Stereoselective synthesis of cationic heterobidentate C(NHC)/SR rhodium(I) complexes using stereodirecting N,N-dialkylamino groups

Article abstract of DOI:10.1016/j.tetasy.2010.04.041

The synthesis of two different types of chiral C/S ligands based upon N-(N,N-dialkylamino)-substituted N-heterocyclic carbenes and thioether functionalities, along with their neutral [RhCl(CNH)(COD)] and cationic [Rh(I)(NHC/S)(COD)]⁺ complexes, has been accomplished. (S)-2-[(Phenylthio)methyl]pyrrolidine, carrying the thioether moiety, and (2S,5S)-2,5-diphenylpyrrolidine, combined with a thioether functionalized side chain, were studied as potential stereodirecting groups. Only the latter provided high selectivity in the formation of the neutral complex, leading to a single atropoisomer (de >98%) of the newly formed, configurationally stable C(NHC)-Rh bond. The synthesis of the corresponding cationic [Rh(I)(NHC/S)(COD)] ⁺ complexes, however, resulted in the formation of single (R _a,S_S) and (S_a,S_S) diastereomers, respectively, of the four possible complexes in each case [combinations of the (R_a/S_a) C(NHC)-Rh axis and the (S_s/R _s) stereogenic S center formed upon coordination]. For the proline derivative, the resolution of the mixture of (R_a/S _a)-[RhCl(CNH)(COD)] neutral complexes proceeds via dynamic kinetic resolution through coordinatively unsaturated Rh(I) intermediates formed after halide abstraction. The absolute configurations of both types of cationic complexes were unequivocally assigned on the basis of X-ray diffraction analysis.

Full text of DOI:10.1016/j.tetasy.2010.04.041

Tetrahedron: Asymmetry 21 (2010) 1557–1562
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective synthesis of cationic heterobidentate C(NHC)/SR rhodium(I)
complexes using stereodirecting N,N-dialkylamino groups
Abel Ros a, Manuel Alcarazo b, , David Monge a, Eleuterio Álvarez b, Rosario Fernández a,
,
*
José M. Lassaletta b,
*
a Departamento de Química Orgánica, Universidad de Sevilla, 41012 Seville, Spain
b Instituto de Investigaciones Químicas (CSIC-Use), C/Américo Vespucio 49, 41092 Seville, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of two different types of chiral C/S ligands based upon N-(N,N-dialkylamino)-substituted N-
heterocyclic carbenes and thioether functionalities, along with their neutral [RhCl(CNH)(COD)] and cat-
ionic [Rh(I)(NHC/S)(COD)]+ complexes, has been accomplished. (S)-2-[(Phenylthio)methyl]pyrrolidine,
carrying the thioether moiety, and (2S,5S)-2,5-diphenylpyrrolidine, combined with a thioether functional-
ized side chain, were studied as potential stereodirecting groups. Only the latter provided high selectivity in
the formation of the neutral complex, leading to a single atropoisomer (de >98%) of the newly formed, con-
figurationally stable C(NHC)–Rh bond. The synthesis of the corresponding cationic [Rh(I)(NHC/S)(COD)]+
complexes, however, resulted in the formation of single (Ra,SS) and (Sa,SS) diastereomers, respectively, of
the four possible complexes in each case [combinations of the (Ra/Sa) C(NHC)–Rh axis and the (Ss/Rs) stere-
ogenic S center formed upon coordination]. For the proline derivative, the resolution of the mixture of (Ra/
Sa)-[RhCl(CNH)(COD)] neutral complexes proceeds via dynamic kinetic resolution through coordinatively
unsaturated Rh(I) intermediates formed after halide abstraction. The absolute configurations of both types
of cationic complexes were unequivocally assigned on the basis of X-ray diffraction analysis.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 8 March 2010
Accepted 20 April 2010
Available online 31 May 2010
Dedicated to Professor Henri Kagan on the
occasion of his 80th birthday
1. Introduction
tions around the N–N bond and (2) introduction of thioether-con-
taining side chains with a design that enables control of the
During the last decade, N-heterocyclic carbenes (NHCs) emerged
as the last big family of ligands with a high impact in transition
metal-mediated homogeneous catalysis.1 Their success can be in
general attributed to an unusual combination of catalytic activity
(provided by their electronic and steric characteristics) and stability,
as transitionmetal complexescontainingNHC ligands are usuallyair
stable and kinetically robust compounds, with a low tendency to
C(carbene)-metal bond dissociation. Such properties are particu-
larly attractive for asymmetric catalysis, and efforts in this field have
allowed the development of applications such as Cu-catalyzed
conjugate additions,2 asymmetric ketone hydrosilylations,3 asym-
metric alkene hydrogenations,4 ring-closing5 and ring-opening6
metathesis, allylic alkylations,7 Cu-catalyzed hydroborations,8 dib-
oration of terminal alkynes,9 and silane conjugate additions.10
In the frame of our interest in the development of N-heterocyclic
carbene architectures, we have investigated new strategies for the
introduction of chiral environments into these systems, namely
(1) introduction of chiral N,N-dialkylamino groups, with emphasis
on C2-symmetric structures to avoid problems related with rota-
absolute configuration of the sulfur stereogenic center formed upon
coordination. The introduction of N-(N,N-dialkylamino) groups was
first reported for imidazolin-2-ylidenes11 and later extended to
mono N,N-dialkylamino imidazol-2-ylidenes12 and triazol-5-yli-
dene complexes.13 On the other hand, we have also reported the
synthesis of Pd complexes with bidentate C/S ligands based on N-
[(2S,5S)-2,5-diphenylpyrrolidin-1-yl]-N0-alkylimidazol-2-ylidenes,12
triazol-5-ylidenes,13 and imidazo[1,5-a]pyridin-3-ylidenes,14 along
with their catalytic performance in allylic substitutions. Herein
we report the results on the stereoselective synthesis of two new
types of chiral Rh(I) complexes [Rh(A)(cod)]+ and [Rh(B)(cod)]+
based on C(NHC)/S(thioether) ligands: a) NHC ligands of type A,
with the thioether group bridged through a N,N-dialkylamino group
and b) NHC ligands of type B, with the thioether moiety bridged
through an aliphatic side chain (Fig. 1).
2. Results and discussion
2.1. Synthesis of type A C(CNH)/S ligands and their Rh(I)
complexes: thioprolinol derivatives
* Corresponding authors.
E-mail addresses: ffernan@us.es (R. Fernández), jmlassa@iiq.csic.es (J.M. Lassaletta).
Present address: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim an
der Ruhr, Germany.
An inexpensive chiral source, proline, and its derivatives have
been widely applied in asymmetric synthesis and catalysis, but,
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.04.041

1558
A. Ros et al. / Tetrahedron: Asymmetry 21 (2010) 1557–1562
R1
R1
tBu
+
N
N
+
N
N
R1
N
N
N
R'
Rh(COD)
[Rh(A)(COD)]+
N
R'
N
N
N
O
THF
N
R'
+
−
Rh
Rh
H
X
91%
O
S
SR
–
de 4%
I
SR
PhS
tBu
6
R
A·HX
A
−
SPh
X
N
N
R2R1N
(COD)Rh
[Rh(B)(COD)]+
SPh
+
N
N
N
R2R1N
N
N
RS
R2R1N
N
N
AgSbF6, CH2Cl2, rt
63%
N
N
I
H
+
S
RS
N
Rh
Rh
R
I
B·HX
B
7
(Sa)-
7
(Ra)-
Figure 1. Heterobidentate C(NHC)/S structures A and B.
+
to the best of our knowledge, no chiral NHCs based on thioether-
functionalized proline derivatives have been documented in the
literature. We envisaged the synthesis of CNH/S [Rh(A)(cod)]+ com-
plexes starting from known (S)-2-(phenylthiomethyl) pyrrolidine
115 as a suitable starting material that incorporates the thioether
moiety as part of the chiral N,N-dialkylamino moiety. Conventional
nitrosation (tBuONO) and reduction (LiAlH4) of the resulting nitro-
samine16 afforded hydrazine 2 in high yield (Scheme 1). This com-
pound was then condensed with (formylamino)acetaldehyde 317
to afford formamide 4 in 63% yield. The synthesis of the required
imidazolium 6 was finally accomplished from 4 by POCl3–promoted
cyclization [?imidazole 5 (21% yield)] and ensuing alkylation with
iPrI [?6, 73% yield)]. It is worth mentioning that the alkylation took
place with complete regioselectivity, as no by-product resulting
from alkylation of the sp3 amino nitrogen could be detected in the
reaction mixture, in spite of its a priori higher nucleophilicity.
–
SbF6
N
N
Rh
Ph
N
S
(Ra,SS)-8
Scheme 2. Synthesis of type A cationic complex (Ra,SS)-8
The mixture of atropoisomers (Ra/Sa)-7 was treated with AgSbF6
as an halide scavenger, enabling intramolecular coordination of the
sulfur atom to afford the expected cationic C/S complex 8 as a fairly
stable compound that was isolated in 63% yield after chromato-
graphic purification on silica. Interestingly, the 1H NMR spectrum
of 8 revealed a single set of peaks, in agreement with the existence
of a single compound out of the four possible diastereomers that
can be formulated as combinations of the absolute configurations
of the (Ra/Sa) C(carbene)–Rh axis and the (Ss/Rs) sulfur atom. Fortu-
nately, good quality crystals of 8 could be grown by slow diffusion
of hexane in a solution of the complex in CH2Cl2, and single crystal
X-ray diffraction analysis allowed the unequivocal assignment of
the (Ra,SS) configuration for this compound (Fig. 2).19
The structure exhibits the expected square-planar coordination
at the Rh(I) center, with a C(1)–Rh(1)-S(1) bite angle of 83.0(2)°
and the imidazole ring near perpendicular to the coordination
plane, as deduced from the torsional S(1)–Rh(1)-C(1)-N(1) angle
of 101.7(7)°. The Rh–C(carbene) bond length of 2.028(7) Å is in
the range of single Rh–NHC bonds, and the mean C(COD)–Rh bond
distances are 2.143 Å (trans to sulfur) and 2.198 Å (trans to the imi-
dazol-2-ylidene ligand), the difference of ca. 0.06 Å reflecting the
O
O
N
H
H
NHCHO
3
NH2
N
1) tBuONO, THF
NH
N
N
MeOH, rt
63%
2) LiAlH4, THF
95%
PhS
PhS
PhS
1
2
4
POCl3
+
N
N
N
N
N
iPrI, THF
73%
N
Toluene 80 °C
–
21%
I
PhS
PhS
higher trans influence associated with the superior
r donor ability
of the NHC ligand. As in other N,N-dialkylamino carbene structures,
the pyramidalization degree at N(3) and the torsional angles C(7/
10)-N(3)-N(2)-C(1/2) indicate the absence of efficient conjugation
between the N.N-dialkylamino group and the heterocycle in the so-
lid state.20
5
6
Scheme 1. Synthesis of type AꢀHX proline-derived imidazolium salt 6.
To explore the properties of the carbene ligand derived from 6,
this compound was made to react with [Rh(tBuO)(COD)]2 (formed
in situ from [RhCl(COD)]2 and tBuONa), and the neutral rhodium-
carbene complex 7 was obtained in high yield (Scheme 2). Com-
pound 7 was formed as a 52:48 inseparable mixture of the (Ra)
and (Sa) atropoisomers, which are configurationally stable due to
highly hindered rotation around the C–Rh bond.18 The low selec-
tivity in the formation of the diastereomers indicates poor discrim-
ination by the chiral N,N-dialkylamino group, probably associated
with a lack of differential steric interactions that in turn is a conse-
quence of the free rotation around the N–N bond.
This dynamic kinetic resolution and selectivity observed in the
formation of (Ra,SS)-8 can be explained by assuming that the C(car-
bene)–Rh bond rotation that interconverts coordinatively unsatu-
rated intermediates I and II has a low energy barrier at the
reaction temperature (Scheme 3). The geometry of intermediate
II, leading to the observed (Ra,SS) absolute configuration, is charac-
terized by a perpendicular arrangement of the imidazole and pyr-
rolidine rings. In this situation, the SPh group and the coordination
vacant on the metal are located at the same side of the imidazole
plane and in suitable positions to immediately form a Rh–S bond;
the (Ss) configuration at sulfur can be explained by the steric inter-

A. Ros et al. / Tetrahedron: Asymmetry 21 (2010) 1557–1562
1559
and the SPh group at the same side of the imidazole plane does
not allow an immediate formation of the Rh–S bond that instead
requires a much more forced situation with a near coplanar dispo-
sition of the heterocyclic planes.
2.2. Synthesis of type B C(CNH)/S ligands and their Rh(I)
complexes: 2,5-diphenylpyrrolidine derivatives
Based on our previous studies on Pd(II) complexes from N-(N,N-
dialkylamino) imidazol-2-yidenes,12 we also decided to synthesize
Rh(I) complexes based on CNH/S ligands containing the 2,5-diphe-
nylpyrrolidine moiety, a group that has demonstrated excellent
stereocontrolling properties as a chiral auxiliary21 and as a key ele-
ment in chiral catalysts22 for a number of asymmetric transforma-
tions. The synthesis of the required imidazolium salt 11 was
accomplished by direct alkylation of N,N-dialkylamino imidazole
9 with known bromide 10 as previously reported.12 Reaction of
azolium 11 with [Rh(tBuO)(COD)]2 (prepared in situ from tBuONa
and [RhCl(COD)]2) in THF afforded the expected complex 12 as
an air- and moisture-stable compound that was isolated in 89%
yield after column chromatography (Scheme 4). The steric hin-
drance to the C(carbene)–Rh bond rotation again makes possible
the formation of two stable atropoisomers. In this case, however,
the reaction proceeds with complete stereoselectivity to afford a
single compound, though the absolute configuration of the stereo-
genic axis could not be established by X-ray diffraction analysis.
Figure 2. ORTEP drawing of complex (Ra,SS)-8. Thermal ellipsoids are shown at the
30% probability level. Hydrogen atoms and the SbF6 counteranion are omitted for
clarity. Selected bond lengths (Å) and bond angles (°): Rh(1)–C(1) 2.028(7), Rh(1)–
S(1) 2.3793(18), Rh(1)–C(22) 2.128(7), Rh(1)–C(23) 2.158(7), Rh(1)–C(18) 2.170(7),
Rh(1)–C(19) 2.226(7), C(1)–Rh(1)–S(1) 83.0(2), S(1)–Rh(1)–C(1)–N(1)101.7(7).
ꢂ
Ph
SPh
SPh
N
N
N
N
N
I
N
I
N
+
Rh
N
Ph
Rh
N
Br
9
SCy
10
Ref. 10
Ph
7
: de 4%
AgSbF6
Ph
AgSbF6
N
Ph
N
N
[Rh(tBuO)(COD)]2
+
N
+
Ph
Rh
THF
89%
SPh
N
−
N
N
N
Br
Br
N
Ph
Rh
N
S
Rh
CyS
N
N
CyS
12: de >98%
11
II
1) Ag2O, CH2Cl2, 99%
2) [Rh(COD)2]PF6, CH2Cl2, rt 92%
I
Fast
Slow
Slow
PF6
+
+
+
N
N
N
AgPF6, CH2Cl2
86%
N
S
N
S
Cy
S
Ph
N
S
N
Rh
N
Rh
Ph
Ph
Rh
Rh
N
N
N
N
Ph
Ph
8
8
(Ra,RS)-
8
(Ra,SS)-
(Sa,SS)-13: de >98%
(Sa,RS/SS)-
(not observed)
(not observed)
Scheme 4. Synthesis of type B cationic complex (Ra,SS)-13
Scheme 3. Selective synthesis of (Ra,SS)-8 via dynamic kinetic resolution.
Cationic CNH/S complex 13 was synthesized according to two
alternative procedures: (a) treatment of imidazolium 11 with sil-
ver oxide and subsequent transmetallation of the resulting crude
action between the SPh and the NiPr groups in the approach lead-
ing to the opposite (Rs) configuration. In intermediate I, on the
other side, the conformation that locates the coordination vacant
silver carbene with ½RhðCODÞ2ꢁþPF to yield the hexafluorophos-
ꢂ
6
phate salt 13 in an excellent 92% yield after chromatographic

1560
A. Ros et al. / Tetrahedron: Asymmetry 21 (2010) 1557–1562
purification and (b) reaction of neutral carbene 12 with AgPF6 to
abstract the bromide, generating vacant coordination and enabling
attack by the thioether sulfur atom to afford 13 in 86% yield. Note-
worthy, 13 was isolated as a single diastereomer independent of
the method used for its synthesis. Fortunately, good quality crys-
tals of 13 could be grown by slow diffusion of n-hexane into a solu-
tion of the complex in CH2Cl2 at room temperature. The molecular
structure was solved by single-crystal X-ray diffraction analysis,
allowing the unequivocal assignment of its absolute configuration
(Fig. 3).19 The complex exhibits the expected square planar geom-
etry with a C(carbene)–Rh–S bite angle of 91.2°. The unsaturation
in the heterocycle forces a boat-like geometry in the chelate 6-
membered ring. The SS configuration at sulfur is imposed by the
trans relative disposition of the isopropyl and S-cyclohexyl groups,
and is mandatory to avoid severe repulsive steric interactions that
would destabilize the cis isomer. In this complex the isopropyl
group is oriented equatorially and, consequently, the S-cyclohexyl
is located in an axial position. As in the precedented case, the dif-
ferent mean C(COD)–Rh bond distance of 2.209 Å (trans to the
imidazol-2-ylidene ligand) and 2.163 Å (trans to sulfur) reflects
the higher trans influence associated better donor ability of the
NHC ligand, and the pyramidalization degree at N(1) indicates
the absence of electronic interaction between the N,N-dialkylami-
no group and the heterocycle.
complexes is efficiently driven to the obtention of single diastereo-
mers in both cases, a process that requires a dynamic kinetic resolu-
tion for the S-phenyl thioprolinol derivative. Application of these
cationic Rh(I) complexes in asymmetric catalysis (ketone hydrosily-
lations, imine hydrogenations, and alkene hydroformylations) will
be reported in due course.
4. Experimental
4.1. General experimental methods
Solvents were purified and dried by standard procedures. Flash
chromatography was carried out on silica-gel (0.040–0.063 mm or
0.015–0.040 mm). Melting points were recorded in a metal block
and are uncorrected. 1H NMR spectra were recorded at 300 MHz,
400 MHz, or 500 MHz; 13C NMR spectra were recorded at 75 MHz,
100 MHz, or 125 MHz, with the solvent peak used as the internal
reference. (S)-2-(Phenylthiomethyl)pyrrolidine 1,15 (2S,5S)-1-ami-
no-2,5-diphenylpyrrolidine 9,22a and (R)-(1-bromo-3-methylb-
utan-2-yl)(cyclohexyl)sulfane 1012 were prepared according to the
literature procedures.
4.1.1. (S)-2-(Phenylthiomethyl)pyrrolidin-1-amine 2
tBuONO (3.1 mL, 26 mmol) was added to a solution of (S)-2-
(phenylthiomethyl)pyrrolidine 1 (2.0 g, 10.4 mmol) in THF (25 mL)
and the reaction mixture was refluxed for 5 h, then concentrated,
and the residue was purified by flash chromatography (1:6 EtOAc–
hexane) to give the corresponding nitrosamine (2.23 g, 96%) as an
orange syrup.16 A solution of this material in dry THF (15 mL) was
added dropwise over a suspension of LiAlH4 (762 mg, 20 mmol) in
dry THF (30 mL). The reaction mixture was stirred at room temper-
ature for 3 h, then the reaction was quenched with saturated Na2SO4
(6 mL), and the reaction mixture was filtered and concentrated to
yield crude 2 (2.0 g, 95%), which was used in the next reaction with-
out further purification. 1H NMR (400 MHz, CDCl3): d 7.29 (d, 2H,
J = 8.0 Hz), 7.19 (t, 2H, J = 8.0 Hz), 7.07 (t, 1H, J = 8.0 Hz), 3.30 (dd,
1H, J = 12.8, 2.8 Hz), 3.21 (dt, 1H, J = 8.0, 2.4 Hz), 3.08 (br s, 2H),
2.86 (dd, 1H, J = 12.8, 8.0 Hz), 2.40 (m, 1H), 2.22 (q, 1H, J = 9.2 Hz),
2.00–1.91 (m, 1H), 1.75–1.59 (m, 2H), 1.56–1.48 (m, 1H). 13C NMR
(100 MHz, CDCl3): d 137.1, 128.9, 128.6, 125.6, 67.7, 60.7, 37.3,
28.8, 20.4. ½a 2D0
¼ ꢂ95:2 (c 1.4, CHCl3). HRMS m/z calcd for
ꢁ
C
11H17N2S 209.1112, found 209.1121.
4.1.2. (2S)-N-[2-(2-Phenylthiomethylpyrrolidin-1-ylimino)
ethyl]formamide 4
To a solution of (2S)-2-(phenylthiomethyl)pyrrolidin-1-amine 2
(416 mg, 2 mmol) in MeOH (2.5 mL) was added formylaminoacetal-
dehyde 3 (525 mg, 5 mmol) and the reaction mixture was stirred
overnight at room temperature. The solvent was removed in vacuo
and the resulting residue was purified by flash chromatography
(50:1?10:1 CH2Cl2/MeOH) to afford 4 (349 mg, 63%) as a colorless
syrup. 1H NMR (300 MHz, CDCl3): d 8.18 (s, 1H), 7.34 (d, 2H,
J = 7.8 Hz), 7.27 (t, 2H, J = 7.8 Hz), 7.14 (t, 1H, J = 7.2 Hz), 6.47 (t,
1H, J = 3.6 Hz), 6.40 (br s, 1H), 4.01 (t, 2H, J = 4.2 Hz), 3.58–3.45 (m,
1H), 3.37 (dd, 1H, J = 12.6, 3.6 Hz), 3.40–3.20 (m, 1H), 2.94 (dd, 1H,
J = 12.6, 8.1 Hz), 2.77 (q, 1H, J = 8.1 Hz), 2.05–1.80 (m, 3H), 1.90–
1.60 (m, 1H). 13C NMR (75 MHz, CDCl3): d 161.3, 137.2, 129.5,
Figure 3. ORTEP drawing of cationic complex (Sa,SS)-13. Thermal ellipsoids are
drawn at the 30% probability level. Hydrogen atoms and PF6 counteranion are
omitted for clarity. Selected bond lengths (Å) and bond angles (°): Rh(1)–C(1)
2.056(6), Rh(1)–S(1) 2.3483(16), Rh(1)–C(31) 2.177(9), Rh(1)–C(32) 2.238(9),
Rh(1)–C(35) 2.163(6), Rh(1)–C(36) 2.163(5), C(1)–Rh(1)–S(1) 91.22(15), S(1)–
Rh(1)–C(1)–N(3) ꢂ40.7(5).
ꢂ
129.2, 129.1, 126.1, 63.5, 49.4, 40.3, 38.2, 28.9, 22.0. ½a D20
¼ ꢂ73:8
ꢁ
(c 1.2, CHCl3). Anal. Calcd for C14H19N3SO: C, 60.62; H, 6.90; N,
3. Conclusions
15.15. Found: C, 60.74; H, 6.99; N, 15.09.
The N,N-dialkylamino moieties introduced in thioether-func-
tionalized N-heterocyclic carbenes behave as efficient stereodirect-
ing groups in both thioprolinol and 2,5-diphenylpyrrolidine
derivatives. Although the initial formation of neutral [RhX(NHC)-
(COD)] is only stereoselective in carbenes bearing the 2,5-diphenyl-
pyrrolidine moiety, the formation of cationic [RhX(NHC/S)(COD)]+
4.1.3. (2S)-1-{2-[(Phenylthio)methyl]pyrrolidin-1-yl}-1H-imida-
zole 5
At first, POCl3 (310 lL, 3.3 mmol) was added to a solution of 4
(300 mg, 1.1 mmol) in toluene (1.5 mL) under an argon atmosphere.
The reaction mixture was stirred at 80 °C for 4 h, the reaction was

A. Ros et al. / Tetrahedron: Asymmetry 21 (2010) 1557–1562
1561
quenched with water (8 mL), and 1 M NaOH was added to the reac-
tion mixture until pH 12. The mixture was extracted with CH2Cl2
(3 ꢃ 10 mL) and the combinedorganic layer was dried (MgSO4), con-
centrated to dryness, and the resulting residue was purified by flash
chromatography (1:1?5:1 EtOAc–hexane) to give 5 (59 mg, 21%).
1H NMR (300 MHz, CDCl3): d 7.59 (s, 1H), 7.40–7.15 (m, 5H), 7.04
(s, 2H), 3.55–3.40 (m, 1H), 3.30 (dq, 1H, J = 8.1, 3.3 Hz), 3.12 (q, 1H,
J = 8.7 Hz), 2.94 (dd, 1H, J = 13.2, 3.6 Hz), 2.76 (dd, 1H, J = 13.2,
5.4 Hz), 2.25–2.15 (m, 1H), 2.00–1.80 (m, 2H), 1.80–1.65 (m, 1H).
13C NMR (75 MHz, CDCl3): d 137.2, 136.1, 129.3, 129.2, 128.9,
and the reaction crude was purified by flash chromatography (10:1
CH2Cl2–MeOH) to give complex 8 as a yellow solid (236 mg, 63%
yield). X-ray quality crystals were grown by slow diffusion of ethyl
ether into a solution of the complex in CH2Cl2. Mp 158–161 °C. 1
H
NMR (300 MHz, CDCl3):
d 7.50–7.35 (m, 6H), 7.11 (d, 1H,
J = 2.1 Hz), 5.05 (m, 1H), 4.45–4.38 (m, 2H), 4.22–4.14 (m, 1H),
4.14–4.08 (m, 1H), 3.62–3.53 (m, 1H), 3.43–3.31 (m, 3H), 2.76
(dd, 1H, J = 12.0, 2.1 Hz), 2.52–2.44 (m, 2H), 2.30–2.10 (m, 7H),
1.90–1.80 (m, 3H), 1.49 (d, 3H, J = 6.6 Hz), 1.47 (d, 3H, J = 6.6 Hz).
13C NMR (75 MHz, CDCl3): d 174.9 (d, JC–Rh = 49 Hz), 131.4, 131.0,
130.4, 130.1, 119.7, 117.6, 95.6 (d, JC–Rh = 8 Hz), 94.1 (d, JC–
Rh = 7 Hz), 84.6 (d, JC–Rh = 12 Hz), 78.2 (d, JC–Rh = 12 Hz), 64.2, 53.0,
126.4, 114.9, 65.7, 57.3, 37.0, 28.6, 21.2. ½a D20
¼ ꢂ37:0 (c 0.8, CHCl3).
ꢁ
Anal. Calcd for C14H17N3S: C, 64.83; H, 6.61; N, 16.20. Found: C,
64.70; H, 6.85; N, 16.01.
52.9, 44.3, 34.3, 31.6, 30.5, 27.8, 24.7, 23.6, 21.8. ½a D20
¼ þ50:0 (c
ꢁ
0.1, MeOH). Anal. Calcd for C25H35F6N3RhSSb: C, 40.13; H, 4.71;
N, 5.62. Found: C, 40.03; H, 4.62; N, 5.64.
4.1.4. (2S)-3-Isopropyl-1-{2-[(phenylthio)methyl]pyrrolidin-1-
yl}-1H-imidazol-3-ium iodide 6
At first, 2-iodopropane (117
l
L, 1.17 mmol) was added to a
4.1.7. 1-[(R)-2-(Cyclohexylthio)-3-methylbutyl]-3-[(2S,5S)-2,5-
diphenylpyrrolidin-1-yl]-imidazol-2-ylidene (1,5-cyclooctadi-
ene)rhodium(I) bromide
solution of 5 (100 mg, 0.39 mmol) in THF (0.5 mL) and the reaction
mixture was stirred at 60 °C for 2 d. The solvent was removed in
vacuo and the resulting residue was purified by flash chromatogra-
phy (10:1 CH2Cl2/MeOH) to give 6 (122 mg, 73%) as a light yellow
oil. 1H NMR (300 MHz, CDCl3): d 10.08 (s, 1H), 7.62 (s, 1H), 7.45 (s,
1H), 7.40–7.20 (m, 4H), 7.18–7.05 (m, 1H), 4.92 (m, 1H), 3.95–3.75
(m, 1H), 3.70–3.45 (m, 3H), 3.03 (dd, 1H, J = 12.6, 5.2 Hz), 2.45–2.35
(m, 1H), 2.20–2.10 (m, 1H), 1.95–1.85 (m, 1H), 1.85–1.75 (m, 1H),
1.59 (d, 6H, J = 6.8 Hz). 13C NMR (75 MHz, CDCl3): d 136.2, 136.0,
129.9, 129.5, 126.9, 122.4, 119.1, 66.3, 58.8, 54.4, 38.3, 29.0, 23.4,
Compound 12: tBuONa (6 mg, 0.05 mmol) was added to a slurry
of [RhCl(COD)]2 (14 mg, 0.025 mmol) in dry THF (0.1 mL) and the
resulting solution was stirred for 30 min at room temperature un-
der argon. A solution of 11 (30 mg, 0.05 mol) in dry THF (0.5 mL)
was then added via a cannula and the reaction mixture was stirred
overnight. The solvent was evaporated in vacuo and the reaction
crude was purified by flash column chromatography (1:1 EtOAc–
hexane) to afford rhodium carbene 12 (34 mg, 89% yield, de
>98%) as a yellow syrup. 1H NMR (400 MHz, CDCl3): d 7.40 (d,
2H, J = 6.8 Hz), 7. 35 (d, 2H, J = 6.8 Hz), 7.25–7.13 (m, 6H), 6.46 (s,
1H), 6.04 (d, 1H, J = 2.0 Hz), 5.79 (br s, 1H), 5.08 (m, 1H), 4.96 (m,
1H), 4.60 (dd, 1H, J = 14.0, 6.8 Hz), 4.40 (t, 1H, J = 8.0 Hz), 4.25
(dd, 1H, J = 14.0, 10.0 Hz), 3.69 (t, 1H, J = 8.0 Hz), 3.50 (m, 1H),
3.05 (m, 1H), 2.83 (m, 1H), 2.73–2.62 (m, 2H), 2.52 (m, 1H),
2.44–2.14 (m, 6H), 2.12–2.00 (m, 4H), 1.87–1.62 (m, 8H), 1.40–
1.25 (m, 2H), 1.14 (d, 3H, J = 6.8 Hz), 0.84 (d, 3H, J = 6.8 Hz). 13C
NMR (100 MHz, CDCl3): d 181 (d, JC–Rh = 51 Hz), 139.3, 138.6,
129.2, 128.8, 128.3, 128.1, 128.0, 119.7, 116.1, 96.2, 95.4, 71.0 (br
s), 67.9, 63.0, 55.6, 51.1, 44.7, 34.7, 34.4, 33.6, 31.9, 31.7, 29.9,
21.8. ½a 2D0
¼ ꢂ25:0 (c 0.3, CHCl3). Anal. Calcd for C17H24N3IS: C,
ꢁ
47.55; H, 5.63; N, 9.79. Found: C, 47.30; H, 5.42; N, 9.71.
4.1.5. (Ra)- and (Sa)-1-Isopropyl-3-{(2S)-2-[(phenylthio)methyl]
pyrrolidin-1-yl}-imidazol-2-ilydene (1,5-cyclooctadiene)
rhodium(I) iodide 7
At first, tBuONa (48 mg, 0.5 mmol) was added to a slurry of
[RhCl(COD)]2 (123 mg, 0.25 mmol) in dry THF (2 mL) under an ar-
gon atmosphere. The resulting solution was stirred for 30 min and
then a solution of 6 (214 mg, 0.5 mol) in dry THF (2 mL) was added
via a cannula. The reaction mixture was stirred under argon over-
night at room temperature, the solvent was removed in vacuo, and
the resulting residue was purified by flash chromatography (1:1
EtOAc–hexane) to afford an inseparable mixture of diastereomers
(de ꢄ4%) of the rhodium carbene 7 as a yellow foam (291 mg,
91% yield). 1H NMR (500 MHz, CDCl3): d 7.34 (d, 2H, J = 9.2 Hz),
7.28–7.20 (m, 4H), 7.20–7.12 (m, 2H), 7.09 (t, 1H, J = 7.9 Hz), 6.99
(d, 1H, J = 2.0 Hz), 6.91 (d, 1H, J = 2.0 Hz), 6.88 (d, 1H, J = 2.0 Hz),
6.73 (d, 1H, J = 2.0 Hz), 5.83 (m, 1H), 5.72 (m, 1H), 5.22–5.12 (m,
4H), 4.16–4.07 (m, 1H), 3.86–3.78 (m, 2H), 3.76–3.70 (m, 1H),
3.72–3.66 (m, 2H), 3.58–3.50 (m, 1H), 3.50–3.46 (m, 1H), 3.44–
3.39 (m, 1H), 3.30 (q, 1H, J = 8.5 Hz), 3.13 (dd, 1H, J = 8.0, 4.5 Hz),
3.11–3.03 (m, 2H), 2.92 (dd, 1H, J = 13.0, 9.5 Hz), 2.40–2.30 (m,
4H), 2.30–2.15 (m, 6H), 2.10–1.90 (m, 6H), 1.90–1.70 (m, 9H),
1.60–1.40 (m, 12H). 13C NMR (75 MHz, CDCl3): d 182.2 (d, JRh–
C = 50 Hz), 180.9 (d, JRh–C = 49 Hz), 137.0, 136.6, 129.5, 129.3,
129.1, 129.0, 126.5, 125.6, 118.0, 117.6, 116.6, 115.9, 99.9, 99.8,
99.7, 77.5, 71.9, 71.8, 71.7, 71.6, 71.5, 71.3, 71.1, 66.1, 62.8, 58.0,
57.6, 53.8, 39.1, 38.0, 37.5, 33.7, 31.5, 31.4, 30.9, 30.7, 29.4, 29.2,
29.0, 24.1, 24.0, 23.2, 23.1, 22.3, 21.1; Anal. Calcd for C25H35N3RhIS:
C, 46.96; H, 5.52; N, 6.57. Found: C, 46.76; H, 5.34; N, 6.41.
28.8, 27.8, 26.5, 26.2, 25.8, 25.7, 20.8, 16.4. ½a D20
¼ ꢂ160:0 (c 0.2,
ꢁ
CHCl3). MS (FAB): m/z (%) = 684 (10, M+–Br), 576 (30), 133 (100).
HRMS (FAB) m/z calcd for C38H51N3SRh 684.2859, found 684.2846.
4.1.8. (Sa,SS)-{1-[(R)-2-(Cyclohexylthio)-3-methylbutyl]-3-[(2S,
5S)-2,5-diphenylpyrrolidin-1-yl]-imidazol-2-ylidene}(1,5-cyclo-
octadiene)rhodium(I) hexafluorophosphate (Sa,SS)-13
Method A: At first, silver (I) oxide (23 mg, 0.1 mmol) was added
to a solution of the imidazolium bromide 11 (111 mg, 0.2 mmol) in
dry CH2Cl2 (3 mL) under argon and was stirred in the dark for 2 h.
The reaction mixture was then filtered through Celite, washed with
CH2Cl2, and concentrated in vacuo to give the silver carbene
(134 mg, 99%). To a solution of this material (82 mg, 0.17 mmol)
in dry CH2Cl2 (2 mL) was added via a cannula a solution of rhodium
biscyclooctadiene hexafluorophosphate (79 mg, 0.17 mmol) in dry
CH2Cl2 (3 mL) under an argon atmosphere. The mixture was stirred
in the dark for 1 h, filtered through Celite, washed with CH2Cl2, and
concentrated in vacuo. Purification of the resulting residue by flash
chromatography (20:1 CH2Cl2–MeOH) gave a yellow oil which was
triturated with pentane to give (Sa,SS)-13 (130 mg, 92% yield) as a
yellow solid. Mp 132–134 °C. 1H NMR (400 MHz, CDCl3): d 7.43–
7.37 (br s, 4H), 7.32 (d, 2H, J = 8.0 Hz), 7.21–7.13 (m, 4H), 6.95
(br s, 2H), 6.87 (s, 1H), 6.16 (br s, 1H), 5.95 (s, 1H), 4.83 (m, 0.5H),
4.78 (br s, 1H), 4.56 (m, 1H), 4.49 (m, 1H), 4.32 (t, 1H, J = 8.4 Hz),
4.29–4.18 (m, 2.5 H), 2.84 (br s, 1H), 2.73–2.61 (m, 3H), 2.60–2.25
(m, 8H), 2.22–2.08 (m, 4H), 2.05–1.91 (m, 1H), 1.88–1.75 (m, 2H),
1.40–1.20 (m, 4H), 1.03 (d, 3H, J = 6.4 Hz), 0.97 (d, 3H, J = 6.4 Hz).
13C NMR (125 MHz, CDCl3): d 171.8 (d, JC–Rh = 52.0 Hz), 137.0,
4.1.6. (2S,Ra,SS)-1-Isopropyl-3-{2-[(phenylthio)methyl]
pyrrolidin-1-yl}-imidazol-2-ilydene (1,5-cyclooctadiene)
rhodium(I) hexafluoroantimonate
(Ra,SS)-8: At first, AgSbF6 (171 mg, 0.5 mmol) was added to a
solution of the diastereomeric mixture of (Ra/Sa)-7 (340 mg,
0.5 mmol) in dry CH2Cl2 (3 mL) and the mixture was stirred in dark
at room temperature for 1 h. The solvent was evaporated in vacuo

1562
A. Ros et al. / Tetrahedron: Asymmetry 21 (2010) 1557–1562
10. Lee, K.-s.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132, 2898–2900.
11. Alcarazo, M.; Roseblade, S. J.; Alonso, E.; Fernández, R.; Álvarez, E.; Lahoz, F. L.;
Lassaletta, J. M. J. Am. Chem. Soc. 2004, 126, 13242–13243.
12. Ros, A.; Monge, D.; Alcarazo, M.; Álvarez, E.; Lassaletta, J. M.; Fernández, R.
Organometallics 2006, 25, 6039–6046.
13. Ros, A.; Alcarazo, M.; Iglesias-Sigüenza, J.; Díez, E.; Álvarez, E.; Fernández, R.;
Lassaletta, J. M. Organometallics 2008, 27, 4555–4564.
14. Roseblade, S. J.; Ros, A.; Monge, D.; Alcarazo, M.; Álvarez, E.; Lassaletta, J. M.;
Fernández, R. Organometallics 2007, 26, 2570–2578.
15. Cran, G. A.; Gibson, C. L.; Handa, S. Tetrahedron: Asymmetry 1995, 6, 1553–1556.
16. Caution: Nitrosamines are potent chemical carcinogens and should be handled
with extreme caution.
17. For the synthesis of N-(formylamino)acetaldehyde see: Hung, R. R.; Straub, J.
A.; Whitesides, G. J. Org. Chem. 1991, 56, 3849–3855.
18. For related examples of hindered Rh–C bonds see: (a) Ku, R. Z.; Huang, J. C.;
Cho, J. Y.; Kiang, F. M.; Reddy, K. R.; Chen, Y. C.; Lee, K. J.; Lee, G. H.; Peng, S. M.;
Liu, S. T. Organometallics 1999, 18, 2145–2154; (b) Herrmann, W. A.; Goossen, L.
J.; Spiegler, M. J. J. Organomet. Chem. 1997, 547, 357–366; (c) Westkamp, T.;
Schattenmann, W. C.; Spiegler, M. J.; Herrmann, W. A. Angew. Chem., Int. Ed.
1998, 37, 2490–2493; (d) Enders, D.; Gielen, H. J. J. Organomet. Chem. 2001, 617,
70–80; (e) Özdemir, I.; Yigit, B.; Çetinkaya, B.; Ülkü, D.; Tahir, M. N.; Arici, C. J.
Organomet. Chem. 2001, 633, 27–32; (f) Chianese, A. R.; Li, X.; Janzen, M. C.;
Faller, J. W.; Crabtree, R. H. Organometallics 2003, 22, 1663–1667.
19. Crystallographic data (excluding structure factors) for the structures of (Ra,SS)-
8 and (Sa,SS)-13 have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication nos. CCDC 767874 and 767875. Copies of
the data can be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, fax: +(44) 1223 336 033, e-mail: deposit@ccdc.cam.
ac.uk.
136.4, 132.1, 132.0, 129.3, 129.1, 128.9, 128.7, 128.5, 128.4, 128.2,
128.1, 121.1, 118.4, 94.7 (br s), 91.6 (d, JC–Rh = 6.9 Hz), 86.0 (d,
JC–Rh = 6.9 Hz), 69.8, 67.7, 63.7 (br s), 55.3, 51.9, 50.8, 35.1, 33.1,
32.8, 30.6, 30.4, 29.8, 28.9, 28.0, 26.9, 26.1, 25.5, 25.2, 20.1, 18.8.
½
a 2D0
ꢁ
¼ ꢂ61:6 (c 0.6, CHCl3). MS (FAB) m/z (%): 684 (100, M+ꢂPF6),
576 (82). HRMS (FAB) m/z calcd for C38H51N3SRh 684.2859, found
684.2872. X-ray quality crystals were grown by slow diffusion of
hexane into a solution of the complex in CH2Cl2.
Method B: AgPF6 (10 mg, 0.04 mmol) was added to a solution of
12 (28 mg, 0.04 mmol) in dry CH2Cl2 (0.5 mL) under an argon
atmosphere and the mixture was stirred in the dark at room tem-
perature for 1 h. The solvent was removed in vacuo and the reac-
tion crude was purified by flash chromatography (2:1 EtOAc–
hexane) to afford complex 13 as a yellow solid (32 mg, 86% yield).
Spectral and analytical data were as described above.
Acknowledgments
We thank the Spanish ‘Ministerio de Educación y Ciencia’
(grants CTQ2007-61915 and CTQ2007-60244), FEDER funds, and
the Junta de Andalucía (grants 2005/FQM-658 and 2008/FQM-
3833) for financial support.
20. The lack of interaction between the dialkylamino group and the heterocyclic
carbene has been also observed in related systems.11,12
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