Development of new transition metal catalysts for the oxidation of a hydroxamic acid with in situ Diels-Alder trapping of the acyl nitroso derivative

Article abstract of DOI:10.1039/b704728b

New transition metal catalysts have been prepared and applied for in situ formation of acyl nitroso dienophiles. The Royal Society of Chemistry.

Full text of DOI:10.1039/b704728b

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Development of new transition metal catalysts for the oxidation of a
hydroxamic acid with in situ Diels–Alder trapping of the acyl
nitroso derivative†
Judith A. K. Howard, Gennadiy Ilyashenko, Hazel A. Sparkes and Andrew Whiting*
Received 29th March 2007, Accepted 17th April 2007
First published as an Advance Article on the web 24th April 2007
DOI: 10.1039/b704728b
New transition metal catalysts have been prepared and
only reported example of an asymmetric acyl nitroso DA reaction;
there are still no catalytic systems available for an asymmetric
intermolecular acyl nitroso DA reaction with the necessary in situ
generation of the acyl nitroso species. It is within this context
that we present the results obtained for the three novel catalytic
systems which were designed to produce efficient oxidation of
hydroxamic acids and potentially give asymmetric induction in
such intermolecular acyl nitroso DA reactions (eqn (1)).
applied for in situ formation of acyl nitroso dienophiles.
The use of nitroso compounds as efficient hetero dienophiles in
[4 + 2]-cycloaddition reactions with conjugated dienes to produce
3,6-dihydro-1,2-oxazines has been studied for over half a century.1
These types of hetero Diels–Alder (DA) reactions have been used
as powerful synthetic tools in the formation of natural products
such as polyhydroxylated alkaloids and their derivatives.2–7
The formation of acyl nitroso dienophiles is usually achieved by
the oxidation of hydroxamic acid via potentially toxic processes
involving n-Bu4IO4, Swern or lead(IV) based oxidants.8,9 These
unstable dienophiles are usually trapped via a DA reaction with a
diene to result in the heterocyclic adducts.10,11 However, the toxicity
and inefficient economy of atom transfer in these oxidations
processes means that there is a need to develop novel clean,
catalytic methods for the conversion of hydroxamic acids to acyl
nitroso derivatives. To this end, both us12 and Iwasa et al.13 have
independently reported different ruthenium based catalyst systems
that are capable of promoting the oxidation of hydroxamic acids to
the corresponding nitroso intermediates, which were subsequently
able to be trapped by several dienes. In the system described by
Iwasa et al.,13 high catalytic loadings of more than 10 mol% and
4 equivalents of oxidant were required to achieve good yields.
In contrast, the salen-based ruthenium system of Whiting et al.12
required only very small catalyst loadings (0.1 mol%) and could be
used in conjunction with various dienes. Unfortunately, with a few
exceptions, the yields were generally poor to moderate. Adamo
and Bruschi recently reported14 that copper, iron and nickel in
conjunction with an achiral amine can also be used to catalyse the
oxidation of N-Boc-hydroxyamine with hydrogen peroxide, in a
similar fashion to that of the Iwasa’s system. Again, high yields
were only obtained when using catalytic loadings of up to 10 mol%
and over long reaction times of up to 8 days.
(1)
The lack of asymmetric induction in the intermolecular cases12
and good e.e.s recorded for the intramolecular reaction15 can
be explained in terms of the relative rates of cyclisation versus
dissociation of the acyl nitroso species from the catalyst. It is
known that intramolecular reactions generally proceed faster than
their intermolecular counterparts;16 and it is therefore expected
to be the case here. Based on the assumption that the rate of
dissociation of the acyl nitroso species from the catalyst controls
the e.e. of the final product, we can postulate that in order to
efficiently transfer chirality from the catalyst to the product it
is necessary to extend the lifetime of the acyl nitroso species–
catalyst complex. In order to try and achieve this, we decided to
use commercially available N-(benzyloxycarbonyl)hydroxylamine
2, which can be viewed as a potential bidentate ligand as shown
in Fig. 1 through chelation to the nitroso-oxygen and either the
urethane-oxygen, or more likely the oxygen atom of the carbonyl
group.
Recently, Chow and Shea reported an asymmetric version of
acyl nitroso DA15 based on our ruthenium–salen system. In this
case, the chiral ruthenium–salen complex was shown to catalyse
oxidation of a hydroxamic acid to give the nitroso species, which
was trapped intramolecularly by a directly attached diene moiety
to give the intramolecular cycloadduct in up to an 82% chemical
yield with 75% e.e.15 This intramolecular reaction is to date the
Fig. 1 Binding of N-(benzyloxycarbonyl)hydroxylamine 2 to a metal
centre.
In addition to the binding modes illustrated in Fig. 1, hydrox-
ylamine 2 and the resulting acyl nitroso species may also form p-
donor, hapto-complexes via the benzene ring. In order to achieve
any of these types of binding mode, however, the metal centre
requires at least two vacant coordination sites cis to each other. We
therefore looked to develop new transition metal complexes which
would retain the ability to carry out the oxidation of a hydroxamic
acid to an acyl nitroso derivative in situ, but which did not have
the problems associated with the salen-ligands, i.e. the lack of
Department of Chemistry, Science Laboratories, Durham University, South
Road, Durham, UK DH1 3LE
† Electronic supplementary information (ESI) available: Synthesis and
characterisation of metal complexes, screening procedure and X-ray
crystallography. See DOI: 10.1039/b704728b
2108 | Dalton Trans., 2007, 2108–2111
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Table 1 Representative bond lengths and angles for the iron complex 5
vacant cis-coordination sites. A study was therefore undertaken
to examine metal complexes of the ligand system 4, since these
would be likely to contain vacant cis-oriented sites which would
be suitable for acyl nitroso coordination. Furthermore, transition
metals complexes derived fromligand 4 should have an asymmetric
three dimensional structure which might restrict the approach of
the diene to the bound and activated acyl nitroso species in a
manner similar to that which has been elegantly demonstrated
in the not unrelated hetero-DA reactions.17 In order to fine-
tune the reactivity and selectivity, if required, analogues of the
commercially available ligand 4 can be readily synthesized through
the use of simple imine formations between arylaldehyde and
chiral 1,2-aminoalcohols. Ruthenium, iron and chromium were
chosen for this study into the complexation of ligand 4 to a metal
because of their rich redox and Lewis acid chemistry.
˚
Bond length/A
Angle/◦
Fe1–O1
Fe1–O2
Fe1–O3
Fe1–N1
Fe1–Cl1
Fe2–O2
Fe2–O3
Fe2–O4
Fe2–N2
Fe2–Cl2
1.874(3)
O(1)–Fe(1)–O(2)
O(1)–Fe(1)–O(3)
O(2)–Fe(1)–O(3)
O(1)–Fe(1)–N(1)
O(2)–Fe(1)–N(1)
O(3)–Fe(1)–N(1)
O(3)–Fe(2)–O(4)
O(2)–Fe(2)–O(4)
O(2)–Fe(2)–O(3)
O(4)–Fe(2)–N(2)
O(3)–Fe(2)–N(2)
O(2)–Fe(2)–N(2)
Fe(1)–O(2)–Fe(2)
Fe(1)–O(3)–Fe(2)
148.54(13)
102.11(14)
74.98(13)
86.76(15)
77.34(14)
139.53(14)
137.72(14)
98.83(14)
75.11(12)
86.68(15)
76.31(14)
142.77(14)
105.38(14)
104.03(14)
2.008(3)
1.971(3)
2.078(4)
2.206(1)
1.950(3)
2.023(3)
1.882(3)
2.086(4)
2.219(2)
of two iron centers which are bridged by the oxygen atoms of the
aminoalcohol part of the ligand, with the metal atoms separated
˚
by 3.149(1) A. Each metal centre is elevated above the least squares
plane created by their respective bound nitrogen and three oxygen
atoms forming an approximately square pyramidal geometry. This
elevation, combined with the steric bulk of the ligand, forces the
complex to adopt a saddle-like structure. The separation of the
metal centers and their arrangement also appears to be almost
ideal for 5 to act as a binuclear catalyst,19 assuming that the
structure remains the same in the solution. This complex, along
with complexes 6 and 7 were screened for catalytic activity and
compared with the salen–ruthenium system 8 in the reaction
described in eqn (1) through a series of parallel reactions carried
out over a 16 h period at room temperature. The results are
presented in Table 2.
Unlike the ruthenium(salen) based system 8, complexes 5–7
did not oxidize the substrate 2 to the corresponding acyl nitroso
compound when employing tert-butyl hydroperoxide, however,
the more environmentally friendly and atom economic hydrogen
peroxide proved to be a successful co-oxidant. This route also
avoids the use of chlorinated solvents which provides further
benefit from the clean catalysis point of view. When complexes
6 and 7 were used for the reaction outlined in eqn (1), the reaction
yields were lower than those recorded with the ruthenium–
salen complex 8. However, complex 5 shows activity which is
comparable to that of the ruthenium–salen system 8. Though
increasing the catalytic loadings to 1 mol% improved the overall
yields and decreased the reaction times, it also increased the
formation of undesired side products, presumably due to over
oxidation. The low yields in entries 6–9 (Table 2) can be attributed
to a competing retro-DA reaction; reversible behaviour that is
well documented.20,21 Unfortunately, none of these catalysts were
capable of inducing asymmetric induction in any of the isolated cy-
cloadducts, which is not contradictory with our previous results.12
It seems likely that this is due to the transition metal–acyl nitroso
complex having insufficient stability to control the subsequent
Diels–Alder reaction. Therefore, although acyl nitroso dienophiles
can be viewed as potentially bidentate metal ligands (Fig. 1),
there is no evidence that they behave this way in intermolecular
cycloadditions,12 and only intramolecular reactions demonstrate
the potential for these types of processes.15
The complexes 5 and 6 were prepared by reacting ligand 4
with the metal salt [FeCl3 and RuCl2(p-cymene), respectively]
in the presence of Et3N; the complexes were isolated after
an aqueous work up in yields of 82% and 48%, respectively.
Chromium complex 7 was prepared using literature methods,12
while ruthenium complex 8 was prepared according to previously
reported procedures17 to act as a comparative model catalyst with
systems 5–7.
The molecular structure of complex 5 was confirmed by single
crystal X-ray crystallography18 and is shown in Fig. 2, with relevant
bond lengths and angles listed in Table 1. The complex 5 consists
Three novel catalytic systems were designed and tested for
activity in asymmetric acyl nitroso DA reactions. Despite the
Fig. 2 ORTEP plot of complex 5 with ellipsoids depicted at the 30%
probability level. Hydrogen atoms are omitted for clarity.
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Table 2 Catalytic results of DA reactions between a series of dienes and acyl nitroso derivative
Yieldsb of Diels–Alder adducts (%)
Catalyst
Entry
1
Diene
Producta
5d
6d
7d
8e
49
32
45
25
95
2
3
4
50; 98c
42
23
22
28
53
69
25
40
7
22
5
6
10f
11
14f
5
9f
14f
15
6
7
23
6
10
16
8
9
0
0
0
0
0
0
0g
0g
a All compounds are known (see ref. 22). b Isolated yields. c Yields obtained from HPLC. d H2O2/Acetone. e BuOOH/DCM. f Mixture of inseparable
isomers. g 1 mol% of catalyst used.
low yields and lack of e.e., these new systems have comparable
activity to previously reported catalysts. Moreover, because these
systems employ stoichiometric amounts of hydrogen peroxide and
non-chlorinated solvent, they are environmentally more benign
than any previously reported. Further investigations into the
mechanistic aspects of the reaction are currently ongoing in our
laboratory and any further results or optimisations will be reported
in due course.
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