Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N-H-insertion products

Article abstract of DOI:10.3762/bjoc.12.180

Rh(II)-catalyzed reactions of aroyldiazomethanes, diazoketoesters and diazodiketones with α,β-unsaturated δ-aminoesters, in contrast to reactions of diazomalonates and other diazoesters, give rise to the Wolff rearrangement and/or oxidative cleavage of the initially formed N-H-insertion products. These oxidation processes are mediated by Rh(II) catalysts possessing perfluorinated ligands. The formation of pyrrolidine structures, characteristic for catalytic reactions of diazoesters, was not observed in these processes at all.

Full text of DOI:10.3762/bjoc.12.180

Unusual reactions of diazocarbonyl compounds with
α,β-unsaturated δ-amino esters: Rh(II)-catalyzed
Wolff rearrangement and oxidative cleavage of
N–H-insertion products
Valerij A. Nikolaev*1, Jury J. Medvedev1, Olesia S. Galkina1, Ksenia V. Azarova1
and Christoph Schneider*2
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2016, 12, 1904–1910.
1Saint-Petersburg State University, Universitetskiy prosp. 26,
St.-Petersburg 198504, Russia and 2Universität Leipzig, Institut für
Organische Chemie, Johannisallee 29, D-04103 Leipzig, Germany
doi:10.3762/bjoc.12.180
Received: 30 June 2016
Accepted: 18 August 2016
Published: 25 August 2016
Email:
Valerij A. Nikolaev* - valerij.nikolaev@gmail.com;
Christoph Schneider* - schneider@chemie.uni-leipzig.de
Associate Editor: D. Y.-K. Chen
* Corresponding author
© 2016 Nikolaev et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
diazo compounds; N–H-insertion; oxidation cleavage;
transition-metal-catalyzed reactions; Wolff rearrangement
Abstract
Rh(II)-сatalyzed reactions of aroyldiazomethanes, diazoketoesters and diazodiketones with α,β-unsaturated δ-aminoesters, in
contrast to reactions of diazomalonates and other diazoesters, give rise to the Wolff rearrangement and/or oxidative cleavage of the
initially formed N–H-insertion products. These oxidation processes are mediated by Rh(II) catalysts possessing perfluorinated
ligands. The formation of pyrrolidine structures, characteristic for catalytic reactions of diazoesters, was not observed in these
processes at all.
Introduction
Transition-metal-catalyzed reactions of diazocarbonyl com- tively straightforward initial compounds [9,10]. The research
pounds (DCC) with different organic substrates comprise a group by Hu and co-workers elaborated recently a diversity of
powerful tool of organic synthesis [1-8]. Of prime importance multicomponent reactions, which includes trapping of onium
was found to be the ability of reactive intermediates generated ylides by different electrophiles, such as activated С=С, С=O,
from diazo compounds (ammonium, oxonium, C=X-ylides and C=N and other bonds [9]. A plethora of works aimed at realiza-
others) to react with a variety of electrophiles/nucleophiles tion of this “metal–carbene” methodology appeared in the last
yielding complex and challenging organic molecules from rela- few years. Thus a diastereoselective approach to the synthesis
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of indolines via intramolecular trapping of ammonium ylides lowed by the intramolecular Michael addition with the conju-
with ketones [11] and double bonds [12] was developed. gated system of the amino ester to afford N-arylpyrrolidines B
C. J. Moody and co-workers elaborated an efficient way for the (Scheme 1).
synthesis of pyrrolidines by trapping of ammonium ylides with
ketones [13], whereas J. Sun and colleagues showed that simi- It was suggested that this strategy for the synthesis of pyrrol-
lar reactions can be extended to compounds with triple bonds idines could be extended to diazo compounds of other types and
and allene fragments [14].
structures, and, as with diazoesters, multi-substituted pyrrol-
idines are the principal reaction products in these processes.
Recently we have shown that the catalytic decomposition of Herein we present the main results of this study.
diazomalonates and other diazoesters using Rh(II)- and Cu(II)-
complexes in the presence of α,β-unsaturated δ-(N-aryl)amino Diazocarbonyl compounds of three classes with dissimilar
esters 1 provides a good way for the synthesis of multi-functio- structures and usually different reactivity were tested in our cur-
nalized N-arylpyrrolidines by the same “metal–carbene” meth- rent research: aroyldiazomethanes 2a–c, diazoketoesters 3a,b
odology with yields of up to 82% [15]. The reactions occur as a and diazodiketones – by the example of dibenzoyldiazo-
domino process involving an initial formation of N-ylides A fol- methane (3с, Figure 1).
Scheme 1: Catalytic reactions of diazocarbonyl compounds with unsaturated δ-amino esters.
Figure 1: The structures of the starting compounds 1–3 and catalysts used in this study.
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Beilstein J. Org. Chem. 2016, 12, 1904–1910.
The Rh(II)-сatalyzed decomposition of diazo compounds 2a–c The structure of formamide 4 was reliably established using 1H,
and 3a–c was carried out in the presence of (E)-ethyl 5-((4- 13C and H,H-COSY NMR spectroscopy, and the composition
methoxyphenyl)amino)-5-phenylpent-2-enoate (1), possessing was confirmed by HRMS.
two main reaction centers – the N–H group and an activated
C=C bond. To estimate the impact of the catalyst and its ligands Quite a different situation was observed with catalytic reactions
on the efficiency of the processes studied, non-fluorinated of the diazoketoesters 3a,b with aminoester 1, which gave rise
rhodium carboxylates (Rh2L4; L = OAc, Oct, Piv) and to the formation of acylamides 6a,b in yields of 51–78%
catalysts with trifluoroacetate or perfluorobutyrate ligands (Table 2; entries 1–3).
[Rh2L4; L = CF3CO2 (tfa), C3F7CO2 (pfb)] were used in this
research.
The highest yield with diazoketoesters 3 was obtained in reac-
tion of benzoyldiazoacetate 3b (70%) which was 20% more
than in the case of amide 6a obtained from the diazoaceto-
Results and Discussion
In the beginning, catalytic reactions of aroyldiazomethanes acetate 3a and aminoester 1. On usage in this reaction of
2a–c were studied. Here, in all experiments formamide 4 was Rh2(OAc)4 instead of Rh2(Oct)4 the efficiency of the process is
isolated as the major reaction product (80–99%) along with the little affected (Table 2, entries 2 and 3).
mixtures of isomeric diarylbutenediones 5, which are formally
‘dimers’ of intermediate aroylcarbenes (yields up to 37%) The structures of the amides 6a,b were established by compari-
(Table 1).
son of their NMR spectra with spectroscopic parameters of the
same compounds obtained by a thermal decomposition of diazo
Due to a high reactivity of diazoketones 2а–с, catalytic reac- compounds 3a,b in the presence of aminoester 1 [16]. It is also
tions were carried out at −3 to −5 °C by gradually adding up to quite evident that the trisubstituted acylamides 6a,b were
3–4 equivalents of diazoketones 2 into reaction mixture, which formed as a consequence of the initial Wolff rearrangement of
was favorable for increasing the yield of the main reaction prod- diazoketoesters 3a,b accompanied by acylation of the N–H-
uct 4 and minimization of the side process with formation of group of aminoester 1 with α-oxoketene formed.
‘dimers’ 5. However, the complete conversion of the initial
aminoester 1 was not achieved even upon using 4 equivalents of When passing from diazoketoesters 3a,b to dibenzoyldiazo-
diazoketones 2 during the reaction progress. Nevertheless, the methane 3с, the formation of N,N-disubstituted 2-oxo-2-phenyl-
yields of formamide 4 in these reactions exceeded 80% (when acetamide 7 was observed in the yields of up to 50% (Table 2,
calculated on the reacted aminoester 1), whereas in the case of entries 5–9) in parallel with the Wolff rearrangement product 6с
p-methoxy-substituted diazoketone 2a the yield of the principal (18–79%; Table 2, entries 4–7). The structures of these com-
reaction product 4 was close to 99% (Table 1, entry 1). At the pounds were established by 1H and 13C NMR, 2D NMR (H,H-
same time, no formation of the assumed pyrrolidines of type B COSY, HMBC, HSQC) spectra, as well as by comparison with
was observed.
the literature data in the case of the amide 6c [16].
Table 1: Rh(II)-Catalyzed reactions of diazoketones 2a–c with aminoester 1.
Entrya
Diazoketone; Ar
Yield 4, %b
1
2
3
2a; p-MeO-C6H4
2b; Ph
78 (99)
56 (92)
53 (80)
2c; p-Br-C6H4
aReactions were carried out at −3 to −5 °C during 5 days using 3–4 equivalents of diazoketone 2. bValues shown in parentheses refer to yields related
to reacted aminoester 1.
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Beilstein J. Org. Chem. 2016, 12, 1904–1910.
Table 2: Rh(II)-Catalyzed reactions of diazodicarbonyl compounds 3a-c with aminoester 1.
Entry
DCC; R1, R2
Catalyst
Yield, %
6a–c
7
Total yield
1a
2a
3c
4a
5c
6c
7c
8c
9a
3a; Me, OMe
3b; Ph, OEt
3b; Ph, OEt
3c; Ph, Ph
3c; Ph, Ph
3c; Ph, Ph
3c; Ph, Ph
3c; Ph, Ph
3c; Ph, Ph
Rh2(Oct)4
Rh2(Oct)4
Rh2(OAc)4
Rh2(Oct)4
Rh2(OPiv)4
Rh2(OAc)4
Rh2(tfa)4
6a; 51
6b; 70
6b; 78
6c; 79
6c; 66
6c; 66
6c; 18
–
–b
51
70
78
79
93
81
46
46
50
–b
–b
–b
27
15
28
46
50d
Rh2(pfb)3(OAc)
Rh2(pfb)4
–
aCH2Cl2, reflux, 2–14 h; bamide 7 was not identified in the reaction mixture; cCH2Cl2, rt, up to 60 h; dbenzoic acid in a yield of 43% was isolated as a
byproduct.
The yield of acetamide 7 was heavily dependent on the Rh(II)- tone 3c with aminoester 1, contrary to the similar reactions of
catаlyst ligand nature, attaining the highest values of 46–50% diazoesters [15], two other reaction processes were observed –
when dirhodium carboxylates with perfluorinated ligands were the Wolff rearrangement and the assumed oxidative cleavage of
used (Table 2, entries 7–9). Most clearly this tendency is the initial reaction products.
evident when comparing the results of entries 7–9, where on
passing from Rh2(tfa)4 to Rh2(pfb)3(OAc) and further to Several examples of Rh-catalyzed reactions of diazocarbonyl
Rh2(pfb)4 the yield of phenylacetamide 7 rises from 28 up compounds with N–H-substrates, which are accompanied by the
to 50%, whereas in the experiment with Rh2(pfb)4 the forma- Wolff rearrangement with formation of corresponding amides,
tion of the Wolff rearrangement product 6с was not observed are known in the literature [17-25]. It is believed that these reac-
at all.
tions follow a usual scheme of thermolysis (or photolysis) of
diazocarbonyl compounds with intermediate formation of
The best catalyst promoting the catalytic Wolff rearrangement ketenes, which further acylate N-nucleophiles presented in the
in this series of experiments was found to be Rh2(Oct)4. Its ap- reaction mixture to produce the corresponding amides [20].
plication provided a means for the preparation of the amide 6с
in a yield of 79% with the total exclusion of the ‘side’ reaction In line with these literature considerations and our results, one
product 7 (Table 2, entry 4). In all other cases the formation of a can suggest the next pathway for the Rh-catalyzed Wolff rear-
mixture of β-ketoacid amide 6с and acetamide 7 was observed rangement (Scheme 2). Decomposition of diazocarbonyl com-
(Table 2, entries 5–9). The total yield of reaction products 6с pounds 3a–c gives rise to generation of Rh-carbenoid С,
and 7 with Rh2(Piv)4 as the catalyst amounted up to 93% ‘inside’ of which nucleophilic 1,2-migration of aryl (Ph) or
(Table 2, entry 5), evidencing on the occurrence of only two alkyl (Me) group R2 occurs, producing α-oxoketene D. The
main processes at this conditions. In the experiment with latter interacts with N–H-group of the aminoester 1 to give
Rh2(pfb)4, along with the two basic reaction products, benzoic acylamides 6a–c.
acid was isolated as well (43%; Table 2, entry 9).
Predominance of the Wolff rearrangement over typical
By this means during the course of Rh(II)-catalyzed reactions of carbenoid reactions (N–H-insertion, etc.) in the case of diazodi-
aroyldiazomethanes 2a–c, diazoketoesters 3a,b and diazodike- carbonyl compounds 3а–с can be apparently explained by some
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Beilstein J. Org. Chem. 2016, 12, 1904–1910.
Scheme 2: The assumed pathway for the occurance of amides 6a–c by way of the catalytic Wolff rearrangement.
sterical reasons and, first of all, by the problems associated with α-aminocarbonyl compounds is also a well-known transition-
the approach of the N–H-group of the bulky secondary amine 1 metal-catalyzed process, which gives rise to the occurrence of
to the electrophilic carbon atom of H-Rh-carbenoid C formamides and carboxylic acids [26,29]. In this case the
(Scheme 2). Carbenoids from perfluorinated carboxylates system O2/TEMPO is used as a catalyst for the cleavage
F-Rh(II) are clearly more electrophilic reagents than their process, but the reaction also proceeds without the addition of
H-counterparts, and this enables the intermolecular process of TEMPO, though with lower yields [29]. Recently, communica-
N–H-insertion to compete successfully with the intramolecular tions appeared related to similar oxidation processes with par-
Wolff rearrangement.
ticipation of rhodium catalysts [30-33].
As it was shown in our study, formamide 4 and phenylacet- Based on the literature data [29,34,35] and our current research,
amide 7 are formed in catalytic reactions of aroyldiazo- one can propose a mechanism for the appearance of the amides
methanes 2a–c and dibenzoyldiazomethane 3c with relatively 4 and 7 during the processes studied (Scheme 3).
high to almost quantitative yields (50–99%). It can be sug-
gested that the appearance of amides 4 and 7 in these catalytic At first, upon catalytic decomposition of diazocarbonyl com-
processes is a result of an oxidative cleavage of some reaction pounds 2a–c and 3c, N-ylide E is generated, stabilization of
products, which were initially formed during the interaction of which by proton transfer produces an ordinary N–H-insertion
aroyldiazomethanes 2 and dibenzoyldiazomethane 3c with product, α-ketoamine F. Similar reactions are well-known for
aminoester 1.
decomposition reactions of diazocarbonyl compounds using Cu
and Fe catalysts [29] and in some cases with the employment of
Oxidative functionalization of α-СН2-groups in the structure of Rh-carboxylates as well [30].
amines is a rather familiar instrument of organic synthesis,
which is widely used for the preparation of amino acids and Ketoamine F proves to be unstable under the reaction condi-
alkaloids [26-28]. Cleavage of σ-С–С bonds in the structure of tions and is oxidized by a rhodium catalyst complex with
Scheme 3: The assumed mechanism for the formation of the amides 4 and 7 during oxidative cleavage of the N–H-insertion products F.
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Beilstein J. Org. Chem. 2016, 12, 1904–1910.
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Scientific research was performed using the resources of the
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