Enantioselective desymmetrization of meso-aziridines with TMSN3 or TMSCN catalyzed by discrete yttrium complexes

Article abstract of DOI:10.1002/anie.200804415

(Chemical Equation Presented) Y is it so? Dimeric yttrium-salen complexes (see structure; N blue, O red, Y magenta) catalyze the highly enantioselective ring-opening of meso-aziridines by TMSCN and TMSN₃. To explain the dramatic differences in

Full text of DOI:10.1002/anie.200804415

Communications
DOI: 10.1002/anie.200804415
Enantioselective Ring-Opening
Enantioselective Desymmetrization of meso-Aziridines with TMSN3 or
TMSCN Catalyzed by Discrete Yttrium Complexes**
Bin Wu, Judith C. Gallucci, Jon R. Parquette,* and T. V. RajanBabu*
Ever since Nugent first reported a practical, catalytic method
for the enantioselective opening of meso-epoxides with
trimethylsilyl azide (TMSN3),[1] such desymmetrization reac-
tions of epoxides[2] and aziridines[2e,3] using a variety of
nucleophiles have been the subject of extensive research. The
less developed ring-opening reactions, those of meso-aziri-
dines by carbon and nitrogen nucleophiles, give direct access
to enantiopure b-amino acids and 1,2-diamines—two classes
of compounds which have broad chemical and pharmaceut-
ical relevance. Li, Fernꢀndez, and Jacobsen first reported
enantioselective ring-opening of meso-aziridines with
TMSN3, which were catalyzed by CrIII complexes of tridentate
Schiff bases.[3f] Then Shibasaki et al. reported Y and Gd com-
[3g]
plexes as catalysts for related reactions with TMSN3 and
TMSCN.[3h] The opening of aziridine rings with TMSN3 under
Brønsted acid catalysis,[3i] and a similar reaction with aryl
amines catalyzed by NbV complexes[2e] are also noteworthy.
Herein we report the synthesis and application of readily
available, discrete dimeric yttrium–salen complexes that
Figure 1. Epoxide ring-opening reaction and structures of yttrium
catalysts.
catalyze highly enantioselective desymmetrization of meso-
aziridines with both TMSN3 and TMSCN. For comparable
substrates, the enantioselectivity in the TMSN3-mediated
reactions exceed the highest values reported to date.
and Yb-catalyzed ring-opening reactions, Jacobsen has quite
convincingly suggested the involvement of two molecules of
the catalyst: one each for the activation of the nucleophile and
the electrophile.[2a] However, by looking at the structure of
our yttrium catalyst (a distorted trigonal bipyramid with
yttrium at the apex, see Figure 1),[4b] it is difficult to envision
how two individual molecules of the yttrium complex can be
involved (as indicated by the transition state suggested by
Jacobsen) in a reaction that proceeds with such high
efficiency. An attractive alternative would be to invoke a
dimeric catalyst along the lines of one suggested by McCle-
land, Nugent, and Finn[7] to explain the observations related
to the (alkanolamine)Zr-mediated ring-opening of epoxides
by TMSN3 (Scheme 1). Anecdotal support for such a hypoth-
esis comes from the ease with which early transition metals,
inclusive of yttrium, form anion-bridged dimers,[8] including
an OH-dimer from 2a which we have isolated and charac-
terized.[5] Changes seen in the IR spectrum of a mixture the
yttrium–salen complex 2a (Figure 1) and excess TMSCN are
also indicative of bridged CN-structures. Kinetic studies
based on in situ IR spectroscopy, though tentative, do not
rule out such a possibility.[5] The veracity of such an idea
notwithstanding, we decided to examine the ring-opening
reactions of N-4-nitrobenzoylaziridines[3c] catalyzed by fully
characterized dimeric yttrium–salen complexes.
In previous work, we reported that YIII alkoxides and
salen complexes are exceptionally efficient catalysts for
transacylation of secondary alcohols[4a] and for ring-opening
of epoxides by TMSCN or TMSN3:[4c,5] only 0.01 mol%
catalyst is required (substrate/catalyst ratio of 10000:1) in the
epoxide ring-opening reactions. Even though the enantiose-
lectivity in these reactions [Eq. (1) in Figure 1; up to 77% ee
for TMSCN-mediated ring-opening of epoxycyclohexane]
never matched the best reported results[6] (91% ee at a
substrate/catalyst ratio of about 9:1), the catalytic efficiency is
unparalleled among epoxide ring-opening reactions, and may
require a different model to describe the transition state. To
explain the second-order dependence of the catalyst on Cr-
[*] Dr. B. Wu, J. C. Gallucci,[+] Prof. J. R. Parquette, Prof. T. V. RajanBabu
Department of Chemistry, The Ohio State University
Columbus, OH 43210 (USA)
E-mail: parquette.1@osu.edu
rajanbabu.1@osu.edu
Homepage: http://www.chemistry.ohio-state.edu/~parquette/
http://www.chemistry.ohio-state.edu/~rajanbabu/
[+] Contact details for the X-ray crystallographic analysis: jgallucc@
chemistry.ohio-state.edu.
[**] This work was supported by the US National Science Foundation
programs CHE-0526864 (Collaborative Research in Chemistry) and
CHE-0610349. TMS=trimethylsilyl.
A variety of yttrium compounds, among them monomeric
complexes 1a, 1b, 2a, 2b, and 2c (Figure 2),[9] were prepared
from Y[N(SiHMe2)2]3·2THF and the corresponding ligands,
as previously described[4b,10] [Eq. (2)]. The dimeric complexes
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200804415.
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Table 1: Catalyst screening for ring-opening of meso-aziridine 5 with
TMSCN.[a]
Entry
Catalyst
Yield [%][b]
ee [%](RR)[c]
1
2
3
4
1a[d]
1a[e]
1b
2a
2b
>99
>99
58
77
85
52
À43[f]
À18
<5
55
5
6
7
2c
3a
>99
79
30
37
8
9
10
11
3b
56
À6
4a[g]
4b[g]
4c
>99
>99
64
8
88 (94)[h]
30
Scheme 1. A proposed mechanism. [L]=lanthanoid complex.
[a] See Equation (4) for the procedure. [b] Yield of isolated product.
[c] Configuration and ee values were determined by HPLC on a chiral
stationary phase. For the synthesis of racemic products, see the
Supporting Information. The absolute configuration was determined
by comparison with authentic samples.[3h] [d] Catalyst was prepared in n-
hexane. [e] Catalyst was prepared in THF. [f] The SS configuration.
[g] 0.1 equivalents of catalyst was used. [h] Reaction was carried out at
À38C, 5 d.
3a, 3b, 4a, 4b, and 4c were prepared by treating
[11]
Y(OCH2CH2NMe2)3
with a solution of salen ligand in
toluene at 708C for 24 hours [Eq. (3)] and isolated by
tantly, the substituents on the aryl imine part of the complex
are critical. Only the 3-methoxy substituent gave acceptable
enantioselectivity (Table 1, entry 10). Recrystallization of the
catalyst is important to achieve high selectivity. We noticed
that before recrystallization, 4b gave an ee value of only 77%
in the ring-opening of 5. Ring-opening reactions of proto-
typical N-acylaziridines by TMSCN were examined under the
optimized reaction conditions (0.1 equiv of 4b, ClCH2CHCl,
RT, 3 days) and the results are shown in Table 2.
Figure 2. Yttrium complexes as catalysts for the asymmetric ring-
opening of meso-aziridines with TMSCN and TMSN3.
Although the cyanide adducts 6–9 were formed in accept-
able yields and selectivity, these readily available dimeric
catalysts were especially suited for reactions of aziridines with
TMSN3 and gave the best yields and selectivity under almost
identical reaction conditions (0.1 equiv of catalyst). These
results are shown in Table 3. Although the products were
formed with excellent selectivity in most cases, the reaction
was very sensitive to steric effects. Notably, the sterically
demanding substrates (Table 3, entries 6 and 7) gave lower
yields under the standard reaction conditions. The corre-
sponding eight-membered aziridine failed to react. A control
experiment demonstrated that the observed lack of reactivity
subsequent removal of the solvent.[8d] The resulting products
were recrystallized to give the active catalysts. In preliminary
experiments, the cyclohexane-derived aziridine 5 was treated
with TMSCN in the presence of catalytic amounts
(0.05 equiv) of yttrium complexes [Eq. (4)], and the results
are shown in Table 1.
Among the monomeric complexes,[9] 1a[12] and 2b gave
the best selectivity (Table 1, entries 1 and 5). In keeping with
our conjecture, the highest selectivity was recorded for a
dimeric complex (4b) with a binaphthyl scaffolding. Impor-
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Table 2: Ring-opening reaction of N-acylaziridines with TMSCN catalyzed by 4b“.
buried in a well-defined chiral cavity. The lack of
reactivity of the larger substrates and the excep-
tional selectivity in the ring-opening reactions are
indicative of an asymmetric induction process. This
process results from an initial coordination of the
substrate and subsequent metal-assisted diastereo-
selective additions within the confines of a well-
Yield [%][a] 87
ee [%][b]
94
85
99
86
92
47
82
[a] Yield of isolated product. [b] The ee values were determined by HPLC methods with defined chiral cavity. The details of this heuristic
a chiral stationary phase.
model and the processes that are invoked remain
Table 3: Ring-opening reaction of N-acylaziridines with TMSN3 catalyzed
by 4b“.
Entry
Product[a]
Yield [%][b]
ee [%][c]
1
2
3
4
5
>99
>99
>99
>99
>99
97
96
98
94
99
Figure 3. Stereoview of the solid-state structure of 4b.
ent-10
ent-11
highly speculative. We plan to seek further validation of the
model while exploring other applications of these yttrium
complexes in organic synthesis.
Received: September 7, 2008
Published online: November 19, 2008
Keywords: asymmetric catalysis · aziridines · ring-opening ·
yttrium
6
7
8
73
47
92[d]
97[d]
90[e]
.
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>99
[a] Ar=4-NO2C6H4. [b] Yield of isolated product. [c] The ee values were
determined by HPLC methods with a chiral stationary phase. [d] Reac-
tion time was 5 d. [e] Reaction time was 7 days.
is not due to deterioration of the catalyst (see the Supporting
Information). Based on relative rates studies, the cyclohexane
derivative 10 is formed at least four times faster than the
cycloheptane analogue 14. Given that both enantiomers of
BINAP(NH2)2 (BINAP = 2,2’-bis(diphenylphosphino)-1,1’-
binaphthyl), and consequently the corresponding yttrium
complexes are readily available, products with the opposite
configuration can also be prepared readily (Table 3, entries 2
and 4).
For insight into the asymmetric induction process, we
examined the solid-state structure of the yttrium–salen
complex 4b.[13] Single crystals of 4b suitable for X-ray analysis
were obtained by the addition of n-hexane to a solution of the
complex in CH2Cl2 (Figure 3). In this highly organized C2-
symmetric structure, the bottom of the Y2O2 core is com-
pletely blocked by the OMe and NMe2 groups. Thus the
yttrium centers, approachable only from the opposite face, are
[4] a) M.-H. Lin, T. V. RajanBabu, Org. Lett. 2000, 2, 997; b) M.-H.
Lin, T. V. RajanBabu, Org. Lett. 2002, 4, 1607; c) M.-H. Lin, PhD
Thesis, Ohio State University (USA), 2002.
[5] B Saha, M.-H. Lin, T. V. RajanBabu, J. Org. Chem. 2007, 72,
8648.
[6] S. E. Schaus, E. N. Jacobsen, Org. Lett. 2000, 2, 1001.
[7] a) B. W. McCleland, W. A. Nugent, M. G. Finn, J. Org. Chem.
1998, 63, 6656; similar models have been invoked by others to
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rationalize asymmetric induction in other metal-catalyzed trans-
formations, for reviews, see: b) M. Kanai, N. Kato, E. Ichikawa,
M. Shibasaki, Synlett 2005, 1491; c) T. R. J. Achard, L. A.
Clutterbuck, M. North, Synlett 2005, 1828.
[12] Curiously, when using catalyst 1a the enantioselectivity in the
ring-opening reaction was depend on the solvent used for its
preparation (see Table 1, entries 1 and 2). For example, the
reaction carried out with the catalyst prepared in n-hexane gave
an enantioselectivity of 52% ee (RR), whereas the catalyst
prepared in THF gave 43% ee (SS), thus suggesting very
subtle effects of aggregation.
[8] a) For titanium examples, see: G. Boche, K. Mꢂbus, K. Harms,
M. Marsch, J. Am. Chem. Soc. 1996, 118, 2770; for yttrium
examples, see: b) (Ln)Y(m-Cl)]2 (several chloride bridged
dimers): W. J. Evans, C. H. Fujimoto, J. W. Ziller, Chem.
Commun. 1999, 311; c) Y(L)(m-OH)]2 (an hydroxide bridged
dimer): C. M. Mascarenhas, S. P. Miller, P. S. White, J. P. Morken,
Angew. Chem. 2001, 113, 621; Angew. Chem. Int. Ed. 2001, 40,
601; d) Y(L)(m-OR)]2 (an alkoxide bridged dimer): T. M. Ovitt,
G. W. Coates, J. Am. Chem. Soc. 2002, 124, 1316; for CN-bridged
complexes, see: e) C. E. Plecnik, S. Liu, S. S. Shore, Acc. Chem.
Res. 2003, 36, 499; f) S. Tanase, J. Reedijk, Coord. Chem. Rev.
2006, 250, 2501.
[9] For a more complete list of complexes and the corresponding
selectivities observed in the reaction shown in [Eq. (4)], see the
Supporting Information.
[10] O. Runte, T. Priermeier, R. Anwander, Chem. Commun. 1996,
1385.
[13] See the Supporting information for the details of the X-ray
crystallographic analysis of 4b. CCDC 701484 contains the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
As the crystals form very thin plates, it was necessary to collect a
data set by using a synchrotron. This data set was collected by
Dr. Jeanette Krause through the SCrALS (Service Crystallog-
raphy at Advanced Light Source) program at the Small-Crystal
Crystallography Beamline 11.3.1 at the Advanced Light Source
(ALS). The ALS is supported by the U.S. Department of Energy,
Office of Energy Sciences, Materials Sciences Division, under
contract DE-AC02-05CH11231 at Lawrence Berkeley National
Laboratory.
[11] S. L. McLain, T. M. Ford, N. E. Drysdale, Polym. Prep. 1992, 33,
463 (Am. Chem. Soc. Div. Polym. Chem.).
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