Stereoselectivity in metal carbene and Lewis acid-catalyzed reactions from diastereomeric dirhodium(II) carboxamidates: Menthyl N-acetyl-2- oxoimidazolidine-4(S)-carboxylates

Article abstract of DOI:10.1016/j.jorganchem.2005.05.032

The influence of a chiral menthyl group as the pendant ester substituent on the N-acetyl-2-oxoimidazolidine-4S-carboxylate ligands in chiral dirhodium(II) imidazolidinone catalysts has been examined. Significant match/mismatch influences are evident in the observed stereocontrol for carbon-hydrogen insertion reactions with diazoacetates, but these effects are minimal in cyclopropanation reactions. Steric restrictions prevent effective enantiocontrol in hetero-Diels-Alder reactions using these menthyl-substituted catalysts.

Full text of DOI:10.1016/j.jorganchem.2005.05.032

Journal of Organometallic Chemistry 690 (2005) 5525–5532
www.elsevier.com/locate/jorganchem
Stereoselectivity in metal carbene and Lewis acid-catalyzed
reactions from diastereomeric dirhodium(II) carboxamidates:
Menthyl N-acetyl-2-oxoimidazolidine-4(S)-carboxylates
*
Michael P. Doyle , John P. Morgan, John T. Colyer
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA
Received 25 April 2005; received in revised form 19 May 2005; accepted 24 May 2005
Available online 6 July 2005
Abstract
The influence of a chiral menthyl group as the pendant ester substituent on the N-acetyl-2-oxoimidazolidine-4S-carboxylate
ligands in chiral dirhodium(II) imidazolidinone catalysts has been examined. Significant match/mismatch influences are evident
in the observed stereocontrol for carbon–hydrogen insertion reactions with diazoacetates, but these effects are minimal in cycloprop-
anation reactions. Steric restrictions prevent effective enantiocontrol in hetero-Diels–Alder reactions using these menthyl-substituted
catalysts.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Dirhodium(II); Metal carbene; Enantioselective; Cyclopropanation; Insertion; Hetero-Diels–Alder
1. Introduction
we have employed is the design of multiple ligand stereo-
centers to control overall catalyst–reactant orientation
which, in turn, influences product stereochemistry
[10,11]. We recently reported that homo-ligated dirho-
dium(II) carboxamidates, because of their structural
rigidity and their suitability as catalysts for several
chemical transformations [12], provide well-defined
frameworks with which to investigate catalyst-controlled
multiple asymmetric induction (‘‘match/mismatch’’
effects) [13]. In particular, additional stereocenters can
be conveniently built on 1-acyl-2-oxoimidazolidine-4-
carboxylate (‘‘imidazolidinone’’) ligands [14]. With cata-
lysts that feature diastereomeric pairs of imidazolidinone
ligands containing 2-phenylcyclopropane and N-benze-
nesulfonylproline attachments at the 1-N-acyl site,
recognizable levels of double asymmetric induction for
carbon–hydrogen insertion, cyclopropanation, and
hetero-Diels–Alder cycloaddition applications were read-
ily achieved [13].
Recent efforts in our research have been directed to-
ward broadening the understanding of stereochemical
factors that allow a chiral catalyst to influence product
configuration [1]. With catalysts whose ligand(s) have
multiple stereogenic elements, configurational and con-
formational conditions arise that can be transmitted
favorably (‘‘matched’’) or unfavorably (‘‘mismatched’’)
for increased or decreased stereocontrol in product for-
mation [2,3]. Numerous examples of this double asym-
metric induction exist in catalytic hydrogenation
chemistry, focusing primarily on match/mismatch effects
on stereoselectivity with bidentate phosphine ligands con-
taining multiple stereocenters [4–8]. Analogous influences
have been reported for a broad selection of catalytic
chemical transformations by the introduction of a
binaphthyl unit into the salen ligand [9]. The strategy that
*
One concern with these studies arises from prior
results which demonstrated that stereoselectivity
Corresponding author. Tel.: +1 301 405 1788; fax: +1 301 314 2779.
E-mail address: mdoylez@umd.edu (M.P. Doyle).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.05.032

5526
M.P. Doyle et al. / Journal of Organometallic Chemistry 690 (2005) 5525–5532
N
we examined stereocontrol in selected metal carbene
O
N
N
O
and Lewis acid-catalyzed reactions with dirhodium(II)
1-acyl-2-oxaimidazolidine-4-carboxylates, in which
additional stereocenters were placed in the 1-acyl site
(1/2 and 3/4 in Scheme 2). In this report we describe a
set of catalysts in which the stereocenters are placed in
the pendant ester group at the 4-position (5/6 in Scheme
2) and their comparative influence on stereocontrol in
the same set of reactions is discussed.
N
Rh
Rh
O
Rh
O
N
O
N
O
Side view
View down
Rh-Rh bond axis
Scheme 1. Dirhodium(II) carboxamidate complex in the (cis-2,2)
configuration.
decreased with dirhodium(II) oxaimidazoline-4-carb-
oxylates in which the pendant ester group was enlarged
from methyl to either ethyl or isobutyl (with a 3-phenyl-
propanoyl attachment at the 1-N-acyl site) [15]. These
experiments showed that increased levels of selectivity
could not be achieved by simply increasing the steric
bulk around the active site. However, decreasing the size
of the 1-N-acyl attachment to N-acetyl brought about a
relative increase in stereoselectivity, suggesting that a
delicate balance in steric distribution around the active
site of the catalyst must be achieved to maximize both
selectivity and reactivity.
Dirhodium(II) carboxamidates are constructed with
four bridging ligands around the dirhodium core so that
two nitrogen and two oxygen donor atoms are attached
to each rhodium with the composite arranged in a cis-
2,2 fashion (Scheme 1) [12]. In the previous report [13]
2. Experimental
2.1. General
1H (300 or 400 MHz) and 13C (75 or 100 MHz) NMR
spectra were recorded on Varian Unity 300 or Bruker
DRX 400 instruments, respectively. Chemical shifts
are reported in parts per million (ppm, d) downfield
from internal standard Me4Si in CDCl3, unless other-
wise noted. High-resolution mass spectra were measured
on JEOL SX102a, Bruker Reflex-III MALDI/TOF, and
JEOL HX110A spectrometers. Desert Analytics in
Tucson, AZ, performed elemental analyses. Melting
points were measured on a Meltemp 3.0 apparatus.
Optical rotations were measured on a Jasco DIP-1000
digital polarimeter. Enantiomeric excesses were deter-
mined on a Varian 3800 gas chromatograph, Hewlett
Packard 5890 gas chromatograph, or Hewlett Packard
1100 series HPLC with Chiraldex GC or Chiralcel
HPLC columns and conditions as noted for each
compound.
Reagents were obtained from Acros or Aldrich
Chemical Company and used without further purifica-
tion (unless otherwise noted). Dichloromethane,
acetonitrile, and chlorobenzene were dried by distilla-
tion over calcium hydride. Diazoacetates were prepared
from the commercially available alcohols by literature
procedure [16], except for ethyl diazoacetate, which
was commercially available. DanishefskyÕs diene was
distilled prior to use.
O
O
N
S
N
S
N
N
O
O
O
O
CH3
O
CH3
O
O
N
O
N
O
O
Rh Rh
Rh Rh
Rh2(4S,2'R-BSPIM)4
Rh2(4S,2'S-BSPIM)4
1
2
O
N
O
N
O
O
CH3
CH3
O
N
O
N
O
O
Rh Rh
Rh Rh
2.2. Synthesis of (10S,20R,50S)-menthyl 3-benzyloxy-
carbonyl-2-oxoimidazolidine-4(S)-carboxylate (12)
Rh2(4S,2'S,3'S-MCPIM)4
Rh2(4S,2'R,3'R-MCPIM)4
3
4
A 250 mL round bottom flask was charged with 3-
benzyloxycarbonyl-2-oxoimidazolidine-4(S)-carboxylic
acid 11 (10.0 g, 37.8 mmol), 4-dimethylaminopyridine
(0.114 g, 9.40 mmol), (1S,2R,5S)-(+)-menthol (5.90 g,
37.8 mmol), and 150 mL dichloromethane and cooled
to 0 ꢁC. A solution of N,N0-dicyclohexylcarbodiimide
(9.78 g, 47.3 mmol) in 30 mL of dichloromethane was
added over 30 min via syringe pump. After stirring for
5 days at room temperature, the white urea precipitate
was removed by filtration, and the resulting yellow
filtrate was concentrated under reduced pressure to
O
O
H3C
N
H3C
N
O
O
O
N
O
N
O
O
Rh Rh
Rh Rh
Rh2(1'S, 2'R, 5'S, 4S-MNACIM)4
Rh2(1'R, 2'S, 5'R, 4S-MNACIM)4
5
6
Scheme 2. Diastereomeric dirhodium(II) 1-acyl-2-oxaimidazolidine-4-
carboxylates.

M.P. Doyle et al. / Journal of Organometallic Chemistry 690 (2005) 5525–5532
5527
afford an orange oil. Ethyl acetate (100 mL) was added,
and the solution was washed with aqueous solutions of
1 M HCl (50 mL), saturated NaHCO3 (50 mL), and
deionized water (100 mL). The combined organics were
dried over anhydrous MgSO4. The resulting solution
was filtered, concentrated, and purified by column
chromatography (SiO2; ethyl acetate: hexanes = 2:1) to
yield 8.39 g of 12 as a white solid (20.8 mmol, 55%
yield). 1H NMR (300 MHz, CDCl3): d 7.37–7.27 (comp,
5H), 6.20 (br s, 1H), 5.26 (d, J = 12.5 Hz, 1H), 5.19 (d,
J = 12.5 Hz, 1H), 4.74–4.66 (comp, 2H), 3.74 (t,
J = 9.9 Hz, 1H), 3.37 (dd, J = 8.9, 3.8 Hz, 1H), 1.73–
1.67 (m, 1H), 1.80–1.59 (comp, 4H), 1.49–1.30 (comp,
2H), 1.13–0.92 (comp, 2H), 0.89 (d, J = 7.3 Hz, 3H),
0.82 (d, J = 6.8 Hz, 3H), 0.70 (d, J = 7.1 Hz, 3H). 13C
NMR (75 MHz, CDCl3): d 169.2, 155.7, 150.9, 135.1,
128.4, 128.3, 128.0, 76.2, 68.0, 55.9, 46.6, 40.8, 40.3,
CH2Cl2). HRMS for C24H33N2Oþ6 . Theoretical:
445.2339. Found: 445.2335.
2.4. Synthesis of (10S,20R,50S)-menthyl 1-acetyl-2-
oxoimidazolidine-4(S)-carboxylate (14)
A 100 mL round bottom flask was charged with
(10S,20R,50S)-menthyl 1-acetyl-3-benzyloxycarbonyl-2-
oxoimidazolidine-4(S)-carboxylate 13 (3.00 g, 6.75
mmol) and 30 mL ethyl acetate and placed under argon.
A
small amount of palladium black (ꢂ5.0 mg,
0.047 mmol) was added and the solution was flushed
with hydrogen from a balloon, stirring overnight at
room temperature. The mixture was subsequently fil-
tered through Celite and concentrated under reduced
pressure. The resulting off-white solid was purified by
column chromatography (SiO2; ethyl acetate:hexanes
3:2) to afford a white solid, which was recrystallized by
slow evaporation of a dichloromethane/hexanes solution
to afford 1.62 g of 14 as colorless crystals (5.33 mmol,
79% yield), m.p. 77–78 ꢁC. 1H NMR (300 MHz,
CDCl3): d 5.48 (s, 1H), 4.75 (dt, J = 11.0, 4.4 Hz, 1H),
4.22 (dd, J = 10.0, 4.9 Hz, 1H), 4.13 (dd, J = 11.5,
10.0 Hz, 1H), 4.01 (dd, J = 11.5, 4.9 Hz, 1H), 2.48 (s,
3H), 1.96 (m, 1H), 1.77 (m, J = 7.0 Hz, 1H), 1.71–1.63
(comp, 3H), 1.53–1.36 (comp, 2H), 1.09–0.92 (comp,
2H), 0.89 (dd, J = 6.7, 3.3 Hz, 6H), 0.90 (d, J = 3.3 Hz,
3H), 0.88 (d, J = 3.4 Hz, 3H), 0.73 (d, J = 6.8 Hz, 3H).
13C NMR (75 MHz, CDCl3): d 170.5, 169.7, 155.3,
34.0, 31.3, 26.0, 22.9, 21.9, 20.7, 15.8. M.p. 114–
24
D
115 ꢁC. ½aꢀ ¼ ꢁ13.6 (c 0.1, CH2Cl2). HRMS for
C22H31N2Oþ5 . Theoretical: 403.2233. Found: 403.2242.
2.3. Synthesis of (10S,20R,50S)-menthyl 1-acetyl-3-
benzyloxycarbonyl-2-oxoimidazolidine-4(S)-carboxylate
(13)
A 100 mL round bottom flask was charged with
(10S,20R,50S)-menthyl 3-benzyloxycarbonyl-2-oxoimi-
dazolidine-4(S)-carboxylate 12 (5.00 g, 12.4 mmol), 4-
dimethylaminopyridine (0.15 g, 1.24 mmol), pyridine
(2.00 mL, 25.0 mmol), and 50 mL dichloromethane.
The reaction vessel was equipped with a condenser,
flushed with nitrogen, and cooled to 0 ꢁC. Acetyl chlo-
ride (1.06 g, 14.9 mmol) was added over 30 min via syr-
inge pump, and the resulting solution was then stirred at
0 ꢁC for 30 min. The system was then heated to reflux
for 18 h to afford an orange solution. An additional
100 mL of dichloromethane was added, and the organic
solution was then washed with aqueous solutions of cold
1 M HCl (2 · 30 mL), saturated NaHCO3 (30 mL), and
saturated brine (30 mL). The solution was dried over
anhydrous MgSO4, filtered, and concentrated to an or-
ange foam, which was purified via column chromatogra-
phy (SiO2; ethyl acetate: hexanes 1:1) to yield 4.20 g of
13 (9.42 mmol, 76% yield) as a white powder. 1H
NMR (300 MHz, CDCl3): d 7.38–7.29 (comp, 5H),
5.27 (s, 2H), 4.69 (dt, J = 11.0, 4.4 Hz, 1H), 4.63 (dd,
J = 10.4, 3.8 Hz, 1H), 3.97 (dd, J = 11.9, 10.4 Hz, 1H),
3.77 (dd, J = 11.9, 3.8 Hz, 1H), 2.53 (s, 3H), 1.90–1.85
(m, 1H), 1.74 (m, J = 6.9 Hz, 1H), 1.70–1.60 (comp,
3H), 1.50–1.33 (comp, 2H), 1.07–0.91 (comp, 2H), 0.89
(d, J = 4.4 Hz, 3H), 0.83 (d, J = 4.4 Hz, 3H), 0.70 (d,
J = 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): d 170.7,
168.9, 150.9, 149.5, 134.7, 128.8, 128.3, 128.1, 77.6,
76.7, 49.7, 46.8, 44.9, 40.6, 34.0, 31.4, 26.2, 23.4, 23.1,
23
21.9, 20.8, 16.0. ½aꢀ ¼ þ110.6 (c 0.1, CH2Cl2). HRMS
D
for C16H27N2Oþ4 . Theoretical: 311.1971. Found:
311.1967. Anal. Calc. for C16H26N2O4: C, 61.95; H,
8.45; N, 9.03. Found: C, 62.11; H, 8.60; N, 9.20%.
2.5. Synthesis of dirhodium(II) tetrakis[(10S,20R,50S)-
menthyl 1-acetyl-2-oxoimidazolidine-4(S)-carboxylate],
Rh2(10S,20R,50S,4S-MNACIM)4(5)
A 25 mL two-neck round bottom flask equipped with
a stirbar, Soxhlet extractor, and condenser was flame-
dried and assembled while still warm under a flow of ar-
gon, utilizing teflon tape to seal all joints. A cellulose
extraction thimble filled with an oven-dried mixture of
sodium carbonate and sand (2:1) and capped with glass
wool was placed in the Soxhlet extractor during assem-
bly. Dirhodium(II) acetate (270 mg, 0.611 mmol) was
added though the open neck, along with (10S,20R,50S)-
menthyl 1-acetyl-2-oxoimidazolidine-4(S)-carboxylate
(14) (1.50 g, 4.83 mmol) and 15 mL chlorobenzene.
The side neck was sealed with a fresh septum, and the
reaction solution was heated to reflux. The progress of
ligand exchange was monitored by TLC using Merck
CN F254 plates in 97:3 methanol:acetonitrile. Heating
was stopped when no further change was observed
(approx. 16 h total heating time). The solution was
69.0, 52.6, 46.8, 42.4, 40.5, 34.1, 31.5, 26.2, 24.1, 23.1,
23
D
22.1, 20.9, 16.0. M.p. 98–99 ꢁC. ½aꢀ ¼ þ25.7 (c 0.1,

5528
M.P. Doyle et al. / Journal of Organometallic Chemistry 690 (2005) 5525–5532
concentrated and purified via column chromatography
on reverse phase Bakerbondꢂ CN resin (1 · anhydrous
THF, 1 · anhydrous ethyl acetate), with the first purple
band collected. The desired (2,2-cis)-isomer 5 was iso-
lated as 405 mg of a purple powder (0.281 mmol, 46%
yield). Attempts to crystallize the powder were unsuc-
cessful. 1H NMR (400 MHz, CDCl3): d 4.77–4.67
(comp, 4H), 4.12 (dd, J = 10.7, 4.8 Hz, 2H), 4.00–3.82
(comp, 6H), 3.56 (dd, J = 11.5, 2.8 Hz, 2H), 3.47 (dd,
J = 11.5, 4.8 Hz, 2H), 2.30 (s, 6H), 2.27 (s, 6H), 2.21–
2.15 (comp, 4H), 1.96 (s, 6H), 1.94 (comp, 2H), 1.84
(m, J = 6.8 Hz, 4H), 1.77–1.40 (comp, 16H), 1.23–1.04
(comp, 7H), 1.01 (d, J = 6.4 Hz, 6H), 0.99–0.94 (comp,
3H), 0.92 (d, J = 6.4 Hz, 6H), 0.91 (d, J = 6.8 Hz, 6H),
0.88 (d, J = 6.8 Hz, 6H), 0.73 (d, J = 7.2 Hz, 6H), 0.69
(d, J = 7.2 Hz, 6H). 13C NMR (100 MHz, CD3CN): d
174.8, 173.6, 169.1, 169.0, 166.3, 165.8, 76.2, 74.7,
60.1, 60.0, 48.7, 48.4, 48.2, 48.1, 43.0, 42.4, 35.1, 34.9,
vial was capped, sealed with parafilm, and stirred over-
night. The following day 3 drops of trifluoroacetic acid
were added and the solution was stirred for 30 min.
The product was then purified by column chromatogra-
phy and analyzed by HPLC for enantioselectivity
according to the literature procedure [21]. Yields were
determined by weight of isolated product after
chromatography.
3. Results and discussion
While ‘‘match/mismatch’’ effects have been observed
in metal carbene and Lewis acid-catalyzed reactions
with imidazolidinone catalysts having chiral N-acyl
attachments [13,21–23], the same attention has not been
given to those that incorporate stereogenic centers on
the ester moiety. In earlier results from several cata-
lytic applications, higher levels of selectivity were ob-
tained with dirhodium(II) tetrakis[20-methyl-10-propyl
1-acetyl-2-oxoimidazolidine-4(S)-carboxylate] Rh2(4S-
BACIM)4 (7, Scheme 3) [15] than with the imidazolidi-
none catalysts that generally provide the highest levels
of stereocontrol: Rh2(4S-MPPIM)4 (8) and dirho-
dium(II) tetrakis[methyl 1-acetyl-2-oxoimidazolidine-
4(S)-carboxylate], Rh2(4S-MACIM)4 (9) [24]. These
results suggested that the N-acetyl group should be pref-
erable if the size of the pendant ester group is increased.
In choosing the identity of this ester group, the high
selectivities shown by another dirhodium(II) catalyst,
Rh2(S,R-MenthAZ)4 (10) in asymmetric intermolecular
cyclopropanation reactions [25], pointed to the menthyl
ester as a logical choice.
32.3, 32.2, 27.2, 27.1, 24.1, 24.0, 23.6, 23.2, 22.8, 22.5,
24
21.1, 21.0, 16.5. ½aꢀ ¼ ꢁ210.6 (c 0.1, CH3CN). HRMS
D
for CsRh2C64H100N8O1þ6. Theoretical: 1575.4336.
Found: 1575.4451. Anal. Calc. for Rh2C66H103N9O16:
C, 53.40; H, 6.99; N, 8.49. Found: C, 53.25; H, 7.14;
N, 8.31%.
2.6. General procedure for the catalytic decomposition of
diazoacetates
A flame-dried 25 mL round bottom flask, equipped
with a condenser and a stirbar, was charged with the
catalyst (0.004 mmol, 1 mol%) and flushed with nitro-
gen. Dichloromethane (5.0 mL) was added via syringe,
and the reaction vessel was heated to 35 ꢁC. The dia-
zoacetate (0.40 mmol) was weighed into an oven-dried
vial (previously flushed with nitrogen). Dichlorometh-
ane (2.0 mL) was added to the diazo compound and
the resulting solution was added over 2 h to the refluxing
catalyst solution via syringe pump. After addition was
complete, the solution was heated at reflux for an addi-
tional hour and then filtered through a silica plug (elut-
ing with dichloromethane) to remove the catalyst. The
resulting solution was concentrated under reduced pres-
sure and the various products were purified by column
chromatography. Enantio- and diastereoselectivities
were measured (prior to chromatographic purification)
by gas chromatography utilizing a chiral GC column
as previously reported [17–20]. Yields were determined
by weight of isolated product after chromatography.
The synthesis of the (ꢁ)-menthyl ester of the
N-acetyl-2-oxaimidazolidine-4(S)-carboxylate ligand has
been reported, and the subsequent preparation of
2.7. General procedure for hetero-Diels–Alder reactions
An oven-dried vial containing a stirbar was charged
with the dirhodium(II) carboxamidate catalyst
(0.002 mmol, 1.0 mol%) and the aldehyde (5.0 eq,
1.0 mmol). Dichloromethane (1.0 mL) and the Dani-
shefsky diene (1.0 eq, 0.20 mmol) were added and the
Scheme 3. Imidazolidinone-ligated dirhodium(II) catalysts.

M.P. Doyle et al. / Journal of Organometallic Chemistry 690 (2005) 5525–5532
5529
O
HN
O
HO
O
OH
H3C
O
N
HN
O
N
H3C
Cl
O
O
O
O
N
O
O
N
DMAP, Pyridine
CH2Cl2
O
O
DCC, DMAP
CH2Cl2
11
O
O
O
76%
12
13
55%
1 atm H2
Pd Black
EtOAc
79%
O
H3C
N
O
N
O
Rh2(OAc)4
O
N
H3C
O
Rh Rh
O
O
PhCl, reflux
46%
O
N
H
Rh2(1'S, 2'R, 5'S, 4S-MNACIM)4
5
14
Scheme 4. Synthesis of imidazolidinone-ligated Rh2(10S, 20R, 50S, 4S-MNACIM)4.
Rh2(10R,20S,50R,4S-MNACIM)4 (6) has been previ-
ously described [26]. The synthesis of the diastereomer
of 5, Rh2(10S,20R,50S,4S-MNACIM)4 (5), proceeded in
an identical fashion (Scheme 4). The d-menthyl ester
12 was formed through a DCC coupling with (+)-men-
thol and the 4(S)-imidazolidinone carboxylic acid 11
to afford the white solid 12 in 55% yield. The N-acetyl
group was then attached in the presence of DMAP
and pyridine to afford the protected ligand 13 in 76%
yield. Exposure to heterogeneous hydrogenation condi-
tions produced the ligand 10S,20R,50S,4S-HMNACIM
(14) in 79% yield after recrystallization. Catalyst 5 was
generated by ligand exchange with rhodium acetate to
produce a red powder in 46% yield. Attempts to obtain
X-ray quality crystals of 5 have thus far been
unsuccessful.
However, the structure of 6 [26] (Fig. 1) exemplifies
the general features of this ligand design. In the depic-
tion presented in Fig. 1, only the attachments on the li-
gands that are closest to the front rhodium are shown.
Thus, there are two chiral menthyl-carboxylate attach-
ments on adjacent quadrants around the rhodium
Fig. 1. Configurational depictions of ‘‘matched’’ (A, complex 5) and ‘‘mismatched’’ (B, complex 6) dirhodium(II) 1-N-acetyl-2-oxaimidazolidine-
4(S)-carboxylates, together with the front view of 6 showing only the attachments that are closest to the front rhodium [26].

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M.P. Doyle et al. / Journal of Organometallic Chemistry 690 (2005) 5525–5532
Table 1
Intramolecular carbon–hydrogen insertion reactions of cyclohexyl diazoacetate
H
H
O
CHN2
O
O
1.0 mol % Rh2L4
CH2Cl2
+
O
O
O
H
H
15
16
17
Catalyst
Overall yield
Ratio of 16:17
16 (% ee)
17 (% ee)
Rh2(10S,20R,50S,4S-MNACIM)4 (5)
Rh2(10R,20S,50R,4S-MNACIM)4 (6)
80%
71%
100:0
79:21
95
84
NA
68
Table 3
Intramolecular carbon–hydrogen insertion reactions of 2-methoxy-1-
ethyl diazoacetate
center, and two achiral N-acetyl substituents lie in the
remaining two quadrants. The positioning of the men-
thyl groups can be aligned with the carboxylate group
(structure A in Fig. 1) or stereochemically opposed to
the configuration of the carboxylates (structure B in
Fig. 1). With its configurational 10-S/4-S match, catalyst
5 has the appearance of A and 6, then, has the appear-
ance of B.
H
1.0 mol % Rh2L4
CH2Cl2
H3CO
O
CHN2
H3CO
O
O
O
20
21
Catalyst
Overall yield of 21
% ee
Rh2(10S,20R,50S,4S-MNACIM)4 (5)
Rh2(10R,20S,50R,4S-MNACIM)4 (6)
66%
75%
93
55
To understand the selectivity differences between cat-
alysts 5 and 6, a selection of substrates was subjected to
each of the two catalysts under standard reaction condi-
tions (1 mol% catalyst loading). With cyclohexyl dia-
zoacetate 15 (Table 1) catalyst 5 exhibited complete
diastereocontrol for carbon–hydrogen insertion, and
the enantiomeric excess for cis stereoisomer 16 was the
highest value seen for these reactions [12]. In contrast,
neither diastereoselectivity nor enantioselectivities were
high using catalyst 6.
A similar outcome is seen in the C–H insertion reac-
tions of cyclopentyl diazoacetate 18 (Table 2), although
with lower enantiomeric excess for 19 than observed
with either Rh2(4S-MACIM)4 (89% ee) [17] or
Rh2(4S-MPPIM)4 (93% ee) [18]. With 2-methoxy-1-
ethyl diazoacetate 20 (Table 3) [19] the difference in
product enantiomeric excess between catalysts 5 and 6
is substantial. Overall, the configurational influence of
the menthyl group on the N-acetyl-2-oxoimidazolidine-
4-carboxylate ligands in dirhodium-catalyzed C–H
insertion reactions is high, and appreciable match/mis-
match effects are present.
In contrast to carbon–hydrogen insertion reactions,
the two diastereomeric catalysts show minimal difference
in stereoselectivity for cyclopropanation reactions. With
methallyl diazoacetate 22 (Table 4) enantioselectivity
using catalysts 5 and 6 for intramolecular cyclopropana-
tion is comparable to that with Rh2(4S-MPPIM)4 [18]
(89% ee) or Rh2(4S-MACIM)4 [20] (78% ee), respectively.
In addition, there is virtually no difference between results
with 5 and 6 in either diastereoselectivity or enantioselec-
tivity for intermolecular cyclopropanation of styrene with
ethyl diazoacetate 24 (Table 5).
The data obtained for hetero-Diels–Alder reactions
between the Danishefsky diene 27 and both 4-nitrobenz-
aldehyde 28 (Table 6) or its thiophene analog 30 (Table
7) show that the menthyl ester prohibits effective stereo-
selective cycloaddition. This observation is consistent
with recent understanding of the steric demands from
the catalyst [21]. In contrast, under the same conditions,
Table 2
Intramolecular carbon–hydrogen insertion reactions of cyclopentyl
diazoacetate
Table 4
Intramolecular cyclopropanation of methallyl diazoacetate
H
O
CHN2
1.0 mol % Rh2L4
CH2Cl2
H3C
O
1.0 mol % Rh2L4
O
CHN2
O
O
CH2Cl2
O
O
O
H
22
23
18
19
Catalyst
Overall yield of 23
% ee
Catalyst
Overall yield of 19
% ee
Rh2(10S,20R,50S,4S-MNACIM)4 (5)
Rh2(10R,20S,50R,4S-MNACIM)4 (6)
70%
62%
83
73
Rh2(10R,20S,50R,4S-MNACIM)4 (5)
Rh2(10S,20R,50S,4S-MNACIM)4 (6)
79%
84%
77
33

M.P. Doyle et al. / Journal of Organometallic Chemistry 690 (2005) 5525–5532
5531
Table 5
Intermolecular cyclopropanation of styrene with ethyl diazoacetate
O
O
1.0 mol % Rh2L4
CH2Cl2
Et
O
CHN2
Et
+
+
O
Et
O
O
trans
cis
26
24
25
Catalyst
Overall yield
Ratio of 25:26
25 (% ee)
26 (% ee)
Rh2(10S,20R,50S,4S-MNACIM)4 (5)
Rh2(10R,20S,50R,4S-MNACIM)4 (6)
61%
56%
49:51
47:53
43
45
28
46
Table 6
Hetero-Diels–Alder reaction of the Danishefsky diene with 4-nitro-
benzaldehyde
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Acknowledgments
Support for this research from the National Science
Foundation and the National Institutes of Health is
greatly appreciated.
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accepted for publication.

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