Interactions of aziridines with nickel complexes: Oxidative-addition and reductive-elimination reactions that break and make C-N bonds

Article abstract of DOI:10.1021/ja017652n

Reaction of the N-tosylaziridines (p-CH₃C₆H₄SO₂)NCH₂CHR (1a, R = H; 1b, R = Me; 1c, R = n-Bu; 1d, R = i-Pr) with (bpy)Ni(cod) (2; bpy = 2,2′-bipyridine; cod = 1,5-cyclooctadiene) or (bpy)NiEt₂

Full text of DOI:10.1021/ja017652n

Published on Web 03/03/2002
Interactions of Aziridines with Nickel Complexes: Oxidative-Addition and
Reductive-Elimination Reactions that Break and Make C-N Bonds
Beatrice L. Lin, Christopher R. Clough, and Gregory L. Hillhouse*
Searle Chemistry Laboratory, Department of Chemistry, The UniVersity of Chicago, Chicago, Illinois 60637
Received November 30, 2001
The past several years have seen significant research attention
focused on reductive-elimination reactions that form C-X bonds
(where X is a heteroatom such as N, O, S, Se, or Te).1-5 These
types of reductive-elimination reactions, which were unknown a
decade ago, are now well established in the Ni triad and have been
incorporated into synthetically useful processes, particularly the
preparation of arylamines and aryl ethers.2 We have reported on a
class of reductive-elimination reactions involving Ni that forms
N-C, O-C, and S-C bonds.3-5 An intriguing feature common to
these reactions is that many of the LxNi(R)(X) complexes are
isolable and thermally robust, with the elimination of R-X
occurring at ambient temperature only when triggered by oxidation
of Ni(II) to Ni(III) (oxidatively induced reductive elimination).3-6
Figure 1. A perspective view of the molecular structure of 4b. H-atoms,
except those attached to C(1) and C(2), have been omitted. Selected metrical
We recognized that the thermal stability of LxNi(R)(X) offered a
unique opportunity to study fundamental mechanistic details of the
reductive-elimination event. By preparing complexes with known
parameters: Ni-N(1) ) 1.911(5), Ni-C(1) ) 1.921(7), C(1)-C(2) )
1.500(9), N(1)-C(2) ) 1.513(8) Å; Ni-N(1)-C(2) ) 92.7(3), N(1)-C(2)-
stereochemistry at the reacting carbon center one could in principle
follow the stereochemical course of the reaction in forming the
R-X product. Herein we report the results of our investigation of
reactions of several aziridines with Ni(0) and Ni(II) complexes that
yield stable Ni(II) azametallacyclobutane products, the preparation
of an H/D isotopic diastereomer of one azametallacyclobutane
complex, and the stereochemical course of the oxidatively induced
reductive elimination that reforms the aziridine on reaction with
dioxygen.
C(1) ) 98.9(5), Ni-C(1)-C(2) ) 92.7(4), N(1)-Ni-C(1) ) 73.4(3)°.
Scheme 1
Reaction of the N-tosylaziridines (p-CH3C6H4SO2)NCH2CHR
(1a, R ) H; 1b, R ) Me; 1c, R ) n-Bu; 1d, R ) i-Pr)7a-b with
(bpy)Ni(cod) (2; bpy ) 2,2′-bipyridine; cod ) 1,5-cyclooctadiene)7c
or (bpy)NiEt2 (3)7d results in elimination of cod or butane from 2
and 3, respectively, and oxidative addition of an aziridine C-N
bond to give the azametallacyclobutane complexes (bpy)Ni-
(NTsCHRCH2) (4a, R ) H; 4b, R ) Me; 4c, R ) n-Bu; 4d, R )
i-Pr) as maroon solids in 50-70% isolated yields (Scheme 1).8 In
these cases, only one regioisomer is observed, with oxidative
addition occurring exclusively at the least-hindered C-N bond.9
These are the first examples of metallacycles isolated from
oxidative-addition reactions of aziridines, although such azametal-
lacyclobutanes have been invoked as intermediates in reactions
involving aziridines, such as catalytic carbonylation of aziridines
to give â-lactams.10
The structure of 4b has been determined by X-ray crystallography
(Figure 1), confirming the presence of a puckered four-membered
azametallacycle (Ni-N(1)-C(2)-C(1) dihedral angle ) 12.6(5)°)
containing a pyramidal nitrogen; the tosyl group on N and the
methyl substituent on the adjacent C are disposed in an anti
conformation.11 The Ni-N(1) bond distance (1.911(5) Å) is at the
high end of the range found in other structurally characterized nickel
amido complexes.12 The methylene and methine protons of the
azametallacycle were clearly located in a difference map, allowing
for the accurate determination of their positions and consequently
the two HCCH dihedral angles (syn ) 15(5)°; anti ) 124(6)°).
To gain mechanistic insight into the oxidative-addition process,
we have followed the relative stereochemistry at the aziridine’s
methylene carbon center. The monodeuterated aziridine syn-(p-
3
CH3C6H4SO2)NCHDCH-n-Bu (1e; JHH ) 7.0 Hz) was prepared
by the Evans aziridination of cis-1-deutero-1-hexene,7a giving 1e
with >95% syn-stereochemistry. 1e reacts with either 2 or 3 to
give (bpy)Ni{NTsCH(n-Bu)CHD} (4e) in 60-65% yield (Scheme
3
2). The observed JHH ) 4.1 Hz for 4e is consistent with a
diastereomer having an anti arrangement of the methine and
methylene protons in the azametallacycle and indicates that >95%
inversion of stereochemistry has occurred at the methylene carbon
during the oxidative-addition reaction (as determined by 1H NMR
integration). This suggests this oxidative addition proceeds via an
SN2-type mechanism involving nucleophilic attack of Ni at C and
then rotation about the C-C bond followed by ring-closure to give
the observed product (shown in Scheme 2).13
Assignment of the two methylene proton resonances in 4c was
essential for interpreting the results of the labeling experiment.
Irradiation of the methine resonance of 4c (δ 3.62) results in a 4.2%
1H nOe intensity enhancement for the methylene proton resonating
* To
whom
correspondence
should
be
addressed.
E-mail:
g-hillhouse@uchicago.edu.
9
2890 VOL. 124, NO. 12, 2002 J. AM. CHEM. SOC.
10.1021/ja017652n CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2
for insightful discussions. The Richter Fund for Undergraduate
Research provided summer support to C.R.C.
Supporting Information Available: Experimental, spectroscopic,
and analytical details; crystallographic details; atomic coordinates; bond
angles and distances; anisotropic thermal parameters; hydrogen atom
coordinates; least-squares planes; torsion angles (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Villanueva, L. A.; Abboud, K. A.; Boncella, J. M. Organometallics
1994, 13, 3921. (b) Baran˜ano, D.; Hartwig, J. F. J. Am. Chem. Soc. 1995,
117, 2937. (c) Mann, G.; Baran˜ano, D.; Hartwig, J. F.; Rheingold, A. L.;
Guzei, I. A. J. Am. Chem. Soc. 1998, 120, 9205.
(2) Selected references: (a) Yang, B. H.; Buchwald, S. L. J. Organomet.
Chem. 1999, 576, 125. (b) Hartwig, J. F. Pure Appl. Chem. 1999, 71,
1417. (c) Wolfe, J. P.; Wagaw, S.; Marcoux, J. F.; Buchwald, S. L. Acc.
Chem. Res. 1998, 31, 805. (d) Hartwig, J. F. Acc. Chem. Res. 1998, 31,
852. (e) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc.
1996, 118, 7215. (f) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996,
118, 7217. (g) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2047.
(3) (a) Koo, K.; Hillhouse, G. L. Organometallics 1995, 14, 4421. (b) Koo,
K.; Hillhouse, G. L. Organometallics 1996, 15, 2669.
Scheme 3
(4) (a) Matsunaga, P. T.; Hillhouse, G. L.; Rheingold, A. L. J. Am. Chem.
Soc. 1993, 115, 2075. (b) Matsunaga, P. T.; Mavropoulos, J. C.; Hillhouse,
G. L. Polyhedron 1995, 14, 175. (c) Koo, K.; Hillhouse, G. L.; Rheingold,
A. L. Organometallics 1995, 14, 456. (d) Han, R.; Hillhouse, G. L. J.
Am. Chem. Soc. 1997, 119, 8135. (e) Koo, K.; Hillhouse, G. L.
Organometallics 1998, 17, 2924.
at δ 0.30, and a 0.8% enhancement for the methylene proton at δ
-0.01, allowing for the assignment of the former as the proton
syn to the methine H and the latter as the anti proton. Similar
assignments follow for the methyl-substituted metallacycle 4b,
where irradiation of the methine proton at δ 3.79 results in a 2.0%
nOe enhancement for the syn methylene proton at δ 0.44, and a
0.1% enhancement for the anti-H resonance at δ -0.05. As an
(5) Han, R.; Hillhouse, G. L. J. Am. Chem. Soc. 1998, 120, 7657.
(6) Oxidatively induced reductive elimination reactions that result in C-C
bond formation are also well established. (a) Takahashi, S.; Suzuki, Y.;
Sonogashira, K.; Hagihara, N. J. Chem. Soc., Chem. Commun. 1976, 839.
(b) Tsou, T. T.; Kochi, J. K. J. Am. Chem. Soc. 1978, 100, 1634. (c) Lau,
W.; Huffman, J. C.; Kochi, J. K. Organometallics 1982, 1, 155.
(7) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc. 1994,
116, 2742. (b) Nadir, U. K.; Sharma, R. L.; Koul, V. K. J. Chem. Soc.,
Perkin Trans. 1991, 2015. (c) Han, K. I.; Pitrowski, A. M.; Eisch, J. J. In
Organometallic Syntheses; King, R. B., Eisch, J. J., Eds.; Elsevier:
Amsterdam, 1986; Vol. 3, p 112. (d) Saito, T.; Uchida, Y.; Misono, A.;
Yamamoto, A.; Morifuji, K.; Ikeda, S. J. Am. Chem. Soc. 1966, 88, 5198.
(8) A representative procedure for the preparation of 4a-e is given for 4b.
(bpy)NiEt2 (3; 0.25 g, 0.75 mmol) was dissolved in 10 mL of THF under
an inert atmosphere. To the stirring solution was added N-p-tolylsulfonyl-
2-methyl aziridine (1b; 0.15 g, 0.71 mmol) in a THF solution. The reaction
mixture was stirred at ambient temperature for 3 h, the resulting dark-red
solution was filtered, and the solids were washed with 3 × 2 mL of THF.
The combined filtrates were reduced in volume to ∼2 mL, and the product
was precipitated by slow addition of hexanes. The red precipitate was
filtered, washed with 3 × 2 mL of hexanes, and dried under vacuum to
afford 4b (0.18 g, 56% yield). An analogous procedure using (bpy)Ni-
(cod) (2) as the Ni source requires longer reaction times but gives similar
yields. Spectroscopic and analytical data are given in the Supporting
Information.
(9) Propylene sulfide reacts with 2 to give a mixture of the thiametallacycles
(bpy)Ni(SCH2CHMe) and (bpy)Ni(SCHMeCH2) in a 1:6 ratio. Matsunaga,
P. T.; Hillhouse, G. L. Angew. Chem., Int. Ed. Engl. 1994, 33, 1748.
(10) (a) Alper, H.; Perera, C. P.; Ahmed, F. R. J. Am. Chem. Soc. 1981, 103,
1289. (b) Piotti, M. E.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
(11) Crystal data for 4b: C20H21N3NiO2S, monoclinic, C2/c, a ) 13.7055(13)
Å, b ) 14.4807(14) Å, c ) 20.1202(19) Å, â ) 102.477(2)°, Z ) 8,
µ(Mo KR) ) 11.22 cm-1, T ) 100 K, V ) 3898.9(6) Å3, λ ) 0.71073 Å,
Dc ) 1.452 mg/mm3. Of 9679 data collected (red crystal, 2.07 e θ e
25.10) 3446 were independent and observed with I > 2σ(I). All non-
hydrogen atoms were anisotropically refined, and hydrogen atoms were
idealized except for those attached to C(1) and C(2), which were located
from the difference map and refined isotropically. R(F) ) 0.081 and R-
(wF2) ) 0.159.
3
independent confirmation, the magnitudes of the JHH for these
resonances are consistent with the syn/anti-assignments made on
the basis of the crystal structure of 4b. Evaluation of the Karplus
equation, relating the dihedral angle between vicinal protons and
3
their JHH, predicts couplings of 7.6 ( 0.3 Hz and 4.4 ( 0.8 Hz
for the syn and anti protons, respectively, using the crystallographi-
cally determined angles (vide supra).14 These values compare
favorably with the measured couplings of 7.8 and 5.0 Hz for 4b,
and 8.3 and 4.1 Hz for 4c.
When the azametallacyclobutane complexes 4a-e are exposed
to oxygen, a reaction ensues giving the free aziridines in 30-60%
isolated yields.15 These oxidatively induced reductive-elimination
reactions are analogous to previously reported examples that give
tertiary amines (from acyclic (bpy)Ni(R)(NR′R′′) complexes) or
five-membered cyclic amines (e.g., pyrrolidines and indolines) from
azametallacycles.3 In the oxidation of 4e, the product aziridine is
spectroscopically identical to its parent, 1e, indicating the elimina-
tion that forms the C-N bond also proceeds with inversion of
stereochemistry (∼92% by 1H NMR integration) at the methylene
carbon (Scheme 2). Four scenarios for the bond-forming event are
illustrated in Scheme 3. The stereochemical result is inconsistent
with a concerted elimination (A, which would give retention at C)
and one involving Ni-C homolysis to generate a primary C radical
(B, giving scrambling). It is consistent with mechanisms involving
Ni-N homolysis (C) or heterolysis (D) followed by ring-closing
displacements (i.e., SH1 or SN2 processes), but does not allow for
differentiation between these latter two mechanisms.
(12) In structures of terminal Ni(I) and Ni(II) amides, Ni-N ranges from 1.93
to 1.82 Å, averaging 1.88 Å. See: Mindiola, D. J.; Hillhouse, G. L. J.
Am. Chem. Soc. 2001, 123, 4623 and references therein.
(13) Such a mechanism is consistent with the observed lack of reactivity of
2,3-disubstituted N-tosylaziridines with 2 and 3.
(14) Gunther, H. NMR Spectroscopy, 2nd ed.; Wiley: New York, 1998.
(15) A representative procedure for oxidation of 4a-e is given for 4e. A 25-
mg sample of 4e (0.05 mmol) was dissolved in 10 mL of benzene and
stirred under 1 atm of O2 for 1 h. GC-MS analysis of the supernatant
showed only 1e and bipyridine to be present. Solvent was removed under
vacuum from the resulting heterogeneous mixture, and the aziridine 1e
(4 mg, 46% yield) was isolated by flash chromatography (silica; hexanes/
EtOAc, 4:1).
Acknowledgment. We thank the National Science Foundation
for financial support, Dan Mindiola for assistance with crystal-
lography, Anne LaPointe for a sample of 1d, and Peter Wolczanski
JA017652N
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