Preparation of Aziridines
cyclopropanation of styrenes and R-methylstyrene, giving
high yields and enantioselectivities, as well as an unusual
selectivity for formation of the cis isomers of these
compounds at very low catalyst loadings of 0.5 mol %.
Furthermore, the catalysts offer a practical advantage
in that they allow for operation at room temperature.
Finally, it was found that complex 2a catalyzes the
aziridination of imines with good diastereoselectivity,
albeit with poor enantioselectivity. Importantly, the
cyclopropanation and aziridination reactions catalyzed
by 2a ,b and 3a ,b show definitively that carbene transfer
can be catalyzed by a paramagnetic monomeric rhodium-
Ca ta lytic Cyclop r op a n a tion Rea ction s. A mixture of 2a
or 2b (0.0050 mmol) and NaBAr (4.5 mg, 0.0050 mmol) was
stirred in dry CH Cl (5 mL) in a glovebox for 2 h. The
resulting solution of 3a or 3b was filtered, and the olefin (5.0
mmol) was added. The reaction flask was fitted with a septum
f
2
2
2 2
and brought out to the benchtop. A CH Cl solution (9 mL) of
ethyl diazoacetate (105 µL, 1.0 mmol) was added to the
reaction mixture via syringe pump over the course of 9 h. The
reaction mixture was stirred for an additional 8 h, then the
volatile materials were removed from the reaction mixture by
rotary evaporation. The pure cyclopropanation products 5a -e
and 6a -e were obtained by chormatographing the residual
1
oil (silica gel, 5% ethyl acetate in hexane). H NMR data for
products 5a -e and 6a -e were compared to reported literature
shifts for these compounds.49 The enantiomeric excesses (ee)
of 5a -e and 6a -e prepared with catalyst 3a were determined
by chiral capillary GC on a G-TA (Chiraldex) column. Enan-
tioenriched samples were compared to racemic samples gener-
ated by catalyst 3b.
(II) complex.
Exp er im en ta l Section
2
Syn th esis of [Rh Cl(OTf){ben box(Me )H}] (2a , 2b). To
a yellow solution of [RhCl
2
{benbox(Me
2
)H}] (1) (0.10 mmol)
Ca ta lytic Azir id in a tion of 7a a n d 7b. In the glovebox,
catalyst 2a (79 mg, 0.12 mmol), imine (430 mg, 2.3 mmol), and
ethyl diazoacetate (300 µL, 2.8 mmol) were dissolved in THF
(5 mL) in a glass vial equipped with a Teflon-coated stirbar.
The vial was capped and the reaction mixture was stirred at
room temperature for 8 h. The reaction vessel was uncapped
occasionally (roughly once every 2 h) to prevent the buildup
of a significant overpressure of nitrogen. After 8 h of stirring,
the vial was brought out of the box and the reaction mixture
was immediatedly chromatographed on silica gel (gradient
elution: hexane f 2% ethyl acetate in hexane f 4% ethyl
acetate in hexane). Product identities were confirmed by GC/
in methylene chloride (5 mL) at ambient temperature was
added AgOTf (25.7 mg, 0.10 mmol) producing a yellow suspen-
sion. After being stirred overnight the suspension was filtered.
The solvent was removed in vacuo, leaving an orange-yellow
microcrystalline solid. Complexes 2a ,b can be recrystallized
from benzene/pentane at room temperature.
[
Rh Cl(OTf){(S,S)-tb-ben box(Me
7%. Mp: 152-154 °C dec. Anal. Calcd for C25
RhS: C, 44.68; H, 5.40; N, 4.17. Found: C, 44.92; H, 5.58; N,
2
)H}] (2a ). Yield: 65 mg,
9
3 2 5
H36ClF N O -
-
1
1
3
C
C
.90. IR (KBr, cm ): 1642, 1630 (ν(CN)). H NMR (300 MHz,
1
9
6
D
D
6
): δ 19.0, 18.6, 10.7, 9.6, -38.6. F NMR (376.1 MHz,
): δ -75.0. EI-MS (m/z): 670 [M - H] , 635 [M - HCl] ,
+
+
MS, and by comparing H NMR resonances to those reported
1
6
6
+
in the literature.24,41 For determination of the ee values of
5
21 [M - HOTf], 485 [M - HOTf - HCl] .
Rh Cl(OTf){d m -ben box(Me )H}] (2b). Yield: 59 mg,
3 2 5
6%. Mp: 148-150 °C dec. Anal. Calcd for C21 28ClF N O -
products prepared with 2a , racemic aziridines 8a ,b and 9a ,b
[
2
were prepared with TiCl
chromatography (conditions described above). For 8a , the ee
was determined by addition of Eu(hfc) to an NMR sample
(C ) of isolated product and compared to authentic racemic
4 2
(THF) and purified by silica gel
9
H
RhS: C, 40.95; H, 4.58; N, 4.55. Found: C, 40.56; H, 4.68; N,
-
1
1
3
4
C
.40. IR (KBr, cm ): 1643, 1632 (ν(CN)). H NMR (300 MHz,
1
9
6 6
D
6
D
6
6 6
): δ 19.8, 15.5, 9.8, -35.1. F NMR (376.1 MHz, C D ):
+
product. For 8b, 9a , and 9b, ee values were determined by
chiral HPLC (Chiraldex OD column: 0.7 mL/min, 10% iso-
propyl alcohol in hexane) of isolated product compared to
isolated racemic samples. Representative data for the previ-
ously reported compounds 8a , 9a , 8b, and 9b are presented
in the Supporting Information.
δ -75.0. EI-MS (m/z): 479 [M - HCl] , 465 [M - HOTf], 430
+
[
M - OTf - HCl] .
2 2
Isola tion of Cr ysta llin e [Rh Cl(CH Cl ){d m -ben box-
(
Me
2
)H}]BAr
)H}] (2b) (12.8 mg, 25 mmol) in methylene chloride
2 mL) at ambient temperature was added a methylene
chloride solution of NaBAr (27 mg, 30 mmol) producing a dark
f
(3b). To a yellow solution of [RhCl(OTf){dm-
benbox(Me
(
2
Ca ta lytic Azir id in a tion of 7c-7g. In the glovebox 2a (4.0
mg, 0.0060 mmol), imine (0.12 mmol), and hexamethylbenzene
f
orange suspension. After the solution was stirred for 1 h,
precipitation of NaOTf was observed, and the suspension was
filtered. Elemental analyses and NMR data indicate that in
the absence of a good trapping ligand (e.g. styrene) 3a ,b are
both thermally sensitive and unstable to vacuum. Hence, these
compounds were used in situ without further characterization.
However, 3b was recrystallized from a concentrated dichlo-
romethane/pentane solution at -30 °C to give a small quantity
of X-ray quality crystals.
(
8
4.0 mg, 0.025 mmol) were dissolved in 300 µL of d -THF. An
1
initial H NMR spectrum was taken. To this mixture was
added ethyl diazoacetate (15 µL, 0.14 mmol) by syringe. The
NMR tube was flame sealed under vacuum and the reaction
1
progress was monitored by H NMR. The reaction was halted
after 8 h, at which point product yields were determined by
1
H NMR integration of the aziridine ring protons versus
internal standard. All products were identified in the crude
1
1
reaction mixtures by GC/MS and H NMR. The H NMR data
X-r a y Str u ctu r e Da ta for 3b. The X-ray crystal structure
was determined by Drs. Fred Hollander and Allan Oliver at
the UCB X-ray facility (CHEXRAY). The crystal was mounted
on a glass fiber with Paratone N hydrocarbon oil. Measure-
ments were made on a SMART CCD area detector with
graphite monochromated Mo KR radiation (λ ) 0.71069 Å).
The data were collected with a detector position of 60.00 mm.
Data were integrated by the program SAINT, and were
corrected for Lorentz and polarization effects. Data were
analyzed for agreement and possible absorption with XPREP.
The structures were solved by direct methods and expanded
with Fourier techniques. The data were collected with use of
for products 8d , 9d , 8e, 9e, 8f, 9f, 8g, and 9g were compared
to literature values for these compounds.2
4,41,47
Authentic
samples of products 8c and 9c were independently prepared
and isolated by using the procedure described by Brookhart
and co-workers for analogous compounds, and are described
in the Supporting Information.41
Ack n ow led gm en t. We are grateful to Dr. Wen hau
Hu and Professor Michael Doyle for help in determining
the enantioselectivities of the product cyclopropanes.
Drs. Fred Hollander and Allan Oliver at the UCB X-ray
diffraction facility (CHEXRAY) are acknowledged for
determination of the crystal structure of 3a . This work
was carried out under the auspices of a CRADA pro-
ject, administered by the Lawrence Berkeley National
1
0-s frames with an ω scan of 0.3°. Empirical absorption
corrections based on comparison of redundant and equivalent
reflections were applied by using SADABS (Tmax ) 0.91, Tmin
)
0.80). The maximum peak in the final difference map was
.99 e /Å , and the minimum peak was -0.96 e /Å .
-
3
-
3
1
J . Org. Chem, Vol. 68, No. 25, 2003 9709