Rhodium-catalyzed stereoselective formation of Z-enamines from allylaziridines

Article abstract of DOI:10.1021/ja0632557

Rhodium (I)-catalyzed isomerization of N-allylaziridines affords isolable Z-enamines in excellent yields and with high stereoselectivity. Cationic [Rh(BINAP)(COD)]OTf and RhH(CO)(PPh₃)₃ follow the same selectivity toward the Z-isomer

Full text of DOI:10.1021/ja0632557

Published on Web 08/22/2006
Rhodium-Catalyzed Stereoselective Formation of Z-Enamines from
Allylaziridines
France-Aime´e Alphonse and Andrei K. Yudin*
DaVenport Research Laboratories, Department of Chemistry, The UniVersity of Toronto, 80 St. George Street,
Toronto, Ontario, Canada M5S 3H6
Received May 9, 2006; E-mail: ayudin@chem.utoronto.ca
Scheme 1
Enols, metal enolates, and enamines are the most important
carbon nucleophiles in both biological and chemical synthesis.1
Many useful reactions owe their efficiency to selective formation
of E or Z metal enolates (Figure 1). In contrast, the chemistry of
enamines is limited to reactions of the E-isomers. The reason is
simple: a classical condensation between an amine and a carbonyl
compound is an equilibrium process that affords the thermodynami-
cally more stable E-isomer. Transition-metal-catalyzed approaches
to enamines include metal-catalyzed isomerization of N-ally-
lamines,2 amination of alkenyl halides,3 hydroamination of alkynes,4
and oxidative amination of olefins.5 Likewise, all of these methods
give the thermodynamic product. There are no useful, kinetically
controlled, reactions that result in Z-enamine formation. Although
strong base-promoted isomerization of N-allylamines to Z-enamines
have been reported,6 attempts to isolate the Z-product result in
Z-to-E isomerization and/or hydrolysis. The present contribution
examines an unexpected rhodium-catalyzed route to chromato-
graphically stable Z-enamines from N-allylaziridines. Since the
aziridine ring is widely considered to be a stepping stone to other
amines via diverse ring-opening processes,7 this chemistry may find
useful synthetic applications.
Table 1. Effect of Rhodium(I) Source and Temperature on
Isomerization of N-Allylaziridine 1a to N-Alkenylaziridines 2a and
3aa
Z/E
entry
catalyst
temp (
°
C),
conv.
(%)c
selectivity
(%)c
time (h)
1b
2
[Rh(BINAP)(COD)]OTf
RhH(CO)(PPh3)3
60, 16
60, 0.2
20, 3
25
100
100
100
60:40
85:15
92:8
3
RhH(CO)(PPh3)3
4
RhH(CO)(PPh3)3
-78, 24
95:5
a [Substrate] ) 0.7 M, [substrate]/[Rh] ) 66 in THF under nitrogen.
b Prepared in situ from [Rh(COD)2]OTf and 2 equiv of rac-BINAP.
c Determined by GC.
Figure 1. Carbon nucleophiles of fundamental significance.
13
When we evaluated RhH(CO)(PPh3)3 as the source of Rh(I)
We recently reported that unsubstituted aziridines undergo facile
palladium-catalyzed allylic amination with allyl acetates and
carbonates in good to excellent yields and with high enantioselec-
tivities.8 The allylaziridines thus obtained were chosen for transition-
metal-catalyzed allylic isomerization. Cationic Rh(I) diphosphine
complexes2a,9 are known to induce selective isomerization of
N-allylamines into E-enamines. A generally accepted mechanistic
description of the reaction is depicted in Scheme 1.2a Upon C-H
activation at the allylic position, organometallic species A, stabilized
through iminium complex B, is generated. Subsequent hydride
migration to the terminal olefinic carbon affords intermediate C
which undergoes decomplexation, releasing the enamine product.
As an indirect piece of evidence of iminium complex formation,
cationic rhodium(I) catalysts failed to isomerize allylamines derived
from ethylene imine.10 With our new approach to allylaziridines,8
we investigated the isomerization of N-allylcyclohexene imine 1a
with 1.5 mol % of [Rh(BINAP)(COD)]OTf as the source of
rhodium(I) prepared in situ from [Rh(COD)2]OTf and rac-BINAP
in THF (60 °C, 16 h). In contrast to previous reports, we did obtain
the N-(1-propenyl)aziridine 2a, albeit with a low 25% conversion.
Interestingly, unexpected selectivity for the Z-isomer 2a was
observed (Table 1, entry 1).11 There was no evidence for isomer-
ization into the E-isomer in the course of isolation.12 The enamine
2a was isolated as a chromatographically stable oil.
in our system, full conversion of N-allylcyclohexene imine 1a to
enamine 2a was achieved in THF in just over 10 min. The
Z-stereoselectivity was increased to 95:5 when the reaction was
performed at -78 °C (Table 1, entries 2-4). The same selectivity
was observed in toluene and dichloromethane. The double bond
migration consistently afforded high Z-selectivity with other
substrates giving N-(1-propenyl)aziridines in excellent isolated
yields (Table 2). The GC analysis of N-allylcyclohexene imine 1a
isomerization, performed with 1.5 mol % of RhH(CO)(PPh3)3 in
THF at room temperature, indicated that E- and Z-isomers do not
interconvert under the reaction conditions.14 Substitution at the
allylic position was found to slow the reaction presumably due to
higher barrier for initial C-H activation. Notably, subjecting allyl
morpholine to the RhH(CO)(PPh3)3-catalyzed isomerization resulted
in exclusive formation of the E-enamine.
A mechanistic scenario consistent with the observed kinetic Z-
selectivity would involve C-H bond activation to give intermediate
D, hydride migration, and C-H bond reductive elimination from
metallocycle E (Scheme 2, path a).15 This deviation from the ac-
cepted tertiary allylamine isomerization mechanism (Scheme 2, path
b) would result from kinetic inaccessibility of the intermediate F.
A glimpse into intriguing and potentially useful properties of
the Z-aziridine enamines was obtained in a preliminary study of
9
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J. AM. CHEM. SOC. 2006, 128, 11754-11755
10.1021/ja0632557 CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Substrate Scope for Isomerization of N-Allylaziridines to
In summary, we have uncovered a novel and highly selective
rhodium-catalyzed pathway from allylaziridines to stable Z-enam-
ines. The observed stereoselectivity favors the formation of
Z-isomers not seen with other systems that produce the thermody-
namically more stable E-enamines. This simple process should
facilitate metal-catalyzed access to Z-enamines, which belong to
an under-explored class of carbon nucleophiles of fundamental
significance (Figure 1). Synthetic applications and detailed mecha-
nistic studies of these reactions are underway.
N-Alkenylaziridines with RhH(CO)(PPh3)3 Catalysta
Acknowledgment. This research was supported by NSERC and
a postdoctoral fellowship to F.-A.A. from MCMM-MRC Global
Health.
Supporting Information Available: Experimental procedures and
characterization data for all unknown products. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Stork, G.; Terrell, R.; Szmuszkovicz, J. J. Am. Chem. Soc. 1954, 76,
2029. (b) The Chemistry of Enamines (Parts 1 & 2); Rappoport, Z., Ed.;
Wiley: New York, 1994. (c) Gawley, R. E.; Aube´, J. In Principles of
Asymmetric Synthesis; Baldwin, J., Williams, R. M., Ba¨ckvall, J.-E., Eds.;
Tetrahedron Organic Chemistry Series 14; Pergamon: Oxford, 1996.
(2) For Rh-catalyzed isomerization of allylamines, see: (a) Noyori, R. Angew.
Chem., Int. Ed. 2002, 41, 2008 and references therein. Ru-catalyzed: (b)
Krompiec, S.; Pigulla, M.; Krompiec, M.; Marciniec, B.; Chadyniak, D.
J. Mol. Catal. A 2005, 237, 17. (c) Zhang, S. W.; Mitsudo, T.; Kondo,
T.; Watanabe, Y. J. Organomet. Chem. 1995, 485, 55. (d) Dominguez,
G.; Casarrubios, L.; Rodriguez-Noriega, J.; Perez-Castells, J. HelV. Chim.
Acta 2002, 85, 2856. Fe-catalyzed: (e) Corriu, R. J. P.; Huynh, V.;
Moreau, J. J. E.; Pataut-Sat, M. J. Organomet. Chem. 1983, 255, 359.
For Ir-catalyzed isomerization, see: (f) Neugnot, B.; Cintrat, J.-C.;
Rousseau, B. Tetrahedron 2004, 60, 3575. Cr-catalyzed: (g) Yamada,
H.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1991, 56, 4569. Cocata-
lyzed: (h) Onishi, M.; Oishi, S.; Sakaguchi, M.; Takaki, I.; Hiraki, K.
Bull. Chem. Soc. Jpn. 1986, 59, 3925. (i) Kumobayashi, H.; Akutagawa,
S.; Otsuka, S. J. Am. Chem. Soc. 1978, 100, 3949. Ti-catalyzed: (j) Akita,
M.; Yasuda, H.; Nagasuna, K.; Nakamura, A. Bull. Chem. Soc. Jpn. 1983,
56, 554. Mo-catalyzed: (k) Tatsumi, T.; Hashimoto, K.; Tominaga, H.;
Mizuta, Y.; Hata, K.; Hidai, M.; Uchida, Y. J. Organomet. Chem. 1983,
252, 105.
a [Substrate] ) 0.7 M, [substrate]/[Rh] ) 66 at -78 °C in THF under
nitrogen. b Determined by GC. c [Substrate]/[Rh] ) 10 at 60 °C, 72 h.
d [Substrate]/[Rh] ) 20 at 60 °C, 24 h. e [Substrate]/[Rh] ) 66 at 20 °C,
24 h. f Only the starting material was recovered.
Scheme 2
(3) For recent reviews, see: (a) Barluenga, J.; Valdes, C. Chem. Commun.
2005, 4891. (b) Dehli, J. R.; Legros, J.; Bolm, C. Chem. Commun. 2005,
973.
(4) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV. 2004, 104, 3079.
(5) Beller, M.; Breindl, C.; Eichberger, M.; Hartung, C. G.; Seayad, J.; Thiel,
O. R.; Tillack, A.; Trauthwein, H. Synlett 2002, 1579.
(6) (a) Sauer, J.; Prahl, H. Chem. Ber. 1969, 102, 1917. (b) Hine, J.; Linden,
S.-M.; Wang, A.; Thiagarajan, V. J. Org. Chem. 1980, 45, 2821. (c)
Bortolussi, M.; Bloch, R.; Conia, J. M. Tetrahedron Lett. 1977, 26, 2289.
(d) Ribereau, P.; Delamare, M.; Celanire S.; Queguiner, G. Tetrahedron
Lett. 2001, 42, 3571.
cycloaddition with DMAD (dimethyl acetylene dicarboxylate). The
syn cyclobutene stereoisomer 4 was isolated in 60% yield upon
heating (Z)-7-(prop-1-enyl)-7-azabicyclo[4.1.0]heptane 2a with
DMAD (eq 1). The preservation of syn stereochemistry implies
that the cycloaddition mechanism involves a zwitterionic intermedi-
ate with a lifetime that is short relative to rotation around the C-N
bond, which would have generated the more stable E-isomer.16
(7) Aziridines and Epoxides in Organic Chemistry; Yudin, A. K., Ed.; Wiley-
VCH: Weinheim, Germany, 2006.
(8) (a) Watson, I. D. G.; Styler, S. A.: Yudin, A. K. J. Am. Chem. Soc. 2004,
126, 5086. (b) Watson, I. D. G.; Yudin, A. K. J. Am. Chem. Soc. 2005,
127, 17516.
(9) Chapuis, C.; Barthe, M.; de Saint Laumer, J.-Y. HelV. Chim. Acta 2001,
84, 230.
(10) Otsuka, S.; Tani, K. Synthesis 1991, 665.
(11) The Z-configuration was confirmed from a medium coupling constant (7.8
Hz) between the olefinic protons. The E-isomer has 13.2 Hz coupling
constant. See also: Mueller, K.; Previdoli, F. HelV. Chim. Acta 1981, 64,
2508.
(12) Pd(II) was found to promote isomerization of 2a into a 55:45 Z/E mixture
(THF, room temperature, 72 h).
(13) Novak reported that RhH(CO)(PPh3)3 prevents enamine-to-imine isomer-
ization during enamine formation from primary allylamines: Novak, B.
M.; Cafmeyer, J. T. J. Am. Chem. Soc. 2001, 123, 11083.
(14) See Supporting Information for details.
(15) A mechanism involving â-hydride elimination is less likely as it is known
to proceed with E-selectivity (see ref 2b).
(16) A concerted pathway cannot be ruled out at this point.
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