Angular ligand constraint yields an improved olefin aziridination catalyst

Article abstract of DOI:10.1021/ol034681p

(Matrix presented) The use of a pyridinophane, a macrocycle composed of three pyridines linked, via all ortho positions through CH₂ or CH₂CH₂ groups, bound to copper, gives good performance (rate and yield) catalyzing the

Full text of DOI:10.1021/ol034681p

ORGANIC
LETTERS
2003
Vol. 5, No. 15
2591-2594
Angular Ligand Constraint Yields an
Improved Olefin Aziridination Catalyst
Andrei N. Vedernikov* and Kenneth G. Caulton*
Department of Chemistry, Indiana UniVersity, Bloomington, Indiana 47405
caulton@indiana.edu; aVederni@indiana.edu
Received April 23, 2003
ABSTRACT
The use of a pyridinophane, a macrocycle composed of three pyridines linked, via all ortho positions through CH or CH CH groups, bound
2
2
2
to copper, gives good performance (rate and yield) catalyzing the conversion of substituted aliphatic olefins and PhINTs to aziridines. Advantages
also derive from using CH Cl2 solvent and the weakly coordinating anions BAr4- (Ar ) C H or 3,5-C H (CF3)2). Reactions are complete in
2
6
5
6 3
minutes at 20 °C, and yields are almost quantitative for olefins not bearing secondary allylic CH bonds; however, cis-cyclooctene gives only
the aziridine despite the allylic hydrogens.
Aziridines serve a significant role as reactive precursors in
the synthesis of a variety of polyfunctional compounds with
C-N bonds.1 One of the important routes to aziridines is
transition-metal-catalyzed transfer of the nitrene moiety to
olefin from a suitable source like ArSO2NIAr, ArN3, ArSO2-
NNa(Cl), etc. eq 1:
anism of the copper-catalyzed aziridination, eq 1, remains a
problem that affects the development of better catalytic
systems.3,6
In this communication we report a new copper catalyst
for olefin aziridination with TsNIPh that allows very fast
(2-10 min at 0-20 °C) and often quantitative conversion
of simple mono-, di-, tri-, and tetrasubstituted olefins
including those with electron-withdrawing groups attached
to the CdC bond, together with an examination of the scope
and limitations of the catalyst.
Faster ligand substitution is important if catalysis involves
coordination of reactants to a metal center. It can be generally
achieved by “preparing” the catalytic metal center with only
weakly binding ligands, whose role is to be displaced by
certain of the reactants in eq 1. One example of this is the
removal of halide ligands with a silver salt of a weakly
coordinating anion (eq 2):
Synthetic interest in aziridines increased after the discovery
of simple and inexpensive copper catalysts.2-4 Nevertheless
copper catalysts have many important limitations such as
high catalyst loading (>5%) and poor yields in the case of
simple aliphatic olefins.5 Limited knowledge of the mech-
LCuCln + nAgSbF6 solvent8
(1) Hassner, A. Small Ring Heterocycles; Wiley: New York, 1983-
LCu(solvent)n+(SbF6 )n + nAgCl (2)
-
1985.
(2) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Org. Chem. 1991, 56,
6744.
(3) Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117,
5889.
In the work described here, this will be accomplished by
(4) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem. Soc. 1994,
116, 2742 and references therein.
(5) Handy, S. T.; Czopp, M. Org. Lett. 2001, 3, 1423.
(6) Brandt, P.; Sodergren, M. J.; Andersson, P. G.; Norrby, P.-O. J. Am.
Chem. Soc. 2000, 122, 8013.
10.1021/ol034681p CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/21/2003

using less ligating anions BAr4- (Ar ) C6H5 or 3,5-bis(CF3)-
C6H3). The polar or ionic catalysts employed demand a polar
solvent. The commonly employed acetonitrile certainly is a
ligand competitive for a metal center with the reactants (eq
1), and so catalysis in the less coordinating dichloromethane
is, in principle, anticipated to be preferable.7
performance for aziridination.19 We report here a test of these
ideas, including the question of precursor metal oxidation
state.
Dichloro (CuII) and monochloro (CuI) pyridinophane
copper complexes were synthesized in almost quantitative
yield by stirring the corresponding anhydrous CuCln with
equimolar L in benzene. When slurried with NaBAr4 in CH2-
Cl2 at 20 °C, the chloro complexes dissolved to produce the
corresponding cationic species, stable for days (n ) 1,
copper(I) complex) or for a few minutes (n ) 2, copper(II)
complex) in the absence of substrate. The catalytic activity
of both catalysts is shown in Table 1. The enhanced solubility
of these catalysts in a weakly coordinating solvent is one of
their advantages.
The work described here tests the above hypothesis but
introduces a new potentially facial tridentate ligand, which
has been shown to be advantageous for other reactivity
objectives8-10 based on the fact that the ligand has a
constrained distorted 3-fold symmetric character. Thus, the
new macrocyclic tripyridine ligand, [2.1.1]-(2,6)-pyridi-
nophane (L), which is readily available from commercial
Initial catalytic studies involved 5% catalyst loading (vs
PhINTs) and an olefin:PhINTs mole ratio of 3-10 and gave
turnover numbers up to 20. Ethylene (entries 1 and 2) reacted
slowly and in poor yield, while propylene (entries 3 and 4)
and cis-2-butene (entries 5 and 6) were much more reactive
and converted into the corresponding aziridines in very high
yields. Partial loss of stereochemistry (entries 5 and 6)
suggests the involvement of an intermediate where the
carbon-carbon π-bond is broken. In contrast, substrates with
secondary allylic CH bonds such as 1-butene, cyclopentene,
and cyclohexene (entries 7-12) produced significant amounts
of products of R-amination in addition to aziridines. Nev-
ertheless, cis-cyclooctene, possessing a weaker and more
reactive CdC bond, can be transformed into the correspond-
ing aziridine almost quantitatively (entries 13 and 14).
Anticipating that substrates with less reactive primary or no
allylic CH bonds might react cleanly, we tried tert-butyl-
ethylene and tri- and tetramethyl-ethylene (entries 19-24).
In all of these cases aziridines were rapidly and quantitatively
obtained. Remarkably, electron-poor substrates such as
methyl acrylate and methyl methacrylate (entries 25-28) also
reacted quantitatively and rapidly.
Using cis-cyclooctene as a test substrate, we explored the
effect of some variation in catalyst loading and composition
on the aziridine yield (entries 13-18). It was found that
(a) Both mono- and dichloro copper-derived catalysts
(entries 13 and 14) showed almost indistinguishably high
activity. The same result was observed for other substrates
listed in Table 1 (compare even and odd entries 1-14, 19-
28). This result is consistent with our observation of
quantitative stoichiometric oxidation of yellow (LCuI)+
tetraarylborate by PhINTs into PhI and a deep purple
dinuclear copper(II) complex [(LCuII)2NTs]2+. The latter is
stable in CH2Cl2 solution and diamagnetic, so allowing its
characterization by 1H and 13C NMR techniques. Thus, easy
oxidation of a CuI precatalyst to a CuII compound proves
that the catalytic environment is sufficiently oxidizing that
no CuI persists.
pyridines,11 has steric and electronic characteristics signifi-
cantly different from those of “pybox” pincer ligands,4
R-diimines,12-14 triazacyclononane,15-17 and even tris-pyra-
zolylborates,18 all of which have been tested for aziridination
catalysis on copper. The macrocycle-constrained deviation
from 3-fold symmetry makes L poorly suitable for the near-
tetrahedral or trigonal planar geometry preferred by d10 Cu-
(I) in the catalyst precursor. The reagent PhINTs commonly
employed in aziridination is a two-electron oxidant (eq 3 )
PhINTs + 2e- f PhI + TsN2-
(3)
and (η3-L)CuI species can be potentially oxidized to Cu-
(III). Therefore, a constrained ligand, destabilizing the reagent
(η3-L)CuI, will help in producing (L)CuIII(NTs)+ and thus
enhances reactivity of (η3-L)CuI toward PhINTs. This
destabilization translates hopefully into enhanced catalytic
(7) Clark, A. J.; Filik, R. P.; Thomas, G. H. Tetrahedron Lett. 1999, 40,
4885.
(8) Vedernikov, A. N.; Huffman, J. C.; Caulton, K. G. New J. Chem.
2003, 27, 665.
(9) Vedernikov, A. N.; Caulton, K. G. Chem. Commun. 2003, 358.
(10) Vedernikov, A. N.; Caulton, K. G. Angew. Chem., Int. Ed. 2002,
41, 4102.
(11) Vedernikov, A. N.; Huffman, J. C.; Caulton, K. G. Inorg. Chem.
2002, 41, 6867.
(12) Gillespie, K. M.; Crust, E. J.; Deeth, R. J.; Scott, R. Chem. Commun.
2001, 785.
(13) Sanders, C. J.; Gillespie, K. M.; Bell, D.; Scott, P. J. Am. Chem.
Soc. 2000, 122, 7132.
(14) Gillespie, K. M.; Sanders, C. J.; O’Shaughnessy, P.; Westmoreland,
I.; Thickitt, C. P.; Scott, P. J. Org. Chem. 2002, 67, 3450.
(15) Halfen, J. A.; Fox, D. C.; Mehn, M. P.; Que, L., Jr. Inorg. Chem.
2002, 40, 5060.
(16) Halfen, J. A.; Uhan, J. M.; Fox, D. C.; Mehn, M. P.; Que, L., Jr.
Inorg. Chem. 2000, 39, 4913.
(b) We tried 1% catalyst loading and found almost the
same performance (entry 15 vs 14). Significant catalyst
degradation (evident by color change from reddish to green)
prevented further reduction of the amount of catalyst.
(17) Halfen, J. A.; Hallman, J. K.; Schultz, J. A.; Emerson, J. P.
Organometallics 1999, 18, 5435.
(18) Perez, P. J.; Brookhart, M.; Templeton, J. L. Organometallics 1993,
12, 261.
(19) Vedernikov, A. N.; Pink, M.; Caulton, K. G. Inorg. Chem. 2003,
42, in press.
2592
Org. Lett., Vol. 5, No. 15, 2003

Table 1. Olefin Aziridination Catalysis with PhINTs, LCuCln, and nNaBAr4 in CH2Cl2
a NMR yield; integration relative to signals of unreacted olefin and/or PhI liberated. b BPh4 derivative. c Yield on olefin. d LCu(OTf)2, no NaBArF e no
.
4
NaBArF
; .
f (tpdm)CuCl + NaBArF
4
4
-
(c) The much less expensive BPh4 salt in place of the
significantly. Finally, the importance of the macrocyclic
feature of the tripyridine ligand attached to copper was shown
by an experiment with (tpdm)CuBArF4 catalyst derived from
tripyridinedimethane (tpdm), a nonmacrocyclic analogue of
L.20 In this case (entry 31) only a very low noncatalytic yield
of aziridine was obtained. Thus a nonmacrocyclic “pincer”
ligand shows diminished performance.
The facts reported here are consistent with hypothesis of
a homolytic mechanism of aziridination with transient radical
species capable of cleaving not only carbon-carbon π-bonds,
which is easier for substituted ethylene as compared with
ethylene itself, but also secondary allylic CH bonds of
olefins.
Free radical reactivity of the LCuII/PhINTs system is
implicated by the results of DFT calculations.21 According
to these results, LCuII(PhINTs)2+ readily loses PhI to produce
a ligand-centered radical, LCuIII(N-Ts)2+, with most of its
spin density localized on the nitrene nitrogen. The species
BArF - analogue showed very fast catalysis, but accompanied
by competitively rapid and complete (color change) catalyst
degradation, resulting in poorer (but still high) yield of the
aziridine (entry 16 vs 14).
4
(d) Aziridinations have traditionally been carried out with
excess olefin, a situation seldom tolerable when a compli-
cated olefinic intermediate is the more valuable reagent. We
therefore tested our reagent at a 1:1 reagent mole ratio.
Stoichiometric (equimolar) substrate loading turned out to
be also a satisfactory condition for fast and high yield
aziridination (entry 17 vs 13).
(e) Finally, the combination of low catalyst loading (1%)
and stoichiometric amount of olefin leads to increased
reaction time and decrease of the yield to 56% (entry 18 vs
17).
The importance of preactivation of the LCuXn complex,
to produce a highly unsaturated catalyst, was illustrated by
experiments with LCu(OTf)2, containing weakly coordinating
triflate (entry 29) and LCuCl2 with strongly copper-bound
chloride (entry 30). In this series, catalytic activity dropped
(20) Vedernikov, A. N.; Huffman, J. C.; Caulton, K. G. Inorg. Chem.
2002, 41, 6244.
(21) See Supporting Information for details.
Org. Lett., Vol. 5, No. 15, 2003
2593

should be able to attack either a CdC or an allylic C-H
bond. Indeed, calculations show that, even in the case of
alkane secondary CH bonds, hydrogen atom abstraction, eq
4, is just (barely) feasible; ∆G°298 ) 1 kcal/mol for eq 4.
reagents also undergo slow (∼12 h) uncatalyzed reaction with
olefins, which can competitively degrade regio- and stereo-
electivity only for a slow-acting catalyst.
Taken together, the observations reported show attractive
performance (low catalyst loading, rate, yield) of new
cationic copper-pyridinophane complexes prepared in low
coordinating solvent, allowing quantitative conversion of
simple (poly)substituted olefins without reactive CH bonds
into corresponding aziridines.
It is currently premature to assert that we know whether
the active catalyst is this mono-copper species or the CuI-
derived dicopper, imide-bridged species discussed above.
However, the oxidizing radical character of the metal
complexes produced by the catalyst recipe seems clearly
demonstrated and should figure in future mechanistic analy-
ses.
Acknowledgment. This work was supported by the U.S.
Department of Energy. A.N.V. is on leave from the Chemical
Faculty, Kazan State University, Kazan, Russia. This work
has been made possible in part due to support from Russian
Foundation for Basic Research (grant 01.03.32692).
The rapid rate shown here yields identifiable benefits. For
example, imino reagents are subject to competitive degrada-
tion by reaction with solvent or with adventitious nucleo-
philes, including water. Such side reactions are less important
for a catalyzed reaction that is complete in minutes. Imino
Supporting Information Available: Computational and
synthetic protocols and results. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL034681P
2594
Org. Lett., Vol. 5, No. 15, 2003