A novel, efficient synthesis of N-aryl pyrroles via reaction of 1-boronodienes with arylnitroso compounds

Article abstract of DOI:10.1039/c3cc42227e

A one-pot hetero-Diels-Alder/ring contraction cascade is presented from the reaction of 1-boronodienes and arylnitroso derivatives to derive N-arylpyrroles in moderate to good yields (up to 82%).

Full text of DOI:10.1039/c3cc42227e

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A novel, efficient synthesis of N-aryl pyrroles via
reaction of 1-boronodienes with arylnitroso
compounds†
Fabien Tripoteau,a Ludovic Eberlin,a Mark A. Fox,b Bertrand Carboni*a and
Andrew Whiting*b
Cite this: Chem. Commun., 2013,
49, 5414
Received 27th March 2013,
Accepted 30th April 2013
DOI: 10.1039/c3cc42227e
www.rsc.org/chemcomm
A one-pot hetero-Diels–Alder/ring contraction cascade is presented
However, instead of cycloadducts of type 3 and/or 4 being observed,
from the reaction of 1-boronodienes and arylnitroso derivatives to the unexpected N-phenylpyrrole 8 was identified (eqn (1)) from the
derive N-arylpyrroles in moderate to good yields (up to 82%).
reaction of boronate ester 7 with nitrosobenzene. This prompted a
more detailed investigation of this novel and intriguing process.
The biological activity associated with pyrroles and N-aryl pyrroles1
makes them a target for the development of novel synthetic
approaches.2 This communication reports a new and unexpected
N-aryl pyrrole synthesis resulting from the reaction of an arylnitroso
compound with a 1-boronodiene.
(1)
The reaction of nitroso compounds with dienes is well known,3
deriving 3,6-dihydro-1,2-oxazines, which can be used as bioactives
and in synthetic applications.4 As part of a programme to examine
When this reaction (eqn (1)) was repeated and followed
1
the potential of nitroso-dienophiles and 1-boronodienes5 for the in situ by H NMR, no cycloadduct (of either type 3 or 4) could
cascade reactions,6 we examined the reaction of dienes 1 with be observed; only 8 and 9 were identified, together with starting
arylnitroso compounds 2 with the expectation of obtaining the materials. After 5 h, the reaction was complete and the pyrrole 8
oxazines 3 and/or 4 from which cascade reactions could be carried was isolated in up to 82% yield (entry 3, Table 1).
out to access allylic alcohols 5 and/or 6 (Scheme 1).
As shown in Table 1, different arylnitroso compounds undergo
this conversion with borylated dienes to provide N-aryl pyrroles
(Table 1). Yields were moderate to good and the reaction could be
conducted in either methanol or DCM (see entries 1, 2, Table 1)
without an obvious solvent effect. A slightly higher yield appears to
result from an excess of the arylnitroso compound (compare entries 3
and 1, Table 1) and hence, 2.5 equivalents of arylnitroso compound
was used for most reactions. Surprisingly, there was no influence of
the nature of the aromatic ring substituent; major electronic effects
were not apparent and yields for pyrroles 10–15 varied from 52 to 82%
(entries 4–9, Table 1).
Diene 16 reacted with nitrosobenzene to give the corresponding
pyrrole 17 in 78% yield. However, with a more sterically hindered
diene 18, there was a significant decrease of yield (16% for the pyrrole
19) even after an extended reaction time (entry 11, Table 1). Changing
the dienylboronate geometry to (Z) as in compound 20 also had a
detrimental effect, with adduct 21 only being isolated in 34% yield,
after 16 h (entry 12, Table 1). Interestingly, this reaction can be also
carried out using a trifluoroborylated diene 22, deriving the pyrroles
10, 14 and 15 with slightly improved yields (entries 13–15, Table 1)
compared to the pinacol esters. We then examined similar reactions
using both t-butylnitroso and acylnitroso7 with diene 7, yet neither
gave nitroso-Diels–Alder adducts.
Scheme 1 Proposed cascade process initiated by a boronodiene-nitroso-dienophile
cycloaddition.
a
´
Institut des Sciences Chimiques de Rennes, UMR 6626 CNRS-Universite de Rennes
1, Campus de Beaulieu, CS 74205, 35042 Rennes CEDEX, France.
E-mail: bertrand.carboni@univ-rennes1.fr
b Centre for Sustainable Chemical Processes, Deptartment of Chemistry,
Durham University, South Road, Durham DH1 3LE, UK.
E-mail: andy.whiting@durham.ac.uk
† Electronic supplementary information (ESI) available: Experimental details,
characterisation data, 1H and 13C NMR spectra. See DOI: 10.1039/c3cc42227e
c
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Table 1 Arylnitroso to N-aryl pyrrole conversions by reaction with dienyl boronates
Entry
Dienea
Nitroso
Product
Conditions
Yieldb (%)
67
1
Ph-NO
ArNO 1.5 equiv., MeOH, RT, 5 h
2
3
7
7
Ph-NO
Ph-NO
8
8
ArNO 1.5 equiv., CH2Cl2, RT, 48 h
ArNO 2.5 equiv., MeOH, RT, 5 h
61
82
4
5
6
7
8
7
7
7
7
7
4-Me-C6H4-NO
4-Cl-C6H4-NO
ArNO 2.5 equiv., MeOH, RT, 5 h
ArNO 2.5 equiv., MeOH, RT, 5 h
ArNO 2.5 equiv., MeOH, RT, 5 h
ArNO 2.5 equiv., MeOH, RT, 5 h
ArNO 2.5 equiv., MeOH, RT, 5 h
60
68
65
57
71
4-Br-C6H4-NO
4-EtO2C-C6H4-NO
4-MeO-C6H4-NO
9
7
2-Me-C6H4-NO
Ph-NO
ArNO 2.5 equiv., MeOH, RT, 5 h
ArNO 2.5 equiv., MeOH, RT, 5 h
52
78
10
11
Ph-NO
ArNO 2.5 equiv., MeOH, RT, 16 h
16
12
13
Ph-NO
ArNO 2.5 equiv., MeOH, RT, 16 h
ArNO 2.5 equiv., MeOH, RT, 5 h
34
66
4-Me-C6H4-NO
10
14
15
22
22
4-MeO-C6H4-NO
2-Me-C6H4-NO
14
15
ArNO 2.5 equiv., MeOH, RT, 5 h
ArNO 2.5 equiv., MeOH, RT, 5 h
77
69
a
b
For diene synthesis, see ref. 8. Yields are isolated yields after silica gel chromatography. Lower yields tend to reflect the difficulty of separating
azo and azo-oxide by-products from the pyrroles; all conversions were high (with the exception entry 11, which is a slow and less efficient reaction).
Interesting results were obtained when MIDA and diethano- [4+2] cycloadduct 24 in 64% yield; the regiochemistry being
lamine dienylboronates were examined with nitroso benzene assigned by NOESY NMR (see ESI†).
(eqn (2)–(4)). Using MIDA boronate 23 modifies the reactivity of
Using the diethanolamine ester 25 (eqn (3)) and following the
1
the adjacent unsaturated moiety,9 hence providing the stable reaction in situ by H NMR, the cycloadduct 26 was identified by
1
comparison of its H NMR with those of 24. After 2 h, all diene was
consumed, the boronated 1,2-oxazine had disappeared and pyrrole 8
(with small amounts of azoxybenzene 9 and 12% cycloadduct 26) were
detected, which shows that the reaction is faster with a diethanolamine
ester (50% conversion after 5 min at rt vs. 5 h for total conversion of the
pinacol ester, Table 1, entry 2). This observation is reinforced by the
reaction of the diethanolamine ester analogue of 18, 2710 which in 2 h
provided a 48% yield of pyrrole 19 (cf. 16% in 16 h, entry 11, Table 1).
(2)
c
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The observation of the boronated 1,2-oxazine 26 shows that in this case, studentship to F.T. This work was supported by CNRS and
pyrrole formation is preceded by a regioselective nitroso-Diels–Alder the University of Rennes 1 through the LIA Rennes-Durham
reaction. It is noteworthy that no pyrrole formation was observed if the (Molecular Materials and Catalysis).
cycloadduct is stable towards hydrolysis, as it is the case for the MIDA
derivatives (see eqn (2)). Hence, tricoordinated sp2 boron species are
required for ring contraction from the oxazine to the pyrrole to take
place. Finally, it appears that the arylnitroso is not required as an
oxidant to effect pyrrole formation, hence a nitroso-based oxidation of
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L. E. thanks the Durham University and the Region Bretagne
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Scheme 2 Proposed mechanism for the reaction of boronodienes arylnitroso
´
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5416 Chem. Commun., 2013, 49, 5414--5416
This journal is The Royal Society of Chemistry 2013