Peroxide-Mediated Oxidative Radical Cyclization to the Quinazolinone System: Efficient Syntheses of Deoxyvasicinone, Mackinazolinone and (±)-Leucomidine C

Article abstract of DOI:10.1055/s-0040-1705975

An efficient protocol for obtaining fused quinazolinones through an oxidative free-radical cyclization under metal- and tin-free conditions is described. The oxidative cyclization of various N -3-ω-iodoalkyl derivatives to provide tricyclic systems using dicumyl peroxide as the sole reagent is studied. The method then is employed for the syntheses of 5-, 6-, and 7-membered fused quinazolinone analogues, including the natural products deoxyvasicinone and mackinazolinone. A xanthate-based oxidative radical cascade addition/cyclization process that allows the production of new menthol- and testosterone-quinazolinone conjugates, as well as the first total synthesis of leucomidine C, are also reported.

Full text of DOI:10.1055/s-0040-1705975

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
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020, 52, A–G
paper
A
en
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
Peroxide-Mediated Oxidative Radical Cyclization to the Quinazoli-
none System: Efficient Syntheses of Deoxyvasicinone, Mackina-
zolinone and (±)-Leucomidine C
Jazmín García-Ramírez
n
Luis D. Miranda*
0
0
0
0
-
0
0
0
3
-
0
3
4
2-8
1
6
0
oxidative radical cyclization
Me
I
R
O
R
O
N
Instituto de Química, Universidad Nacional Autónoma de
México, Circuito Exterior S. N., Ciudad Universitaria,
Coyoacán, Ciudad de México, 04510, México
lmiranda@unam.mx
n
N
N
RO OR
n
N
xanthate
chemistry
R
R1
O
R
MeO
O
R1
cascade
process
leucomidine C
LIe nuMsi tsa i itDClu ol. tmrMo r iedirrsaeapnnQoddnuaadí@mi nu i gnc aaA,muU t. nmh i ovx re rsidad Nacional Autónoma de México, Circuito Exterior S. N., Ciudad Universitaria, Coyoacán, Ciudad de México, 04510, México
Received: 28.08.2020
Accepted after revision: 15.10.2020
Published online: 19.11.2020
O
N
N
O
N
O
N
N
DOI: 10.1055/s-0040-1705975; Art ID: ss-2020-m0460-op
N
mackinazolinone (4)
Abstract An efficient protocol for obtaining fused quinazolinones
through an oxidative free-radical cyclization under metal- and tin-free
conditions is described. The oxidative cyclization of various N-3--iodo-
alkyl derivatives to provide tricyclic systems using dicumyl peroxide as
the sole reagent is studied. The method then is employed for the syn-
theses of 5-, 6-, and 7-membered fused quinazolinone analogues, in-
cluding the natural products deoxyvasicinone and mackinazolinone. A
xanthate-based oxidative radical cascade addition/cyclization process
that allows the production of new menthol- and testosterone-
quinazolinone conjugates, as well as the first total synthesis of leucomi-
dine C, are also reported.
R
O
3
O
MeO
vasicinone R = OH (2)
N 2
1
leucomidine C (5)
N
deoxyvasicinone R = H (3)
1
Figure 1 Structurally related quinazolinone natural products
Synthetically, the main approach for the preparation of
quinazolinone derivatives is by the de novo construction of
the heterocyclic system from anthranilic acid derivatives
6
(i.e., 2-aminobenzamide, isatoic anhydride, etc.). Several
cascade processes for the construction of the quinazolinone
skeleton have also been devised. A conceptually different
Key words quinazolinone, free radicals, peroxides, xanthates, leuco-
midine C
7
approach is the direct functionalization of the quinazoli-
none system itself. Therefore, the construction of the skele-
ton of fused derivatives (i.e., 1–4) relies on N-3 alkylation
and direct C–H functionalization at the C-2 position (or vice
versa). To this end, different catalytic methods have been
devised for the latter process, mainly using expensive pre-
Quinazolinone (e.g., 1), a benzo-fused pyrimidinone
heterocyclic system, is a privileged structure that covers
1
about two hundred naturally occurring alkaloids and sev-
2
eral synthetic commercially important drugs (Figure 1).
6
,8
Members of this class of alkaloids display a wide range of
pharmacological activities such as antipsychotic, analgesic,
anti-inflammatory, anti-oxidant, antimicrobial, and antihy-
pertensive. Examples of this family of natural products are
the bronchodilator alkaloid vasicinone (2) and deoxyvasici-
none (3), both isolated from the aerial parts of the ever-
green subherbaceous bush Adhatoda vasica, which is used
in traditional medicine for the treatment of colds, coughs,
cious metal salts. The other general approach is via the
9
oxidative radical inter- or intramolecular C–H functional-
ization at C-2 (Scheme 1). Although these types of reactions
have been increasingly used for C–H functionalization of a
wide range of heterocyclic systems, this methodology has
not been widely exploited for the assembly of quinazoli-
none-fused scaffolds. This method offers the advantage that
alkyl, aryl, and acyl radicals can be cyclized to the
quinazolinone system, as demonstrated in a pioneering
3
bronchitis, and asthma. The homologue, piperidine-fused
1
0
alkaloid mackinazolinone (4), was isolated from the leaves
of Mackinlaya subulate, and showed antidepressive, anti-
study conducted by Bowman et al. However, highly toxic
and difficult to remove tin reagents were used in their
work, and the presence of a mixture of side-products re-
sulted in diminished yields (Scheme 1). More recently, a
silver-mediated oxidative decarboxylative radical cycliza-
tion was described by Mhaske and Mahajan, starting from
4
bacterial, and anti-inflammatory properties. Furthermore,
the alkaloid leucomidine C (5), isolated from the bark of
Leuconotis griffithii, is another alkylated piperidine-fused
5
quinazolinone that exhibits important cytotoxic activity.
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
proline derivatives.11 Unfortunately, the products were ob-
tained in low yields. In other work, Procter et al. described a
reductive homolytic cyclization to obtain the corresponding
process, under previously examined tin-based conditions,
afforded natural products 2 and 4, but only in 20% and 30%
yields, respectively, from the same starting materials and
with all the inconvenience that the use of tin reagents im-
dihydroquinazolinone-fused products under SmI -cata-
2
12
10
lyzed conditions.
plies. Furthermore, under the DCP-mediated conditions,
the quinazolinone derivatives 14c–g were produced in fair-
ly good yields from the corresponding iodide derivatives
13c–g (entries 3–7), including those bearing an electron-at-
tracting chlorine substituent on the aromatic system (en-
tries 5–7). Hence, not only were 5- and 6-membered tricy-
clic analogues obtained efficiently, the 7-membered fused
azepine 14g was also prepared in 90% yield.
Previous work (Me3Sn)2, tert-BuPh, reflux, hν
low yields
9
O
N
8
O
N
O
n
n
R
n
N
R
R
N
N
1
R
R1
I
H
N
H
R1
n = 1, 2, 3
°, 2°, 3° radicals
1
10
Me
7
path a
Δ
cascade process
metal- and tin-free
process
path b
Table 1 Oxidative-Radical Cyclization on Quinazolinone Systemsa
6
Ph
Ph
O
O
11
O
n
12
dicumyl peroxide
N
R
Entry
1
Substrate
Product (yield)
this work
R1
O
N
H
O
O
Scheme 1 Homolytic oxidative cyclization onto quinazolinones
N
N
N
N
I
13a, 92%
deoxyvasicinone (2), 80%
In this context, expanding the synthetic utility of free
radicals to explore novel strategies for assembling unique
heterocycle-fused systems is ongoing. Herein, we report an
efficient protocol for obtaining fused quinazolinones
through a free-radical cyclization under metal- and tin-free
conditions. This methodology relies on the use of dicumyl
peroxide (DCP) as the only reagent, a procedure that we had
O
O
N
N
2
3
4
N
N
I
1
3b, 93%
mackinazolinone (4), 83%
O
N
O
N
N
N
previously developed for the cyclization of a series of alkyl
iodides onto different heteroaromatic systems.13 Under
13c, 95%
I
14c, 79%
these conditions, we proposed that the methyl radical gen-
erated by the thermal decomposition of DCP would abstract
the iodine atom and release the alkyl radical 9, which is ox-
idatively cyclized to the heterocyclic system to afford the
tricyclic system 10 (path a, Scheme 1). We also anticipated
that implementing a cascade addition/cyclization process
O
N
O
N
I
N
N
Me
Me
13d, 90%
14d, (79%)
O
O
N
N
N
N
Cl
Cl
(
also via 9, path b) with the alkene 11 and radical 12 would
5
6
7
N
N
Me
I
lead to a new series of fused scaffolds, including a facile
synthesis of leucomidine C, for which no total synthesis has
yet been reported (Scheme 1). Under these conditions the
use of a stoichiometric amount of the peroxide facilitates
the oxidation process necessary to restore the conjugated
Me
14e, 89%
13e, 95%
O
O
N
Cl
Cl
N
Me
N
1
3
I
system.
Me
Our endeavor started with the synthesis of N-alkyl io-
dides 13a–j through the alkylation of commercial
quinazolinones with the corresponding dihaloalkyl com-
pounds, followed by a Finkelstein-type process to introduce
the iodide substituent. Next, by utilizing reaction condi-
tions described previously,13 quinazolinones 13a,b were al-
lowed to react with 1.5 equivalents of DCP (added portion-
wise) in refluxing chlorobenzene. Gratifyingly, the desired
tricyclic compounds deoxyvasicinone (2) and mackinazoli-
none (4) were isolated in 80% and 83% yields, respectively
13f, 94%
14f, 93%
O
O
N
Cl
Cl
N
N
Me
I
Me
13g, 96%
14g, 90%
O
N
n
13h n = 1
3i n = 2
13j n = 3
8
MeO
MeO
no reaction
1
N
I
a
Reaction conditions: 13 (1 equiv), DCP (1.5 equiv added portionwise),
PhCl (0.02 M), reflux.
(
Table 1, entries 1 and 2). It is worth noting that the same
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

C
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
The cyclization of a secondary radical such as in the case
of 13d (Table 1, entry 4) was also implemented efficiently.
Interestingly, when iodides 13h–j, bearing methoxy sub-
stituents at the C-6 and C-7 positions, were subjected to the
same conditions, the formation of the desired cyclized
products was not observed (entry 8). Most of the starting
materials were recovered unchanged in these three experi-
ments. These reactions are inhibited for reasons that we do
not currently understand.
At this point, we recognized that implementing a radical
cascade addition/cyclization process might be useful to fur-
ther study these oxidative cyclizations (Table 2). This pro-
cess not only would allow the generation of secondary and
eventually tertiary radicals, but would also expand the
structural diversity of the products with the simultaneous
construction of two C–C bonds. Xanthate-based radical
chemistry, used in related cascade processes,14 was of par-
ticular importance for this purpose, since under the stan-
dard conditions of these reactions, dilauryl peroxide (DLP)
also acts as an initiator and oxidant,15 similar to conditions
using DCP.
Accordingly, olefin 15, prepared from the N-alkylation
of the quinazolinone and 5-bromo-1-pentene, was reacted
with the xanthate 16a to test the feasibility of the proposed
protocol. In the first experiment, DLP (1.5 equiv) was added
to a refluxing solution (DCE, 0.017 M) of substrates 15 and
16a (1.2 equiv). Under these conditions, quinazolinone 17a
was isolated in 48% yield. Further experimentation led us to
discover that increasing the amount of 16a to 1.5 equiva-
lents and performing the reaction under microwave irradia-
tion [DLP (1.5 equiv), 0.3 equiv/15 min], resulted in an in-
creased yield of 68% (Table 2, entry 1) in a shorter reaction
time (75 min). With optimized conditions in hand, we next
explored the scope of the cascade reaction using xanthates
derived from menthol (16b) and testosterone (16c).16 To
our delight, the tandem reactions of these xanthates with
olefin 15 proceeded efficiently and allowed access to novel
quinazolinone conjugates 17b and 17c in good yields and as
1
1:1 diastereomeric mixtures (determined by H NMR) (en-
tries 2 and 3). In the same way, the use of the acetonitrile-
derived xanthate 16d offered good performance and afford-
ed the tricyclic product 17d in good yield.
Table 2 Synthesis of Quinazolinones via Radical Cascade Reactionsa
O
O
S
DLP (1.5 equiv)
N
N
+
EtO
S
R
DCE, MW
N
N
16
1
5
17
R
Entry
1
R (xanthate 16)
Product (yield)
O
N
O
OEt
N
16a
OEt
17a, 68%
O
O
N
N
O
O
Me
2
Me
Me
O
O
Me
16b
17b, 65%
dr (1:1)
Me
Me
O
N
N
Me
17c, 55%
dr (1:1)
Me
H
O
O
3
H
O
H
Me
H
O
Me
H
O
16c
H
O
H
H
O
N
N
N
4
N
16d
1
7d, 66%
a
Reaction conditions: 15 (1.0 equiv), 16 (1.5 equiv), DLP (1.5 equiv), DCE (0.017 M), microwave irradiation (100 W).
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

D
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
Thus, through this study, we have shown that the oxida-
tive addition/cyclization cascade process represents a valu-
able and practical procedure for the preparation of a variety
of quinazoline-fused scaffolds from relatively simple sub-
strates.
Future studies will expand on this chemistry and explore
its usefulness in the synthesis of more complex molecules
in order to investigate their biological properties.
We then turned our attention to the study of the oxida-
tive cyclization of a tertiary radical. At the outset of these
studies, we recognized that this process could be coupled
with a short total synthesis of leucomidine C (5), by using
the same oxidative addition/cyclization cascade process be-
tween olefin 20 and xanthate 21 (Scheme 2). Therefore, the
required starting material 20 was prepared by the alkyla-
tion of quinazolinone 18 with known tosylate 19. Next,
according to the reaction conditions for the cascade process
outlined earlier, DLP (1.5 equiv) was slowly added to olefin
The starting materials and solvents were purchased from commercial
suppliers and were used without prior purification. Solvents (THF,
DMF and DME) were dried using standard procedures. All reactions
were performed under an argon atmosphere. The reaction progress
was monitored by analytical thin-layer chromatography using GF sili-
ca gel plates purchased from Merck. Visualization was achieved under
short-wave UV light (254 nm). Column chromatography was per-
formed on Aldrich silica gel (230–400 mesh particle size). Reactions
under microwave irradiation were performed using a Microwave Syn-
thesis System - CEM-Discover instrument. Melting points were deter-
1
7
1
13
mined on a Fisher apparatus and are not corrected. H and C NMR
spectra were recorded on Jeol Eclipse-300 MHz and Bruker Avance
2
2
0 in the presence of the methyl acetate derived xanthate
1 (1.5 equiv) in refluxing 1,2-dichloroethane under micro-
5
00 MHz spectrometers using CDCl3 as the solvent. Chemical shifts
are reported in parts per million (ppm) downfield from tetramethyl-
wave irradiation. We were pleased to observe that under
these conditions (±)-leucomidine C (5) was obtained in 68%
yield. This process highlights important issues such as the
oxidative addition of a tertiary radical to the conjugated
silane as the internal standard ( = 0.0), or from the solvent as a refer-
1
13
ence (CDCl ,  = 7.26 for H;  = 77.16 for C). NMR coupling con-
3
stants are reported in hertz (Hz). Low- and high-resolution DART+
mass spectra were obtained on a Jeol JMS-T100LC spectrometer.
1
8
system that forged the all-carbon quaternary center, as
present in the natural product structure, along with the for-
mation of two new C–C bonds. All spectroscopic data
N-Alkyl Iodides 13a–g; General Procedure
To a suspension of NaH (95%, 72.5 mg, 3.02 mmol) in DMF (2 mL) and
1,2-dimethoxyethane (2 mL) was added a solution of the 4-hydroxy-
quinazolin-4(3H)-one (18) (300 mg, 2.01 mmol) in DME at 0 °C. After
5
matched those previously reported for the natural product.
1
5 min, the reaction mixture was treated with LiBr (357 mg, 4.1
O
mmol) and stirred for 15 min. The corresponding dihaloalkyl com-
pound (1,3-dibromopropane, 1,4-dibromobutane, 1,4-dibromopen-
tane or 1,4-dibromopentane) (0.2 mL, 2.05 mmol) was then added
dropwise. The reaction mixture was stirred at room temperature for
5–6 h and then quenched with ice water. The resulting mixture was
extracted with ethyl acetate and the combined organic layer was
washed with water and brine, dried over Na SO , filtered and concen-
NH
O
NaH
N
N
1
8
N
+
DME/DMF, 0 °C
2
0
(
92%)
TsO
O
S
OMe
O
1
9
OMe
OEt
2
4
O
S
DLP,
DCE,
reflux, MW
trated. The residue was used in the next step without further purifi-
cation. The crude bromide was converted into the corresponding io-
dide by reaction with sodium iodide (4 equiv) in acetonitrile (30 mL/g
bromide) at reflux for 24 h. After cooling, the solution was poured
into water and extracted with dichloromethane. The organic layer
was washed with saturated aqueous sodium sulfite solution and wa-
ter, and then dried over Na SO . The solvent was removed in vacuo
N
21
N
(
68%)
OMe
(±)-5
O
Scheme 2 Total synthesis of leucomidine C (5)
2
4
and the residue was purified by flash silica gel column chromatogra-
phy (hexanes/ethyl acetate, 1:1) to provide pure product 13.
In conclusion, an efficient protocol for obtaining fused
quinazolinones through an oxidative free-radical cycliza-
tion under metal- and tin-free conditions is described. In
the first part, we streamlined the oxidative cyclization of
various N-3--iodoalkyl derivatives to provide the tricyclic
system using dicumyl peroxide as the sole reagent. Under
these conditions, the oxidative cyclization process was
much more efficient than previously reported with tin re-
agents. Thus, 5-, 6-, and 7-membered fused quinazolinone
analogues, including the natural products deoxyvasicinone
3
-(3-Iodopropyl)quinazolin-4(3H)-one (13a)
Yield: 395 mg (92%); white solid; mp 95 °C.
1
H NMR (300 MHz, CDCl ):  = 8.29 (d, J = 8.0 Hz, 1 H), 8.10 (s, 1 H),
3
7
.74 (dt, J = 14.5, 8.1 Hz, 2 H), 7.51 (t, J = 7.3 Hz, 1 H), 4.11 (t, J = 6.7 Hz,
2 H), 3.18 (t, J = 6.5 Hz, 2 H), 2.32 (quin, J = 6.5 Hz, 2 H).
13
C NMR (75 MHz, CDCl ):  = 161.26, 148.17, 146.56, 134.49, 127.65,
3
127.54, 126.72, 122.12, 47.55, 32.00, 2.12.
HRMS-DART: m/z [M + H]+ calcd for C11H12IN O: 314.99943; found:
2
(
3) and mackinazolinone (4), were efficiently obtained. We
314.99880.
also implemented a xanthate-based oxidative radical cas-
cade addition/cyclization process that allowed the produc-
tion of new menthol- and testosterone-quinazolinone con-
jugates, and the first total synthesis of leucomidine C (5).
3-(4-Iodobutyl)quinazolin-4(3H)-one (13b)
Yield: 417 mg (93%); white solid; mp 74 °C.
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

E
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
1
+
H NMR (300 MHz, CDCl ):  = 8.24 (td, J = 7.6, 1.7 Hz, 1 H), 7.99 (s, 1
HRMS-DART: m/z [M + H] calcd for C14H17ClIN O: 391.00741; found:
3
2
H), 7.75–7.60 (m, 2 H), 7.45 (d, J = 6.3 Hz, 1 H), 3.97 (t, J = 6.1 Hz, 2 H),
391.00835.
3.15 (t, J = 5.2 Hz, 2 H), 1.95–1.77 (m, 4 H).
1
3
C NMR (75 MHz, CDCl ):  = 161.06, 148.12, 146.38, 134.34, 127.54,
Oxidative-Radical Cyclization on Quinazolinone Systems; General
Procedure
3
1
27.41, 126.72, 122.10, 45.79, 30.46, 30.32, 5.45.
HRMS-DART: m/z [M + H]+ calcd for C12H14IN O: 329.01508; found:
In a round-bottomed flask, the alkyl iodide derivative 13a–g (100 mg,
2
0
.31 mmol) was dissolved in degassed chlorobenzene (2.2 mL) and
329.01707.
heated to reflux. Dicumyl peroxide (DCP) (129 mg, 0.47 mmol) was
added in portions (0.3 equiv/1 h) under an N atmosphere for 5 h. Af-
2
3
-(5-Iodopentyl)quinazolin-4(3H)-one (13c)
ter consumption of the starting material, the reaction mixture was
then allowed to cool to room temperature and the solvent was evapo-
rated in vacuo. The residue was purified by flash column chromatog-
raphy (n-hexane/EtOAc, 7:3) to afford the products 2, 4 and 14c–g.
Yield: 445 mg (95%); white solid; mp 88 °C.
1
H NMR (300 MHz, CDCl ):  = 8.24 (td, J = 7.7, 2.2 Hz, 1 H), 8.05–7.96
3
(m, 1 H), 7.66 (tt, J = 8.8, 4.7 Hz, 2 H), 7.51–7.39 (m, 1 H), 3.95 (q, J =
7.1 Hz, 2 H), 3.19–3.06 (m, 2 H), 1.79 (m, 4 H), 1.56–1.36 (m, 2 H).
1
3
C NMR (75 MHz, CDCl ):  = 161.05, 148.17, 146.52, 134.26, 127.51,
Deoxyvasicinone (2)
3
1
27.35, 126.70, 122.17, 46.85, 32.84, 28.35, 27.59, 6.40.
Yield: 47 mg (80%); yellow solid; mp 110 °C.
HRMS-DART: m/z [M + H]+ calcd for C13H16IN O: 343.03073; found:
1
2
H NMR (300 MHz, CDCl ):  = 8.35–8.25 (m, 1 H), 7.77–7.68 (m, 1 H),
3
343.02932.
7
4
.64 (ddd, J = 8.2, 1.3, 0.6 Hz, 1 H), 7.44 (ddd, J = 8.1, 7.0, 1.3 Hz, 1 H),
.29–4.15 (m, 2 H), 3.18 (t, J = 8.0 Hz, 2 H), 2.36–2.21 (m, 2 H).
3
-(4-Iodopentyl)quinazolin-4(3H)-one (13d)
13
C NMR (75 MHz, CDCl ):  = 161.07, 159.54, 149.19, 134.25, 126.85,
3
Yield: 315 mg (90%); white solid; mp 91 °C.
126.44, 126.31, 120.53, 46.58, 32.59, 19.58.
1
HRMS-DART: m/z [M + H]+ calcd for C11H11N O: 187.08714; found:
H NMR (300 MHz, CDCl ):  = 8.30 (ddd, J = 8.0, 1.5, 0.6 Hz, 1 H), 8.03
3
2
(
4
s, 1 H), 7.80–7.66 (m, 2 H), 7.50 (ddd, J = 8.2, 6.8, 1.5 Hz, 1 H), 4.24–
.09 (m, 1 H), 4.09–3.94 (m, 2 H), 2.03–1.84 (m, 6 H), 1.77–1.64 (m, 1
H).
187.08788.
Mackinazolinone (4)
1
3
C NMR (75 MHz, CDCl ):  = 161.14, 148.16, 146.40, 134.37, 127.57,
3
Yield: 50 mg (83%); yellow solid; mp 100 °C.
1
27.45, 126.79, 122.15, 45.94, 39.54, 29.94, 28.99, 28.47.
1
H NMR (300 MHz, CDCl ):  = 8.24 (dd, J = 7.9, 1.6 Hz, 1 H), 7.70 (ddt,
3
HRMS-DART: m/z [M + H]+ calcd for C13H16IN O: 343.03073; found:
3
2
J = 9.7, 7.0, 1.4 Hz, 1 H), 7.61–7.55 (m, 1 H), 7.45–7.37 (m, 1 H), 4.06 (t,
J = 6.1 Hz, 2 H), 2.99 (t, J = 6.5 Hz, 2 H), 2.10–1.83 (m, 4 H).
43.03058.
1
3
C NMR (75 MHz, CDCl ):  = 162.28, 154.97, 147.50, 134.27, 126.73,
3
6-Chloro-3-(3-iodopropyl)-8-methylquinazolin-4(3H)-one (13e)
1
26.48, 126.17, 120.52, 42.42, 32.03, 22.20, 19.42.
Yield: 354 mg (95%); white solid; mp 80 °C.
HRMS-DART: m/z [M + H]+ calcd for C12H13N O: 201.10279; found:
201.10270.
2
1
H NMR (300 MHz, CDCl ):  = 8.13–8.07 (m, 2 H), 7.55 (dq, J = 2.5, 0.9
3
Hz, 1 H), 4.10 (t, J = 6.6 Hz, 2 H), 3.17 (t, J = 6.5 Hz, 2 H), 2.57 (s, 3 H),
2
.31 (quin, J = 6.6 Hz, 2 H).
7
,8,9,10-Tetrahydroazepino[2,1-b]quinazolin-12(6H)-one (14c)
1
3
C NMR (75 MHz, CDCl ):  = 160.52, 145.51, 145.36, 138.41, 135.11,
3
Yield: 49 mg (79%); yellow solid; mp 95 °C.
132.71, 123.60, 123.06, 47.55, 31.87, 17.41, 2.20.
1
H NMR (300 MHz, CDCl ):  = 8.29–8.23 (m, 1 H), 7.71 (ddd, J = 8.4,
3
+
HRMS-DART: m/z [M + H] calcd for C12H ClIN O: 362.97611; found:
13
2
7.1, 1.5 Hz, 1 H), 7.65–7.58 (m, 1 H), 7.43 (ddd, J = 8.1, 7.1, 1.3 Hz, 1 H),
4
362.97599.
.45–4.35 (m, 2 H), 3.13–3.03 (m, 2 H), 1.86 (dd, J = 12.2, 7.7 Hz, 6 H).
1
3
C NMR (75 MHz, CDCl ):  = 162.04, 159.83, 147.50, 134.25, 127.12,
3
6-Chloro-3-(4-iodobutyl)-8-methylquinazolin-4(3H)-one (13f)
1
26.85, 126.48, 120.33, 42.97, 37.81, 29.66, 28.18, 25.51.
Yield: 363 mg (94%); white solid, mp 91 °C.
HRMS-DART: m/z [M + H]+ calcd for C13H15N O: 215.11844; found:
215.11841.
2
1
H NMR (300 MHz, CDCl ):  = 8.12–8.05 (m, 1 H), 8.00 (s, 1 H), 7.59–
3
7.49 (m, 1 H), 4.00 (t, J = 6.7 Hz, 2 H), 3.19 (t, J = 6.3 Hz, 2 H), 2.55 (s, 3
H), 1.89 (tt, J = 6.6, 2.5 Hz, 4 H).
6
-Methyl-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-one
1
3
C NMR (75 MHz, CDCl ):  = 160.43, 145.38, 145.29, 138.33, 135.04,
(14d)
3
1
32.67, 123.71, 123.10, 45.87, 30.39, 30.26, 17.39, 5.33.
Yield: 49 mg (79%); yellow solid; mp 89 °C.
+
HRMS-DART: m/z [M + H] calcd for C13H ClIN O: 376.99176; found:
1
15
2
H NMR (300 MHz, CDCl ):  = 8.24 (d, J = 8.0 Hz, 1 H), 7.74–7.59 (m, 2
3
376.99139.
H), 7.45–7.36 (m, 1 H), 4.27 (dt, J = 14.1, 5.9 Hz, 1 H), 3.90 (ddd, J =
3.4, 7.4, 5.8 Hz, 1 H), 3.03 (dt, J = 8.7, 6.7 Hz, 1 H), 2.16–1.92 (m, 3 H),
1.68–1.57 (m, 1 H), 1.48 (d, J = 7.0 Hz, 3 H).
1
6
-Chloro-3-(5-iodopentyl)-8-methylquinazolin-4(3H)-one (13g)
1
3
Yield: 346 mg (96%); white solid, mp 93 °C.
C NMR (75 MHz, CDCl ):  = 162.36, 158.58, 147.53, 134.12, 126.81,
3
1
126.67, 126.16, 120.26, 42.25, 35.56, 27.69, 20.24, 19.61.
H NMR (300 MHz, CDCl ):  = 8.14–8.06 (m, 1 H), 8.01 (s, 1 H), 7.53
3
HRMS-DART: m/z [M + H]+ calcd for C13H15N O: 215.11844; found:
(t, J = 3.3 Hz, 1 H), 3.98 (dd, J = 8.8, 5.7 Hz, 2 H), 3.17 (t, J = 6.8 Hz, 2 H),
2
2.56 (s, 3 H), 1.94–1.74 (m, 4 H), 1.59–1.42 (m, 2 H).
215.11941.
1
3
C NMR (75 MHz, CDCl ):  = 160.44, 145.45, 138.29, 134.99, 132.60,
3
123.70, 123.18, 100.00, 46.95, 32.84, 28.29, 27.59, 17.40, 6.30.
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

F
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
7
-Chloro-5-methyl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-
3-(4-Methylenehexyl)quinazolin-4(3H)-one (20)
one (14e)
Yield: 372 mg (90%); yellow oil.
Yield: 57 mg (89%); yellow solid; mp 81 °C.
1
H NMR (300 MHz, CDCl ):  = 8.31 (ddd, J = 8.0, 1.4, 0.6 Hz, 1 H), 8.02
3
1
H NMR (300 MHz, CDCl ):  = 8.04 (d, J = 2.5 Hz, 1 H), 7.48 (d, J = 2.5
(s, 1 H), 7.81–7.66 (m, 2 H), 7.51 (ddd, J = 8.1, 6.8, 1.6 Hz, 1 H), 4.94–
3
Hz, 1 H), 4.17 (t, J = 7.3 Hz, 2 H), 3.16 (t, J = 8.0 Hz, 2 H), 2.54 (s, 3 H),
4.61 (m, 2 H), 4.15–3.94 (m, 2 H), 2.17–1.93 (m, 6 H), 1.03 (t, J = 7.4
2.27 (quin, J = 7.8 Hz, 2 H).
Hz, 3 H).
1
3
13
C NMR (75 MHz, CDCl ):  = 160.39, 158.60, 146.57, 137.61, 134.81,
C NMR (75 MHz, CDCl ):  = 161.19, 149.58, 148.22, 146.76, 134.27,
3
3
1
31.28, 123.35, 121.54, 46.58, 32.70, 19.66, 17.69.
127.52, 127.36, 126.78, 122.28, 108.92, 46.91, 33.11, 28.69, 27.09,
12.40.
+
HRMS-DART: m/z [M + H] calcd for C12H12ClN O: 235.06382; found:
2
235.06408.
HRMS-DART: m/z [M + H]+ calcd for C15H19N O: 243.14974; found:
2
2
43.14898.
2
-Chloro-4-methyl-6,7,8,9-tetrahydro-11H-pyrido-
[
2,1-b]quinazolin-11-one (14f)
Radical Cascades; General Procedure
Yield: 61 mg (93%); yellow solid; mp 84 °C.
A solution of quinazolinone 15 or 20 (50 mg, 0.23 mmol), xanthate 16
or 21 (73 mg, 0.35 mmol), dilauroyl peroxide (DLP) (30 mg, 0.07
mmol) in degassed 1,2-dichloroethane (1.1 mL) was heated in a sealed
vial at 85 °C under microwave irradiation (100 W) for 15 min under
and argon atmosphere, and then DLP (0.3 equiv) was added every 15
min five times. The reaction mixture was cooled to room temperature
and diluted with dichloromethane. The resulting mixture was washed
with water and brine. The organic layer was separated, dried over
Na SO , filtered and concentrated. The residue was purified by flash
1
H NMR (300 MHz, CDCl ):  = 8.08 (d, J = 2.5 Hz, 1 H), 7.51 (dd, J = 2.5,
3
0.8 Hz, 1 H), 4.08 (t, J = 6.3 Hz, 2 H), 3.01 (t, J = 6.7 Hz, 2 H), 2.57 (s, 3
H), 2.08–1.91 (m, 4 H).
1
3
C NMR (75 MHz, CDCl ):  = 161.61, 153.82, 144.74, 137.35, 134.65,
3
130.97, 123.43, 121.32, 42.41, 32.12, 22.10, 19.35, 17.15.
+
HRMS-DART: m/z [M + H] calcd for C13H14ClN O: 249.07947; found:
2
249.07925.
2
4
column chromatography (n-hexane/EtOAc, 7:3) to afford the products
2
1
-Chloro-4-methyl-7,8,9,10-tetrahydroazepino[2,1-b]quinazolin-
2(6H)-one (14g)
17a–d and 5.
Yield: 60 mg (90%); yellow solid; mp 89 °C.
Ethyl 3-(11-Oxo-6,8,9,11-tetrahydro-7H-pyrido[2,1-b]quinazolin-
1
6-yl)propanoate (17a)
H NMR (300 MHz, CDCl ):  = 8.01–7.97 (m, 1 H), 7.45–7.35 (m, 1 H),
.33–4.25 (m, 2 H), 3.02–2.98 (m, 2 H), 2.48 (s, 3 H), 1.83–1.70 (m, 6
3
Yield: 48 mg (68%); yellow oil.
4
H).
1
H NMR (300 MHz, CDCl ):  = 8.23 (ddd, J = 8.0, 1.6, 0.7 Hz, 1 H),
3
1
3
7.72–7.66 (m, 1 H), 7.61 (ddd, J = 8.2, 1.3, 0.6 Hz, 1 H), 7.44–7.37 (m, 1
H), 4.31–4.22 (m, 1 H), 4.14–4.03 (m, 2 H), 3.97–3.86 (m, 1 H), 2.95–
C NMR (75 MHz, CDCl ):  = 161.42, 158.55, 144.71, 137.74, 134.64,
3
1
31.31, 123.82, 121.19, 43.08, 37.87, 29.62, 28.10, 25.53, 17.08.
2
.89 (m, 1 H), 2.60–2.53 (m, 2 H), 2.48–2.36 (m, 1 H), 2.05–1.93 (m, 4
+
HRMS-DART: m/z [M + H] calcd for C14H16ClN O: 263.09512; found:
2
2
H), 1.68–1.60 (m, 1 H), (t, J = 7.2 Hz, 3 H).
63.09506.
1
3
C NMR (75 MHz, CDCl ):  = 173.55, 162.25, 156.96, 147.33, 134.10,
3
1
2
26.99, 126.66, 126.29, 120.34, 60.53, 41.60, 39.70, 32.16, 28.36,
5.13, 20.27, 14.31.
N-Alkylation of 3H-Quinzolin-4-ones; General Procedure
To a suspension of NaH (95%, 72.5 mg, 3.02 mmol) in DMF (2 mL) and
HRMS-DART: m/z [M + H]+ calcd for C17H21N O : 301.15522; found:
3
1
,2-dimethoxyethane (2 mL) was added a solution of 4-hydroxy-
quinazolin-4(3H)-one (18) (300 mg, 2.01 mmol) in DME at 0 °C. After
5 min, the reaction mixture was treated with LiBr (357 mg, 4.1
mmol) and stirred for 15 min, then 5-bromo-1-pentene (95%, 0.42 ml,
.25 mmol) or tosylate 19 (0.26 mL, 2.26 mmol) was added dropwise.
2
3
01.15512.
1
(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 3-(11-Oxo-6,8,9,11-
tetrahydro-7H-pyrido[2,1-b]quinazolin-6-yl)propanoate (17b)
2
The reaction mixture was stirred at room temperature for 5–6 h and
then quenched with ice water. The resulting mixture was extracted
with ethyl acetate, and the organic layer was separated, washed with
water and brine, dried over Na SO , filtered and concentrated. The
product was purified by flash silica gel column chromatography (hex-
anes/EtOAc, 1:1) to provide pure N-alkylated products.
Yield: 75 mg (65%); yellow oil; dr = 1:1.
1
H NMR (500 MHz, CDCl ):  = 8.25 (d, J = 8.0 Hz, 1 H), 7.70 (t, J = 7.6
3
Hz, 1 H), 7.62 (d, J = 8.1 Hz, 1 H), 7.41 (t, J = 7.5 Hz, 1 H), 4.68 (qd, J =
2
4
1
0.8, 4.4 Hz, 1 H), 4.27 (dq, J = 17.1, 5.6 Hz, 1 H), 3.92 (td, J = 13.9, 6.0
Hz, 1 H), 2.99–2.85 (m, 1 H), 2.56 (t, J = 7.4 Hz, 2 H), 2.46 (dq, J = 13.9,
.5 Hz, 1 H), 2.13 (dq, J = 13.0, 6.4 Hz, 1 H), 2.04–1.92 (m, 4 H), 1.86
ddq, J = 13.5, 6.7, 3.4, 2.5 Hz, 1 H), 1.66 (ddt, J = 13.2, 10.3, 4.6 Hz, 3
6
(
3
-(Pent-4-en-1-yl)quinazolin-4(3H)-one (15)
H), 1.47 (dddt, J = 15.4, 9.9, 6.6, 3.4 Hz, 1 H), 1.36 (ddt, J = 14.7, 6.6, 3.2
Hz, 1 H), 1.04 (dddd, J = 18.5, 14.7, 9.9, 5.4 Hz, 1 H), 0.98–0.91 (m, 1
H), 0.91–0.86 (m, 7 H), 0.75 (t, J = 7.1 Hz, 3 H).
Yield: 405 mg (92%); white solid; mp 70–71 °C.
1
H NMR (300 MHz, CDCl ):  = 8.34–8.27 (m, 1 H), 8.00 (s, 1 H), 7.78–
3
1
3
7
1
.66 (m, 2 H), 7.54–7.45 (m, 1 H), 5.80 (ddtd, J = 16.9, 10.3, 6.6, 0.9 Hz,
H), 5.14–4.99 (m, 2 H), 3.99 (t, J = 7.3 Hz, 2 H), 2.14 (q, J = 7.0 Hz, 2
C NMR (125 MHz, CDCl ):  = 173.14, 162.29, 157.03, 147.44,
3
134.12, 127.08, 126.70, 126.31, 120.40, 74.37, 47.14, 41.62, 41.05,
39.77, 34.36, 32.52, 31.49, 28.44, 26.40, 25.11, 23.56, 22.14, 20.89,
20.33, 16.48.
HRMS-DART: m/z [M + H]+ calcd for C25H35N O : 411.26477; found:
H), 1.90 (quin, J = 7.3 Hz, 2 H).
1
3
C NMR (75 MHz, CDCl ):  = 161.17, 148.21, 146.68, 136.95, 134.25,
3
127.52, 127.34, 126.76, 122.26, 116.10, 46.56, 30.65, 28.23.
2
3
HRMS-DART: m/z [M + H]+ calcd for C13H15N O: 215.11844; found:
411.26551.
2
215.11884.
©
2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

G
Synthesis
J. García-Ramírez, L. D. Miranda
Paper
(
2
8R,9S,10R,13S,14S,17S)-10,13-Dimethyl-3-oxo-
,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopen-
Acknowledgment
We thank R. Patiño, A. Peña, E. Huerta, I. Chávez, H. Ríos, R. Gaviño, B.
Quiroz, Ma. C. García-González, L. Velasco and J. Pérez for technical
support.
ta[a]phenanthren-17-yl 3-(11-Oxo-6,8,9,11-tetrahydro-7H-pyri-
do[2,1-b]quinazolin-6-yl)propanoate (17c)
Yield: 84 mg (55%); yellow oil; dr = 1:1.
1
H NMR (500 MHz, CDCl ):  = 8.24 (d, J = 8.0 Hz, 1 H), 7.69 (t, J = 7.6
3
Hz, 1 H), 7.61 (d, J = 8.2 Hz, 1 H), 7.41 (t, J = 7.5 Hz, 1 H), 5.71 (s, 1 H),
Supporting Information
4.60 (t, J = 8.4 Hz, 1 H), 4.31–4.21 (m, 1 H), 3.96–3.87 (m, 1 H), 2.92
Supporting information for this article is available online at
(
2
1
quin, J = 6.7 Hz, 1 H), 2.58 (t, J = 7.5 Hz, 2 H), 2.46–2.25 (m, 5 H), 2.19–
.09 (m, 2 H), 1.99 (dd, J = 14.5, 8.6 Hz, 4 H), 1.85–1.75 (m, 2 H), 1.68–
.48 (m, 6 H), 1.36 (ddd, J = 25.0, 12.6, 4.8 Hz, 2 H), 1.17 (m, 4 H), 1.04
https://doi.org/10.1055/s-0040-1705975. Su
p
p
orting Inform atio
n
Su
p
p
orting Inform atio
n
(
1
m, 2 H), 0.95–0.89 (m, 1 H), 0.83 (s, 3 H).
References
3
C NMR (125 MHz, CDCl ):  = 199.58, 173.53, 171.07, 162.25,
3
1
5
3
1
56.96, 147.38, 134.11, 127.01, 126.69, 126.30, 124.04, 120.37, 82.60,
3.75, 50.29, 42.61, 41.64, 39.73, 38.68, 36.74, 35.77, 35.46, 34.01,
2.81, 32.29, 31.55, 28.44, 27.61, 25.11, 23.57, 20.60, 20.30, 17.47,
2.20.
(1) (a) Michael, J. P. Nat. Prod. Rep. 2004, 21, 650. (b) Kshirsagar, U.
A. Org. Biomol. Chem. 2015, 13, 9336.
(2) For reviews, see: (a) Han, Y. Y.; Jiang, H.; Wang, R. Z.; Yu, S. Y.
J. Org. Chem. 2016, 81, 7276. (b) Tiwary, B. K.; Pradhan, K.;
Nanda, A. K.; Chakraborty, R. J. Chem. Biol. Ther. 2016, 1, 104.
HRMS-DART: m/z [M + H]+ calcd for C34H43N O : 543.32228; found:
2
4
(
c) Selvam, T. P.; Kumar, P. V. Res. Pharm. 2011, 1, 1.
543.32199.
(
3) (a) Amin, A. H.; Mehta, D. R. Nature 1959, 184, 1317. (b) Mehta,
D. R.; Naravane, J. S.; Desai, R. M. J. Org. Chem. 1963, 28, 445.
3
-(11-Oxo-6,8,9,11-tetrahydro-7H-pyrido[2,1-b]quinazolin-6-
(c) Ghosal, S.; Chauhan, P. B. P. S.; Mehta, R. Phytochemistry
yl)propanenitrile (17d)
1
975, 14, 830.
Yield: 47 mg (66%); yellow oil.
(
4) (a) Liljegren, D. R. Phytochemistry 1968, 7, 1299. (b) Al-Shamma,
A.; Drake, S.; Flynn, D. L.; Mitscher, L. A.; Park, Y. H.; Rao, G. S. R.;
Wu, S. T.-S. J. Nat. Prod. 1981, 44, 745. (c) Johns, S. R.;
Lamberton, J. A. Chem. Commun. 1965, 12, 267a.
1
H NMR (300 MHz, CDCl ):  = 8.27 (dt, J = 8.0, 1.6 Hz, 1 H), 7.73 (ddt,
3
J = 8.4, 7.1, 1.5 Hz, 1 H), 7.68–7.59 (m, 1 H), 7.45 (ddt, J = 8.2, 7.0, 1.4
Hz, 1 H), 4.42 (dtd, J = 13.9, 6.0, 1.5 Hz, 1 H), 3.94–3.78 (m, 1 H), 3.05–
2
.90 (m, 1 H), 2.91–2.69 (m, 2 H), 2.56–2.45 (m, 1 H), 2.20 (dq, J =
(5) Motegi, M.; Nugroho, A. E.; Hirasawa, Y.; Arai, T.; Hadi, A. H. A.;
Morita, H. Tetrahedron Lett. 2012, 53, 1227.
12.9, 6.5 Hz, 1 H), 2.09–1.96 (m, 3 H), 1.69–1.59 (m, 1 H).
1
3
(6) For reviews, see: (a) Rohokale, R. S.; Kshirsagar, U. A. Synthesis
C NMR (75 MHz, CDCl ):  = 161.91, 155.96, 147.07, 134.25, 127.03,
3
2
016, 48, 1253. (b) Khan, I.; Zaib, S.; Batool, S.; Abbas, N.; Ashraf,
1
1
26.77, 126.60, 120.45, 119.86, 41.02, 38.84, 28.70, 25.55, 20.61,
5.77.
Z.; Iqbal, J.; Saeed, A. Bioorg. Med. Chem. 2016, 24, 2361.
7) For selected recent publications, see: (a) Larraufie, M. H.;
Courillon, C.; Ollivier, C.; Lacôte, E.; Malacria, M.; Fensterbank,
L. J. Am. Chem. Soc. 2010, 132, 4381. (b) Larraufie, M. H.;
Malacria, M.; Courillon, C.; Ollivier, C.; Fensterbank, L.; Lacôte,
E. Tetrahedron 2013, 69, 7699. (c) Xu, G.; Tong, C.; Cui, S.; Dai, L.
Org. Biomol. Chem. 2018, 16, 5899. (d) Baguia, H.; Deldaele, C.;
Romero, E.; Michelet, B.; Evano, G. Synthesis 2018, 50, 3022.
8) For a review, see: Ghosh, P.; Ganguly, B.; Das, S. Org. Biomol.
Chem. 2020, 18, 4497.
(
HRMS-DART: m/z [M + H]+ calcd for C15H16N O: 254.12934; found:
2
3
54.13002.
(
±)-Leucomidine C (5)
Yield: 44 mg (68%); yellow amorphous solid.
1
H NMR (300 MHz, CDCl ):  = 8.23 (ddd, J = 8.1, 1.6, 0.7 Hz, 1 H), 7.69
3
(
(
(ddd, J = 8.4, 7.0, 1.6 Hz, 1 H), 7.60 (ddd, J = 8.2, 1.4, 0.7 Hz, 1 H), 7.48–
7
2
0
.37 (m, 1 H), 4.15–3.93 (m, 2 H), 3.53 (s, 3 H), 2.50–2.40 (m, 1 H),
.36–2.21 (m, 2 H), 2.08–1.89 (m, 5 H), 1.76 (dd, J = 13.7, 7.1 Hz, 2 H),
.86 (t, J = 7.4 Hz, 3 H).
9) Molander, G. A.; Colombel, V.; Braz, V. A. Org. Lett. 2011, 13,
1852.
(
10) Bowman, W. R.; Elsegood, M. R. J.; Stein, T.; Weaver, G. W. Org.
1
3
C NMR (75 MHz, CDCl ):  = 174.18, 162.85, 158.80, 147.33, 134.02,
3
Biomol. Chem. 2007, 5, 103.
1
2
27.25, 126.53, 126.27, 119.95, 51.72, 43.81, 43.70, 34.94, 33.28,
9.55, 28.89, 19.10, 8.61.
(
(
11) Mahajan, P. S.; Mhaske, S. B. Org. Lett. 2018, 20, 2092.
12) Huang, H. M.; Adams, R. W.; Procter, D. J. Chem. Commun. 2018,
54, 10160.
HRMS-DART: m/z [M + H]+ calcd for C18H23N O : 315.17087; found:
3
2
3
15.17077.
(13) Menes, M.; Martínez, R.; Cruz, R.; Muchowski, J. M.; Osornio, Y.
M.; Miranda, L. D. J. Org. Chem. 2004, 69, 4001.
(
14) For selected examples, see: (a) Zard, S. Z. Acc. Chem. Res. 2018,
51, 1722. (b) Blechy, A.; Zard, S. Z. Org. Lett. 2009, 11, 2800.
Funding Information
(
c) Huang, Q.; Zard, S. Z. Org. Lett. 2018, 20, 5304. (d) Paleo, E.;
Financial support from Programa de Apoyo a Proyectos de Investi-
gación e Innovación Tecnológica-Dirección General de Asuntos del
Personal Académico, Universidad Nacional Autónoma de México
Osornio, Y. M.; Miranda, L. D. Org. Biomol. Chem. 2011, 9, 361.
(e) Osornio, Y. M.; Miranda, L. D. Rev. Soc. Quím. Méx. 2004, 48,
288.
(
PAPIIT-DGAPA) (Project IN208719) is gratefully acknowledged. JG-R
(15) Quiclet-Sire, B.; Zard, S. Z. Synlett 2016, 27, 680.
(16) López, P.; Díaz, J. E.; Loaiza, A. E.; Miranda, L. D. Tetrahedron
2018, 74, 5494.
thanks the Consejo Nacional de Ciencia y Tecnología (CONACYT) for a
Ph.D. scholarship (No. 577203).
D
i
erci
ó
n
G
eneral
d
e
Asuntos
d
e
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