Rh2(esp)2-Catalyzed Coupling of α-Diazo-γ-butyrolactams with Aromatic Amines

Article abstract of DOI:10.1002/ejoc.201900565

Decomposition of α-diazo-γ-butyrolactams in the presence of aromatic and heteroaromatic amines, under Rh₂(esp)₂ catalysis, led to corresponding α-arylamino-γ-butyrolactams, which are of significant value for medicinal chemistry. The reaction scope encompasses primary as well as secondary, diversely substituted anilines and heteroaromatic amines. Insertion into the anilinic amino group was shown to be selective over amide and sulfonamide N–H insertion.

Full text of DOI:10.1002/ejoc.201900565

A Journal of
Accepted Article
Title: Rh2(esp)2-catalysed coupling of α-diazo-γ-butyrolactams with
aromatic amines
Authors: Daniil Zhukovsky, Dmitry Dar'in, and Mikhail Krasavin
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900565
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900565
Supported by

10.1002/ejoc.201900565
European Journal of Organic Chemistry
Rh2(esp)2-catalysed coupling of α-diazo-γ-butyrolactams with
aromatic amines
Daniil Zhukovsky,[a] Dmitry Dar’in[a] and Mikhail Krasavin*[a]
[a] D. Zhukovsky, Dr. D. Dar’in, Prof. Dr. M. Krasavin
Saint Petersburg State University, Saint Petersburg, 199034 Russian Federation
E-mail: m.krasavin@spbu.ru
http://www.krasavin-group.org/
Supporting information and ORCID(s) from the author(s) for this article are available on the
WWW under http://dx.doi.org/10.1002/ejoc.xxxxxxxxx.
Saint Petersburg State University, Saint Petersburg, 199034 Russian Federation
E-mail: m.krasavin@spbu.ru
http://www.krasavin-group.org/
Supporting information and ORCID(s) from the author(s) for this article are available on the
WWW under http://dx.doi.org/10.1002/ejoc.xxxxxxxxx.
ABSTRACT
Decomposition of α-diazo-γ-butyrolactams in the presence of aromatic and heteroaromatic
amines, under Rh2(esp)2 catalysis, led to corresponding α-arylamino--butyrolactams, which are
of significant value for medicinal chemistry. The reaction scope encompasses primary as well as
secondary, diversely substituted anilines and heteroaromatic amines. Insertion into the anilinic
amino group was shown to be selective over amide and sulfonamide N-H insertion.
Introduction
The chemistry of α-diazocarbonyl compounds has attracted much attention from the synthetic
organic and medicinal chemistry community,[1]–[5] as it offers a wealth of powerful synthetic
transformations including those which involve generation of metal carbene species.[6][7] One such
transformation, allowing for direct functionalization of a carbo- or heterocyclic core, is the
formal insertion of metal carbenes into the N–H bond of aromatic[8]–[10] and aliphatic amines,[11]–
amides[14][15] as well as azaheterocycles.[16][17] However, quite a number of chemistries
[13]
involving α-diazocarbonyl compounds remain unexplored for some medicinally useful cores,
and thus has not been validated for use in drug design. One such class is α-diazo-γ-
butyrolactams, which has only sporadically appeared in the literature.[18][19] In our recent work
we reported the first general method for the synthesis of these compounds, we investigated their
stability, and we proved them valid partners for metal-catalyzed O–H insertion and 1,2-hydride
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
shift reactions.[20] Next, it came to our attention that the respective N–H insertion reactions have
not been investigated for α-diazo-γ-butyrolactams. This is seemed like a significant methodology
void considering the utility of the respective α-amino-γ-butyrolactams for medicinal chemistry.
Indeed, compounds based on such cores have displayed various types of biological activity such
as factor Xa inhibition,[21][22] selective inhibition of histone deacetylase 6 (HDAC6)[23] as well as
modulation of the dopamine D2 receptor.[24][25]
This motivated us to continue the synthetic exploration of α-diazo-γ-butyrolactams, especially in
light of the N-H insertion reactions reported in the literature for 3-diazoindolin-2-ones.[26]
Herein, we present the results of our investigation of the formal N–H insertion reactions of
Rh(II) carbenes (generated from these diazo compounds) into various amines as a new way to
access a vast diversity of druglike molecular scaffolds.
Results and discussion
The initial experiments were conducted with N-phenyl α-diazo-γ-butyrolactam (1a) and p-
[27][28]
toluidine (2a) (Table 1). With Rh2(OAc)4
employed as the catalyst, 50% of the desired
1
product (3a) was observed by H NMR analysis of the crude mixture (entry 1). With more
[29][30]
reactive Rh2(esp)2
employed in 5 mol% quantity (entry 2), the NH-insertion product 3a
NMR yield was raised to 62% and remained virtually identical when the catalyst amount was
reduced 10-fold (entry 3). Notably, the latter reaction repeated on a preparative scale resulted in
69% isolated yield of 3a (vide infra). Other Rh or Cu catalysts (entries 4-6) resulted in
1
appreciable, albeit substantially lower H NMR conversion while Cu(OTf)2 (entry 7) proved
ineffective. Attempted catalyst-free thermal generation of carbene[31] led to decomposiotion of
1a an no product formation (entry 8).
Table 1. Condition finding experiments using 1a and 2a as reaction partners.
Entrya
Catalyst
Rh2(OAc)4
Rh2(esp)2
Quantity
5 mol %
5 mol %
Solvent
CH2Cl2
CH2Cl2
Temperature
20 °C
Time
10 min
10 min
10 min
24 h
Yieldb
50%
62%
61%
24%
1
2
3
4
20 °C
Rh2(esp)2 0.5 mol % CH2Cl2
Rh2(TFA)4 5 mol % CH2Cl2
20 °C
20 °C
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
5
6
7
8
Rh2(OPiv)4
Cu(acac)2
Cu(OTf)2
None
5 mol %
5 mol %
5 mol %
-
CH2Cl2
CH2Cl2
CH2Cl2
PhCF3
20 °C
20 °C
20 °C
80 °C
10 min
3 h
49%
26%
trace
0%
10 min
16 h
aReaction conditions: catalyst was added to a mixture of 0.025 mmol diazo lactam 1a with 0.025
mmol of p-toluidine 2a in CD2Cl2 (0.5 ml); and the solution was stirred for appropriate time
bYields was determined by 1H NMR with isoquinoline as internal standard
With the workable conditions in hand, we investigated a wider range of Rh2(esp)2-catalyzed N-H
insertion reactions (Scheme 1).
Scheme 1. Rh2(esp)2-catalyzed N-H insertion reactions of α-diazo γ-butyrolactams.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
a Reaction was carried out in 1,4-dioxane
b Product was isolated by HPLC
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
In general, reactions were conducted in dichloromethane. However, for substrates displaying
limited solubility (such as 3p and 3s), 1,4-dioxane was successfully employed as a solvent. Five
α-diazo-γ-butyrolactams (1a-e) carrying different donor and acceptor aromatic substituents on
nitrogen were employed as diazo component and no significant difference in their reactivity was
observed.
The reaction was found somewhat insensitive sensitive to the steric hindrance at the aromatic
amine. Thus, in the row of p-toluidine (2a) - o-toluidine (2b) - 2,6-xylidine (2j), no noticeable
change in the product yield was observed. However, with a more sterically demanding
diphenylamine (2h), the yield was markedly lower. At the same time, the reaction with
secondary anilines (2g, 2k and 2r) worked similarly well compare to their primary counterparts.
Unfortunately, the reaction displayed no selectivity toward primary vs. secondary aniline (or vice
versa) as observed for the reaction of 6-aminoindoline delivering a mixture of insertion products
including double insertion (data not shown).
In order to further explore the generality of this transformation, a wide range of anilines carrying
different electron-donating (2e and 2q) as well as electron-withdrawing (2c, 2d, 2f, 2v and 2w)
substituents were examined and no particular correlation between the reaction yield and the
electronic properties of the substituent was observed. Aminopyridines (2i and 2u), as well as
Gewald-type aminothiophene (2l) worked well while 2-aminothiazole (2n) and 2-
aminopyrimidines (2m and 2t) gave significantly lower yields. Notably, in the latter case, the
labile 4-chloropyrimidine moiety remained intact in the product obtained (3t), offering an
opportunity for further scaffold decoration.
Reassuringly, the N-H insertion into aromatic amino group under these conditions demonstrated
selectivity over the insertion into amide or sulfonamide N-H bond. Thus, in the case of
anthranilamide 2o and sulfanilamide (2p), only the products of insertion into the aromatic amino
group were obtained. Structure of 3p was confirmed by HMBC and HSQC spectra (Figure 1).
Figure 1. Key HMBC correlations confirmed the structure of 3p
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
We also tried to carry out decomposition of diazo lactams in the presence of aliphatic amines.
Unfortunately, the test experiment with cyclopropylamine 2y provided N-H insertion product 3y
only in moderate yield. Moreover, it was contaminated with side product enamine 4 which is
presumably formed by oxidation of diazo lactam 1a (a process described in the literature for
other -dazocarbonyl compounds[31]) followed by nucleophilic attack (Scheme 2). Adding more
catalyst in several portions (up to four times the initial amount) in order to drive the reaction to
completion, only led to catalyst inactivation and incomplete conversion. This limitation seems to
be general for aliphatic amines as a similar reaction with n-propylamine gave an even more
complex mixture of unidentified by-products.
Scheme 2. Rh2(esp)2-catalyzed N-H insertion reaction into cyclopropylamine.
Rh2(esp)2 2 mol %
NH2
N
+
+
O
N
N
O
O
DCM, 40 min
N+
N-
HN
3y, 37%
HN
4, 19%
1a
2y
Some of the compounds obtained have particular value in medicinal chemistry, as documented in
the literature. For instance, compound 3f was employed as an advanced intermediate for HDAC
6 inhibitors[23] while compound 3v has been reported as a precursor to Rho kinase inhibitors.[32]
While being comparable to these syntheses in terms of the number of steps, our approach
involves a mild Rh(II)-catalyzed N-H carbene insertion step and is likely to display a different
functional group tolerance profile. Furthermore, the presence of a primary sulfonamide group in
compound 3p makes it a potential carbonic anhydrase inhibitor[33]–[35]. As already noted above,
the active chlorine in compound 3t could be easily substituted by different amines thus
delivering the ubiquitous bioactive 2,4-diaminopyrimidine scaffold[36][37]
.
Conclusion
Thus, we reported Rh2(esp)2-catalyzed reaction of rare -diazo -butyrolactams with aromatic
amines. This transformation was found to be somewhat insensitive to steric hindrance and
electronic properties of the amine partner and worked well for a wide range of primary and
secondary anilines. Aminoheterocycles were also found employable in the reaction albeit they
provided lower product yield. In addition, N-H insertion into aromatic amino group
demonstrated selectivity over insertion into N-H bond of amide and sulfonamide groups. Along
with dichloromethane, 1,4-dioxane was found suitable as a solvent and could be used to
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
overcome reagent solubility issues. The reaction provides a hitherto unexplored, one-step entry
into medicinally relevant compounds.
Experimental part
General considerations. Diazo compounds were prepared according to our previously reported
method,[20] other reagents were obtained from commercial sources and used without additional
purification. 1,4-Dioxane, tetrahydrofuran, diethyl oxalate and dichloromethane were distilled
over suitable drying agents. Mass spectra were recorded with a Bruker Maxis HRMS-ESI-qTOF
spectrometer (electrospray ionization mode). NMR spectroscopic data were recorded with
Bruker Avance 400 spectrometer (400.13 MHz for 1H, 100.61 MHz for 13C and 376.50 MHz for
19F) and were referenced to residual solvent proton peaks and solvent carbon peaks. Melting
points were determined with a Stuart SMP50 instrument in open capillary tubes. HPLC
preparative chromatography was performed with Agilent PrepHT XDB-C18 preparative
cartridge 21.2 × 150 mm 5 μm. Products 3p and 3s were purified by HPLC eluting with H2O-
MeCN with addition of 0.1% TFA (elution gradient MeCN: 40 → 60%); flow rate 12 mL/min,
column temperature 40 °C.
General procedure for Rh2(esp)2-catalysed decomposition of α-diazo γ-butyrolactams in
presence of aromatic amines (preparation of 3a-x). To a vigorous stirred solution of
corresponding amine (0.3 mmol) and diazo lactam (0.3 mmol) in dichloromethane (5 ml) (1,4-
dioxane for 3p and 3s) was added Rh2(esp)2 (1.1 mg, 0.0015 mmol, 0.5 mol %). After
completion of nitrogen evolution the resulting cloudy mixture was evaporated to dryness and
purified using column chromatography on silica gel. Compounds 3p and 3s were purified by
HPLC using above described conditions.
1-Phenyl-3-(p-tolylamino)pyrrolidin-2-one (3a). Eluent ethyl acetate – n-hexane 1:3. Yield 55
1
mg, 69%. White solid, mp 143.2-144.4 °C. H NMR (400 MHz, CDCl3) δ 7.89 – 7.58 (m, 2H),
7.58 – 7.38 (m, 2H), 7.26 – 7.14 (m, 1H), 7.07 (d, J = 8.0 Hz, 2H), 6.78 – 6.56 (m, 2H), 4.52 (s,
1H), 4.13 (ddd, J = 9.8, 7.6, 1.7 Hz, 1H), 3.99 – 3.75 (m, 2H), 2.88 (dddd, J = 14.0, 7.9, 3.8, 1.6
Hz, 1H), 2.29 (s, 3H), 2.14 – 1.98 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 172.5, 145.1, 139.2,
129.9, 129.0, 127.8, 125.0, 119.8, 113.9, 56.7, 45.3, 29.3, 20.4. HRMS (ESI/Q-TOF) m/z:
[M+H]+ Calcd for C17H18N2O 267.1492; Found 267.1502.
1-Phenyl-3-(o-tolylamino)pyrrolidin-2-one (3b). Eluent ethyl acetate – n-hexane 1:3. Yield 57
mg, 69%. Colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.82 – 7.69 (m, 2H), 7.54 – 7.39 (m, 2H),
7.27 – 7.18 (m, 2H), 7.18 – 7.12 (m, 1H), 6.81 (td, J = 7.4, 1.1 Hz, 1H), 6.69 (dd, J = 8.0, 1.1 Hz,
1H), 4.57 (s, 1H), 4.19 (ddd, J = 10.0, 7.8, 1.7 Hz, 1H), 3.99 – 3.84 (m, 2H), 2.93 (dddd, J =
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
13
12.4, 7.8, 6.1, 1.8 Hz, 1H), 2.31 (s, 3H), 2.18 – 2.00 (m, 1H). C NMR (101 MHz, CDCl3) δ
172.6, 145.5, 139.1, 130.4, 129.0, 127.0, 125.1, 123.5, 119.7, 118.3, 110.6, 56.4, 45.3, 29.4,
17.6. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C17H18N2O 267.1492; Found 267.1498.
3-((4-Fluorophenyl)amino)-1-phenylpyrrolidin-2-one (3c). Eluent ethyl acetate – n-hexane
1
1:3. Yield 43 mg, 53%. White solid, mp 144.8-146.4 °C. H NMR (400 MHz, CDCl3) δ 7.76 –
7.59 (m, 2H), 7.51 – 7.37 (m, 2H), 7.26 – 7.18 (m, 1H), 7.03 – 6.89 (m, 2H), 6.77 – 6.63 (m,
2H), 4.51 (s, 1H), 4.10 (dd, J = 10.5, 7.8 Hz, 1H), 3.97 – 3.83 (m, 2H), 2.86 (dddd, J = 12.4, 7.9,
6.0, 1.9 Hz, 1H), 2.19 – 1.99 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 172.3, 156.5 (d, J = 236.0
Hz), 143.8 (d, J = 2.2 Hz), 139.1, 129.0, 125.1, 119.8, 115.8 (d, J = 22.3 Hz), 114.7 (d, J = 7.6
Hz), 56.9, 45.2, 29.0. 19F NMR (377 MHz, CDCl3) δ -126.74. HRMS (ESI/Q-TOF) m/z: [M+H]+
Calcd for C16H15FN2O 271.1241; Found 271.1245.
3-((3-Fluorophenyl)amino)-1-phenylpyrrolidin-2-one (3d). Eluent ethyl acetate – n-hexane
1:3. Yield 59 mg, 73%. Yellow solid, mp 100.9-101.8 °C. 1H NMR (400 MHz, CDCl3) δ 7.76 –
7.63 (m, 2H), 7.51 – 7.39 (m, 2H), 7.26 – 7.20 (m, 1H), 7.20 – 7.12 (m, 1H), 6.56 – 6.47 (m,
2H), 6.46 – 6.35 (m, 1H), 4.76 (s, 1H), 4.13 (ddd, J = 10.7, 7.8, 3.0 Hz, 1H), 3.99 – 3.77 (m, 2H),
2.85 (dddd, J = 12.3, 7.8, 6.0, 1.7 Hz, 1H), 2.02 (dtd, J = 12.4, 10.4, 9.1 Hz, 1H). 13C NMR (101
MHz, CDCl3) δ 172.0, 164.1 (d, J = 242.9 Hz), 149.2 (d, J = 10.7 Hz), 139.0, 130.5 (d, J = 10.1
Hz), 129.1, 125.2, 119.8, 109.6 (d, J = 2.3 Hz), 104.8 (d, J = 21.5 Hz), 100.4 (d, J = 25.0 Hz),
56.2, 45.2, 28.9. 19F NMR (377 MHz, CDCl3) δ -112.57. HRMS (ESI/Q-TOF) m/z: [M+H]+
Calcd for C16H15FN2O 271.1241; Found 271.1242.
3-((4-Methoxyphenyl)amino)-1-phenylpyrrolidin-2-one (3e). Eluent ethyl acetate – n-hexane
1
1:3. Yield 43 mg, 49%. White solid, mp 148.9-150.4 °C. H NMR (400 MHz, CDCl3) δ 7.75 –
7.64 (m, 2H), 7.50 – 7.37 (m, 2H), 7.25 – 7.14 (m, 1H), 6.96 – 6.80 (m, 2H), 6.77 – 6.69 (m,
2H), 4.36 (s, 1H), 4.09 (dd, J = 10.4, 7.8 Hz, 1H), 3.96 – 3.84 (m, 2H), 3.79 (s, 3H), 2.85 (dddd,
J = 12.3, 7.8, 6.0, 1.9 Hz, 1H), 2.07 (dtd, J = 12.3, 10.2, 9.1 Hz, 1H). 13C NMR (101 MHz,
CDCl3) δ 172.6, 153.0, 141.5, 139.2, 129.0, 125.0, 119.8, 115.2, 115.0, 57.3, 55.8, 45.3, 29.2.
HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C17H18N2O2 283.1441; Found 283.1443.
Methyl 4-((2-oxo-1-phenylpyrrolidin-3-yl)amino)benzoate (3f). Eluent ethyl acetate – n-
hexane 1:2. Yield 61 mg, 66%. Yellow solid, mp 129.ii6-131.2 °C. 1H NMR (400 MHz, CDCl3)
δ 7.97 – 7.91 (m, 2H), 7.74 – 7.67 (m, 2H), 7.49 – 7.39 (m, 2H), 7.27 – 7.20 (m, 1H), 6.82 – 6.68
(m, 2H), 4.98 (d, J = 3.3 Hz, 1H), 4.26 (ddd, J = 11.0, 7.8, 3.4 Hz, 1H), 4.01 – 3.86 (m, 2H), 3.89
13
(s, 3H), 2.94 (dddd, J = 12.4, 7.7, 6.0, 1.5 Hz, 1H), 2.07 (dtd, J = 12.4, 10.4, 9.0 Hz, 1H). C
NMR (101 MHz, CDCl3) δ 171.7, 167.2, 151.1, 138.9, 131.6, 129.1, 125.2, 119.8, 119.7, 112.5,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
55.7, 51.6, 45.2, 28.8. HRMS (ESI/Q-TOF) m/z: [M+Na]+ Calcd for C18H18N2O3 333.1210;
Found 333.1210.
3-(Methyl(phenyl)amino)-1-phenylpyrrolidin-2-one (3g). Eluent ethyl acetate – n-hexane 1:3.
1
Yield 47 mg, 59%. White solid, mp 113.4-114.7 °C. H NMR (400 MHz, CDCl3) δ 7.78 – 7.69
(m, 2H), 7.48 – 7.38 (m, 2H), 7.32 – 7.25 (m, 2H), 7.24 – 7.18 (m, 1H), 6.94 – 6.87 (m, 2H),
6.85 – 6.74 (m, 1H), 4.80 (dd, J = 10.4, 8.6 Hz, 1H), 3.94 – 3.78 (m, 2H), 2.97 (s, 3H), 2.51
13
(dddd, J = 12.9, 8.8, 6.1, 2.8 Hz, 1H), 2.21 (ddt, J = 12.9, 10.5, 9.4 Hz, 1H). C NMR (101
MHz, CDCl3) δ 171.4, 149.8, 139.4, 129.2, 129.0, 124.9, 119.7, 118.0, 113.9, 62.4, 44.8, 34.1,
21.6. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C17H18N2O 267.1492; Found 267.1485.
3-(Diphenylamino)-1-phenylpyrrolidin-2-one (3h). Eluent ethyl acetate – n-hexane 1:3. Yield
1
27 mg, 27%. Yellow oil. H NMR (400 MHz, CDCl3) δ 7.67 – 7.58 (m, 2H), 7.50 – 7.36 (m,
2H), 7.34 – 7.25 (m, 4H), 7.24 – 7.16 (m, 1H), 7.12 – 7.00 (m, 6H), 4.99 (t, J = 9.2 Hz, 1H), 3.79
(ddd, J = 9.6, 8.4, 7.5 Hz, 1H), 3.63 (ddd, J = 9.7, 8.9, 2.9 Hz, 1H), 2.50 (dddd, J = 12.9, 8.9, 7.5,
2.9 Hz, 1H), 2.39 (ddt, J = 12.9, 9.6, 8.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 171.8, 147.1,
139.4, 129.3, 128.9, 124.8, 123.0, 122.6, 119.7, 62.2, 45.0, 22.7. HRMS (ESI/Q-TOF) m/z:
[M+Na]+ Calcd for C22H20N2O 351.1468; Found 351.1458.
1-Phenyl-3-(pyridin-2-ylamino)pyrrolidin-2-one (3i). Eluent ethyl acetate – n-hexane 1:1.
Yield 46 mg, 61%. White solid, mp 103.8-105.1 °C. 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J =
5.4, 1.9 Hz, 1H), 7.80 – 7.65 (m, 2H), 7.55 – 7.37 (m, 3H), 7.24 – 7.16 (m, 1H), 6.75 – 6.63 (m,
1H), 6.58 (d, J = 8.3 Hz, 1H), 5.17 (s, 1H), 4.63 (ddd, J = 11.4, 7.9, 3.9 Hz, 1H), 4.02 – 3.75 (m,
2H), 3.05 (dddd, J = 12.4, 7.7, 6.1, 1.4 Hz, 1H), 2.02 (dtd, J = 12.4, 10.6, 8.9 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ 172.9, 158.0, 147.8, 139.3, 137.1, 128.9, 124.9, 119.7, 113.7, 109.4, 54.7,
45.4, 28.8. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C15H15N3O 254.1288; Found 254.1297.
3-((2,6-Dimethylphenyl)amino)-1-(4-methoxyphenyl)pyrrolidin-2-one (3j). Eluent ethyl
1
acetate – n-hexane 1:3. Yield 75 mg, 81%. Colorless oil. H NMR (400 MHz, CDCl3) δ 7.68 –
7.52 (m, 2H), 7.05 (d, J = 7.4 Hz, 2H), 6.99 – 6.92 (m, 2H), 6.89 (t, J = 7.5 Hz, 1H), 3.98 (dd, J
= 10.9, 7.9 Hz, 1H), 3.87 – 3.80 (m, 4H), 3.80 – 3.64 (m, 2H), 2.62 (dddd, J = 12.4, 7.8, 6.0, 1.7
Hz, 1H), 2.43 (s, 6H), 2.18 – 2.02 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 173.3, 156.7, 145.3,
132.6, 130.5, 128.9, 122.6, 121.3, 114.1, 60.8, 55.5, 45.1, 29.3, 19.0. HRMS (ESI/Q-TOF) m/z:
[M+H]+ Calcd for C19H22N2O2 311.1754; Found 311.1767.
3-(Indolin-1-yl)-1-(4-methoxyphenyl)pyrrolidin-2-one (3k). Eluent ethyl acetate – n-hexane
1
1:2. Yield 55 mg, 60%. White solid, mp 129.3-130.8 °C. H NMR (400 MHz, CDCl3) δ 7.67 –
7.55 (m, 2H), 7.19 – 7.10 (m, 1H), 7.07 (td, J = 7.6, 1.2 Hz, 1H), 7.00 – 6.90 (m, 2H), 6.75 –
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
6.67 (m, 1H), 6.52 (d, J = 7.8 Hz, 1H), 4.56 (dd, J = 9.9, 8.7 Hz, 1H), 3.95 – 3.76 (m, 5H), 3.61 –
13
3.44 (m, 2H), 3.15 – 2.96 (m, 2H), 2.56 – 2.35 (m, 1H), 2.30 – 2.16 (m, 1H). C NMR (101
MHz, CDCl3) δ 170.7, 156.8, 150.6, 132.6, 130.2, 127.2, 124.7, 121.4, 118.1, 114.1, 107.4, 58.7,
55.5, 49.0, 45.5, 28.4, 20.1. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C19H20N2O2 309.1598;
Found 309.1610.
Ethyl
2-((1-(4-methoxyphenyl)-2-oxopyrrolidin-3-yl)amino)-4,5,6,7-
tetrahydrobenzo[b]thiop-hene-3-carboxylate (3l). Eluent ethyl acetate – n-hexane 1:3. Yield
67 mg, 54%. White solid, mp 135.5-136.9 °C. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 5.4 Hz,
1H), 7.63 – 7.52 (m, 2H), 7.03 – 6.86 (m, 2H), 4.28 (q, J = 7.1 Hz, 2H), 4.20 (ddd, J = 10.4, 8.1,
5.4 Hz, 1H), 3.91 – 3.74 (m, 2H), 3.81 (s, 3H), 2.82 (dddd, J = 12.5, 8.1, 6.3, 1.7 Hz, 1H), 2.78 –
2.74 (m, 2H), 2.59 – 2.52 (m, 2H), 2.16 – 1.98 (m, 1H), 1.86 – 1.69 (m, 4H), 1.36 (t, J = 7.1 Hz,
3H). 13C NMR (101 MHz, CDCl3) δ 170.2, 166.1, 162.6, 156.8, 133.4, 132.3, 121.3, 117.4,
114.1, 104.7, 59.4, 58.7, 55.5, 45.3, 27.5, 26.9, 24.6, 23.3, 22.9, 14.5. HRMS (ESI/Q-TOF) m/z:
[M+H]+ Calcd for C22H26N2O4S 415.1686; Found 415.1693.
1-(4-Methoxyphenyl)-3-(pyrimidin-2-ylamino)pyrrolidin-2-one (3m). Eluent ethyl acetate.
Yield 27 mg, 32%. White solid, mp 160.1-161.3 °C. 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J =
4.8 Hz, 2H), 7.68 – 7.51 (m, 2H), 7.03 – 6.85 (m, 2H), 6.62 (t, J = 4.8 Hz, 1H), 5.96 (s, 1H), 4.70
(ddd, J = 10.8, 8.1, 5.3 Hz, 1H), 3.92 – 3.74 (m, 2H), 3.82 (s, 3H), 2.92 (dddd, J = 12.4, 7.9, 6.1,
1.5 Hz, 1H), 2.05 (dtd, J = 12.2, 10.4, 9.0 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 171.6, 162.2,
158.0, 156.8, 132.5, 121.4, 114.1, 111.5, 55.5, 54.2, 45.6, 28.0. HRMS (ESI/Q-TOF) m/z:
[M+Na]+ Calcd for C15H16N4O2 307.1165; Found 307.1166.
1-(4-Methoxyphenyl)-3-((4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)amino)pyrrolidin-2-one
(3n). Eluent ethyl acetate – n-hexane 3:1. Yield 27 mg, 22%. Pale pink solid, mp 164.3-165.1
1
°C. H NMR (400 MHz, CDCl3) δ 7.82 – 7.40 (m, 2H), 7.08 – 6.77 (m, 2H), 5.64 (s, 1H), 4.45
(dd, J = 10.7, 7.9 Hz, 1H), 3.82 (s, 3H), 4.09 – 3.58 (m, 2H), 2.99 (dddd, J = 12.6, 7.8, 6.2, 1.3
13
Hz, 1H), 2.77 – 2.48 (m, 4H), 2.22 – 1.97 (m, 1H), 1.92 – 1.59 (m, J = 5.1, 4.6 Hz, 4H). C
NMR (101 MHz, CDCl3) δ 171.1, 165.5, 156.9, 145.8, 132.3, 121.5, 117.6, 114.2, 56.8, 55.5,
45.8, 28.4, 26.8, 23.5, 23.2, 23.1. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C18H21N3O2S
344.1427; Found 344.1432.
N-Butyl-2-((1-(4-methoxyphenyl)-2-oxopyrrolidin-3-yl)amino)benzamide (3o). Eluent ethyl
acetate – n-hexane 1:1. Yield 63 mg, 55%. Colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.05 (d,
J = 5.5 Hz, 1H), 7.71 – 7.52 (m, 2H), 7.37 (dd, J = 7.8, 1.6 Hz, 1H), 7.33 – 7.14 (m, 1H), 6.96 –
6.89 (m, 2H), 6.83 (d, J = 8.3 Hz, 1H), 6.63 (t, J = 7.5 Hz, 1H), 6.39 – 6.29 (m, 1H), 4.29 (ddd, J
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
= 9.9, 8.1, 5.5 Hz, 1H), 3.94 – 3.71 (m, 2H), 3.81 (s, 3H), 3.55 – 3.26 (m, 2H), 2.74 (dddd, J =
12.5, 8.5, 6.7, 2.2 Hz, 1H), 2.32 – 1.99 (m, 1H), 1.73 – 1.52 (m, 2H), 1.52 – 1.34 (m, 2H), 0.96
13
(t, J = 7.3 Hz, 3H). C NMR (101 MHz, CDCl3) δ 171.9, 169.5, 156.7, 148.5, 132.6, 132.4,
127.4, 121.3, 116.7, 115.9, 114.1, 112.6, 55.5, 55.3, 45.4, 39.5, 31.7, 27.8, 20.2, 13.8. HRMS
(ESI/Q-TOF) m/z: [M+H]+ Calcd for C22H27N3O3 382.2125; Found 382.2141.
4-((1-(4-Methoxyphenyl)-2-oxopyrrolidin-3-yl)amino)benzenesulfonamide (3p). HPLC Rt =
16.7 min. Yield 27 mg, 25%. White solid, mp 230.9-232.7 °C. 1H NMR (400 MHz, DMSO-d6) δ
7.72 – 7.57 (m, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.08 – 6.96 (m, 2H), 6.94 (s, 2H), 6.79 (d, J = 8.5
Hz, 2H), 6.68 (d, J = 7.5 Hz, 1H), 4.73 – 4.34 (m, 1H), 3.97 – 3.62 (m, 2H), 3.76 (s, 3H), 2.74 –
2.56 (m, 1H), 2.03 – 1.81 (m, 1H). 13C NMR (101 MHz, DMSO-d6) δ 172.1, 156.5, 151.3, 133.2,
131.2, 127.7, 121.5, 114.4, 112.0, 55.7, 54.8, 45.3, 26.6. HRMS (ESI/Q-TOF) m/z: [M+Na]+
Calcd for C17H19N3O4S 384.0988; Found 384.0987.
3-((4-(Adamantan-1-yl)phenyl)amino)-1-(4-methoxyphenyl)pyrrolidin-2-one (3q). Eluent
ethyl acetate – n-hexane 1:1. Yield 88 mg, 70%. White solid, mp 143.2-144.4 °C. 1H NMR (400
MHz, CDCl3) δ 7.60 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 8.5 Hz, 2H), 6.73
(d, J = 8.1 Hz, 2H), 4.56 (s, 1H), 4.12 (t, J = 9.1 Hz, 1H), 3.95 – 3.71 (m, 2H), 3.84 (s, 3H), 2.87
13
(dt, J = 13.4, 7.1 Hz, 1H), 2.22 – 2.00 (m, 4H), 1.98 – 1.88 (m, 6H), 1.87 – 1.71 (m, 6H). C
NMR (101 MHz, CDCl3) δ 172.1, 156.9, 145.2, 141.8, 132.4, 125.7, 121.5, 114.2, 113.5, 56.4,
55.5, 45.7, 43.4, 36.9, 35.4, 29.5, 29.1. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C27H32N2O2 417.2537; Found 417.2551.
4-(3-(3,4-Dihydroquinolin-1(2H)-yl)-2-oxopyrrolidin-1-yl)benzonitrile (3r). Eluent ethyl
acetate – n-hexane 1:3. Yield 58 mg, 61%. White solid, mp 198.7-200.2 °C. 1H NMR (400 MHz,
CDCl3) δ 7.88 (d, J = 8.9 Hz, 2H), 7.78 – 7.49 (m, 2H), 7.07 (td, J = 7.8, 1.6 Hz, 1H), 7.03 (dd, J
= 7.4, 1.5 Hz, 1H), 6.82 – 6.53 (m, 2H), 4.82 (dd, J = 10.6, 8.7 Hz, 1H), 4.13 – 3.69 (m, 2H),
3.35 (ddd, J = 11.0, 6.9, 4.0 Hz, 1H), 3.22 (ddd, J = 11.2, 8.0, 3.8 Hz, 1H), 2.83 (t, J = 6.5 Hz,
2H), 2.55 (dddd, J = 12.9, 8.9, 7.0, 2.0 Hz, 1H), 2.38 – 2.20 (m, 1H), 2.18 – 2.05 (m, 1H), 2.04 –
13
1.90 (m, 1H). C NMR (101 MHz, CDCl3) δ 172.2, 144.7, 143.1, 133.1, 129.6, ij127.0, 124.0,
119.2, 118.8, 117.2, 111.1, 107.6, 60.9, 44.7, 44.5, 28.0, 22.4, 20.8. HRMS (ESI/Q-TOF) m/z:
[M+H]+ Calcd for C20H19N3O 318.1601; Found 318.1609.
4-(2-Oxo-3-(thiazol-2-ylamino)pyrrolidin-1-yl)benzonitrile (3s). HPLC Rt = 18.5 min. Yield
23 mg, 27%. White solid, mp 169.9-171.0 °C. 1H NMR (400 MHz, acetone-d6) δ 8.05 – 7.95 (m,
2H), 7.89 – 7.75 (m, 2H), 7.35 (d, J = 4.1 Hz, 1H), 6.92 (d, J = 4.1 Hz, 1H), 6.41 (s, 1H), 4.71
(dd, J = 10.7, 8.4 Hz, 1H), 4.18 – 3.94 (m, 2H), 2.89 (dddd, J = 12.5, 8.4, 6.4, 1.8 Hz, 1H), 2.47
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
– 2.23 (m, 1H). 13C NMR (101 MHz, acetone-d6) δ 171.0, 170.9, 143.4, 132.9, 131.2, 119.2,
118.4, 108.0, 107.2, 58.6, 44.4, 25.0. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C14H12N4OS
285.0805; Found 285.0811.
4-(3-((4-Chloro-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)amino)-2-oxopyrrolidin-1-
yl)ben-zonitrile (3t). Eluent ethyl acetate – n-hexane 3:1. Yield 38 mg, 36%. White solid, mp
218.2-219.8 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 – 7.79 (m, 2H), 7.74 – 7.57 (m, 2H), 6.17 (s,
1H), 4.76 (ddd, J = 10.9, 8.5, 5.8 Hz, 1H), 4.00 – 3.76 (m, 2H), 3.03 – 2.73 (m, 5H), 2.27 – 1.97
13
(m, 3H). C NMR (101 MHz, CDCl3) δ 176.6, 172.4, 160.9, 157.3, 142.9, 133.1, 123.0, 119.2,
118.7, 107.6, 54.5, 44.9, 34.6, 28.2, 26.8, 21.6. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C18H16ClN5O 354.1116; Found 354.1120.
4-(2-Oxo-3-(pyridin-3-ylamino)pyrrolidin-1-yl)benzonitrile (3u). Eluent ethyl acetate – n-
hexane 3:1. Yield 48 mg, 58%. Brown semi-solid. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 2.9
Hz, 1H), 8.06 (dd, J = 4.7, 1.4 Hz, 1H), 7.90 – 7.78 (m, 2H), 7.74 – 7.62 (m, 2H), 7.13 (dd, J =
8.2, 4.6 Hz, 1H), 7.02 (ddd, J = 8.2, 2.9, 1.4 Hz, 1H), 4.65 (s, 1H), 4.22 (ddd, J = 10.6, 7.9, 2.6
Hz, 1H), 3.91 (dd, J = 9.7, 3.9 Hz, 2H), 2.90 (ddt, J = 12.1, 7.9, 3.9 Hz, 1H), 2.32 – 1.94 (m,
1H). 13C NMR (101 MHz, CDCl3) δ 172.7, 143.0, 142.6, 140.2, 136.3, 133.1, 123.8, 120.1,
119.3, 118.6, 108.0, 56.0, 44.8, 28.2. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C16H14N4O
279.1240; Found 279.1234.
1-(4-Bromophenyl)-3-((3-methoxyphenyl)amino)pyrrolidin-2-one (3v). Eluent ethyl acetate –
n-hexane 1:3. Yield 52 mg, 48%. Beige solid, mp 111.0-112.6 °C. 1H NMR (400 MHz, CDCl3) δ
7.67 – 7.58 (m, 2H), 7.57 – 7.46 (m, 2H), 7.15 (t, J = 8.1 Hz, 1H), 6.39 (dd, J = 8.2, 2.3 Hz, 1H),
6.35 (dd, J = 7.9, 2.2 Hz, 1H), 6.29 (t, J = 2.3 Hz, 1H), 4.60 (s, 1H), 4.14 (dd, J = 10.5, 7.8 Hz,
1H), 3.95 – 3.76 (m, 2H), 3.81 (s, 3H), 2.88 (dddd, J = 12.4, 7.8, 5.9, 1.9 Hz, 1H), 2.19 – 1.94
13
(m, 1H). C NMR (101 MHz, CDCl3) δ 172.4, 160.9, 148.7, 138.1, 132.0, 130.2, 121.1, 117.9,
106.8, 103.6, 100.0, 56.4, 55.2, 45.1, 29.0. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C17H17BrN2O2 361.0546; Found 361.0537.
4-((2-Oxo-1-(thiazol-2-yl)pyrrolidin-3-yl)amino)benzonitrile (3w). Eluent ethyl acetate – n-
hexane 3:1. Yield 60 mg, 70%. White solid, mp 206.8-207.7 °C. 1H NMR (400 MHz, DMSO-d6
- CDCl3) δ 7.43 (d, J = 3.5 Hz, 1H), 7.38 – 7.26 (m, 2H), 7.05 (d, J = 3.5 Hz, 1H), 6.80 – 6.68
(m, 2H), 6.54 (d, J = 7.1 Hz, 1H), 4.52 (ddd, J = 9.6, 8.3, 7.1 Hz, 1H), 4.25 (ddd, J = 11.1, 9.0,
2.3 Hz, 1H), 3.97 (ddd, J = 10.9, 9.3, 7.1 Hz, 1H), 2.71 (dddd, J = 12.8, 8.4, 7.2, 2.3 Hz, 1H),
2.21 – 2.04 (m, 1H). 13C NMR (101 MHz, DMSO-d6 - CDCl3) δ 171.5, 157.4, 151.2, 137.8,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
133.4, 120.4, 114.2, 113.0, 98.5, 54.4, 44.8, 26.8. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for
C14H12N4OS 285.0805; Found 285.0814.
3-(Naphthalen-1-ylamino)-1-(thiazol-2-yl)pyrrolidin-2-one (3x). Eluent ethyl acetate – n-
hexane 1:2. Yield 61 mg, 66%. White solid, mp 184.3-185.1 °C. 1H NMR (400 MHz, CDCl3) δ
8.01 – 7.93 (m, 1H), 7.88 – 7.79 (m, 1H), 7.56 (d, J = 3.6 Hz, 1H), 7.53 – 7.44 (m, 2H), 7.42 –
7.34 (m, 2H), 7.11 (d, J = 3.5 Hz, 1H), 6.68 (dd, J = 5.9, 2.7 Hz, 1H), 5.11 (s, 1H), 4.46 (dd, J =
10.0, 8.0 Hz, 1H), 4.39 (ddd, J = 10.9, 9.3, 1.5 Hz, 1H), 4.08 (ddd, J = 11.0, 10.0, 6.9 Hz, 1H),
13
3.10 – 2.89 (m, 1H), 2.28 – 2.05 (m, 1H). C NMR (101 MHz, CDCl3) δ 172.1, 157.5, 142.0,
137.9, 134.3, 128.6, 126.2, 126.1, 125.3, 124.1, 120.3, 119.2, 114.4, 105.7, 55.9, 45.1, 28.8.
HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C17H15N3OS 310.1009; Found 310.1006.
Rh2(esp)2-catalysed decomposition of N-phenyl α-diazo γ-butyrolactam (1a) in presence of
cyclopropylamine. To a vigorous stirred solution of cyclopropylamine (17 mg, 0.3 mmol) and
N-phenyl α-diazo γ-butyrolactam (56 mg, 0.3 mmol) in dichloromethane (5 ml) was added
Rh2(esp)2 (4.4 mg, 0.006 mmol, 2 mol %) in several portions during 20 minutes and the resulting
mixture was stirred for another 20 minutes. The suspension obtained was evaporated to dryness
and the residue was subjected to column chromatography on silica gel.
3-(Cyclopropylamino)-1-phenylpyrrolidin-2-one (3y). Eluent ethyl acetate – n-hexane 1:3.
Yield 24 mg, 37%. White solid, mp 89.8-90.9 °C. 1H NMR (400 MHz, CDCl3) δ 7.72 – 7.60 (m,
2H), 7.45 – 7.34 (m, 2H), 7.22 – 7.13 (m, 1H), 3.80 (dd, J = 9.5, 4.5 Hz, 2H), 3.72 (dd, J = 10.2,
8.0 Hz, 1H), 2.78 – 2.46 (m, 2H), 2.29 (tt, J = 6.6, 3.7 Hz, 1H), 2.17 – 1.93 (m, 1H), 0.87 – 0.48
(m, 2H), 0.47 – 0.32 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 173.7, 139.3, 128.9, 124.7, 119.7,
60.6, 45.5, 29.0, 27.1, 6.6, 5.9. HRMS (ESI/Q-TOF) m/z: [M+H]+ Calcd for C13H16N2O
217.1335; Found 217.1333.
3-(Cyclopropylamino)-1-phenyl-1,5-dihydro-2H-pyrrol-2-one (4). Eluent ethyl acetate – n-
1
hexane 1:3. Yield 12 mg, 19%. Brown amorphous solid. H NMR (400 MHz, CDCl3) δ 7.95 –
7.70 (m, 2H), 7.51 – 7.35 (m, 2H), 7.24 – 7.05 (m, 1H), 5.59 (t, J = 2.5 Hz, 1H), 4.51 (s, 1H),
4.32 (dd, J = 2.6, 0.8 Hz, 2H), 2.82 – 2.37 (m, 1H), 0.80 – 0.64 (m, 2H), 0.62 – 0.44 (m, 2H). 13C
NMR (101 MHz, CDCl3) δ 166.6, 140.9, 139.5, 129.1, 124.0, 118.6, 98.3, 49.4, 25.2, 6.5. HRMS
(ESI/Q-TOF) m/z: [M+H]+ Calcd for C13H14N2O 215.1179; Found 215.1177.
ASSOCIATED CONTENT
Supporting Information
Synthetic procedures, analytical data, copies of the 1H, 13C and 19F NMR spectra.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
AUTHOR INFORMATION
Corresponding Author
* E-mail: m.krasavin@spbu.ru.
ORCID
Dmitry Dar’in: 0000-0002-0413-7413
Mikhail Krasavin: 0000-0002-0200-4772.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
This research was supported by the Russian Foundation for Basic Research (project grant 19-03-
00775). We thank Research Centre for Magnetic Resonance and the Center for Chemical
Analysis and Materials Research of Saint Petersburg State University Research Park for
obtaining the analytical data.
KEYWORDS: -diazo lactams; -amino lactams; N-H insertion; rhodium (II) catalysis; γ-
butyrolactams
REFERENCES
[1] S.E. Cleary, X. Li, L.-C. Yang, K.N. Houk, X. Hong, M. Brewer, J. Am. Chem. Soc. 2019,
141, 3558.
[2] D.P. Hari, J. Waser, J. Am. Chem. Soc. 2016, 138, 2190.
[3] B. Shen, B. Wan, X. Li, Angew. Chem. Int. Ed. 2018, 57, 15534.
[4] J.D. Neuhaus, A. Bauer, A. Pinto, N. Maulide, Angew. Chem. Int. Ed. 2018, 57, 16215.
[5] X. Lin, Y. Tang, W. Yang, F. Tan, L. Lin, X. Liu, X. Feng, J. Am. Chem. Soc. 2018, 140,
3299.
[6] A. Ford, H. Miel, A. Ring, C.N. Slattery, A.R. Maguire, M.A. McKervey, Chem. Rev.
2015, 115, 9981. (b) M.P. Doyle, M.A. McKervey, T. Ye, Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds, John Wiley & Sons, Inc., New York, NY, 1998.
[7] T. Ye, M.A. McKervey, Chem. Rev. 1994, 94, 1091.
[8] J. Ueda, S. Harada, H. Nakayama, T. Nemoto, Org. Biomol. Chem. 2018, 16, 4675.
[9] H. Yang, A.M. Swartz, H.J. Park, P. Srivastava, K. Ellis-Guardiola, D.M. Upp, G. Lee, K.
Belsare, Y. Gu, C. Zhang, R.E. Moellering, J.C. Lewis, Nat. Chem. 2018, 10, 318.
[10] Z. Wang, A.G. Herraiz, A.M. del Hoyo, M.G. Suero, Nature 2018, 554, 86.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
[11] I.D. Jurberg, H.M.L. Davies, Chem. Sci. 2018, 9, 5112.
[12] L. Chen, H. Cui, Y. Wang, X. Liang, L. Zhang, C.-Y. Su, Dalton Trans. 2018, 47, 3940.
[13] N.L. Loskutova, N.V. Shvydkiy, Y.V. Nelyubina, D.S. Perekalin, J. Organomet. Chem.
2018, 867, 86.
[14] J. Kang, L. Chen, H. Cui, L. Zhang, C.-Y. Su, Chin. J. Chem. 2017, 35, 964.
[15] S.M. Nicolle, C.J. Hayes, C.J. Moody, Chem. - Eur. J. 2015, 21, 4576.
[16] K. Wang, P. Chen, D. Ji, X. Zhang, G. Xu, J. Sun, Angew. Chem. Int. Ed. 2018, 57, 12489.
[17] V. Arredondo, S.C. Hiew, E.S. Gutman, I.D.U.A. Premachandra, D.L. Van Vranken,
Angew. Chem. Int. Ed. 2017, 56, 4156.
[18] A. DeAngelis, O. Dmitrenko, J.M. Fox, J. Am. Chem. Soc. 2012, 134, 11035.
[19] R.M. Sultanova, A.N. Lobov, L.V. Spirikhin, Chem. Heterocycl. Compd. 2015, 51, 1048.
[20] D. Zhukovsky, D. Dar’in, G. Kantin, M. Krasavin, Eur. J. Org. Chem. 2019, 2019, 2397.
[21] W.R. Ewing, M.R. Becker, V.E. Manetta, R.S. Davis, H.W. Pauls, H. Mason, Y.M. Choi-
Sledeski, D. Green, D. Cha, A.P. Spada, D.L. Cheney, J.S. Mason, S. Maignan, J.-P.
Guilloteau, K. Brown, D. Colussi, R. Bentley, J. Bostwick, C.J. Kasiewski, S.R. Morgan,
R.J. Leadley, C.T. Dunwiddie, M.H. Perrone, V. Chu, J. Med. Chem. 1999, 42, 3557.
[22] Y.M. Choi-Sledeski, D.G. McGarry, D.M. Green, H.J. Mason, M.R. Becker, R.S. Davis,
W.R. Ewing, W.P. Dankulich, V.E. Manetta, R.L. Morris, A.P. Spada, D.L. Cheney, K.D.
Brown, D.J. Colussi, V. Chu, C.L. Heran, S.R. Morgan, R.G. Bentley, R.J. Leadley, S.
Maignan, J.-P. Guilloteau, C.T. Dunwiddie, H.W. Pauls, J. Med. Chem. 1999, 42, 3572.
[23] X. Lin, W. Chen, Z. Qiu, L. Guo, W. Zhu, W. Li, Z. Wang, W. Zhang, Z. Zhang, Y. Rong,
M. Zhang, L. Yu, S. Zhong, R. Zhao, X. Wu, J.C. Wong, G. Tang, J. Med. Chem. 2015, 58,
2809.
[24] M.G.R. Beyaert, R.P. Daya, B.A. Dyck, R.L. Johnson, R.K. Mishra, Eur.
Neuropsychopharmacol. 2013, 23, 253.
[25] D. Basu, Y. Tian, J. Bhandari, J.R. Jiang, P. Hui, R.L. Johnson, R.K. Mishra, PLoS ONE
2013, 8, e70736.
[26] S. Muthusamy, T. Karikalan, Org Biomol Chem 2014, 12, 9243.
[27] H. Huang, Y. Wang, Z. Chen, W. Hu, Adv. Synth. Catal. 2005, 347, 531.
[28] R. Dada, Z. Wei, R. Gui, R.J. Lundgren, Angew. Chem. Int. Ed. 2018, 57, 3981.
[29] S. Jansone-Popova, J.A. May, J. Am. Chem. Soc. 2012, 134, 17877.
[30] A.C. Hunter, K. Chinthapally, I. Sharma, Eur. J. Org. Chem. 2016, 2016, 2260.
[31] S.R. Hansen, J.E. Spangler, J.H. Hansen, H.M.L. Davies, Org. Lett. 2012, 14, 4626.
[32] P.W. Glunz, D.F. Sitkoff, M.S. Bodas, N.D. Yadav, S. Patil, P.S.M. Rao, K. Thiyagarajan,
T.K. Maishal, PCT Int Appl WO2016144936; Chem Abstr 2016, 165, 416522.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
[33] C.T. Supuran, J.-Y. Winum, Future Med. Chem. 2015, 7, 1407.
[34] C.T. Supuran, V. Alterio, A. Di Fiore, K. D’ Ambrosio, F. Carta, S.M. Monti, G. De
Simone, Med. Res. Rev. 2018, 38, 1799.
[35] M. Krasavin, A. Shetnev, S. Baykov, S. Kalinin, A. Nocentini, V. Sharoyko, G. Poli, T.
Tuccinardi, M. Korsakov, T.B. Tennikova, C.T. Supuran, Eur. J. Med. Chem. 2019, 168,
301.
[36] A.V. Galkin, J.S. Melnick, S. Kim, T.L. Hood, N. Li, L. Li, G. Xia, R. Steensma, G.
Chopiuk, J. Jiang, Y. Wan, P. Ding, Y. Liu, F. Sun, P.G. Schultz, N.S. Gray, M. Warmuth,
Proc. Natl. Acad. Sci. 2007, 104, 270.
[37] E.D. Deeks, Target. Oncol. 2016, 11, 693.
Graphical abstract
Ar
N
Ar
N
Rh2(esp)2 0.5 mol %
DCM or 1,4-dioxane
O
O
H
+
N
Ar'
R
N+
N-
Ar'
N
R
24 examples
up to 81%
TOC text
-Arylamino--butyrolactams are valuable scaffolds in medicinal chemistry. Their assembly has
been achieved via NH-insertion into an anilinic amino group of metal carbene species generated,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900565
European Journal of Organic Chemistry
via the use of Rh2(esp)2 catalyst, from the hitherto poorly explored -diazo--butyrolactams.
The reaction works well for aromatic and heteroaromatic (but not aliphatic) amines.
Key topic
Diazo compounds
This article is protected by copyright. All rights reserved.