Bis(2-alkylpyrrolidin-1-yl)methylidenes as chiral acyclic diaminocarbene ligands

Article abstract of DOI:10.1021/om901112n

2-Alkylpyrrolidines were used as building blocks for acyclic diaminocarbenes (ADCs). First, ureas were made from the corresponding amines, and then the ureas were converted to chloroamidiniums. The chloroamidiniums served as direct precursors to ADCs, and

Full text of DOI:10.1021/om901112n

Organometallics 2010, 29, 1729–1739 1729
DOI: 10.1021/om901112n
Bis(2-alkylpyrrolidin-1-yl)methylidenes as Chiral Acyclic
Diaminocarbene Ligands
David R. Snead, Sebastien Inagaki, Khalil A. Abboud, and Sukwon Hong*
Department of Chemistry, University of Florida, P.O. Box 117200, Gainesville, Florida 32611-7200
Received December 23, 2009
2-Alkylpyrrolidines were used as building blocks for acyclic diaminocarbenes (ADCs). First,
ureas were made from the corresponding amines, and then the ureas were converted to chloro-
amidiniums. The chloroamidiniums served as direct precursors to ADCs, and palladium complexes
were made utilizing oxidative addition, whereas lithium-halogen exchange was performed to
generate rhodium complexes. The carbene ligands were characterized through use of NMR, mass
spectrometry, and X-ray analysis, and from X-ray structures, steric parameters were calculated as
% VBur values. The ability of these ligands to direct stereochemistry and enhance activity was
explored in the Suzuki cross-coupling reaction and the 1,2 addition of arylboronic acids to
aldehydes.
Introduction
N-Heterocyclic carbenes (NHCs) are frequently encoun-
tered as ancillary ligands in organometallic catalysis
owing to their ability to act as strong σ donors and
also because of their atmospheric and thermal stability.1
Acyclic diaminocarbenes (ADCs) are of particular interest,
as they possess different electronic and steric para-
Figure 1. ADCs feature N-C-N carbene bond angles of
greater width than NHCs.
more strongly donating and sterically demanding ligand
(Figure 1).2a,c,3-6
meters from NHCs. This difference stems from ADCs’
larger N-C-N carbene bond angle, which generates a
The first isolable ADC was discovered by Alder in 1996,2c
and following this report, Herrmann and co-workers pre-
pared ADC complexes with a variety of metals (Figure 2).3
Results detailing ADC-promoted catalytic activity have
recently surfaced with efforts exploring the Suzuki cross-
coupling,4c-e,5c,7a olefin metathesis,5a and allylic alkyla-
tion6b among other reactions. While many examples of chiral
NHCs exist,1d,e the first chiral ADC complex was recently
prepared by Slaughter and co-workers, featuring a bidentate
Chugaev-type carbene bound to palladium.4a,b The prolif-
eration of ADCs has lagged behind that of NHCs partially
due to challenges associated with synthesis of amidinium
precursors and ADC metal complexes, and this has inspired
alternative routes of accessing ADC compounds. For exam-
ple, while imidazolium (NHC) and amidinium (ADC) ions
are the most common precursors to free carbene, ureas or
*Corresponding author. E-mail: sukwon@ufl.edu.
ꢀ
(1) (a) Dıez-Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009,
´
109, 3612–3676. (b) Tapu, D.; Dixon, D. A.; Roe, C. Chem. Rev. 2009, 109,
3385–3407. (c) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47,
3122–3172. (d) Snead, D. R.; Seo, H.; Hong, S. Curr. Org. Chem. 2008, 12,
1370–1387. (e) Gade, L. H.; Bellemin-Laponnaz, S. Top. Organomet.
Chem. 2007, 21, 117–157. (f) Glorius, F. Top. Organomet. Chem. 2007,
21, 1–20. (g) Kantchev, E. A. B.; O'Brien, C. J.; Organ, M. G. Angew. Chem.,
Int. Ed. 2007, 46, 2768–2813. (h) Nolan, S. P., Ed. N-heterocyclic Carbenes
in Synthesis; Wiley-VCH: Weinheim, Germany, 2006. (i) Herrmann, W. A.
Angew. Chem., Int. Ed. 2002, 41, 1290–1309.
(2) (a) Alder, R. W.; Blake, M. E.; Chaker, L.; Harvey, J. N.; Paolini,
€
F.; Schutz, J. Angew. Chem., Int. Ed. 2004, 43, 5896–5911. (b) Alder,
R. W.; Blake, M. E.; Bufali, S.; Butts, C. P.; Orpen, A. G.; Sch€utz, J.;
Williams, S. J. J. Chem. Soc., Perkin Trans. 1 2001, 1586–1593. (c) Alder,
R. W.; Allen, P. R.; Murray, M.; Orpen, A. G. Angew. Chem., Int. Ed. 1996,
€
35, 1121-1123. Recent review: (d) Vignolle, J.; Cattoen, X.; Bourissou, D.
Chem. Rev. 2009, 109, 3333–3384.
(3) (a) Frey, G. D.; Rentzsch, C. F.; von Preysing, D.; Scherg, T.;
€
Muhlhofer, M.; Herdtweck, E.; Herrmann, W. A. J. Organomet. Chem.
2006, 691, 5725–5738. (b) Frey, G. D.; Herdtweck, E.; Herrmann, W. A.
J. Organomet. Chem. 2006, 691, 2465–2478. (c) Frey, G. D.; Herrmann,
W. A. J. Organomet. Chem. 2005, 690, 5876–5880. (d) Herrmann, W. A.;
Ofele, K.; von Preysing, D.; Herdtweck, E. J. Organomet. Chem. 2003, 684,
235–248. (e) Denk, K.; Sirsch, P.; Herrmann, W. A. J. Organomet. Chem.
2002, 649, 219–224.
(4) (a) Wanniarachchi, Y. A.; Kogiso, Y.; Slaughter, L. M. Organo-
metallics 2008, 27, 21–24. (b) Wanniarachchi, Y. A.; Slaughter, L. M. Chem.
Commun. 2007, 3294–3296. (c) Moncada, A. I.; Manne, S.; Tanski, J. M.;
Slaughter, L. M. Organometallics 2006, 25, 491–505. (d) Moncada, A. I.;
Manne, S.; Tanski, J. M.; Slaughter, L. M. J. Organomet. Chem. 2005, 690,
6247–6251. (e) Moncada, A. I.; Khan, M. A.; Slaughter, L. M. Tetrahedron
Lett. 2005, 46, 1399–1403.
(5) (a) Rosen, E. L.; Sung, D. H.; Chen, Z.; Lynch, V. M.; Bielawski,
C. W. Organometallics, 2009, ASAP. (b) Rosen, E. L.; Sanderson, M. D.;
Saravanakumar, S.; Bielawski, C. W. Organometallics 2007, 26, 5774–5777.
(c) Dhudshia, B.; Thadani, A. N. Chem. Commun. 2006, 668–670.
(6) (a) Snead, D. R.; Ghiviriga, I.; Abboud, K. A.; Hong, S. Org. Lett.
2009, 11, 3274–3277. (b) Hirsch-Weil, D.; Snead, D. R.; Inagaki, S.; Seo, H.;
Abboud, K. A.; Hong, S. Chem. Commun. 2009, 2475–2477.
€
€
(7) (a) Kremzow, D.; Seidel, G.; Lehmann, C. W.; Furstner, A.
Chem.;Eur. J. 2005, 11, 1833–1853. (b) Arduengo, A. J.III; Tapu, D.;
Marshall, W. J. J. Am. Chem. Soc. 2005, 127, 16400–16401. (c) F€urstner, A.;
Seidel, G.; Kremzow, D.; Lehmann, C. W. Organometallics 2003, 22, 907–
909. (d) McGuinness, D. S.; Cavell, K. J.; Yates, B. F.; Skelton, B. W.; White,
A. H. J. Am. Chem. Soc. 2001, 123, 8317–8328.
r
2010 American Chemical Society
Published on Web 03/16/2010
pubs.acs.org/Organometallics

1730 Organometallics, Vol. 29, No. 7, 2010
Snead et al.
Figure 2. Routes to acyclic diaminocarbenes (ADCs).
thioureas can also be used as carbene synthons. Early
research by Lappert8 and Stone9 laid the groundwork for
€
the methods of Cavell, Furstner, and Arduengo in the
conversion of ureas to chloroimidazoliums and subsequent
oxidative addition by an electron-rich metal center (Ni, Pd,
7
€
or Pt) to make carbenoid species. Specifically, Furstner used
this methodology to generate acyclic diaminocarbenes,7a,c
and following that report, we used lithium-halogen
exchange to convert chloroamidiniums into carbenes and
bind the ADC to metal.6a
Figure 3. Potential conformers associated with carbenes
designed about 2-substituted pyrrolidines.
metal center might promote some selectivity in catalytic
reactions and is less intruding into the metal coordination
sphere (conformer B). The rotamer with both substituents
positioned away from the metal center is expected to display
the lowest levels of selectivity in catalysis and exhibits the
least steric hindrance (conformer C). Bielawski and co-
workers have already demonstrated that the rotamers of
ADCs can be controlled to some extent.5a,b
Complexes capable of conformational flexibility can lead
to high catalytic activity, as illustrated by Glorius and co-
workers, since a transition metal promoted transformation
might require both an unhindered (open) and congested
(closed) environment during a catalytic cycle (Figure 4).10
For example oxidative addition is facilitated by a non-
crowded coordination sphere, whereas reductive elimination
is promoted by a sterically congested environment around
the metal. In reactions such as the Suzuki cross-coupling,
both processes are often important within the same catalytic
cycle, and while the needs of oxidative addition and reductive
We envisioned that ADCs based upon a 2-substituted
pyrrolidine framework could demonstrate interesting prop-
erties. Depending on the conformational preference of the
chiral substituents, the ligands might show an ability to
influence stereochemical outcomes in catalysis. Addition-
ally, the ligands might show high activity based upon con-
formational flexibility. Rotation about the N-C bond of the
carbene would provide a ligand capable of drastic alterations
in its steric profile (Figure 3). Adoption of a conformer with
both chiral groups situated close to the metal center might
afford a catalyst capable of displaying high enantioselecti-
vities and additionally is quite sterically hindered (conformer
A), while a conformer with one chiral group proximal to the
(8) (a) Hartshorn, A. J.; Lappert, M. F.; Turner, K. J. Chem. Soc.,
Dalton Trans. 1978, 348–356. (b) Hartshorn, A. J.; Lappert, M. F.; Turner, K.
J. Chem. Soc., Chem. Commun. 1975, 929–930. (c) Lappert, M. F.
J. Organomet. Chem. 1975, 100, 139–159. (d) Lappert, M. F.; Oliver,
A. J. J. Chem. Soc., Dalton Trans. 1974, 65–68. (e) Cetinkaya, M.; Lappert,
M. F.; Turner, K. J. Chem. Soc., Chem. Commun. 1972, 851–852.
(9) (a) Green, M.; Stone, F. G. A.; Underbill, M. J. Chem. Soc.,
Dalton Trans. 1975, 939–943. (b) Fraser, P. J.; Roper, W. R.; Stone, F. G. A.
J. Chem. Soc., Dalton Trans. 1974, 760–764. (c) Fraser, P. J.; Roper, W. R.;
Stone, F. G. A. J. Chem. Soc., Dalton Trans. 1974, 102–105.
(10) (a) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
J. Am. Chem. Soc. 2004, 126, 15195–15201. (b) Altenhoff, G.; Goddard, R.;
Lehmann, C. W.; Glorius, F. Angew. Chem., Int. Ed. 2003, 42, 3690–3693.

Article
Organometallics, Vol. 29, No. 7, 2010 1731
Figure 5. Potential conformers of ureas.
Figure 4. Unique abilities of conformationally flexible ligands.
(A) Potential conformers of a bis-oxazoline-based NHC where
the leftmost structure is relatively nonhindered and the structure
on the right is most hindered. (B) High catalytic activity of
conformationally flexible ligand.
Scheme 1. Synthesis of Ureas from 2-Substituted Pyrrolidine
Derivatives
Figure 6. Molecular structure of urea 1a. Thermal ellipsoids are
drawn at the 50% probability level. Selected bond lengths (A)
and angles (deg): O1-C1 1.235(1), N1-C1 1.373(1), N2-C1
1.374(1), N1-C1-N2 116.57(9), N2-C1-N1-C2 34.7(2),
N1-C1-N2-C7 33.6(2).
located distal to the carbonyl group. Indeed, when a single
crystal was obtained for ureas 1a and 1c, isomer A was
observed (Figures 6 and 7). The two pyrrolidine ring systems
are not coplanar. In the solid state, 1a demonstrates a
dihedral angle of ∼34° for N(2)-C(1)-N(1)-C(2) and N-
(1)-C(1)-N(2)-C(7), and in urea 1c these dihedral angles
are larger at ∼40°. Urea 1a possesses an N-C-N bond angle
of 116.57(9)°, but when the diphenyl methyl group of 1c is
incorporated, this value shrinks to 113.3(5)°, further deviat-
ing from the ideal 120° and pushing the methylene groups
adjacent to nitrogen closer together.
If a similar conformational preference is assumed for the
carbene analogues, 2-substituted pyrrolidines might serve as
good sources of chirality. In the solid state the ureas show a
conformational preference for A over B/C, and there seems
to be a degree of repulsion between C(2) and C(7) in 1a and
C(2) and C(19) in 1c. Carbenes should be less able to
accommodate the strain induced from conformations such
as B and C since they tend to be flatter and more conjugated
due to the empty p-orbital centered on carbon.
elimination appear to be at odds, they can be met with the use
of a conformationally flexible ligand.
Herein we report the synthesis and structural character-
ization of 2-alkylpyrrolidine-based chiral ADC-metal com-
plexes (Pd and Rh). Structural features of the ADC ligands
will be discussed through X-ray analysis including the steric
parameter, % VBur, and their catalytic performance in the
Suzuki reaction and 1,2 addition of 1-naphthylboronic acid
to o-anisaldehyde will be presented.
Results and Discussion
Commercially available amines (S)-(þ)-2-methylpyrroli-
dine and (R)-(þ)-2-(diphenylmethyl)pyrrolidine, as well as
two other readily accessible amines, (R)-(þ)-2-isopropylpyr-
rolidine and (R)-(þ)-2-benzylpyrrolidine, were treated with
phosgene to give symmetrically substituted ureas (1a-d) in
good yields (Scheme 1). N-Boc-(R)-(þ)-2-isopropylpyrroli-
dine and (R)-(þ)-2-benzylpyrrolidine were synthesized from
valine and phenylalanine, respectively, following a modified
procedure.11 Carbamate 2 was employed due to volatility of
the corresponding free amine, 2-isopropylpyrrolidine (see
Supporting Information for details).
Crystal structures of ureas 1a and 1c were obtained to
better understand conformational preference of the alkyl
substituents and to discern whether the ensuing carbenes
might be suitable as chiral ligands. Three different confor-
mers, A, B, and C, are attainable as rotation about the amide
bond is possible (Figure 5). Conformer A places the aliphatic
substituents proximal to the carbonyl functionality. This
isomer was expected to predominate over B and C, as it
relieves steric hindrance associated with an alkyl substituent
Ureas were treated with a chlorinating agent such as oxalyl
chloride to generate the chloroamidinium salts. Anion
exchange was performed on these salts to make them less
hygroscopic, and the chloride anion was substituted with a
tetrafluoroborate anion. The isolated chloroamidinium salts
were then reacted with Pd(PPh3)4 in toluene at 100 °C for two
hours, and the product was purified by recrystallization,
following Furstner’s protocols7a,c (Scheme 2).
€
Chloroamidiniums featuring primary alkyl substituents
such as 3a (methyl group) and 3b (benzyl group) afforded
ADC-Pd complexes in good yield. However, more congested
secondary alkyl-substituted carbene precursors 3c (CHPh2)
and 3d (i-Pr) did not afford the desired complex as an isolable
substance. Metal complexes4aand4bwere fullycharacterized
by mass spectroscopy and NMR, and a crystal structure of 4a
was obtained as well. Unfortunately, conclusive NMR and
massspectroscopy were not obtained for complexes 4cand 4d.
The X-ray crystal structure of complex 4a depicts an image
of a somewhat strained molecule (Figure 8). In contrast to
(11) (a) Kerr, M. S.; Read de Alaniz, J.; Rovis, T. J. Org. Chem. 2005,
ꢀ
70, 5725–5728. (b) Smrcina, M.; Majer, P.; Majerova, E.; Guerassina, T. A.;
Eissenstat, M. A. Tetrahedron 1997, 53, 12867–12874.

1732 Organometallics, Vol. 29, No. 7, 2010
Snead et al.
Figure 7. Molecular structure of urea 1c. Thermal ellipsoids are drawn at the 50% probability level. Selected bond lengths (A) and
angles (deg): O1-C1 1.242(6), N1-C1 1.372(6), N2-C1 1.373(7), N1-C1-N2 113.3(5), N2-C1-N1-C2 40.0(8), N1-C1-N2-C19
43.0(8).
Figure 8. Molecular structure of complex 4a. Thermal ellipsoids are drawn at the 50% probability level. Hydrogen atoms and C80
omitted for clarity. Selected bond lengths (A) and angles (deg): Pd1-C1 2.022(3), Pd1-Cl1 2.3514(7), Pd1-P1 2.3440(7), Pd1-P2
2.3413(7), N1-C1-N2 123.9(2), N2-C1-N1-C5 12.6(5), N1-C1-N2-C10 14.8(5).
Scheme 2. Synthesis of Chloroamidinium Salts and Pd-Carbene Complexes
the urea crystal structure, the methyl groups are positioned
away from the metal center, apparently to reduce steric
repulsions with the triphenyl phosphine ligands. The phenyl
rings of triphenyl phosphine are staggered with respect to the
chloride ligand yet eclipsed with regard to the carbene. This
close proximity and resulting repulsion certainly play a role
in the orientation of the methyl groups.
€
Similarly to crystal structures obtained by Furstner and
co-workers,7a,c the plane of the carbene created by N(1)-C-
(1)-N(2) is nearly orthogonal to the metal coordination

Article
Organometallics, Vol. 29, No. 7, 2010 1733
Table 1. Substrate Scope and Optimization of Suzuki Cross-Coupling Reaction
plane defined by the four ligands P(1), P(2), Cl(1), and C(1).
The dihedral angles of N(2)-C(1)-N(1)-C(5) and N(1)-C-
(1)-N(2)-C(10) are less than those observed with the
corresponding urea. They are 12.6(5)° and 14.8(5)°, respec-
tively, still showing a slight divergence from coplanarity
and complete conjugation. The N-C-N carbene bond angle
is 123.9(2)° with a palladium carbene bond length of
2.022(2) A. When bulky chloroamidiniums such as 3c and
3d are used, the corresponding carbene ligands will have
greater steric repulsion toward the backside of the ADC.
This destabilizing interaction may account for the difficulty
in obtaining the more complex compounds 4c and 4d.
Palladium complexes of electron-rich, sterically demand-
ing phosphines or NHC ligands are effective catalysts for
sterically demanding Suzuki couplings, and those ligands are
believed to stabilize a putative monoligated Pd complex.12 It
is known that the oxidative addition step is promoted by a
highly σ-donating ligand to stabilize the PdII oxidation state,
whereas the reductive elimination step can be accelerated by
a sterically demanding ligand. Therefore, the highly σ-donating
and bulky ADC ligand is perfect, meeting those exact
requirements. In fact, Thadani and co-workers reported that
ADC-Pd complexes efficiently catalyze demanding Suzuki
couplings, and therefore application of chiral ADC-Pd
complexes in the asymmetric Suzuki coupling reaction is
promising.5c Prior to our studies, Furstner and co-workers
€
reported use of the cationic palladium-carbene complexes in
the Suzuki reaction. Using 1 mol % of 5, phenyl boronic acid
and 4-bromoacetophenone were coupled in 89% yield (eq 1).
Application of the reported conditions for 5 led to low to
moderate yields in the coupling of simple substrates with the
new ADC-Pd complexes (entries 1 and 2, Table 1). Optimiz-
ing the conditions by changing the base and increasing the
amount of catalyst improved the yield (entry 3). Hindered
(12) (a) Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott,
N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128, 4101–4111. (b)
Christmann, U.; Vilar, R. Angew. Chem., Int. Ed. 2005, 44, 366–374. (c)
Suzuki, A. Proc. Jpn. Acad., Ser. B 2004, 80, 359–371. (d) Bellina, F.;
Carpita, A.; Rossi, R. Synthesis 2004, 15, 2419–2440.

1734 Organometallics, Vol. 29, No. 7, 2010
Snead et al.
Table 2. Sterically Demanding Suzuki Cross-Coupling by ADC-
Pd Catalystsa
Figure 9. Molecular structure of complex 8a. Thermal ellipsoids
are drawn at the 50% probability level. Selected bond lengths (A)
and angles (deg): Rh1-C9 2.021(2), Rh1-Cl1 2.3884(6), Rh1-C1
2.111(2), Rh1-C2 2.103(2), Rh1-C5 2.241(2), Rh1-C6 2.197(2),
C13-H13A, 0.91(3), C13-H13B 0.95(4), C10-H10A 0.94(3),
C10-H10B 1.06(3), C17-H17A 0.97(3), C17-H17B 0.97(3),
C14-H14A 0.92(3), C14-H14B 0.91(3), N1-C9-N2 117.9(2),
N2-C9-N1-C10 25.5(3), N1-C9-N2-C14 26.8(3).
were low and ranged from 3% to 4%. We speculated that
upon dissociation of the phosphines at elevated temperature,
the chiral centers might not reposition to be proximal to the
metal center.
a Conditions: 3 mol % [Pd], 1 equiv of ArBr, 1.2 equiv of ArB(OH)2,
2.8 equiv of CsF, THF, 100 °C. b Complex generated in situ and used
without further purification.
Recently, we reported a new and complementary metho-
dology to oxidative addition for the generation of diamino-
carbene species through lithium-halogen exchange.6a
Chloroamidiniums based upon 2-alkylpyrrolidines were
complexed to rhodium centers utilizing this technique, yield-
ing chiral complexes 8a through 8e (eq 2). Again, carbenes
with methyl and benzyl substituents were capable of binding
to a transition metal; however, using the new protocol and
[Rh(COD)Cl]2 as a precursor, bulkier substituents such as
isopropyl and diphenylmethyl (CHPh2) were successfully
incorporated. All metal complexes were characterized by
1H NMR, 13C NMR, and HRMS.
tri-ortho-substituted biaryls were produced in excellent
yields (entries 5 and 6), and the catalysts tolerated both
methoxy and nitro functionalities (entry 7). However,
attempting the very challenging synthesis of tetra-ortho-
substituted biaryls did not result in product formation
(entries 8 and 9).
The catalyst was varied when producing biaryl 7, and it is
interesting to note that the carbenes showing the most steric
hindrance provided the lowest yields in Suzuki cross-
coupling reactions (Table 2). This might be attributed to
the increasing steric repulsion, perhaps causing the ligands to
become more labile. Although difficult to isolate, in situ
generation of catalyst 4c was attempted from chloroamidi-
nium and Pd(PPh3)4 and tested in catalysis, resulting in 64%
yield of 7 (entry 4, Table 2). Pd(PPh3)4 was tested separately
in the Suzuki reaction, to ensure catalysis with 4c was not
solely a result of residual Pd(PPh3)4 (entry 5, Table 2). The
observed ee’s in this asymmetric Suzuki coupling reaction13
Interestingly, X-ray analysis of complexes 8b and 8e
showed the chiral groups (Me and i-Pr) positioned toward
the metal center, which is different from the ADC-Pd
complexes, since the coordination sphere is ostensibly less
crowded in the absence of the triphenyl phosphine ligands
(Figures 9, 10, and 11). Complexes 8a and 8b exhibit nearly
identical N-C-N carbene bond angles of 117.9(2)° and
117.8(2)°, while 8e actually imparts the smallest bond angle
(116.3(2) A). The chiral carbene ligands show longer metal
to carbene bonds with the methyl and isopropyl variants
possessing Rh-ADC bonds of 2.052(3) and 2.060(2) A,
(13) (a) Uozumi, Y.; Matsuura, Y.; Arakawa, T.; Yamada, Y. M. A.
Angew. Chem., Int. Ed. 2009, 48, 2708–2710. (b) Bermejo, A.; Ros, A.;
Fernandez, R.; Lassaletta, J. M. J. Am. Chem. Soc. 2009, 130, 15798–15799.
ꢀ
(c) Sawai, K.; Tatumi, R.; Nakahodo, T.; Fujihara, H. Angew. Chem., Int. Ed.
2008, 48, 6917–6919. (d) Genov, M.; Almorin, A.; Espinet, P. Chem.;Eur.
J. 2006, 12, 9346–9352. (e) Baudoin, O. Eur. J. Org. Chem. 2005, 4223–
4229. (f) Mikami, K.; Miyamoto, T.; Hatano, M. Chem. Commun. 2004,
2082–2083. (g) Cammidge, A. N.; Crepy, K. V. L. Tetrahedron 2004, 60,
4377–4386. (h) Jensen, J. F.; Johannsen, M. Org. Lett. 2003, 5, 3025–3028.
(i) Castanet, A.; Colobert, F.; Broutin, P.; Orbringer, M. Tetrahedron:
Asymmetry 2002, 13, 659–665. (j) Yin, J.; Buchwald, S. L. J. Am. Chem.
Soc. 2000, 122, 12051–12052. (k) Cammidge, A. N.; Crepy, K. V. L. Chem.
Commun. 2000, 1723–1724.

Article
Organometallics, Vol. 29, No. 7, 2010 1735
olefin) and tangential to the coordination sphere of rhodium
(Figures 10 and 11).
This causes the hydrogen atoms adjacent to nitrogen to be
directed toward the open apical positions of rhodium, and
the carbon-hydrogen bond becomes parallel to the carbene
metal bond (Figure 12). For chiral complexes 8b and 8e,
these hydrogen atoms are in closer proximity to Rh (2.53(3)/
2.56(4) A and 2.51(2)/2.65(2) A, respectively) than for achiral
complex 8a (2.85(3)/2.97(3) A and 3.08(3)/3.26(4) A) due to
the reorientation of the ligand.
The 1H NMR signal corresponding to the protons proxi-
mal to the metal center were determined through use
of 2D NMR (see Supporting Information). The signal shifts
approximately 2 ppm downfield to about 6.5 ppm for chiral
analogues 8b and 8e, whereas the peaks appear near 4.5 ppm
for achiral complex 8a (Figure 12). That two protons are
shifted downfield in samples of both 8b and 8e seems to
suggest that a species similar to conformer A in Figure 1 is
present in solution. Samples of 8b and 8e in toluene were
heated in 10 °C increments from 25 to 95 °C; however, the
signal of the protons adjacent to the metal center did
not shift substantially or disappear (see Supporting Infor-
mation).
The electronic parameters of ADCs have been dis-
closed,2a,3,4a,4c,5b but the steric parameters have not been
detailed. ADCs possess larger carbene bond angles than
NHCs, positioning N-substituents closer to a metal’s coor-
dination sphere. Thus, ADCs are expected to be more
sterically demanding than similarly substituted NHCs.
Cavallo published a nice method for determining the steric
constraints of carbene ligands that has gained traction in the
carbene community recently.14,15 % VBur measures the
amount of a theoretical sphere surrounding a metal center
that is occupied by a ligand. Graciously, a Web application
was made available in order that values might be easily
calculated from crystallographic files.16
Figure 10. Molecular structure of complex 8b. Thermal ellip-
soids are drawn at the 50% probability level. Selected bond
lengths (A) and angles (deg): Rh1A-C1A 2.052(3), Rh1A-
Cl1A 2.3929(7), Rh1A-C12A 2.205(3), Rh1A-C13A 2.218(2),
Rh1A-C16A 2.098(3), Rh1A-C17A 2.119(3), C5A-H5AA
1.03(4), C2A-H2AA 0.96(4), C2A-H2AB 0.96(4), C10A-
H10AA 0.95(3), C7A-H7AA 0.91(5), C7-H7AB 0.88(4),
N1A-C1A-N2A 117.8(2), C7A-N2A-C1A-N1A 34.0(4),
C2A-N1A-C1A-N2A 20.1(4).
The bis(pyrrolidine) ADC ligand of complex 8a shows a
2.5% increase in % VBur over the N-methyl-substituted
imadazolidine ligand of 9 (entry 1 vs entry 5, Table 3) and
a 2% increase over the N-ethyl imadazole ligand (entry 1 vs
entry 6). While the ADCs do indeed appear to be bulkier
than comparable NHC ligands, the affects of a larger
carbene bond angle are not so dominant. In fact, simple
ADCs are less bulky than commonly used NHCs equipped
with substituents such as Mes, DIPP, and adamantyl. The
further substituted ligand of complex 8b leads to a % VBur
value of 29.7% (entry 2), which is quite similar to the value
we obtained when calculating the steric parameters from
Herrmann’s crystal structure of bis(diisopropylamino)carbene
(14) (a) Poater, A.; Cosenza, B.; Correa, A.; Giudice, S.; Ragone, F.;
Scarano, V.; Cavallo, L. Eur. J. Inorg. Chem. 2009, 1759–1766. (b) Kelly,
R. A.III; Clavier, H.; Giudice, S.; Scott, N. M.; Stevens, E. D.; Bordner, I.;
Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P. Organometallics 2008,
27, 202–210. (c) Fantasia, S.; Petersen, J. L.; Jacobsen, H.; Cavallo, L.;
Nolan, S. P. Organometallics 2007, 26, 5880–5889. (d) Dorta, R.; Stevens,
E. D.; Scott, N. M.; Costabile, C.; Cavallo, L.; Hoff, C. D.; Nolan, S. P.
J. Am. Chem. Soc. 2005, 127, 2485–2495. (e) Viciu, M. S.; Navarro, O.;
Germaneau, R. F.; Kelly, R. A.III; Sommer, W.; Marion, N.; Stevens, E. D.;
Cavallo, L.; Nolan, S. P. Organometallics 2004, 23, 1629–1635. (f) Hillier,
A. C.; Sommer, W. J.; Yong, B. S.; Petersen, J. L.; Cavallo, L.; Nolan, S. P.
Organometallics 2003, 22, 4322–4326.
Figure 11. Molecular structure of complex 8e. Thermal ellip-
soids are drawn at the 50% probability level. Selected bond
lengths (A) and angles (deg): Rh1-C1 2.060(2), Rh1-Cl1
2.3840(5), Rh1-C16 2.194(2), Rh1-C17 2.222(2), Rh1-C20
2.098(2), Rh1-C21 2.122(2), C5-H5 0.97(2), C2-H2A 0.96(2),
C2-H2B 0.91(2), C9-H9 0.98(2), N1-C1-N2 116.3(2),
C6-N2-C1-N1 33.0(2), C2-N1-C1-N2 27.6(3).
(15) (a) Wuertz, S.; Lohre, C.; Froehlich, R.; Bergander, K.; Glorius,
F. J. Am. Chem. Soc. 2009, 131, 8344–8345. (b) Fey, N.; Haddow, M. F.;
Harvey, J. N.; McMullin, C. L.; Orpen, A. G. Dalton Trans. 2009, 39, 8183–
8196. (c) Gusev, D. G. Organometallics 2009, 28, 6458–6461.
respectively, whereas the achiral complex has a shorter bond
length of 2.021(2) A. Rather than pointing toward rhodium,
the chiral groups adopt a conformation placing them parallel
to the axis created by ligands syn to carbene (chlorine and
(16) http://www.molnac.unisa.it/OMtools.php.

1736 Organometallics, Vol. 29, No. 7, 2010
Snead et al.
Figure 12. X-ray and 1H NMR comparisons of rhodium complexes 8a and 8b.
Table 3. Calculated % VBur Values for ADC Ligandsc
yield than NHC complexes or [Rh(COD)Cl]2.6a,17,18 The
highest enantioselectivity achieved with use of a carbene
ligand is 38% ee,19 and we sought to establish transfer of
chirality from our bis(2-alkylpyrrolidin-1-yl)carbene ligands
(Table 4). Achiral complex 8a was the most efficient catalyst,
converting the aldehyde to the diaryl methanol in 96%
within one hour (entry 1). The chiral catalysts were less
effective, requiring longer reaction times and producing
lower yields. Conversion to product often ceased after
several hours, as determined by TLC. Chiral HPLC was
used to determine the enantiomeric excess of the reaction,
and complex 8d induced the highest selectivity, 12% ee
(entry 5).
(17) For reviews see: (a) Miyaura, N. Bull. Chem. Soc. Jpn. 2008, 81,
1535–1553. (b) Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108, 288–325. (c)
Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev. 2006,
35, 454-470. For recent examples with NHCs see: (d) Trindade, A. F.; Gois,
ꢀ
P. M. P.; Veiros, L. F.; Andre, V.; Duarte, M. T.; Afonso, C. A. M.; Caddick, S.;
Cloke, F. G. N. J. Org. Chem. 2008, 73, 4076–4086. (e) Imlinger, N.; Wurst,
K.; Buchmeiser, M. R. J. Organomet. Chem. 2005, 690, 4433–4440. (f)
Imlinger, N.; Mayr, M.; Wang, D.; Wurst, K.; Buchmeiser, M. R. Adv. Synth.
Catal. 2004, 346, 1836–1843. (g) F€urstner, A.; Krause, H. Adv. Synth.
Catal. 2001, 343, 343–350.
a Mes = 2,4,6-trimethylphenyl. b DIPP = 2,6-diisopropylphenyl.
c Calculated with Bondi radii scaled by 1.17, 3.5 A radius of the sphere,
and 2.1 A distance of the ligand from the sphere. NHC values reported
by Cavallo and Nolan.14b
(18) For recent examples with phosphines see: (a) Jagt, R. B. C.;
Toullec, P. Y.; de Vries, J. G.; Feringa, B. L.; Minnaard, A. J. Org.
Biomol. Chem. 2006, 4, 773–775. (b) Duan, H.-F.; X., J.-H.; Shi, W.-J.;
Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479–1481. (c) Pucheault, M.;
Darses, S.; Genet, J.-P. Chem. Commun. 2005, 4714–4716. (d) Sakai, M.;
Ueda, M.; Miyaura, N. Angew. Chem., Int. Ed. 1998, 37, 3279–
3281.
(19) (a) Focken, T.; Rudolph, J.; Bolm, C. Synthesis 2005, 429–436.
(b) Arao, T.; Sato, K.; Kondo, K.; Aoyama, T. Chem. Pharm. Bull. 2006, 54,
1576–1581.
(entry 3).3e Fashioning the pyrrolidine ring with an isopropyl
group as in complex 8e increased the % VBur only to 30.7%
since the alkyl groups are not oriented toward the metal
coordination sphere (entry 4).
Previously we investigated the 1,2 addition of arylboronic
acids to aldehydes and observed that ADC ligands promoted
the formation of the diaryl methanol products in higher

Article
Organometallics, Vol. 29, No. 7, 2010 1737
Table 4. 1,2 Asymmetric Addition of 1-Naphthylboronic Acid to
o-Anisaldehyde
CH2Cl2, and Et2O were passed through two packed columns of
neutral alumina under positive pressure of dry nitrogen prior to
use. Toluene was passed through an alumina column and a
copper(II) oxide column under positive pressure of dry nitrogen
prior to use. Palladium carbene complex 6 and bis(pyrrolidinyl)
chloroamidinium tetrafluoroborate were prepared according to
7a
€
the method described by Furstner and co-workers. Iridium
complex 9 was prepared as previously described.6a All other
chemicals were commercially available and were used as re-
ceived without further purification. NMR spectra were recorded
using a FT-NMR apparatus, operating at 300 MHz for 1H
NMR and 75.4 MHz for 13C NMR. All chemical shifts for 1H
and 13C NMR spectroscopy were referenced to residual signals
from CDCl3, (1H) 7.27 ppm and (13C) 77.23 ppm. High-resolution
mass spectra were recorded on a GC/MS spectrometer or a TOF-
LC/MS spectrometer.
Bis((S)-2-methylpyrrolidin-1-yl)methanone, 1a. (S)-2-Methyl-
pyrrolidine (890 μL, 8.82 mmol), triethyl amine (3.68 mL, 26.4
mmol), and CH2Cl2 (17.6 mL) were added to a flame-dried
Schlenk flask, and the solution was stirred and cooled to 0 °C.
Phosgene (2.32 mL, 4.40 mmol) was slowly added in the form of
a 20 wt % solution in toluene, and the Schlenk flask was sealed
to prevent loss of gaseous phosgene. The reaction was vigor-
ously stirred for 4 h, at which point extra phosgene (1.16 mL,
2.20 mmol) was added to ensure complete reaction of the amine.
Stirring continued for an additional 4 h, and then the reaction
was quenched with water. The aqueous layer was extracted with
CH2Cl2 (20 mL ꢀ 3), dried with MgSO4, and concentrated. The
crude product was purified by silica gel column chromatogra-
phy (hexanes/ethyl acetate, 1:1) to give the pure urea (615 mg,
71%). 1H NMR (300 MHz, CDCl3): δ 3.87-4.07 (m, 2 H),
3.18-3.40 (m, 4 H), 1.98-2.16 (m, 2 H), 1.76-1.91 (m, 2 H),
1.59-1.76 (m, 2 H), 1.31-1.51 (m, 2 H), 1.16 (d, J = 6 Hz, 6 H).
13C NMR (75 MHz, CDCl3): δ 161.5, 54.0, 49.7, 34.1, 25.5, 21.0.
HRMS: calcd for C11H20N2O [M þ H]þ 197.1648, found 197.1643.
Bis((R)-2-benzylpyrrolidin-1-yl)methanone, 1b. This compound
was prepared analogously to 1a, using (R)-2-benzylpyrrolidine.
Yield: 76%. 1H NMR (300 MHz, CDCl3): δ 7.47-7.09 (m, 10
H), 4.28 (dd, J = 3.4, 6.3 Hz, 2 H), 3.45-3.05 (m, 6 H), 2.60 (dd,
J = 8.8, 12.9 Hz, 2 H), 1.90 (td, J = 2.6, 5.7 Hz, 2 H), 1.84-1.44
(m, 8 H). 13C NMR (75 MHz, CDCl3): δ 161.6, 139.4, 129.9,
128.3, 126.2, 59.6, 50.2, 40.8, 30.7, 25.5. HRMS: calcd for
C23H28N2O [M þ H]þ 349.2274, found 349.2279.
Conclusion
Simple ureas constructed from chiral 2-alkyl pyrrolidines were
synthesized as ADC precursors, and interest in these ligands lay
in their potential for heightened activity and potential to transfer
chirality. The ureas were treated with oxalyl chloride to generate
chloroamidinium salts. In the case of palladium, oxidative
addition was utilized to produce metal complexes for the Suzuki
cross-coupling reaction, and lithium-halogen exchange was
performed to make rhodium compounds for 1,2 addition of
aryl boronic acids to aryl aldehydes. It was envisioned that the
potential for conformational flexibility might improve the cata-
lytic ability of ADCs; however, the nonsubstituted achiral
catalysts demonstrated the highest activity.
X-ray structures were obtained for palladium complex 4a and
also for rhodium complexes 8a, 8b, and 8e. Notably, the
orientation of the chiral substituents was dependent upon the
other ligands surrounding the metal. In the case of bulky ligands
such as triphenylphosphine, the chiral groups positioned them-
selves away from the metal center, whereas with less sterically
demanding ligands, the chiral substituents were arranged in
close proximity to the metal. From the crystal structures, the
steric parameters of ADC ligands were characterized for the first
time, showing that ADCs are more sterically demanding than
similar NHCs. The results of these studies will aid the design of
better chiral ADC ligands in the future.
Bis((R)-2-(diphenylmethyl)pyrrolidin-1-yl)methanone, 1c. This
compound was prepared analogously to 1a, using (R)-2-(diphe-
nylmethyl)pyrrolidine. Yield: 84%. 1H NMR (300 MHz,
CDCl3): δ 7.47-7.16 (m, 18 H), 7.16-6.86 (m, 2 H), 5.21-
4.93 (m, 2 H), 3.94 (d, J = 9.3 Hz, 2 H), 3.12-2.90 (m, 2 H), 2.78
(d, J = 9.9 Hz, 2 H), 1.92-1.63 (m, 4 H), 1.63-1.39 (m, 4 H). 13
C
NMR (75 MHz, CDCl3): δ 162.2, 143.3, 142.6, 129.1, 128.8,
128.5, 128.1, 126.6, 126.2, 60.0, 56.1, 49.0, 28.7, 24.9. HRMS:
calcd for C35H36N2O [M þ H]þ 501.2900, found 501.2973.
Bis((R)-2-isopropylpyrrolidin-1-yl)methanone, 1d. Boc-pro-
tected amine 2 (1.00 g, 4.69 mmol) and ether (1 mL) were added
to a flame-dried Schlenk flask and cooled to 0 °C. Slowly, 4 M
HCl in dioxane (5.87 mL, 23.5 mmol) was added to the vigo-
rously stirred solution. The reaction was stirred at room tem-
perature for 3 h, and a white salt precipitated out of solution.
Solvent was removed in situ, and the solid was washed twice with
ether. The solid was dried in vacuo, and the general procedure
described above was used for formation of urea 1d (395 mg,
67%). 1H NMR (300 MHz, CDCl3): δ 4.27-3.91 (m, 2 H),
3.41-3.06 (m, 4 H), 2.05 (dd, J = 6.7, 12.7 Hz, 2 H), 1.83 (d, J =
5.4 Hz, 4 H), 1.77-1.63 (m, 2 H), 1.63-1.44 (m, 2 H), 0.98-0.73
(m, 12 H). 13C NMR (75 MHz, CDCl3): δ 162.4, 62.6, 50.9, 41.7,
30.3, 25.7, 19.7, 16.5. HRMS: calcd for C15H28N2O [M þ H]þ
253.2274, found 253.2264.
Experimental Section
(S)-1-(Chloro((S)-2-methylpyrrolidin-1-yl)methylene)-2-methyl-
pyrrolidin-1-ium Tetrafluoroborate, 3a. Bis((S)-2-methylpyrroli-
din-1-yl)methanone (1a) (400 mg, 2.09 mmol) was mixed with
General Remarks. All reactions were conducted in flame-
dried glassware under an inert atmosphere of dry argon. THF,

1738 Organometallics, Vol. 29, No. 7, 2010
Snead et al.
toluene (10.5 mL) in a flame-dried Schlenk flask. To this
solution was added oxalyl chloride (1.70 mL, 20.1 mmol), and
the reaction mixture was heated to 50 °C. The reaction was
stirred overnight, at which point, a brown, oily residue precipi-
tated out of solution. The reaction was cooled to room tem-
perature, and the toluene resting on top of the precipitate was
removed with a syringe. The oily residue was washed twice with
ether, dissolved in copious amounts of THF, and precipitated
with pentanes as a slightly orange solid. CH2Cl2 (12 mL) and
AgBF4 (407 mg, 2.09 mmol) were added to the solid. The
reaction was stirred for 1 h. After this time, the CH2Cl2 was
removed by filtration and transferred into a dry Schlenk flask
under an argon atmosphere, and the solids were washed with
CH2Cl2, collecting the organics. Volatiles were removed, and
the solid was dissolved with generous amounts of THF. The
product was precipitated with ether, resulting in a white solid
(445 mg, 70%). 1H NMR (300 MHz, CDCl3): δ 4.20-4.56 (m, 2
H), 3.90-4.13 (m, 2 H), 3.68-3.90 (m, 2 H), 2.25-2.56 (m, 2 H),
MHz, CD2Cl2): δ 134.6, 132.2, 132.0, 130.0, 129.7, 129.3, 129.3,
129.2, 59.0, 57.0, 54.4, 54.0, 53.7, 53.3, 52.9, 34.3, 32.1, 30.0,
22.9, 22.5, 21.7, 20.9, 20.2, 14.0. HRMS: calcd for
C47H50BClF4N2P2Pd [M - BF4]þ 845.2181, found 845.2152.
Chlorobis((R)-2-benzylpyrrolidinyl)methylidenebistriphenyl-
phosphinepalladium Tetrafluoroborate, 4b. This compound was
prepared analogously to 4a, using the chloroamidinium tetra-
fluoroborate 3b. Yield: 49%. 1H NMR (300 MHz, CD2Cl2): δ
7.83-7.63 (m, 5 H), 7.54 (br s, 10 H), 7.50-7.31 (m, 6 H),
7.31-7.01 (m, 17 H), 7.01-6.80 (m, 4 H), 5.49 (dt, J = 5.6, 11.5
Hz, 2 H), 4.48-4.28 (m, 2 H), 3.85-3.66 (m, 2 H), 2.96 (dd, J =
4.8, 13.9 Hz, 2 H), 2.72-2.49 (m, 2 H), 2.13-1.96 (m, 1 H),
1.96-1.81 (m, 2 H), 1.81-1.52 (m, 3 H), 1.43 (br s, 1 H),
1.34-1.01 (m, 3 H). 13C NMR (75 MHz, CD2Cl2): δ 185.8,
137.1, 135.3, 134.7, 134.3, 132.4, 131.6, 130.2, 129.1, 128.8,
128.5, 126.8, 71.5, 54.3, 40.0, 25.8, 22.8. HRMS: calcd for
C59H58BClF4N2P2Pd [M - BF4]þ 997.2810, found 997.2817.
General Procedure for Suzuki Cross-Coupling Reaction.
Synthesis of 2-Methoxy-1,10-binaphthalene. 1-Naphthylboronic
acid (46.4 mg, 0.269 mmol), 1-bromo-2-methoxynaphthalene
(52.4 mg, 0.221 mmol), palladium complex 4a (6.0 mg, 6.6
μmol), and CsF (94.0 mg, 0.619 mmol) were added to a flame-
dried Schlenk flask. THF (3.5 mL) was added to the solids, and
the reaction was heated at reflux for 16 h. After this time, the
reaction mixture was diluted with water and extracted with ethyl
acetate (3.5 mL ꢀ 3). The organic layers were combined, dried
with MgSO4, and concentrated. The crude product was purified
by column chromatography (hexanes/ethyl acetate, 50:1), re-
sulting in pure biaryl (59.7 mg, 95%). Enantiomeric excess was
determined by HPLC analysis using a chiral column (Chiralcel
OJ-H; hexane/2-propanol, 4:1; flow rate 1 mL/min; tR 8.5 and
13.5 min). 1H NMR (300 MHz, CDCl3): δ 8.12-7.82 (m, 4 H),
7.74-7.58 (m, 1 H), 7.55-7.41 (m, 3 H), 7.41-7.13 (m, 5 H),
3.78 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ 154.9, 134.8, 134.5,
134.0, 133.2, 129.7, 129.3, 128.7, 128.5, 128.1, 128.0, 126.6,
126.4, 126.1, 125.9, 125.8, 125.8, 123.8, 123.5, 114.1, 57.0.
HRMS: calcd for C21H16O [M]þ 284.1196, found 284.1190.
2,6-Dimethyl-1,10-biphenyl. This compound was prepared
analogously to 2-methoxy-1,10-binaphthalene. Yield: 100%.
1H NMR (300 MHz, CDCl3): δ 7.58-7.31 (m, 3 H),
7.29-7.01 (m, 5 H), 2.07 (s, 6 H). 13C NMR (75 MHz, CDCl3):
δ 142.1, 141.3, 136.3, 129.3, 128.7, 127.5, 127.3, 126.8, 21.1.
HRMS: calcd for C14H14 [M]þ 182.1090, found 182.1088.
2-Methyl-1,10-binaphthalene. This compound was prepared
2.11 (dd, J = 5, 1 Hz, 4 H), 1.63-1.88 (m, 2 H), 1.39 (d, 6 H). 13
C
NMR (75 MHz, CDCl3): δ 152.7, 62.4, 55.9, 33.5, 25.4, 20.3.
HRMS: calcd for C11H20BClF4N2 [M - BF4]þ 215.1310, found
215.1310.
(R)-2-Benzyl-1-(((R)-2-benzylpyrrolidin-1-yl)chloromethylene)-
pyrrolidin-1-ium Tetrafluoroborate, 3b. This compound was
prepared analogously to 3a, using bis((R)-2-benzylpyrrolidin-
1-yl)methanone, 1b. Yield: 57%. 1H NMR (300 MHz, CDCl3):
δ 7.34-7.11 (m, 10 H), 4.48 (br s, 2 H), 3.82 (br s, 4 H), 3.08 (dd,
J = 3.5, 14.6 Hz, 2 H), 2.82 (br s, 2 H), 2.11 (br s, 4 H), 2.04-1.82
(m, 4 H). 13C NMR (75 MHz, CDCl3): δ 152.9, 136.2, 129.9,
129.5, 129.1, 128.9, 128.6, 127.5, 67.4, 56.3, 40.3, 30.4, 24.9.
HRMS: calcd for C23H28BClF4N2 [M - BF4]þ 367.1936, found
367.1973.
(R)-2-Benzhydryl-1-(((R)-2-benzhydrylpyrrolidin-1-yl)chloro-
methylene)pyrrolidin-1-ium Tetrafluoroborate, 3c. This com-
pound was prepared analogously to 3a, using bis((R)-2-(diphe-
nylmethyl)pyrrolidin-1-yl)methanone, 1c. Yield: 52%. 1H
NMR (300 MHz, CDCl3): δ 7.35-7.18 (m, 20 H), 5.40-5.17
(m, 2 H), 3.99 (d, J = 10.0 Hz, 2 H), 3.21-2.95 (m, 2 H), 2.56 (t,
J = 9.4 Hz, 2 H), 1.98-1.83 (m, 4 H), 1.71-1.52 (m, 4 H). 13
C
NMR (75 MHz, CDCl3): δ 152.5, 140.3, 139.3, 129.2, 129.1,
129.0, 128.6, 128.4, 127.9, 127.7, 69.6, 55.5, 28.6, 24.0, 14.5.
HRMS: calcd for C35H36BClF4N2 [M - BF4]þ 519.2562, found
519.2585.
(R)-1-(Chloro((R)-2-isopropylpyrrolidin-1-yl)methylene)-2-
isopropylpyrrolidin-1-ium Tetrafluoroborate, 3d. This com-
pound was prepared analogously to 3a, using bis((R)-2-isopro-
1
analogously to 2-methoxy-1,10-binaphthalene. Yield: 93%. H
NMR (300 MHz, CDCl3): δ 8.13-7.85 (m, 4 H), 7.66 (dd, J =
7.0, 8.2 Hz, 1 H), 7.61-7.39 (m, 4 H), 7.37-7.19 (m, 4 H), 2.18 (s,
3 H). 13C NMR (75 MHz, CDCl3): δ 137.8, 136.4, 134.7, 134.0,
133.8, 132.9, 132.3, 128.9, 128.6, 128.0, 127.9, 127.8, 126.6,
126.4, 126.3, 126.2, 126.2, 125.9, 125.1, 20.8. HRMS: calcd for
C21H16 [M]þ 268.1247, found 268.1246.
1
pylpyrrolidin-1-yl)methanone, 1d. Yield: 61%. H NMR (300
MHz, CDCl3): δ 4.27 (br s, 2 H), 3.68 (br s, 4 H), 2.09 (br s, 8 H),
1.32 (br s, 2 H), 0.91 (br s, 6 H), 0.82 (br s, 6 H). 13C NMR (75
MHz, CDCl3): δ 156.4, 153.5, 71.7, 58.2, 57.7, 49.1, 30.6, 25.4,
25.0, 19.5, 16.0, 13.1. HRMS: calcd for C15H28BClF4N2 [M -
BF4]þ 271.1936, found 271.1928.
2-Methoxy-1-(2-nitrophenyl)naphthalene. This compound
was prepared analogously to 2-methoxy-1,10-binaphthalene.
Yield: 75%. 1H NMR (300 MHz, CDCl3): δ 8.18-8.05 (m,
1 H), 8.00-7.79 (m, 2 H), 7.79-7.65 (m, 1 H), 7.65-7.52 (m,
1 H), 7.51-7.27 (m, 5 H), 3.81 (s, 3 H). 13C NMR (75 MHz,
CDCl3): δ 153.5, 150.5, 133.9, 132.9, 132.9, 131.7, 130.3, 129.4,
128.6, 128.5, 127.2, 124.6, 124.3, 124.0, 120.7, 113.2, 56.6.
HRMS: calcd for C17H13NO3 [M]þ 279.0890, found 279.0890.
2-Methyl-1-phenylnaphthalene. This compound was prepared
Chlorobis((S)-2-methylpyrrolidinyl)methylidenebistriphenyl-
phosphinepalladium Tetrafluoroborate, 4a. Amidinium chloride
3a (40.8 mg, 0.140 mmol) was added to a flame-dried Schlenk
flask along with toluene (10 mL). To the suspension was added
Pd(PPh3)4 (162 mg, 0.140 mmol). The yellow solution was
heated to 100 °C, whereupon it quickly turned deep red in color.
The reaction was stirred for 2 h, at which point, a yellow solid
precipitated from solution. The mixture was allowed to cool to
room temperature, and the toluene was evaporated. Pentane
was added to the resulting solid (10 mL ꢀ 2), which was stirred
for 1 h before being decanted. CH2Cl2 was used to dissolve the
product, and insoluble salts were filtered off. Pentane was
layered on top of the filtrate to purify the product by recrys-
tallization (78 mg, 65%). 1H NMR (300 MHz, CD2Cl2): δ
7.81-7.53 (m, 25 H), 7.51-7.28 (m, 2 H), 7.23 (br s, 2 H), 4.85
(q, J = 9.1 Hz, 1 H), 4.07-3.70 (m, 3 H), 2.01-1.79 (m, 1 H),
1.79-1.60 (m, 2 H), 1.60-1.42 (m, 2 H), 1.34-1.21 (m, 1 H),
0.96-0.76 (m, 5 H), 0.54 (d, J = 6.6 Hz, 1 H). 13C NMR (75
1
analogously to 2-methoxy-1,10-binaphthalene. Yield: 98%. H
NMR (300 MHz, CDCl3): δ 7.90 (d, J = 8.1 Hz, 1 H), 7.84 (d,
J = 8.5 Hz, 1 H), 7.61-7.24 (m, 9 H), 2.30 (s, 3 H). 13C NMR (75
MHz, CDCl3): δ 140.0, 138.4, 133.3, 133.2, 132.2, 130.4, 128.8,
128.6, 128.0, 127.4, 127.2, 126.4, 126.0, 125.0, 21.0. HRMS:
calcd for C17H14 [M þ H]þ 219.1174, found 219.1184.
Chloro(η4-1,5-cyclooctadiene)bis(pyrrolidinyl)methylidene-
rhodium(I), 8a. To a Schlenk flask in a glovebox was added
100 mg (0.364 mmol) of bis(pyrrolidinyl)chloroamidinium tetra-
fluoroborate, and the flask was connected to a Schlenk line

Article
Organometallics, Vol. 29, No. 7, 2010 1739
outside the glovebox. THF (2 mL) was added, and the suspen-
sion was cooled to -78 °C with a dry ice/acetone bath. After
cooling, 2.5 M n-BuLi in hexanes (153 μL) was added. After 5
min, the suspension turned to a clear and slightly yellowish
solution upon formation of carbene. After stirring for 1 h at
-78 °C, [Rh(COD)Cl]2 (89.6 mg, 0.182 mmol) was added, and
the reaction slowly warmed to room temperature. Stirring at
room temperature proceeded for 12 h, at which point, solvent
was evaporated. To remove any remaining [Rh(COD)Cl]2, the
product was purified by chromatography on a very short pad of
silica gel. Columns were run starting with a mixture of 2:1
hexanes/ethyl acetate and proceeding to pure ethyl acetate.
The complexes showed very slight decomposition on silica gel,
so the product was further purified by dissolving the product in
ethyl acetate and then precipitating impurities with addition of
hexanes, giving 94 mg (65%) of complex. The product is
126.2, 98.1, 98.0, 97.8, 97.7, 78.6, 70.8, 69.5, 69.3, 69.1, 67.7,
67.5, 60.6, 60.0, 56.1, 55.8, 54.5, 54.1, 53.3, 49.0, 32.9, 32.8,
31.2, 31.2, 28.7, 28.6, 28.1, 26.7, 26.0, 25.8, 24.9, 23.8, 21.3,
14.4. HRMS: calcd for C43H48ClN2Rh [M - Cl]þ 695.2867,
found 695.2868.
Chloro(η4-1,5-cyclooctadiene)bis((R)-2-isopropylpyrrolidinyl)-
methylidenerhodium(I), 8e. This compound was prepared ana-
logously to 8a. Yield: 64%. 1H NMR (300 MHz, CDCl3): δ 5.85
(t, J = 5.7 Hz, 1 H), 5.54 (d, J = 6.2 Hz, 1 H), 4.96 (br s, 1 H),
4.78 (d, J = 4.7 Hz, 1 H), 3.74-3.58 (m, 1 H), 3.43-3.06 (m, 4
H), 3.06-2.81 (m, 2 H), 2.55-2.13 (m, 5 H), 2.13-1.45 (m, 13
H), 1.14-0.64 (m, 12 H). 13C NMR (75 MHz, CDCl3): δ 221.7,
221.1, 97.6, 97.5, 97.4, 97.3, 71.9, 69.8, 69.0, 68.8, 67.4, 67.2,
62.7, 54.7, 53.8, 51.0, 33.6, 33.5, 32.8, 32.6, 30.3, 29.4, 28.1, 26.0,
25.8, 24.8, 23.9, 23.8, 20.5, 20.2, 19.8, 19.7, 18.2, 16.5, 16.1.
HRMS: calcd for C23H40ClN2Rh [M - Cl]þ 447.2241, found
447.2256.
1
sufficiently soluble in hexanes. H NMR (300 MHz, CDCl3):
δ 4.80 (br s, 4 H), 4.44 (br s, 2 H), 3.40 (br s, 4 H), 3.18 (m, 2 H),
2.52-2.17 (m, 4 H), 2.10-1.71 (m, 12 H). 13C NMR (75 MHz,
CDCl3): δ 216.8, 216.2, 96.7, 96.6, 68.3, 68.1, 55.7, 51.9, 32.8,
28.9, 26.5, 24.9. HRMS: calcd for C17H28ClN2Rh [M - Cl]þ
363.1302, found 363.1312.
Procedure for 1,2-Addition of 1-Naphthylboronic Acid to
o-Anisaldehyde. Synthesis of (2-Methoxyphenyl)(1-naphthalenyl)-
methanol, 10. To a flame-dried Schlenk flask under argon were
added 50.0 mg (0.364 mmol) of o-anisaldehyde, 125 mg (0.728
mmol) of 1-naphthylboronic acid, 82.6 mg (0.728 mmol) of potas-
sium tert-butoxide, and 2.0 mg (5.2 μmol) of rhodium catalyst 8a.
Then 1.22 mL of DME and 0.33 mL of water were added, and the
solution was heated to 40 °C. The mixture was stirred for 1 h and
monitored by TLC (Rf 0.38, 4:1 hexanes/ethyl acetate). The solu-
tion was diluted with 10 mL of diethyl ether and 10 mL of water and
was then extracted three times. The organic layer was dried,
concentrated, and then purified by silica gel chromatography (8:1
hexanes/ethyl acetate) to isolate the product as a clear oil (92 mg,
96% yield). Enantiomeric excess was determined by HPLC analysis
with a chiral column (Chiralcel IA; hexanes/2-propanol, 9:1; flow
rate 1 mL/min; tR 12.5 and 13.8 min). 1HNMR(300MHz, CDCl3):
δ 8.05 (d, J = 7.4 Hz, 1 H), 7.96-7.79 (m, 2 H), 7.71 (d, J = 7.1 Hz,
1 H), 7.60-7.39 (m, 3 H), 7.37-7.22 (m, 1 H), 7.11-6.78 (m, 4 H),
3.91 (s, 3 H), 3.22 (br s, 1 H). 13C NMR (75 MHz, CDCl3): δ 157.2,
138.4, 134.0, 131.6, 131.3, 129.2, 128.9, 128.7, 128.3, 126.2, 125.7,
124.6, 124.5, 121.1, 110.8, 68.6, 55.8. HRMS: calcd for C18H16O2
[M - OH]þ 247.1177, found 247.1176.
Chloro(η4-1,5-cyclooctadiene)bis((S)-2-methylpyrrolidinyl)-
methylidenerhodium(I), 8b. This compound was prepared ana-
logously to 8a. Yield: 65%. 1H NMR (300 MHz, CDCl3): δ 6.42
(br s, 1 H), 5.93 (br s, 1 H), 5.57 (br s, 0.4 H), 5.09-4.62 (m, 2.3
H), 4.23-3.70 (m, 1.4 H), 3.28 (br s, 5 H), 1.82 (br s, 22 H). 13
C
NMR (75 MHz, CDCl3): δ 97.0, 97.0, 68.6, 68.4, 66.9, 66.7, 63.3,
61.9, 51.2, 50.9, 34.9, 33.2, 33.0, 32.6, 31.6, 31.1, 29.8, 29.3, 28.6,
28.3, 25.0, 23.3, 23.0, 21.0, 20.5, 14.3. HRMS: calcd for
C19H32ClN2Rh [M - Cl]þ 391.1615, found 391.1616.
Chloro(η4-1,5-cyclooctadiene)bis((R)-2-benzylpyrrolidinyl)-
methylidenerhodium(I), 8c. This compound was prepared ana-
1
logously to 8a. Yield: 36%. H NMR (300 MHz, CDCl3): δ
7.57-7.41 (m, 2 H), 7.39-7.08 (m, 8 H), 6.58-6.40 (m, 1 H),
6.26 (td, J = 3.2, 6.9 Hz, 1 H), 5.20-5.01 (m, 1 H), 4.89 (br s, 1
H), 4.41-4.20 (m, 1 H), 3.77-3.54 (m, 2 H), 3.54-3.34 (m, 2 H),
3.34-3.11 (m, 4 H), 3.02 (dd, J = 4.4, 13.5 Hz, 1 H), 2.77 (dd,
J = 10.4, 13.6 Hz, 1 H), 2.70-2.54 (m, 2 H), 2.54-2.22 (m, 4 H),
2.19-1.57 (m, 9 H). 13C NMR (75 MHz, CDCl3): δ 218.9, 218.3,
161.6, 139.8, 139.4, 138.9, 130.0, 129.9, 129.4, 128.8, 128.5,
128.3, 126.8, 126.3, 126.2, 97.5, 97.4, 97.3, 69.7, 69.4, 68.5,
68.1, 66.7, 66.5, 59.6, 52.2, 52.0, 50.3, 42.1, 40.9, 40.8, 33.2,
32.9, 30.7, 29.9, 29.0, 28.7, 28.1, 26.6, 25.5, 24.8, 23.2. HRMS:
calcd for C31H40ClN2Rh [M - Cl]þ 543.2241, found 543.2248.
Chloro(η4-1,5-cyclooctadiene)bis((R)-2-(diphenylmethyl)pyr-
rolidinyl)methylidenerhodium(I), 8d. This compound was pre-
pared analogously to 8a. Yield: 60%. 1H NMR (300 MHz,
CDCl3): δ 7.53 (d, J = 7.3 Hz, 2 H), 7.47-7.11 (m, 12 H), 6.96
(t, J=6.6 Hz, 1 H), 6.69-6.51 (m, 1 H), 5.71 (d, J = 3.8 Hz,
1 H), 4.81 (br s, 2 H), 4.36 (d, J = 6.2 Hz, 1 H), 3.20-2.99 (m,
2 H), 2.93 (dd, J = 5.3, 10.0 Hz, 1 H), 2.83-2.60 (m, 2 H),
2.49-2.12 (m, 3 H), 2.12-1.84 (m, 3 H), 1.84-1.40 (m, 7 H),
1.39-1.13 (m, 4 H). 13C NMR (75 MHz, CDCl3): δ 222.5,
221.9, 143.3, 143.2, 142.8, 142.6, 142.0, 141.6, 131.0, 129.9,
129.4, 129.3, 129.1, 129.0, 128.8, 128.6, 128.5, 128.4, 128.3,
128.0, 127.5, 127.4, 127.3, 127.1, 126.8, 126.7, 126.5, 126.2,
Acknowledgment. The authors thank the James &
Esther King Biomedical Research Program and Florida
Department of Health (08KN-04), the Donors of the
Petroleum Research Fund administered by the American
Chemical Society (PRF 46157-G1), and the University of
Florida for support of this research. S.H. thanks Oak
Ridge Associated Universities for the Ralph E. Powe
Junior Faculty Enhancement Award, and K.A.A. wishes
to acknowledge the National Science Foundation and the
University of Florida for funding of the purchase of the
X-ray equipment.
Supporting Information Available: Synthetic procedures,
analytical data for new compounds (pdf), and X-ray crystallo-
graphic data for 1a, 1c, 4a, 8a, 8b, and 8e (cif). This material is
available free of charge via the Internet at http://pubs.acs.org