A Novel Three-Component Reaction Catalyzed by Dirhodium(II) Acetate: Decomposition of Phenyldiazoacetate with Arylamine and Imine for Highly Diastereoselective Synthesis of 1,2-Diamines

Article abstract of DOI:10.1021/ol035490p

(Matrix presented) A practical highly diastereoselective synthesis of 1,2-diamines through carbon-carbon bond formation involving an ammonium ylide intermediate is reported for the first time. By treating methyl phenyldiazoacetate with arylamine and imine in the presence of dirhodium acetate, the erythro diastereomer of methyl 1,2-diaryl-1,2-diaminopropanoate is formed with stereochemical preferences greater than 10:1.

Full text of DOI:10.1021/ol035490p

ORGANIC
LETTERS
2
003
Vol. 5, No. 21
923-3926
A Novel Three-Component Reaction
Catalyzed by Dirhodium(II) Acetate:
Decomposition of Phenyldiazoacetate
with Arylamine and Imine for Highly
Diastereoselective Synthesis of
3
1,2-Diamines
†
†
†
†
,†
Yuanhua Wang, Yanxin Zhu, Zhiyong Chen, Aiqiao Mi, Wenhao Hu,* and
,‡
Michael P. Doyle*
Key Laboratory for Asymmetric Synthesis and Chirotechnology of Sichuan ProVince,
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu 610041, China, and Department of Chemistry, UniVersity of Arizona,
Tucson, Arizona 85721
huwh@cioc.ac.cn; mdoyle3@umd.edu
Received August 7, 2003
ABSTRACT
A practical highly diastereoselective synthesis of 1,2-diamines through carbon−carbon bond formation involving an ammonium ylide intermediate
is reported for the first time. By treating methyl phenyldiazoacetate with arylamine and imine in the presence of dirhodium acetate, the erythro
diastereomer of methyl 1,2-diaryl-1,2-diaminopropanoate is formed with stereochemical preferences greater than 10:1.
Metal-mediated carbenoid reactions have gained wide ap-
plication in synthetic organic chemistry in the past decades.
decomposition of phenyldiazoacetate in the presence of
arylamine and imine.
1
Many studies of such reactions have focused on cyclopro-
panation, X-H (X ) C, N, O, Si, S) insertion, and ylide
generation, and these reactions have also been used to prepare
complex synthetic targets. Here we report a novel three-
component reaction of rhodium(II) acetate catalyzed diazo
Rhodium(II) acetate catalyzed diazo decomposition of
diazoacetates with imines or amines to give aziridine or N-H
1
insertion product, respectively, have been reported. Recently
2
two methodologies for aziridine formation from diazoacetates
through ylide intermediates have been described. We reported
stereospecific ring closure of phenyldiazoacetate-derived
immonium ylide to form (E)-aziridines stereospecifically and
†
Chinese Academy of Sciences.
University of Arizona; now at the University of Maryland.
‡
3
in high yields (Scheme 1). Aggarwal developed an alterna-
(1) Doyle, M. P.; McKervey, M. A.; Ye, T. Modem Catalytic Methods
for Organic Synthesis with Diazo Compounds; John Wiley and Sons: New
York, 1998.
tive pathway for aziridine formation whereby an organic
(2) Padwa, A.; Hornbuckle, S. Chem. ReV. 1991, 91, 263.
(3) Doyle, M. P.; Hu, W.; Timmons D. J. Org. Lett. 2001, 3, 933.
1
0.1021/ol035490p CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/16/2003

Scheme 1
Table 1. Three-Component Reaction of Methyl
Phenyldiazoacetate with Aniline and Imine Catalyzed by
Dirhodium(II) Acetate
sulfide intercepts the metal carbene, and aziridination takes
4,5
place via nucleophilic addition of a sulfur ylide to an imine.
The insertion of a metal carbenoid generated from a diazo
compound into an N-H bond, which leads to C-N bond
formation (Scheme 2), is a known process.1 There have been
,6
yield,a
%
isomer ratio of 5b
entry
Ar
R
4:5b
threo:erythro
Scheme 2
a
b
c
d
e
C6H5
H
H
H
H
H
68
72
76
72
58
60:40
64:36
54:46
31:69
14:86
9:91
6:94
4:96
4:96
4:96
p-FC6H4
p-ClC6H4
p-CF3C6H4
p-NO2C6H4
a
Isolated yield of 4 + 5 after column chromatography purification.
b
1
Determined by H NMR of crude product.
numerous demonstrations of the versatility of this reaction.
For example, this approach has been particularly fruitful in
7
the synthesis of penicillins and related â-lactams.
Further investigation revealed that the concentration of
imine was an important factor for driving the reaction to
A novel three-component reaction is reported here. By
reaction of phenyldiazoacetate with both imine and amine
in the presence of dirhodium acetate catalyst, no aziridine
product is obtained. Instead, we find a 1,2-diamine product.
For example, treatment of phenyldiazoacetate 1 with a
mixture of equal amounts of arylamine 2 and imine 3 with
dirhodium acetate catalyst gives N-H insertion product 4
8
and 1,2-diamines 5 in good yield (Table 1). While the
product ratio is dependent on electronic features from aryl
substitution of the corresponding amine (Table 1), diaste-
reoselectivity of 5 is consistently high.
As seen from Table 1, the more electron withdrawing is
the substituent attached to the arylamine, the higher is the
ratio of diamines product 5 over N-H insertion 4 (Table 1,
entries c, d, and e). The structure and relative configuration
of major diastereomer 5a was confirmed by single-crystal
9
X-ray analysis to be erythro (Figure 1).
Figure 1. X-ray structure of erythro-5a.
(
4) (a) Li, A. H.; Dai, L. X.; Aggarwal, V. K. Chem. ReV. 1997, 97,
341. (b) Aggarwal, V. K. Synlett 1998, 329.
5) (a) Aggarwal, V. K.; Ferrara, M.; O’Brien, C. J.; Thompson, A.; Jones,
2
(
R. V. H.; Fieldhouse, R. J. Chem. Soc., Perkin Trans. 1 2001, 1635. (b)
Aggarwal, V. K.; Alonso, E.; Fang, G. Y.; Ferrara, M.; Hynd, G.; Porcelloni,
M. Angew. Chem., Int. Ed. 2001, 40, 1433.
diamine formation (Table 2). As expected from such a
competitive process, increasing the initial concentration of
(
6) For reviews of this area, see: (a) Maas, G. Top. Curr. Chem. 1987,
1
37, 75. (b) Davies, H. M. L. In ComprehensiVe Organic Synthesis; Trost,
(9) (a) Crystal data for 5a(erythro): C28H25N3O4, MW ) 467.51,
orthorhombic, space group Pna2(1), a ) 26.465(5) Å, b ) 9.181(1) Å, c
B. M., Ed.; Pergamon: Oxford, UK, 1991; Vol. 4, Chapter 4.8. (c) Padwa,
A.; Krumpe, K. E. Tetrahedron 1992, 48, 5385. (d) Kirmse, G. Carbene
Chemistry, 2nd ed.; Academic: New York, 1971; pp 409-412. (e) Aller,
E.; Buck, R. T.; Drysdale, M. J.; Ferris, L.; Haigh, D.; Moody, C. J.; Pearson,
N. D.; Sanghera, J. B. J. Chem. Soc., Perkin Trans. 1 1996, 2879.
3
3
) 9.973(2) Å, V ) 2423.2(9) Å , Z ) 4, pcalcd ) 1.281 Mg/m , F(000) )
-
1
984, λ ) 0.71073 Å, T ) 296(2) K, µ(Mo KR) ) 0.087 mm . Data for
the structure were collected on a Siemens P-4X four-circle diffractometer.
Intensity measurements were performed on a crystal (dimensions 0.58 ×
0.56 × 0.30 mm) in the range 3.08 < 2θ < 55.98°. Of the 3568 measured
reflections, 3077 were independent (Rint ) 0.0087). The structure was solved
by direct methods (SHELXS-97) and refined by full-matrix least-squares
(7) (a) Lama, L. D.; Christensen, B. G. Tetrahedron Lett. 1978, 19, 4233.
(
b) Salzmann, T. N.; Ratcliffe, R. W.; Christensen, B. G.; Bouffard, F. A.
J. Am. Chem. Soc. 1980, 102, 6161. (c) Melillo, D. G.; Shinkai, I.; Liu, T.;
Ryan, K.; Sletzinger, M. Tetrahedron Lett. 1980, 21, 2783.
2
on F . The final refinements converged at R1 ) 0.0366 for I > 2σ(I), wR2
(
8) For review and recent reports on 1,2-diamines synthesis, see: (a)
Lucet, D.; Gall, T. Le.; Mioskowski, C. Angew. Chem., Int. Ed. 1998, 37,
581. (b) Westermann, B. Angew. Chem., Int. Ed. 2003, 42, 151.
) 0.0720 for all data. The final difference Fourier synthesis gave a min/
-
3
max residual electron density of -0.126/+0.139 eÅ . (b) CCDC-211231
2
contains the supplementary crystallographic data for this paper. These data
3924
Org. Lett., Vol. 5, No. 21, 2003

Scheme 3. A Plausible Mechanism for 1,2-Diamine Formation (Pathway B)
imine results in higher yields of the 1,2-diamine products.
reaction is proposed. The existence of dimer when using
electron-deficient 2,4-dinitroaniline indicates a slow process.
Adding to this that no aziridine was formed even with higher
imine concentration, the key intermediate is likely to be
For example, the ratio of 5d/4d increased from 69:31 to 92:8
when the molar ratio of 3/1 increased from 1.2 to 6. No
further change occurred in this ratio with even higher imine
concentration.
Table 3. Three-Component Reaction of Dirhodium(II) Acetate
Catalyzed Diazo Decomposition of Phenyldiazoacetate with
Arylamines and Imine under Optimized Conditionsa
Table 2. The Effect of Imine Concentration on Yield and
Product Ratio of the Three-Component Reaction of 1, 2d, and 3
Catalyzed by Rhodium(II) Acetate
yield,b
%
isomer ratio of 5c
yield,b
isomer ratio of 5d c
entry
Ar
R
4:5c
threo:erythro
molar
a
4d :5d c
entry
ratio 3/1
%
threo:erythro
a
b
c
d
e
f
C6H5
H
92
87
84
82
82
79
60
28:72
30:70
18:82
8:92
12:88
9:91
p- FC6H4
H
1
2
3
4
5
1.2
2
72
75
80
82
85
31:69
19:81
14:86
8:92
4:96
7:93
7:93
7:93
8:92
p-ClC6H4
p-CF3C6H4
p-NO2C6H4
2,4-(NO2)2C6H4
C6H5
H
9:91
H
7:93
4
H
4:96
4:9610
15:85
6:94
<3:97d
6
H
10
8:92
g
CH3
87:13
a
b
Molar ratio of 2d/1 is 1.2. Isolated yield of 4d + 5d after purification.
c
1
a
1/2/3 ) 1:1.2:6. b Isolated yield of 4 + 5. Determined by H NMR.
c
1
Determined by H NMR.
d
1
Only one isomer was detected by H NMR.
The optimized conditions (Table 2, entry 4) were applied
ammonium ylide 61,11 (Scheme 3). The reaction can be
to a series of reactions, and the results are summarized in
Table 3. In all cases with aniline, 1,2-diamines 5 were the
dominant products. However, the use of N-methylaniline
produced a dramatic decrease in the yield of diamines (Table
considered to proceed via initial formation of ammonium
ylide 6, which then undergoes product formation through
two competitive reaction pathways: (A) a [1,2]-hydrogen
12
shift to give the N-H insertion product 4 and (B)
3
, entry g), but exceptionally high diastereoselecitvity. It is
nucleophilic addition to imine through a concerted five-
membered ring transition state to give the observed 1,2-
diamines 5.
worth noting that carbene dimer formation was observed
when 2,4-dinitroaniline, but not any of the other anilines,
was used (Table 3, entry f).
Although detailed mechanistic studies have not been
undertaken, a plausible mechanism for this three-component
(10) A minor byproduct mixed with 4f was also isolated but not fully
characterized. Identification of the structure of the byproduct is now in
progress.
(
11) Padwa, A.; Weingarten, M. D. Chem. ReV. 1996, 96, 223.
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
(12) For examples of [l,2]-Stevens rearrangement of ammonium ylides
derived from metal carbenoids, see: (a) West, F. G.; Naidu, B. N. J. Am.
Chem. Soc. 1993, 115, 1177. (b) West, F. G.; Naidu, B. N. J. Am. Chem.
Soc. 1994, 116, 8420.
(
or from the Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB21EZ, UK; fax (+44) 1223-336-033; or deposit@
ccdc.cam.ac.uk).
Org. Lett., Vol. 5, No. 21, 2003
3925

This competition pathway is influenced by the stability
of ammonium ylide 6. The more stable ammonium ylide
from the anilines with electron-donating substituents favors
formal N-H insertion (pathway A) whereas the less stable
ylide from anilines with electron-withdrawing substituents
favors formation of the 1,2-diamine product (pathway B).
For example, the use of N-methylaniline gave mainly the
N-H insertion product, while 1,2-diamine was the exclusive
product with p-nitroaniline. Assuming an approach of the
ammonium ylide to the imine, two transition states a and b
lead to the erythro- and threo-diamines, respectively. In both
transition states, addition to the imine is activated by
intramolecular hydrogen bonding through a five-membered
ring. However, in transition states a, an additional π-π
interaction between two phenyl groups accounts for the
nearly exclusive formation of erythro-5.
light of the mechanism proposed for diamine formation
(Scheme 3). The energy difference between the two transition
states a and b with aldehyde instead of imine could be
negligible due to lack of π-π interaction with the aldehyde
alternative. The structure and configuration of the major
diastereomer, erythro-7, was ascertained by single-crystal
X-ray analysis. A detailed study with aldehydes will be
reported in due course.
In conclusion, we have discovered a novel three-
component reaction for the preparation of 1,2-diamines with
high diastereoselectivity. To our knowledge, this is the first
report of C-C bond formation in which ammonium ylides
could be trapped by imines or an aldehyde. Further invest-
gations to explore the reactivity of other ammonium ylides
and reactions with aldehydes and other electronphiles are in
progress.
The nucleophilicity of this ammonium ylide was further
studied by examining the process with an aromatic aldehyde.
Methyl phenyldiazoacetate treated with an equal amount of
O-anisidine 2h and 2-nitrobenzaldehyde gave 1,2-amino
alcohols13 7 in 90% yield (Scheme 4).14 The poor diaste-
Acknowledgment. We are grateful for financial support
from the Chinese Academy of Sciences and the National
Science Foundation of China (Grant No. 20202011). We
thank Prof. Kaibei Yu of Chengdu Institute of Organic
Chemistry for X-ray measurement. M.P.D. is grateful to the
U.S. National Science Foundation and National Institutes of
Health for their support.
reoselectivity (erythro:threo ) 58:42) was not surprising in
Supporting Information Available: Experimental pro-
cedures and product analyses, as well as crystallographic
information. This material is available free of charge via the
Internet at http://pubs.acs.org.
Scheme 4
OL035490P
(
13) Bergmeier, S. C. Tetrahedron 2000, 56, 2561.
(14) Reaction of methyl phenyldiazoacetate with aromatic aldehydes
alone in the presence of dirhodium catalyst gave only expoxides, see: (a)
Doyle, M. P.; Hu, W.; Timmons, D. J. Org. Lett. 2001, 3, 933. (b) Davies,
H. M. L.; DeMeese, J. Tetrahedron Lett. 2001, 42, 6803.
3926
Org. Lett., Vol. 5, No. 21, 2003