8e
1H NMR (300.13 MHz, CDCl3) d, ppm: 8.00 (br s, 1H, NH), 7.15, 6.92
(d, J = 8.6 Hz, 1H, Hf + Hg), 6.93 (s, 1H, Hh), 3.87 (s, 3H, OMe), 3.66,
3.55 (dd, J = 10.6, 5.4 Hz, 2H, Ha + Hb), 3.00, 2.70 (dd, J = 14.7,
6.6 Hz, 2H, Hd + He), 2.61 (s, 3H, Me12), 2.05 (ps, 1H, J = 6.7 Hz,
Hc), 1.30 (br s, 1H, OH), 1.02 (d, J = 6.7 Hz, 3H, Me13). 13C NMR
(75.48 MHz, CDCl3) d, ppm: 151.40 (C7), 132.88, 126.93, 118.65,
115.39 (C4, C5, C6, C10) 124.10 (C11), 110.18, 108.72 (C8, C9), 67.98
(C1), 58.26 (OMe), 37.44 (C2), 31.11 (C3), 16.96 (Me13), 12.01
(Me12). HPLC: Chiralpak AS-H (97:3, n-hexane/ethanol, 1.0 mL/
min); tR, min: 50.8 (major), 61.4 (minor). Yield: 16%. Ee: 26%.
OMe
Me
*
CH2OH
NMe2
1H NMR (300.13 MHz, CDCl3) d, ppm: 3.85 (s, 3H, OMe), 2.95 (s, 6H,
NMe2), 1.03 (d, J = 6.6 Hz, 3H, Me). 13C NMR (75.48 MHz, CDCl3) d,
ppm: 55.56 (OMe), 40.85 (NMe2), 19.66 (Me). HPLC: Chiralpak

D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
901
4.2.9. Characterization of the alcohol derived from 8j
4.2.13. Characterization of the alcohol derived from 8n
Me13
Hd
*
He
Hd
Hf
2
2
Me
Hf
OH
Ha
He
OH
Hb Ha
Me12
1
*
1
3
3
Hg
Hh
Hc
6
Hg
Hh
Hc
6
4
5
4
5
7
8
7
8
Hb
Me
11
11
10
10
9
9
N
N
H
Me
Hi
Hi
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.42 (br d, 1H, Hf), 7.29 (br d,
1H, Hi), 7.19 (pt, 1H, Hh), 7.08 (pt, 1H, Hg), 3.69 (s, 3H, NMe), 3.61,
3.51 (m, 2H, Ha + Hb), 2.85, 2.59 (m, 2H Hd + He), 2.40 (s, 3H,
Me12), 2.05 (m, 1H, J = 6.8 Hz, Hc), 0.91 (d, J = 6.8 Hz, 3H, Me13).
13C NMR (100.61 MHz, CDCl3) d, ppm: 136.56–107.15 (aromatic
carbons), 68.20 (C1), 37.63 (C2), 29.56 (NMe), 28.84 (C3), 17.10
(Me13), 10.46 (Me12). HPLC: Chiralpak AS-H (97:3, n-hexane/etha-
nol, 1.0 mL/min); tR, min: 13.6 (minor), 16.1 (major). Yield: 33%.
Ee: 33%.
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.91 (br s, 1H, NH), 7.62 (d,
J = 7.9 Hz, 1H, Hf), 7.30 (d, J = 7.9 Hz, 1H, Hi), 7.09 (pt, 1H, Hh),
7.03 (pt, 1H, Hg), 3.53 (m, 2H, Ha + Hb), 3.17 (m, 2H, Hc + Hd), 2.41
(s, 3H, C11Me), 2.06 (m, 1H, J = 6.8 Hz, Hc), 1.45 (d, J = 7.1 Hz, 3H,
C3Me). 13C NMR (100.61 MHz, CDCl3) d, ppm: 135.60, 130.63,
127.42, 115.22 (C4, C5, C10, C11), 120.50 (C8), 119.11 (C6), 118.64
(C7), 110.28 (C9), 61.68 (C1), 39.52 (C2), 27.77 (C3), 21.11 (Me).
HPLC: Chiralpak AD-H (90:10, n-hexane/ethanol, 1.0 mL/min); tR,
min: 14.5 (minor), 19.2 (major). Yield: 16%. Ee: 5%.
4.3. General procedure for the reaction between aromatics or
4.2.10. Characterization of the alcohol derived from 8k
heteroaromatics and trans-b-nitrostyrenes
Me
Hd
2
Hf
He
OH
Ha
*
1
A Schlenk flask equipped with a magnetic stirrer was intro-
duced in a thermostatic bath at ꢀ10 °C. Under argon, 0.03 mmol
of (SM,RC)-[Cp⁄M{(R)–Prophos}(H2O)](SbF6)2, CH2Cl2 (4 mL), the
corresponding trans-b-nitrostyrene (0.60 mmol) and about
100 mg of 4 Å MS were added. The resulting red mixture was stir-
red for 15 min and then the corresponding aromatic or heteroaro-
matic reagent (0.60 mmol) was added. The reaction was monitored
by TLC. After the appropriate reaction time, the suspension was
vacuum-concentrated until dryness. The residue was extracted
with Et2O (3 ꢁ 5 mL) and the solution vacuum-evaporated until
dryness rendering a white or pale yellow solid that was analysed
and characterized by NMR and HPLC techniques.
3
Hg
Hh
6
Hc
4
5
7
8
Hb
Hj
11
10
9
N
Me
Hi
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.60 (d, J = 7.9 Hz, 1H, Hf),
7.28 (d, J = 8.2 Hz, 1H, Hi), 7.22 (pt, 1H, Hh), 7.12 (pt, 1H, Hg), 6.84
(s, 1H, Hj), 3.74 (s, 1H, NMe), 3.58, 3.50 (dd, J = 10.5, 5.9 Hz, 2H,
Ha + Hb), 2.84, 2.60 (dd, J = 14.4, 6.5 Hz, 2H, Hd + He), 2.05 (ps, 1H,
J = 6.8 Hz, Hc), 1.61 (br s, 1H, OH), 0.97 (d, J = 6.5 Hz, 3H, Me). 13C
NMR (75.48 MHz, CDCl3) d, ppm: 137.00 (C10), 128.24, 113.05 (C4,
C5), 126.98 (C11), 121.45 (C7), 119.15 (C9), 118.64 (C8), 109.16 (C6),
68.06 (C1), 32.60 (NMe), 36.87 (C2), 28.84 (C3), 17.05 (Me). HPLC:
Chiralpak AS-H (95:5, n-hexane/ethanol, 1.0 mL/min); tR, min:
14.4 (minor), 15.9 (major). Yield: 25%. Ee: 28%.
4.3.1. 3-Methoxy-N,N-dimethyl-4-(2-nitro-1-phenilethyl)aniline
10a
H2
4.2.11. 3-(1-Methyl-1H-indole-3-yl)butanal 8l
Hc
C
*
NO2
Ph
OMe
Me
Hd
He
*
O
Hf
N
NMe2
Me
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.45–7.36 (m, 5H, Ph), 6.78 (d,
J = 9.4 Hz, He), 6.14–6.13 (m, 2H, Hd + Hf), 5.06 (dd, J = 8.3, 6.1 Hz,
Hc), 4.82–4.93 (m, 2H, CH2), 3.73 (s, 3H, OMe), 2.84 ppm (s, 6H,
NMe2). HPLC: Chiralcel AD-H (95:5, n-hexane/2-propanol, 0.5 mL/
min); tR, min: 27.3 (minor), 28.4 min (major). Ee: 5%.
This compound was characterized by comparison of its spectro-
scopic data with those reported in the literature.48 Yield: 58%. Ee:
21% (S).
4.2.12. Characterization of the alcohol derived from 8m
4.3.2. 2-(1-Phenyl-2-nitroethyl)-1,3,5-trimethoxybenzene 10c
Me
Hd
2
Hf
He
OH
Ha
*
1
3
Br
Hg
6
Hc
Hg
4
5
7
8
Hb
Hi
11
OMe3
Me4O
Hh
10
9
NO2
8
N
7
6
9
1
10
Me
11
Hh
CH2
2
*
OMe5
Ha
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.72 (s, 1H, Hf), 7.17 (br d, 2H,
Hg + Hh), 6.88 (s, 1H, Hi), 3.77 (s, 3H, NMe), 3.56 (m, 2H, Ha + Hb),
2.83, 2.57 (dd, J = 14.3, 6.7 Hz, 2H, Hd + He), 2.04 (m, 1H, Hc), 1.27
(br s, 1H, OH), 0.99 (d, J = 6.7 Hz, 3H, Me). 13C NMR (75.48 MHz,
CDCl3) d, ppm: 135.67, 129.92, 112.82, 112.13 (C4, C5, C7, C10),
128.15 (C11), 124.22, 110.66 (C8, C9), 121.69 (C6), 67.88 (C1), 36.77
(C2), 32.83 (NMe), 28.62 (C3), 16.95 (Me). HPLC: Chiralpak AS-H
(97:3, n-hexane/ethanol, 1.0 mL/min); tR, min: 22.3 (major), 24.2
(minor). Yield: 11%. Ee: 19%.
Hb
Hc
He
12
15
13
14
17
16
Hd
Hf
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.33 (d, J = 7.8 Hz, 2H,
Hb + Hc), 7.28 (pt, J = 6.8 Hz, 2H, Hd + He), 7.21 (pt, J = 6.8 Hz, 1H,
Hf), 6.15 (s, 2H, Hg + Hh), 5.52 (pt, J = 7.95 Hz, 1H, Ha), 5.26, 5.16
(dd, J = 12.7, 7.9 Hz, 2H, C1H2), 3.82 (s, 9H, OMe). 13C NMR

902
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
(100.61 MHz, CDCl3) d, ppm: 160.52, (C9), 158.91 (C7, C11), 140.46
(C6), 128.78, 128.74 (C13, C17), 128.67, 128.06 (C16, C14), 125.94
(C15), 108.58 (C12), 91.17 (C8, C10), 78.10 (C1), 55.16–55.78 (C3, C4,
C5), 38.55 (C2). HPLC: Chiralpak AD-H (90:10, n-hexane/2-propanol,
0.5 mL/min); tR, min: 14.3 (minor), 15.0 (major).
6.19 (s, 2H, Hb + Hc), 5.80 (pt, J = 6.1 Hz, 1H, Ha), 5.20, 5.07 (dd,
J = 18.6, 6.1 Hz, 2H, C1H2), 3.89, 3.84, 3.79 (s, 12H, OMe). 13C NMR
(100.61 MHz, CDCl3) d, ppm: 160.59 (C9), 159.17 (C7, C11), 157.16,
(C17), 129.14 (C13), 127.96 (C15), 127.48 (C6), 120.33 (C14), 110.43
(C16), 107.39 (C12), 91.24 (C8, C10), 77.31 (C1), 55.82, 55.44, 55.30
(C3, C4, C5, OMe18), 34.10 (C2). HPLC: Chiralpak AD-H (98:2, n-hex-
ane/2-propanol, 0.25 mL/min); tR, min: 78.0 (minor), 80.3 (major).
4.3.3. 2-(1-Phenyl-2-nitroethyl)-pyrrole 10d
NO2
Ph
4.3.7. 2-(1-(3-Methoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10h
*
CH2
2
1
N
Me
Ha
Hb
Me4O
Hc
OMe3
NO2
CH2
8
7
6
9
10
1
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.07–7.21 (m, 5H, Ph), 6.43 (s,
1H, Hpy), 6.01–6.06 (m, 2H, Hpy), 4.52–4.76 (m, 3H, CH2 + Ha), 3.05
(s, 3H, NMe). HPLC: Chiralcel OD-H (80:20, n-hexane/2-propanol,
1 mL/min); tR, min: 22.8 (minor), 29.5 (major).
11
2
*
Ha
OMe5
Hg
Hd
He
12
15
13
14
17
16
OMe18
Hf
4.3.4. 3-(1-Phenyl-2-nitroethyl)-indole 10e
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.19 (pt, 1H, He), 6.92 (d,
J = 8.5 Hz, 1H, Hd), 6.90 (t, J = 1.9 Hz, 1H, Hg), 6.74 (dd, J = 8.5,
1.9 Hz, 1H, Hf), 6.14 (s, 2H, Hb + Hc), 5.48 (pt, J = 7.7 Hz, 1H, Ha),
5.23, 5.13 (dd, J = 20.3, 7.7 Hz, 2H, C1H2), 3.79 (s, 3H, OMe4); 3.82,
3.81, 3.78 (s, 12H, OMe). 13C NMR (100.61 MHz, CDCl3) d, ppm:
160.61, (C9), 159.51, (C16), 159.00 (C7, C11), 142.15 (C6), 129.21
(C14), 120.03 (C13), 113.97 (C17), 111.54 (C15), 108.58 (C12), 91.24
(C8, C10), 78.35 (C1), 55.80, 55.30, 55.10 (C3, C4, C5, OMe18), 38.58
(C2). HPLC: Chiralpak AD-H (95:5, n-hexane/2-propanol, 1 mL/
min); tR, min: 13.4 (minor), 14.7 (major).
H2
Ph
*
C
Hb
2
1
NO2
Hc
Hd
Ha
5
3
4
9
6
7
10
Hf
8
N
H
He
This compound was characterized by comparison of its spectro-
scopic data with those reported in the literature.23 Ee: 3% (R).
4.3.5. 2-(1-(4-Methylphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10f
4.3.8. 2-(1-(4-Methoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10i
Hb
OMe3
NO2
Me4O
Hc
8
7
6
9
Hb
1
10
11
2
CH2
Ha
Me4O
Hc
OMe3
NO2
CH2
*
8
7
6
9
10
OMe5
1
11
2
Hg
Hf
*
Hd
12
OMe5
Ha
13
14
17
16
15
Hg
Hf
He
Hd
He
12
13
14
17
16
Me
15
OMe18
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.11 (d, J = 8.0 Hz, 2H,
Hd + Hg), 6.97 (d, J = 7.7 Hz, 2H, He + Hf), 6.04 (s, 2H, Hb + Hc), 5.37
(pt, J = 7.8 Hz, 1H, Ha), 5.13, 5.04 (dd, J = 12.9, 7.8 Hz, 2H, C1H2),
3.72 (s, 6H, OMe3 + OMe5), 3.71 (s, 3H, OMe4), 2.21 (s, 3H, Me).
13C NMR (100.61 MHz, CDCl3) d, ppm: 160.67, (C9), 158.97, (C7,
C11), 137.62 (C6), 136.46 (C15), 129.04 (C13, C17) 127.51 (C14, C16),
109.04 (C12), 91.17 (C8, C10), 78.52 (C1), 55.80, 55.32 (C3, C4, C5),
38.32 (C2), 21.04 (Me). HPLC: Chiralpak AD-H (95:5, n-hexane/2-
propanol, 0.5 mL/min); tR, min: 16.5 (minor), 18.2 (major).
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.21 (d, J = 8.6 Hz, 2H,
Hd + Hg), 6.76 (d, J = 8.6 Hz, 2H, He + Hf), 6.10 (s, 2H, Hb + Hc), 5.39
(pt, J = 7.7 Hz, 1H, Ha), 5.16, 5.06 (dd, J = 20.1, 7.7 H, 2H, C1H2),
3.77 (s, 6H, OMe3 + OMe5), 3.76, 3.73 (s, 6H, OMe4 + OMe18). 13C
NMR (75.48 MHz, CDCl3) d, ppm: 160.55 (C9), 158.53 (C7, C11),
158.21, (C15), 132.60 (C6), 128.69 (C14, C16), 113.69 (C13, C17),
108.83 (C12), 91.15 (C8, C10), 78.78 (C1), 55.80, 55.29, 55.18 (C3, C4,
C5, OMe18), 38.02 (C2). HPLC: Chiralpak AD-H (95:5, n-hexane/2-
propanol, 0.5 mL/min); tR, min: 28.8 (minor), 33.8 min (major).
4.3.6. 2-(1-(2-Methoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10g
4.3.9. 2-(1-(2-Benzyloxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10j
Hb
OMe3
Me4O
Hc
NO2
CH2
8
Hb
7
6
9
1
10
Me4O
OMe3
NO2
8
11
2
*
7
6
9
Ha
1
OMe5
10
11
2
CH2
Hc
OMe18
Hg
*
Hd
12
Ha
OMe5
13
14
17
16
Ph
15
O
He
Har
12
C
13
14
17
16
H2
Hf
15
Har
Har
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.24 (pt, 1H, Hf), 7.03 (d,
J = 8.5 Hz, 1H, Hd), 6.87 (d, J = 8.5 Hz, 1H, Hg), 6.83 (pt, 1H, He),
Har

D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
903
1H NMR (400.16 MHz, CD3COCD3) d, ppm: 7.52–6.82 (m, 9H, Har),
6.27 (s, 2H, Hb + Hc), 5.93 pt, J = 7.2 Hz, 1H, Ha), 5.22–5.05 (m, 4H,
C1H2 + CH2Ph), 3.82 (s, 3H, OMe4), 3.74 (s, 6H, OMe3 + OMe5). 13C
NMR (100.61 MHz, CD3COCD3) d, ppm: 160.90, 159.75, 156.22 (C7,
1H NMR (400.16 MHz, CDCl3) d, ppm: 6.95, 6.81, 6.80 (3H, Har), 6.14
(s, 2H, Hb + Hc), 5.78 (pt, J = 6.9 Hz, 1H, Ha), 5.01, 5.18 (dd, J = 19.5,
6.9, 2H, C1H2), 3.88, 3.86, 3.81, 3.79 (s, 15H, OMe). 13C NMR
(100.61 MHz, CDCl3) d, ppm): 160.67, (C9), 159.52, 152.68 (C7,
C11), 147.1, 133.49 (C16, C17), 123.49 (C6), 120.86 (C13), 111.11
(C14), 125.94 (C15), 107.73 (C12), 91.26 (C8, C10), 77.34 (C1), 60.44–
55.28 (C3, C4, C5, C18, C19), 33.94 (C2). HPLC: Chiralpak AD-H (95:5,
n-hexane/2-propanol, 0.5 mL/min); tR, min: 34.3 (minor), 35.9
(major).
C9, C11, C17), 137.62 (C6), 129.14–112.11 (C13, C14, C15, C16, C12
,
and C, Ph), 91.35 (C8, C10), 76.85 (C1), 69.77 (CH2Ph), 55.20, 54.70
(C3, C4, C5), 33.86 (C2). HPLC: Chiralpak AD-H (95:5, n-hexane/2-
propanol, 0.25 mL/min); tR, min: 75.2 (minor), 77.3 (major).
4.3.10. 2-(1-(3-Benzyloxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10k
4.3.13. 2-(1-(2,4-Dimethoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10n
Hb
OMe3
Me4O
Hc
NO2
CH2
8
Hb
7
6
9
10
1
OMe3
Me4O
11
2
NO2
8
7
6
9
10
*
1
OMe5
Ha
11
2
CH2
Hc
Me5O
Me18
*
Har
Har
12
Ha
13
14
17
16
H2
C
Har
Har
O
15
12
Har
O
Ph
13
14
17
16
Har
15
Har
OMe19
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.50–6.81 (m, 9H, Har), 6.14 (s,
2H, Hb + Hc), 5.47 (pt, J = 7.8 Hz, 1H, Ha), 5.23, 5.12 (dd, J = 12.8,
7.8 Hz, 2H, C1H2), 5.03 (s, 2H, CH2Ph), 3.81 (s, 3H, OMe4),3.79 (s,
6H, OMe3 + OMe5). 13C NMR (100.61 MHz, CDCl3) d, ppm: 161.94,
160.59, 158.98, 158.76 (C7, C9, C11, C16), 142.17 (C6), 137.04–
108.47 (C13, C14, C15, C17, C12, and C, Ph), 92.90 (C8, C10), 76.85
(C1), 69.77 (CH2Ph), 55.20, 54.70 (C3, C4, C5), 33.86 (C2). HPLC: Chir-
alpak AD-H (95:5, n-hexane/2-propanol, 0.5 mL/min); tR, min: 34.6
(minor), 38.4 (major).
1H NMR (400.16 MHz, CDCl3) d, ppm: 6.95–6.80 (m, 3H, Har), 6.14 (s,
2H, Hb + Hc), 5.30 (pt, J = 7.0 Hz, 1H, Ha), 4.80, 4.64 (dd, J = 11.8,
7.0 Hz, 2H, C1H2), 3.58 (s, 6H, OMe3 + OMe5), 3.57, 3.55, 3.52 ppm
(s, 9H, OMe4 + OMe18 + OMe19). HPLC: Chiralpak AD-H (95:5, n-hex-
ane/2-propanol, 0.5 mL/min); tR, min: 36.8 (minor), 38.4 (major).
4.3.14. 2-(1-(2,5-Dimethoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10o
4.3.11. 2-(1-(4-Benzyloxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10l
Hb
Me4O
Hc
OMe3
NO2
CH2
8
7
6
9
10
1
Hb
11
2
OMe3
Me4O
Hc
NO2
CH2
*
8
Ha
7
6
OMe5
9
10
1
11
2
Me18
O
Hf
*
12
13
14
17
16
OMe5
Ha
15
OMe19
Hg
Hd
Hd
12
13
14
17
16
He
15
He
Hf
O
1H NMR (400.16 MHz, CDCl3) d, ppm: 6.71 (d, J = 8.8 Hz, 1H, Hd),
6.63 (dd, J = 8.8, 3.0 Hz, 1H, He), 6.56 (d, J = 3.0 Hz, 1H, Hf), 6.07 (s,
2H, Hb + Hc), 5.67 (pt, J = 8.6 Hz, 1H, Ha), 5.10, 4.94 (dd, J = 12.4,
8.5 Hz, 2H, C1H2), 3.77, 3.73, 3.59 (s, 9H, OMe4 + OMe18 + OMe19),
3.70 (s, 6H, OMe3 + OMe5). HPLC: Chiralpak AD-H (95:5, n-hex-
ane/2-propanol, 0.5 mL/min); tR, min: 31.2 (minor), 34.3 (mayor).
CH2
Ph
1H NMR (500.13 MHz, CDCl3) d, ppm: 7.44–7.32 (m, 5H, Har), 7.27
(d, J = 13.7 Hz, 2H, Hd + Hg), 6.77 (d, J = 13.7 Hz, 2H, He + Hf), 6.04
(s, 2H, Hb + Hc), 5.46 (pt, J = 7.8 Hz, 1H, Ha), 5.22, 5.12 (dd,
J = 19.76, 7.40, 2H, C1H2), 5.04 (CH2Ph), 3.83 (s, 6H, OMe3 + OMe5),
3.82 (s, 3H, OMe4). 13C NMR (125.77 MHz, CDCl3) d, ppm: 160.52,
158.93, 157.54 (C7, C9, C11, C15), 137.13 (C6), 132.93, 128.76,
128.59, 127.95, 127.49, 114.65, 108.93 (C13, C14, C16, C17, C12, and
C, Ph), 91.22 (C8, C10), 78.68 (C1), 70.01 (CH2Ph), 55.83, 55.33 (C3,
C4, C5), 38.07 (C2). HPLC: Chiralpak AD-H (95:5, n-hexane/2-propa-
nol, 0.5 mL/min); tR, min: 32.4 (minor), 36.5 (major).
4.3.15. 2-(1-(3,4-Dimethoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10p
Hb
OMe3
Me4O
Hc
NO2
CH2
8
7
6
9
1
10
11
2
4.3.12. 2-(1-(2,3-Dimethoxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10m
*
OMe5
Ha
Hf
Hd
12
13
14
17
16
Hb
Me4O
Hc
OMe3
Me18
O
15
He
8
NO2
7
6
9
OMe19
1
10
11
CH2
2
*
OMe5
Ha
1H NMR (400.16 MHz, CDCl3) d, ppm: 6.92 (d, J = 1.9 Hz, 1H, Hd),
6.89 (dd, J = 8.3, 1.9 Hz, 1H, Hf), 6.77 (d, J = 8.3 Hz, 1H, He), 6.14 (s,
2H, Hb+ Hc), 5.44 (pt, J = 7.8 Hz, 1H, Ha), 5.22, 5.11 (dd, J = 12.7,
7.8 Hz, 2H, C1H2), 3.85 (s, 6H, OMe3 + OMe5), 3.84 (s, 6H,
OMe18 + OMe19), 3.81 (s, 3H, OMe4). 13C NMR (100.61 MHz, CDCl3)
OMe18
OMe19
Har
12
13
14
17
16
15
Har
Har

904
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
d, ppm: 161.55, 160.53, 158.91, 148.68, 147.79 (C7, C9, C11, C14, C15),
133.10 (C6), 119.77 (C17), 11.33 (C13), 111.01 (C16), 108.84 (C12),
91.26 (C8, C10), 78.77 (C1), 55.81–55.32 (C3, C4, C5, C18, C19), 38.48
(C2). HPLC: Chiralpak AD-H (90:10, n-hexane/2-propanol, 1 mL/
min); tR, min = 35.5 (minor), 53.4 (major).
J = 7.8 Hz, 1H, Ha), 5.05–4.92 (m, 4H, C1H2 + CH2Ph), 3.76, 3.71 (s,
6H, OMe4 + OMe19), 3.64 (s, 6H, OMe3 + OMe5). 13C NMR
(75.48 MHz, CDCl3) d, ppm: 160.50, 158.86 (C7, C9, C11, C14, C15),
148.48–108.86 (C6, C12, C13, C16, C17, and C, Ph), 91.27 (C8, C10),
78.64 (C1), 71.12 (CH2Ph14), 56.00, 55.75, 55.30 (C3, C4, C5, C19),
38.26 (C2). HPLC: Chiralpak AD-H (90:10, n-hexane/2-propanol,
1 mL/min); tR, min: 21.8 (minor), 36.1 (major).
4.3.16. 2-(1-(3,4-Dibenzyloxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10q
4.3.19. 2-(1-(2-Fluorophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10t
Hb
Me4O
Hc
OMe3
NO2
CH2
8
7
6
9
10
1
Hb
11
2
Me4O
Hc
OMe3
NO2
CH2
*
8
Ha
Me5O
Hd
7
6
9
10
1
11
2
Hf
12
*
13
14
17
16
OMe5
Ha
Ph18H2CO
15
He
Har
F
12
OCH2Ph19
13
14
17
16
15
Har
Har
1H NMR (500.13 MHz, CDCl3) d, ppm: 7.44–7.28 (m, 10H,
Ph18 + Ph19), 6.94 (br d, 1H, Hd), 6.83 (m, 2H, He + Hf), 6.12 (s, 2H,
Hb + Hc), 5.38 (pt, J = 7.8 Hz, 1H, Ha), 5.16–4.98 (m, 6H,
C1H2 + CH2Ph18 + CH2Ph19), 3.81 (s, 3H, OMe4), 3.75 (s, 6H,
OMe3 + OMe5). 13C NMR (125.77 MHz, CDCl3) d, ppm: 160.52,
Har
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.28–6.93 (m, 4H, Har), 6.16 (s,
2H, Hb + Hc), 5.78 (pt, J = 8.0 Hz, 1H, Ha), 5.16 (d, J = 7.8 Hz, 2H,
C1H2), 3.82 (s, 3H, OMe4), 3.81 (s, 6H, OMe3 + OMe5). 13C NMR
(100.61 MHz, CDCl3) d, ppm: 160.52, (C9), 158.97 (C7, C11), 137.47,
136.15 (C17, C6), 129.02, 127.50 (C13, C14, C15, C16), 108.80 (C12),
91,19 (C8, C10), 78.52 (C1), 55.80, 55.30 (C3, C4, C5), 38.32 (C2). HPLC:
Chiralpak AD-H (95:5, n-hexane/2-propanol, 0.5 mL/min); tR, min:
18.9 (minor), 20.0 (major).
158.88, (C7, C9, C11, C14, C15), 137.46 (C6), 148.58–108.78 (C13, C16
C17, C12, and C, Ph), 91.25 (C8, C10), 78.60 (C1), 71.42, 71.31 (CH2Ph18
,
,
CH2Ph19), 55.77, 55.31 (C3, C4, C5), 38.25 (C2). HPLC: Chiralpak AD-H
(80:20, n-hexane/2-propanol, 1 mL/min); tR, min: 20.5 (minor), 34.2
(major).
4.3.17. 2-(1-(3,5-Dibenzyloxyphenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10r
4.3.20. 2-(1-(2-Chlorophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10u
Hb
Hb
OMe3
OMe3
Me4O
Hc
Me4O
Hc
NO2
CH2
NO2
CH2
8
8
7
6
7
6
9
10
9
10
1
1
11
11
2
2
*
*
OMe5
Ha
OMe5
Ha
Hf
Hd
Ph18H2CO
Har
Cl
12
15
12
13
14
17
16
13
14
17
16
OCH2Ph19
15
Har
Har
He
Har
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.32–7.21 (m, 10H,
Ph18 + Ph19), 6.48 (d, J = 2.0 Hz, 2H, Hd + Hf), 6.37 (t, J = 2.0 Hz, 1H,
He), 6.02 (s, 2H, Hb + Hc), 5.32 (pt, J = 7.8 Hz, 1H, Ha), 5.08–4.99
(dd, J = 12.9, 7.8, 2H, C1H2), 4.89 (br s, 4H, CH2Ph), 3.70 (s, 3H,
OMe4), 3.66 (s, 6H, OMe3 + OMe5). 13C NMR (125.77 MHz, CDCl3)
d, ppm: 160.62, 159.80, 159.00 (C7, C9, C11, C14, C16), 142.95–
108.38 (C6, C12, C, Ph), 107.19 (C13, C17), 100.15 (C15), 91.24 (C8,
C10), 78.31 (C1), 70.06 (CH2Ph18, CH2Ph19), 55.82, 55.33 (C3, C4,
C5), 38.72 (C2). HPLC: Chiralpak AD-H (80:20, n-hexane/2-propanol,
1 mL/min); tR, min: 11.2 (minor), 13.4 (major).
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.32, 7.14 (m, 4H, Har), 6.12 (s,
2H, Hb + Hc), 5.80 (pt, J = 7.0 Hz, 1H, Ha), 5.19, 4.99 (dd, J = 20.1,
7.0 Hz, 2H, C1H2), 3.79 (s, 3H, OMe4); 3.76 (s, 6H, OMe3 + OMe5).
13C NMR (100.61 MHz, CDCl3) d, ppm: 160.84, (C9), 159.51 (C7,
C11), 137.25, 133.99 (C17, C6), 129.83, 129.72, 128.07, 126.62 (C13
,
C14, C15, C16), 106.70 (C12), 91,19 (C8, C10), 76.44 (C1), 55.77, 55.30
(C3, C4, C5), 36.85 (C2). HPLC: Chiralpak AD-H (95:5, n-hexane/2-
propanol, 0.5 mL/min); tR, min: 19.1 (minor), 20.3 (major).
4.3.21. 2-(1-(2-Bromophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10v
4.3.18. 2-(1-(3-Benzyloxy-4-methoxyphenyl)-2-nitroethyl)-
1,3,5-trimethoxybenzene 10s
Hb
OMe3
Me4O
Hc
NO2
CH2
8
7
6
Hb
9
10
1
11
OMe3
Me4O
Hc
2
NO2
CH2
8
*
7
6
9
10
Ha
OMe5
1
11
2
Br
Hg
*
Hd
12
Ha
13
14
17
16
OMe5
15
Hf
He
Hd
12
15
13
14
17
16
Hf
Ph18H2CO
He
OMe19
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.55 (d, J = 8.2 Hz, 1H, Hg),
7.34 (d, J = 7.7 Hz, 1H, Hd), 7.21 (pt, J = 7.2 Hz, 1H, Hf), 7.08 (pt,
J = 7.7 Hz, 1H, He), 6.15 (s, 2H, Hb + Hc), 5.77 (pt, J = 8.2 Hz, 1H,
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.32–7.18 (m, 5H, Ph18), 6.80
(m, 2H, He + Hf), 6.70 (br d, 1H, Hd), 6.02 (s, 2H, Hb + Hc), 5.27 (pt,

D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
905
Ha), 5.25, 4.95 (dd, J = 12.8, 8.2, 2H, C1H2), 3.81 (s, 3H, OMe4), 3.79 (s,
4.3.25. 2-(1-(2,4-Dichlorophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10z
6H, OMe3 + OMe5). 13C NMR (75.48 MHz, CDCl3) d, ppm: 160.85
(C9), 159.56 (C7, C11), 139.01, 124.52 (C17, C6), 133.10, 130.10,
128.38, 127.36 (C13, C14, C15, C16), 106.97 (C12), 91.29 (C8, C10),
76.49 (C1), 55.77, 55.30 (C3, C4, C5), 39.61 (C2). HPLC: Chiralpak
AD-H (95:5, n-hexane/2-propanol, 0.5 mL/min); tR, min: 18.6 (min-
or), 19.2 (major).
Hb
OMe3
Me4O
Hc
NO2
CH2
8
7
6
9
1
10
11
2
*
OMe5
Ha
Hf
Cl
12
13
14
17
16
4.3.22. 2-(1-(4-Chlorophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10w
15
Hd
He
Cl
Hb
1H NMR (500.13 MHz, CDCl3) d, ppm: 7.37 (d, J = 2.2 Hz, 1H, Hd),
7.30 (d, J = 8.6 Hz, 1H, Hf), 7.15 (dd, J = 8.6, 2.2 Hz, 1H, He), 6.14 (s,
2H, Hb + Hc), 5.77 (pt, J = 8.6 Hz, 1H, Ha), 5.14, 5.01 (dd, J = 12.7,
8.6 Hz, 2H, C1H2), 3.82 (s, 3H, OMe4), 3.79 (s, 6H, OMe3 + OMe5).
13C NMR (125.77 MHz, CDCl3) d, ppm: 161.01 (C9), 159.37 (C7,
C11), 136.02, 134.67 (C13, C15), 133.07 (C6), 130.65 (C17), 129.43
(C14), 126.86 (C16), 106.17 (C12), 91.15 (C8, C10), 76.27 (C1), 55.74,
55.32, (C3, C4, C5), 36.36 (C2). HPLC: Chiralpak AD-H (95:5, n-hex-
ane/2-propanol, 0.5 mL/min); tR, min: 24.3, 26.7.
Me4O
Hc
OMe3
NO2
8
7
6
9
10
1
11
2
CH2
*
OMe5
Ha
Har
Har
Har
Har
12
13
14
17
16
15
Cl
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.29–7.22 (m, 4H, Har), 6.14 (s,
2H, Hb + Hc), 5.47 (pt, J = 8.1 Hz, 1H, Ha), 5.26, 5.06 (dd, J = 12.8,
8.1 Hz, 2H, C1H2), 3.82 (s, 6H, OMe3 + OMe5), 3.81 (s, 3H, OMe4).
13C NMR (100.61 MHz, CDCl3) d, ppm: 160.77 (C9), 158.83 (C7,
C11), 139.11 (C15), 132.33 (C6), 129.01, 128.42 (C13, C14, C16, C17),
108.18 (C12), 91.13 (C8, C10), 78.08 (C1), 55.80, 55.35 (C3, C4, C5),
37.98 (C2). HPLC: Chiralpak AD-H (95:5, n-hexane/2-propanol,
0.5 mL/min); tR, min: 34.6 (minor), 40.2 min (major).
4.3.26. 2-(1-(2-Chloro-6-fluorophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10ac
Hb
OMe3
Me4O
Hc
NO2
CH2
8
7
6
9
10
1
11
2
*
Ha
OMe5
4.3.23. 2-(1-(4-Bromophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10x
Cl
F
12
15
13
17
16
14
Har
Har
Har
Hb
Me4O
Hc
OMe3
NO2
8
1H NMR (400.16 MHz, CDCl3) d, ppm: 7.41–6.48 (m, 3H, Har), 6.05 (s,
2H, Hb + Hc), 5.61 (pt, J = 8.0 Hz, 1H, Ha), 5.15, 4.88 (m, 2H, C1H2),
3.75 (s, 3H, OMe4), 3.68 (s, 6H, OMe3 + OMe5). HPLC: Chiralpak
AD-H (95:5, n-hexane/2-propanol, 0.5 mL/min); tR, min: 18.4 (ma-
jor), 20.5 (minor).
7
6
9
10
1
11
2
CH2
Ha
*
OMe5
Hg
Hf
Hd
He
12
15
13
14
17
16
Br
4.4. Preparation of the complexes (SM,RC)-[(Cp⁄M{(R)-
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.37 (d, J = 8.4 Hz, 2H,
He + Hf), 7.19 (d, J = 8.4 Hz, 2H, Hd + Hg), 6.12 (s, 2H, Hb + Hc), 5.45
(pt, J = 7.4 Hz, 1H, Ha), 5.24, 5.04 (dd, J = 19.8, 7.4 Hz, 2H, C1H2),
3.80 (s, 9H, OMe). 13C NMR (75.48 MHz, CDCl3) d, ppm: 160.83
prophos}(9m)](SbF6)2 [M = Rh 11, Ir 12]
At ꢀ25 °C, under argon, to a solution of 0.12 mmol of the corre-
sponding complex (SM,RC)-[Cp⁄M(R-prophos)(H2O)](SbF6)2 [M = Rh
1 136.8 mg, Ir 2 149.6 mg] in CH2Cl2 (20 mL), 75.3 mg (0.36 mmol)
of 9m and 100 mg of 4 Å MS were added. The resulting red suspen-
sion was stirred for 1 h and then filtered through a cannula. The fil-
trate was vacuum-concentrated to approximately 3 mL. The
addition of 20 mL of n-hexane afforded an orange-red solid that
was filtered off, washed with n-hexane (5 ꢁ 20 mL) and vacuum-
dried. Yield: 81.3 % 11, 78.8 % 12.
(C9), 158.86 (C7, C11), 139.69 (C15), 131.36 (C14, C16), 129.37 (C13
,
C17), 120.43 (C6), 108.22 (C12), 91.24 (C8, C10), 78.00 (C1), 55.80,
55.33, (C3, C4, C5), 38.06 (C2). HPLC: Chiralpak AD-H (90:10, n-hex-
ane/2-propanol, 0.5 mL/min); tR, min: 14.6 (minor), 16.6 (major).
4.3.24. 2-(1-(2,3-Dichlorophenyl)-2-nitroethyl)-1,3,5-
trimethoxybenzene 10y
Hb
4.4.1. (SRh,RC)-[Cp⁄Rh{(R)-prophos}(9m)](SbF6)2 11
Me4O
Hc
OMe3
NO2
8
7
6
9
1
10
(SbF6)2
11
CH2
2
*
OMe5
Ha
O
N
Ha
4
OMea
OMeb
Cl
Cl
Har
12
15
Ph3
Ph4
13
14
17
16
3
Rh
Ph1
Ph2
Har
O
P1
Har
P2
Hb
H11
*
1
1H NMR (300.13 MHz, CDCl3) d, ppm: 7.60–6.64 (m, 3H, Har), 6.14 (s,
2H, Hb + Hc), 5.78 (pt, J = 6.9 Hz, 1H, Ha), 5.22, 4.95 (dd, J = 12.7, 6.9,
2H, C1H2), 3.75 (s, 3H), 3.81, 3.69 (s, 9H, OMe3 + OMe4 + OMe5).
HPLC: Chiralpak AD-H (95:5, n-hexane/2-propanol, 0.5 mL/min);
tR, min: 26.7, 28.9.
2
Me
H21
H22
1H NMR (400.16 MHz, CD2Cl2, ꢀ25 °C) d, ppm: 7.85–6.95 (23H, Ph),
7.47 (d, J = 13.9 Hz, 1H, Ha), 7.31 (d, J = 13.9 Hz, 1H, Hb), 3.89 (s, 3H,

906
D. Carmona et al. / Tetrahedron: Asymmetry 22 (2011) 893–906
OMeb), 3.87 (s, 3H, OMea), 3.59 (dm, J(P,H) = 52.7 Hz, 1H, H21), 3.19
(m, 1H, H11), 2.70 (t, J = 16.1 Hz 1H, H22), 1.44 (pt, J = 3.3 Hz, 15H,
C5Me5), 1.31 (dd, J(P,H) = 13.5, 7.0 Hz, 3H, Me). 13C NMR
(100.61 MHz, CD2Cl2, ꢀ25 °C) d, ppm: 152.85–118.98 (Ph), 142.56
(C4), 134.98 (C3), 107.29 (br s, C5Me5), 61.67 (OMeb), 56.00 (OMea),
33.5 (dd, J(P,C) = 35.1, 13.9 Hz, C2), 31.22 (dd, J(P,C) = 31.5, 9.5 Hz,
C1), 15.86 (dd, J(P,C) = 17.6, 5.1 Hz, Me), 10.08 (C5Me5). 31P NMR
(161.96 MHz, CD2Cl2, ꢀ25 °C) d, ppm: 75.99 (dd, J(Rh,P1) = 130.8 Hz,
J(P2,P1) = 38.3 Hz, P1), 51.52 ppm (dd, J(Rh,P2) = 133.1 Hz, P2). IR
Catalizadores Organometálicos Enantioselectivos) for financial
support. C.B. thanks the IUCH for a grant.
References
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47H53F12RhO4NP2Sb2: C, 42.4; H, 4.0. Found: C, 42.3; H, 4.0.
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11. Erker, G.; Vanderzeijden, A. A. H. Angew. Chem., Int. Ed. Engl. 1990, 29, 512–514.
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O
N
Ha
4
OMea
OMeb
Ph3
Ph4
3
Ir
O
P1
Ph1
P2
Hb
H11
*
1
Ph2
2
Me
H21
H22
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1H NMR (400.16 MHz, CD2Cl2, ꢀ25 °C) d, ppm: 7.60 (br d, 1H, Ha),
7.59–7.26 (m, 23H, Ph), 7.35 (br d, 1H, Hb), 3.91 (s, 6H, OMea + O-
Meb), 3.57 (dm, J(P,H) = 48.1 Hz, 1H, H21), 3.14 (m, 1H, H11), 2.64
(m, 1H, H22), 1.53 (br s, 15H, C5Me5), 1.35 (dd, J(P,H) = 16.1,
9.5 Hz, 3H, Me). 13C NMR (100.61 MHz, CD2Cl2, ꢀ25 °C) d, ppm:
143.93 (C3), 134.28–119.83 (Ph, C4), 101.40 (C5Me5), 61.69, 56.00
(OMea, OMeb), 33.90, 31.67 (m, C1, C2), 14.76 (dd, J(P,C) = 16.3,
3.8 Hz, 3H, Me), 9.67 ppm (C5Me5). 31P NMR (161.96 MHz, CD2Cl2,
ꢀ25 °C) d, ppm: 49.04 (d, J(P2,P1) = 10.7 Hz, P1), 27.71 ppm (d, P2).
16. Carmona, D.; Lamata, M. P.; Viguri, F.; Rodríguez, R.; Barba, C.; Lahoz, F. J.;
Martín, M. L.; Oro, L. A.; Salvatella, L. Organometallics 2007, 26, 6493–6496.
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IR (KBr, cmꢀ1):
m(SbF6): 658 s. Elemental Anal. Calcd for C47H53F12Ir-
O4NP2Sb2: C, 39.7; H, 3.7. Found: C, 39.6; H, 3.7.
4.5. NMR measurements for the 11/4c system
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At ꢀ25 °C, under argon, to a solution of 36.4 mg (0.03 mmol) of
(SRh,RC)-[Cp⁄Rh{(R)-prophos}(H2O)](SbF6)2 1, in CD2Cl2 (1.0 mL),
12.6 mg (0.06 mmol) of 9m and 20 mg of 4 Å MS were added.
The suspension was stirred for 1 h and placed into a 5-mm NMR
tube. At ꢀ50 °C, 1H and 31P NMR spectra showed the complete for-
mation of complex 11. Then, 5.0 mg (0.03 mmol) of 1,3,5-trime-
thoxybenzene were added and the system was monitored by 1H
and 31P NMR spectroscopies from ꢀ50 to ꢀ10 °C.
4.6. NMR measurements for the 1/10m system
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In
a
5-mm NMR tube, 36.4 mg (0.03 mmol) of (SRh,RC)-
were dissolved in CD2Cl2
[Cp⁄Rh{(R)-prophos}(H2O)](SbF6)2
1
(0.5 mL). At ꢀ50 °C, 11.3 mg (0.03 mmol) of 10m and 20 mg of
4 Å MS were added. The reaction was monitored by 1H and 31P
NMR spectroscopy.
45. Sohtome, Y.; Shin, B.; Horitsugi, N.; Takagi, R.; Noguchi, K.; Nagasawa, K.
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Acknowledgements
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We thank the Ministerio de Educación y Ciencia (Grant CTQ
2009-10303/BQU) and Gobierno de Aragón (Grupo Consolidado: