Oxaziridine cleavage with a low-valent nickel complex: Competing C-O and C-N fragmentation from oxazanickela(II)cyclobutanes

Article abstract of DOI:10.1039/c7cc07690h

Reacting the low-valent nickel complex [(dtbpe)Ni]₂(μ-η²:η²-C₆H₆) with oxaziridines was found to form mixtures of imine, amide and aldehyde products. If the N-substituent of the oxaziridine is sufficiently bulky, a short-lived intermediate can be isolated and characterized by X-ray diffraction studies as an oxazanickela(ii)cyclobutane. This is the first well-defined example of N-O oxidative addition of an oxaziridine to a transition metal. Subsequent fragmentation of this oxazanickelacyclobutane forms a complex mixture of products, including a nickel(ii) imido complex, demonstrating that oxaziridines can serve as nitrene precursors. Preliminary mechanistic analysis is consistent with a bimetallic mechanism of fragmentation of the oxazanickelacyclobutane to form the nickel imido and η²-aldehyde complexes.

Full text of DOI:10.1039/c7cc07690h

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Oxaziridine cleavage with a low-valent nickel
complex: competing C–O and C–N fragmentation
Cite this:DOI: 10.1039/c7cc07690h
from oxazanickela(II)cyclobutanes†
Received 3rd October 2017,
Accepted 29th October 2017
Addison N. Desnoyer, * Weiling Chiu,
Jennifer A. Love
Candy Cheung, Brian O. Patrick
and
*
DOI: 10.1039/c7cc07690h
rsc.li/chemcomm
Reacting the low-valent nickel complex [(dtbpe)Ni]2(l-g2:g2-C6H6) stoichiometric and catalytic processes. Thus, we set out to study
with oxaziridines was found to form mixtures of imine, amide the fundamental reactivity of oxaziridines with well-defined, low-
and aldehyde products. If the N-substituent of the oxaziridine is valent transition metal complexes in order to gain valuable
sufficiently bulky, a short-lived intermediate can be isolated and insight that will allow for the rational design of new catalytic
characterized by X-ray diffraction studies as an oxazanickela(II)cyclo- transformations of oxaziridines. We hypothesized that the
butane. This is the first well-defined example of N–O oxidative addition strongly oxidizing nature of oxaziridines would make them
of an oxaziridine to a transition metal. Subsequent fragmentation of this reactive substrates for nickel(0). In particular, we anticipated
oxazanickelacyclobutane forms a complex mixture of products, includ- facile oxidative addition of the weak N–O bond of the oxaziridine
ing a nickel(II) imido complex, demonstrating that oxaziridines can serve moiety across the nickel centre. To our surprise, although
as nitrene precursors. Preliminary mechanistic analysis is consistent with oxidative addition of the N–O bond of an oxaziridine has been
a bimetallic mechanism of fragmentation of the oxazanickelacyclo- invoked in iron-catalyzed oxyamination,8 rhodium-catalyzed
butane to form the nickel imido and g2-aldehyde complexes.
isomerization9 and palladium-catalyzed ethoxycarbonylation,10
no examples of well-defined oxazametallacyclobutanes have
Oxaziridines are commonly used reagents in organic synthesis, been prepared via this synthetic route.
but have been sparsely utilized in the field of organometallic
Recently, our group has been interested in exploring the
chemistry relative to other three-membered heterocycles.1 fundamental reactivity of low-valent nickel complexes with simple
Nevertheless, their versatility, tunability, ease of preparation and organic molecules containing C–X (X = O or S) bonds, and our
handling, and the ability to render them rigorously anhydrous all studies examining epoxides,11 as well as esters and thioesters12
demonstrate that oxaziridines can be valuable reagents in inorganic have already been reported. In this current manuscript, we present
chemistry, offering complementary reactivity to other oxidants like our findings on the reactivity of [(dtbpe)Ni]2(m-Z2:Z2-C6H6), dtbpe =
H2O2 and dimethyldioxirane.3 A common mode of reactivity of 1,2-bis(di-tert-butylphosphino)ethane13 (1) with oxaziridines,
2
oxaziridines with redox-active transition metal complexes is their including the first well-defined example of N–O oxidative addi-
isomerization to the corresponding amides.1,4 Oxaziridines can tion of oxaziridines with a transition metal complex, as well as
also be used as electrophilic O-atom transfer (OAT) reagents.1 In a unprecedented cleavage of the resulting oxazanickelacyclo-
recent example, Puddephatt and co-workers reported that, in protic butane to form a nickel(II) imido complex.
solvents, oxaziridines can oxidize dimethylplatinum(II) complexes
Addition of Davis’ oxaziridine14 (2) to a C6D6 solution of 1
to platinum(IV) hydroxo species via hemiaminal intermediates.5 resulted in the formation of two organometallic products,
Seminal work from the Yoon group has also demonstrated that complexes 3 and 4, as determined by 31P{1H} NMR spectro-
oxaziridines can be used as coupling partners for copper- and scopy. The major product, complex 3, which displays two [AB]
iron-catalyzed oxyamination of olefins,6 as well as intramolecular doublets at 85.1 and 84.1 ppm with a JP,P of 43 Hz, was
2
C–H bond amination.7 These reports clearly show that oxaziridines determined to be the Z2-imine complex shown in Scheme 1.15
can react cleanly with a variety of late transition metals in both Complex 3 was also prepared independently by addition of the
imine TsNQCHPh (5) to 1. Complex 3 was fully characterized by
1H and 13C{1H} NMR spectroscopy, as well as EI mass spectro-
metry. Dark red, X-ray quality crystals could be grown via slow
Department of Chemistry, The University of British Columbia, Vancouver, Canada.
E-mail: adesnoye@umn.edu
† Electronic supplementary information (ESI) available: Experimental data for all
evaporation of a saturated Et2O solution at room temperature
new compounds. CCDC 1537039 (3), 1537040 (4) and 1537041 (8). For ESI and
(see Fig. 1 for solid-state structure). The C–N bond length is
appreciably lengthened at 1.409(4) Å, which is longer than that of
crystallographic data in CIF or other electronic format see DOI: 10.1039/
c7cc07690h
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1
change in the product distribution by either H NMR spectro-
scopy or GC/MS. In addition, we did not detect any anthracene,
which would be the product of oxidation of DHA. Thus, we
believe a process involving O- or N-based radicals to be unlikely.
Although we initially hypothesized that 4 was formed via
hydrolysis of either the free imine TsNQCHPh (5) or the bound
imine of 3, there was no trace of free H2NTs in the 1H NMR
spectrum of the reaction mixtures. In addition, both 3 and 5 have
been found to be stable in the presence of a large excess of water
in C6D6 over 24 hours. Based on these data, we deemed hydrolysis
by adventitious water to be unlikely, and were thus interested in
determining the mechanism of formation of both 3 and 4.
Low-temperature (À50 1C) addition of 2 to 1 in tol-d8 did not
reveal the presence of any intermediates detectable by 31P{1H}
NMR spectroscopy. Speculating that the reaction could be slowed
by the addition of a bulkier substituent at the N-position, we
prepared N-adamantyl oxaziridine (7) according to a literature
procedure20 and reacted it with 1 in C6D6 (Scheme 2). In this case,
low-temperature (À50 1C) addition of 7 to 1 in tol-d8 resulted in
an immediate colour change from red-orange to dark purple.
31P{1H} NMR spectroscopy revealed two resonances of equal
intensity (d = 66.1 ppm and 51.6 ppm), which broaden signifi-
cantly upon warming to À30 1C, and are undetectable when the
solution is further warmed to 0 1C (see Fig. S8, ESI†).21 A 31P–1H
Scheme 1 Synthesis of 3, 4 and 6. (a) 1H NMR yields in parentheses (b)
UPLC yield in parentheses.
Fig. 1 ORTEP diagrams (50% probability ellipsoids) of complexes 3 (left)
and one of two independent molecules of 4 (right). All H atoms except H1
of 4 removed for clarity.
several related structures.16 Curiously, although 5 is the byproduct HMBC experiment at À20 1C shows that both of these 31P resonances
1
of OAT from 2 and dtbpe is prone to oxidation, we did not detect are coupled to a broad peak at 6.87 ppm in the H NMR spectrum
any dtbpeO or dtbpeO211,12,17 in these reaction mixtures.
(see Fig. S9, ESI†). In addition, we also observed a corresponding set
The minor product of the reaction (4) displays two [AB] of aromatic resonances for a phenyl group.21 Together, these data
2
doublets at 90.1 and 88.1 ppm with large JP,P values of 70 Hz. indicate successful incorporation of the oxaziridine moiety into the
The similarities to related complexes prepared by our group11,12 (dtbpe)nickel fragment. Indeed, if care is taken to keep the reaction
hinted that this product could be an Z2-carbonyl complex of cold, large purple blocks of 8 can be grown from a concentrated Et2O
nickel(0). Indeed, a 31P–1H HMBC experiment showed cross solution on standing at À30 1C. Single crystal X-ray diffraction
peaks between the two [AB] doublets and a resonance in the experiments determined that the structure of 8 is the nickel(II)
1H NMR spectrum at 5.92 ppm. This resonance appears as a oxazanickelacyclobutane depicted in Fig. 2, formed via oxidative
doublet of doublets ( JH,P = 6.2 and 4.2 Hz) which collapses to a addition of the N–O bond across the metal centre.
broad singlet upon 31P decoupling. An HSQC experiment showed a
The only other examples of well-defined oxazanickelacyclo-
strong cross peak for this H resonance with a 13C resonance at butanes have been reported by the Hillhouse group, formed via
78.8 ppm. The chemical shift and multiplicity (d, JC,P = 22 Hz) of reactions of imido complexes (dtbpe)Ni(NR) with carbonyl-
this 13C resonance are also consistent with a p-bound aldehyde containing molecules like CO2 and benzaldehyde.22 Similarly,
complex. The product was ultimately identified as the Z2-benz- oxazametallacycles of early transition metals have been reported
aldehyde complex 4, which was again confirmed via independent by similar synthetic routes.23 To the best of our knowledge, this
synthesis and comparison of the spectral data with that of the is the first well-defined example of N–O oxidative addition of
reaction mixture. Like 3, complex 4 was fully characterized via oxaziridines with a transition metal.
1
NMR spectroscopy, elemental analysis, EI mass spectrometry
and X-ray diffraction (see Fig. 1 for solid-state structure).
If the reaction is performed at room temperature, the solution
changes from purple to brown-red over the course of 2 hours, and
Analysis of the reaction mixture by UPLC also shows the analysis by 31P{1H} and 1H NMR spectroscopy shows the formation
formation of amide 6 in low yields. After optimization studies, of a mixture of products. Importantly, we observed an upfield singlet
we found that the highest yields of 6 (31% by UPLC) were at 126.9 ppm in the 31P{1H} NMR spectrum, which was assigned to
obtained after gently heating the reaction at 60 1C for 1 hour in the previously reported imido complex (dtbpe)Ni(NAd)24,25 (9).
THF. This isomerization process is not unexpected,4,18 as we This assignment was confirmed by spiking reaction mixtures
have recently found that 1 can rapidly isomerize epoxides to with independently prepared 9.26 In addition, the 31P{1H} NMR
either the corresponding ketones or aldehydes.11b Given that resonance of 9 appears as a doublet (2JP,N = 19 Hz)21 when
oxaziridine isomerizations typically are induced by single- prepared from isotopically labelled 15N-7 and 1. While nitrene
electron processes,1 we performed the reaction of 1 with 2 in release from an oxaziridine has been invoked once previously
the presence of excess 9,10-dihydroanthracene (DHA), which under photolytic conditions,27 this is the first example of nitrene
has very weak C–H bonds.19 However, we found no significant formation upon reaction of an oxaziridine with a transition
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Scheme 2 Synthesis and reactivity of 8. (a) Isolated yield (b) 31P{1H} NMR yield in parentheses (c) 1H NMR yields in parentheses (d) UPLC yield in
parentheses.
This is not unexpected, given that 8 appears capable of reacting
via a variety of different pathways at room temperature. The
instability of 8 is remarkable, given that the only other examples
of oxazanickelacyclobutanes, reported by the Hillhouse group,22
do not undergo these fragmentations observed here.
In conclusion, we have shown that 1 reacts with oxaziridines
to form complex mixtures of products. In the case of Davis
oxaziridine 2, the main reaction products are imine complex 3
and benzaldehyde complex 4. In the case of adamantyl oxaziridine
7, a short-lived purple intermediate 8, a rare example of an
oxazanickelacyclobutane, was identified. Complex 8 was found
to fragment to a complex mixture of products including 4, nickel(II)
imido complex 9, as well as imine 10. Preliminary mechanistic data
Fig. 2 ORTEP diagram (50% probability ellipsoids) of complex 8. All H
atoms removed for clarity.
indicate that 9 is formed via a bimetallic pathway. The formation
of 9 suggests that oxaziridines have potential synthetic utility
as nitrene transfer reagents, with future work in our laboratory
delving into tuning the structural and electronic properties of
oxaziridines toward potential catalytic reactivity.
metal complex. In addition to complex 4 (15% NMR yield)
and dtbpeO (8% NMR yield), we also observe free imine
AdNQCHPh (10, 14% NMR yield) in solution. In contrast to
the Davis system described above, we do not observe clean
formation of an Z2-imine complex when we react 1 with 10.
We attribute this to increased steric hindrance between the
N-adamantyl group of 10 with the (dtbpe)nickel moiety. Lastly,
under analogous conditions to the reaction of 1 with Davis’
oxaziridine 2, we also identified amide 11 in 30% yield by UPLC
analysis after reacting 1 with 7 for 1 hour at 60 1C.
To probe the mechanism of this unusual fragmentation
process, we monitored the rate of decay of 8 using UV/vis
spectrophotometry. Indeed, preliminary results show that 1
promotes the decomposition of 8. We propose this is due to a
rate-limiting intermolecular reaction of 8 with (dtbpe)nickel(0)
We thank the University of British Columbia (Laird and 4YF
to A. N. D.), NSERC (Discovery grant, Research Tools and
Instrumentation grants to J. A. L.; CGS-D3 and MSFSS to
A. N. D.) and the Canada Foundation for Innovation for
supporting our research. A. N. D. is grateful to the Izaak Walton
Killam Foundation for a doctoral scholarship. W. C. is grateful
for support from the CREATE SusSyn program. We thank
D. Dawson Beattie for aid with X-ray crystallography, Ryan
Chung and Prof. Jason Hein for help with UPLC analysis, and
Eric G. Bowes for helpful discussions.
to form 4 and 9, as opposed to unimolecular fragmentation of 8 Conflicts of interest
to form 4 and a reactive nitrene intermediate (see Scheme S1,
There are no conflicts to declare.
ESI†).21 This unimolecular pathway would also likely result in
the formation of AdNQNAd24,28 or possibly PhNHAd29 (from
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