Direct Synthesis of Pyrrolo[1,2-α]quinoxalines via Iron-Catalyzed Transfer Hydrogenation between 1-(2-Nitrophenyl)pyrroles and Alcohols

Simin Chun, Jiwon Ahn, Ramachandra Reddy Putta, Seok Beom Lee, Dong-Chan Oh,

Article

Direct Synthesis of Pyrrolo[1,2-α]quinoxalines via Iron-Catalyzed

Transfer Hydrogenation between 1‑(2-Nitrophenyl)pyrroles and

Alcohols

and Suckchang Hong*

Cite This: https://dx.doi.org/10.1021/acs.joc.0c02145

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sı Supporting Information

ABSTRACT: Herein, we describe novel iron-catalyzed transfer

hydrogenation between alcohols and 1-(2-nitrophenyl)pyrroles for

the synthesis of pyrrolo[1,2-α]quinoxalines. The tricarbonyl (η -

cyclopentadienone) iron complex catalyzed the oxidation of

alcohols and the reduction of nitroarenes, and the corresponding

aldehydes and aniline were generated in situ. The resulting Pictet−

Spengler-type annulation/oxidation completed the quinoxaline

structure formation. The protocol tolerated various kinds of

functional groups and provided 29 samples of 4-substituted

pyrrolo[1,2-α]quinoxalines. The developed method was also

applied for the synthesis of additional polyheterocycles.

INTRODUCTION

■

The transfer hydrogenation strategy has become an attractive

tool in organic synthesis. Based on this strategy, the borrowing

hydrogen process has provided a convenient method for new

bond formation between nucleophiles and alcohol substrates.

In the borrowing hydrogen process, this bond formation

usually proceeds in the following sequence (Figure 1 top): (i)

the dehydrogenation of alcohol generates a more reactive

carbonyl intermediate, (ii) the more reactive intermediate can

undergo further transformations with a nucleophile to give an

unsaturated intermediate, and (iii) the unsaturated intermedi-

ate will be hydrogenated to produce alkylated products. The

catalyst mediates the hydrogen transfer from the alcohol to the

unsaturated bond during the process. According to this

strategy, bench-stable and inexpensive alcohol can be applied

as an alkylating reagent, and only water is liberated as a

stoichiometric byproduct during the intermediate reaction.

Thus, the borrowing hydrogen reaction is an atom-eﬃcient

and environmentally benign method. Many kinds of transition

metals have been employed as catalysts in C−C or C−N bond

formations by the borrowing hydrogen strategy. In addition to

Figure 1. New bond formation through transfer hydrogenation and

the representative iron catalyst.

1c,2

commonly used precious metal catalysts,

considerable

progress has also been made recently with base metal

catalysts, such as Fe, Co, Mn, Ni, and Cu. Among

those, iron is the most abundant transition metal with low

price and toxicity; thus, it has received signiﬁcant attention as a

catalyst in transfer hydrogenation.

Received: September 4, 2020

The representative catalyst, tricarbonyl (η -cyclopentadie-

none) iron complex, was originally described by Kno

lker in

999. Several pioneering studies by Casey and Guan revealed

XXXX American Chemical Society

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Article

its catalytic activity for hydrogen transfer from alcohol to

carbonyl compound. Subsequently, Feringa and Barta

Scheme 1. Synthesis of Pyrrolo[1,2-α]quinoxaline from 1-

(2-Nitrophenyl)pyrrole

discovered that this iron complex could mediate the transfer

hydrogenation from alcohol to imine during the reductive

10a

amination process, and it has been widely applied in C−N

bond formation using alcohol through the borrowing hydrogen

strategy. Although C−N bond formation was successfully

achieved using Knolker’s complex, previous borrowing hydro-

gen studies have applied nucleophilic amines directly. We

envisioned the feasibility of nitroarene as a pronucleophile to

form C−N bonds with alcohol based on the transfer

hydrogenation mechanism. In our strategy, nucleophilic

amine and electrophilic aldehyde can be generated in situ

from nitroarene and alcohol, respectively, through transfer

hydrogenation processes. Followed by the condensation of

these two intermediates, a new C−N bond was constructed

(Figure 1 bottom). To the best of our knowledge, this iron

complex has not been explored for the reduction of nitro

groups via the transfer hydrogenation reaction, and no study

on C−N bond formation by directly employing nitroarene has

been reported.

Pyrrolo[1,2-α]quinoxalines are important components

found in many biologically active molecules. In addition to

their various biological activities, their ﬂuorescence and

photophysical properties have generated interest in the

synthesis of biomarkers, dyes, and materials. Therefore,

much attention has been devoted to the synthesis of

pyrrolo[1,2-α]quinoxaline derivatives until now. The most

common method is the Pictet−Spengler-type condensation of

aldehydes with 1-(2-aminophenyl)pyrroles which is usually

obtained by the reduction of 1-(2-nitrophenyl)pyrroles.

Table 1. Optimization of the Reaction Conditions

Although the one-pot synthesis of pyrrolo[1,2-α]-

quinoxalines from 1-(2-nitrophenyl)pyrroles provides a short-

cut synthetic route, only a few examples have been reported

(Scheme 1). In 2012, iron-mediated reduction of nitroarene

and alcohol oxidation followed by cyclization to pyrrolo[1,2-

a]quinoxaline was reported by Pereira. Sanz’s group

developed a molybdenum-catalyzed redox reaction between

nitroarenes and 1,2-diol substrates. Recently, an activated

carbon/water catalytic system between 1-(2-nitrophenyl)-

pyrroles and arylamines was also reported by Wang.

entry

solvent

T (°C) time (h) 3aa (%)

3aa′ (%)

31 (24)

gas

CPME

toluene

xylene

CPME

140

150

160

air

Although these one-pot approaches provided a shortcut

synthesis of pyrrolo[1,2-α]quinoxaline and employed bench-

stable alcohols or amines, they still suﬀer from several

drawbacks, such as excess amounts of metal and alcohol,

strong acidic conditions, limitation of substrate scope, and the

generation of additional stoichiometric byproducts. Consider-

ing the limitations of the previous procedures, a simpler,

milder, aﬀordable, and environmentally friendly system for the

synthesis of pyrrolo[1,2-a]quinoxalines is still desirable. As part

of our process for developing a synthetic method for the N-

heterocycle, we examined the direct pyrrolo[1,2-α]quinoxaline

synthesis between a simple alcohol and 1-(2-nitrophenyl)-

93 (90)

66 (68)

(96)

Reaction condition: 1a (0.3 mmol), 2a (0.9 mmol), Fe I (6 mol %),

TMAO (12 mol %), and molecular sieve (50 mg) in solvent (0.3 mL).

The reaction vessel was recharged with gas and sealed. NMR yield

using dimethyl sulfone as the internal standard. Isolated yield in

parentheses. 2a (0.6 mmol). Without a molecular sieve. Without

Fe I and TMAO. 1 mmol scale reaction of 1a and Fe I (15 mol %)

pyrrole using Kno

lker’s complex (Scheme 1 bottom).

RESULTS AND DISCUSSION

■

In the beginning, we selected commercially or readily available

-(2-nitrophenyl) pyrrole (1a) and benzyl alcohol (2a) as

model substrates for testing our initial hypothesis. A standard

Knolker complex (Fe I) and trimethylamine N-oxide

TMAO), which was used to activate Fe I and liberate a

vacant site in situ, were applied in cyclopentyl methyl ether

CPME) at 140 °C under Ar for 40 h. As shown in Table 1,

and TMAO (30 mol %) were used.

only trace amounts of the desired product (3aa) were obtained

in the ﬁrst trial (5%, entry 1). However, this result showed that

it was possible to reduce the nitro group by transfer

hydrogenation using the iron complex Fe I. Next, the reaction

(

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temperature was increased to achieve a higher conversion

Table 2. Scope of Alcohols

(

entries 2−3). Even when 1a was consumed completely at 160

C, the desired product 3aa was formed along with an

unoxidized product 3aa′. To improve selectivity for 3aa, the

reaction vessel was charged with air and O gas (entries 4−5).

We hypothesized that O may help the ﬁnal oxidation from

3aa′ to 3aa, which was not favored under Ar. The reaction

proceeded quickly and reached full conversion within 24 h

with O₂gas, and quinoxaline product 3aa was obtained

selectively in high yield (90% isolated yield, entry 5). To

examine the solvent eﬀect, we employed diﬀerent types of

solvents. However, low selectivity between 3aa and 3aa′ was

observed in toluene, and low conversion was observed in

xylene (entries 6−7). At this time, we detected that a small

amount of 3aa′ was converted to 3aa in silica gel during

column chromatography. Additionally, we reduced the amount

of alcohol 2a in the reaction; however, lower conversion was

observed, and nitroarene 1a remained in the mixture (entry 8).

We speculate that at least 3 equivalents of alcohol are required

to reduce 1 equivalent of nitroarene. The reaction without the

molecular sieve was slow and not completed in 24 h, indicating

that the reaction was retarded by water which is generated in

situ (entry 9). To demonstrate the crucial role of the iron

complex in the transfer hydrogenation process, a control

experiment was also performed in the absence of Fe I (entry

0). As we expected, no products were formed and most of 1a

and 2a were remained. Various types of iron complexes have

also been explored to estimate their activity. Among the

explored iron complexes, Fe I showed the best eﬃciency in the

reaction system, and the results of each complex are included

in the Supporting Information. These results also suggested

that TMAO is essential to activate Fe I. We carried out 1

mmol scale reaction to demonstrate the practical utility of the

method, and 3aa was obtained in high yield (96% isolated

yield, entry 11).

Reaction condition: 1a (0.3 mmol), 2 (0.9 mmol), Fe I (6 mol %),

TMAO (12 mol %), molecular sieve (50 mg), and CPME (0.3 mL) at

60 °C for 24 h under O in sealed tubes. Isolated yield. Reaction

After optimization of the reaction conditions, a wide range

of alcohol 2 was employed for annulation with 1a to explore

the reaction scope (Table 2). Benzylic alcohols containing

various substituents reacted with 1a to the corresponding

quinoxaline products 3ab−3ap. In general, benzylic alcohols

containing electron-donating groups, such as methyl, t-butyl,

and methoxy groups, were less reactive than those with

electron-withdrawing groups. All of the methoxy benzyl

alcohols resulted in low yields even with longer reaction

times (3ad, 3ag, and 3aj). In the case of more electron-

enriched 4-(dimethylamino) benzyl alcohol, no desired

product was obtained. These electronic eﬀects of benzyl

alcohol suggest that the annulation process shows more

inﬂuence on the product formation than the transfer

hydrogenation process. Although electron-rich benzylic alco-

hols can act as strong reductants in the transfer hydrogenation

process, they can act as less-active electrophiles in the

annulation process. The steric eﬀect of substituents did not

directly inﬂuence the formation of the product (3ab−3aj). The

electron density of benzylic carbon according to the position of

the substituent showed more inﬂuence than the steric eﬀect.

The electron-donating methoxy group on ortho- and para-

position gave the desired products 3ad and 3aj in poor yields.

In contrast with the methoxy group, benzyl alcohols containing

ortho- and para-ﬂuorine aﬀorded the annulated product in

higher yield than that of meta-ﬂuoro benzyl alcohol (3ac, 3ai vs

time: 40 h.

α]quinoxalines (3aq−3at). For further expansion of the

alcohol scope, allylic, propargylic, and aliphatic alcohols were

also investigated. Cinnamyl alcohol reacted with 1a, and the

desired product 3au was obtained in good yield. However, in

the case of geraniol, partial hydrogenation of oleﬁn occurred,

and the messy reaction mixture was observed in TLC.

Comparing reactions with cinnamyl alcohol and geraniol,

highly conjugated oleﬁn of 3au was inactive in hydrogenation,

but it could be assumed that nonconjugated oleﬁn in geraniol

can be aﬀected by hydrogenation under the reaction condition.

In addition, 3-phenylpropargyl alcohol and aliphatic alcohols

could participate in the reaction, even if the products 3av−3ax

were obtained in low yields.

Next, we employed various types of 2-pyrrole nitroarenes for

further extension of the substrate scope (Table 3). In the case

of 1-(2-nitrophenyl) pyrroles, electron-withdrawing substitu-

ents on benzene (chloro and triﬂuoromethyl groups, 3da−

3ea/3ha) generally aﬀorded the corresponding products in

higher yields than electron-donating substituents (methyl and

methoxy groups, 3ba−3ca/3fa−3ga). Interestingly, the posi-

tion of the substituent played a crucial role in the reaction,

regardless of the electron density. The 4-substituted 1-(2-

nitrophenyl) pyrroles were more reactive than the 5- or 6-

substituted analogues (3ba−3ea vs 3fa−3ia). Additionally, 3-

nitro-2-(1H-pyrrol-1-yl)pyridine could also be applied in the

3af). Various heteroaromatic groups and naphthalene could

also be employed at the 4-position of the pyrrolo[1,2-

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Table 3. Scope of 2-Pyrrole Nitroarenes

Further control experiments were performed to evaluate the

mechanism of hydrogen transfer (Scheme 3). As shown in

Scheme 3. Mechanistic Studies

Reaction condition: 1 (0.3 mmol), 2a (0.9 mmol), Fe I (6 mol %),

TMAO (12 mol %), molecular sieve (50 mg), and CPME (0.3 mL) at

60 °C for 24 h under O in sealed tubes. Isolated yield. The

reaction proceeded at 170 °C for 40 h.

Scheme 3a, when 2-(1H-pyrrol-1-yl)aniline 1a′ was directly

treated with benzyl alcohol 2a under the standard reaction

conditions, only negligible product formation occurred in the

absence of the nitro functionality. Similarly, the nitro reduction

did not occur in the absence of alcohol when benzaldehyde 2a′

was used instead of benzyl alcohol 2a (Scheme 3b). These

results indicated that both the hydrogen acceptor nitro group

and the hydrogen donor alcohol are required for the balance of

hydrogen transfer. When prereduced 1a′ was reacted with

preoxidized 2a′ under the standard conditions, 3aa was

obtained regardless of the presence of Fe I. Therefore, the

iron complex was determined to be a hydrogen mediator

between the nitro and alcohol groups but was not involved in

the ﬁnal oxidation of intermediate 3aa′ to form 3aa. According

reaction and yielded annulated product 3ja. In addition to the

-position of pyrrole, we hypothesized that the 3-position of

pyrrole can also participate in the annulation. Accordingly, 2-

2-nitrophenyl)-pyrrole substrates were also subjected to the

(

reaction conditions. Although longer reaction times and higher

temperatures were required, pyrrolo[3,2-c]quinoline products

ka and 3la were obtained in moderate yields.

We also attempted the annulation using a secondary alcohol

to synthesize a dihydropyrrolo[1,2-α]quinoxaline structure

Scheme 2). Although the desired product 5 could not be

(

Scheme 2. Trial to Synthesize Dihydropyrrolo[1,2-

α]quinoxaline Using Secondary Alcohol 4

to the results in Table 1, O gas could accelerate this ﬁnal

oxidation process.

Based on the abovementioned results, a plausible mecha-

nism of hydrogen transfer and the cyclization process are

depicted in Scheme 4. Iron-mediated oxidation of alcohol 2a

leads to aldehydes 2a′ and [Fe]−H , which reduce nitro-

benzene 1a to aniline 1a′. For the balance of hydrogen, [Fe]

transfers six hydrogens from 3 equivalent of alcohols to one

nitro group. After the hydrogen transfer process, condensation

between aniline 1a′ and aldehyde 2a′ forms imine intermediate

, followed by a nucleophilic attack of pyrrole that produces

cyclized intermediate 3aa′. The imine intermediate 6 was

directly observed in the NMR spectrum of the crude reaction

mixture (see details in the Supporting Information). The ﬁnal

oxidative aromatization occurs with the assistance of O gas.

obtained, both 2-(1H-pyrrol-1-yl)aniline 1a′ and ketone 4′

were observed in the reaction mixture. This result conﬁrmed

our hypothesis that nitroarene is reduced as a hydrogen

acceptor and that alcohol is oxidized as a hydrogen donor in

the transfer hydrogenation mechanism. Notably, almost 3

equivalents of alcohol were consumed to reduce one nitro

functionality.

Thus, a total of 4 equiv of H O are generated as a byproduct,

including the reduction of the nitro group and the

condensation step. In addition, 3 equivalents of alcohol are

required as a hydrogen donor to reduce the nitro functionality.

Although the 16-electron iron complex [Fe] has been

proposed as an active species in the mechanism, the possibility

that another active species can be generated under O gas

NMR yield using dimethyl sulfone as the internal standard.

could not be ruled out.

J. Org. Chem. XXXX, XXX, XXX−XXX

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Article

synthesized through known procedures and characterization data

Scheme 4. Proposed Mechanism

13f

were consistent with the literature.

Synthesis of 2-(2-nitrophenyl)-1H-pyrrole (1k). 1-Bromo-2-

nitrobenzene (2 mmol, 404 mg), cesium carbonate (4 mmol, 1.3 g),

and pyrrole (4 mmol, 0.28 mL) were added to anhydrous acetonitrile

(20 mL) and the mixture was reﬂuxed at 92 °C in an oil bath. After 12

h, pyrrole (4 mmol, 0.28 mL) was added to the reaction mixture.

After 1 day, the reaction mixture was cooled to room temperature,

diluted with water (25 mL), and extracted with EtOAc (15 mL) three

times. The organic layer was dried over anhydrous MgSO₄and

concentrated. After puriﬁcation by ﬂash column chromatography

(

hexane/EtOAc = 50:1 to 10:1), 1k was obtained as a red solid (189

mg, 50% yield); mp 44−46 °C; H NMR (400 MHz, CDCl ): δ 8.91

(

s, 1H), 7.72 (dd, J = 8.6, 1.2 Hz, 2H), 7.52−7.61 (m, 4H), 7.33−

.37 (m, 2H), 6.91−6.93 (m, 2H), 6.48−6.50 (m, 2H), 6.31−6.33

(m, 2H); C{ H} NMR (100 MHz, CDCl ): δ 148.1, 132.4, 130.8,

27.2, 127.0, 126.3, 124.5, 120.6, 111.0, 110.1; HRMS (FAB) m/z:

calcd for C H N O [M] , 188.0586; found, 188.0588.

Synthesis of 1-Methyl-2-(2-nitrophenyl)-1H-pyrrole (1l).

1-Iodo-2-nitrobenzene (20 mmol), lithium hydroxide (80 mmol, 1.92

g), and 1-methyl pyrrole (60 mmol, 5.3 mL) were added to anhydrous

DMSO (11 mL) and the mixture was reﬂuxed at 100 °C in an oil

bath. After 2 h, 1-methyl pyrrole was added (60 mmol, 5.3 mL) to the

reaction mixture and stirred for overnight at 110 °C. The reaction

mixture was cooled to room temperature, diluted with water (100

mL), and extracted with EtOAc (30 mL) three times. The organic

layer was dried over anhydrous MgSO₄and concentrated. After

puriﬁcation by ﬂash column chromatography (hexane/EtOAc = 50:1

CONCLUSIONS

■

In conclusion, we described the iron-catalyzed synthesis of

pyrrolo[1,2-α]quinoxalines by the economical transfer hydro-

genative coupling of 1-(2-nitrophenyl)pyrroles and alcohols.

The developed transfer hydrogenation process allows for

reduction of nitroarene and oxidation of alcohol in the

to 10:1), 1l was obtained as a red solid (3.64 g, 90% yield); mp 58−

60 °C; H NMR (400 MHz, CDCl ): δ 7.94 (d, J = 7.9 Hz, 1H), 7.62

(dd, J = 7.3, 6.1 Hz, 1H), 7.46−7.53 (m, 2H), 6.76 (t, J = 2.4 Hz,

presence of the tricarbonyl (η -cyclopentadienone) iron

1H), 6.21 (t, J = 3.1 Hz, 1H), 6.15 (q, J = 1.8 Hz, 1H), 3.45 (s, 3H);

C{1H} NMR (100 MHz, CDCl ): δ 150.0, 133.5, 132.4, 128.8,

complex. It is the ﬁrst discovery that this iron catalyst has

potential to reduce nitro functionality via hydrogen transfer.

Iron is an earth-abundant and low-toxicity metal, and only

water is liberated as the reaction byproduct. Additionally,

alcohol is readily available and used in the reaction both as a

reductant and coupling reagent; thus, any external redox

reagent is not required. Therefore, this methodology provides

an ecofriendly alternative for the synthesis of pyrrolo[1,2-

α]quinoxalines. Further expansion of the iron-catalyzed

transfer hydrogenation strategy to access other types of N-

heterocycles is currently investigated by our research group.

28.4, 128.0, 124.2, 123.8, 109.7, 108.2, 34.4; HRMS (FAB) m/z:

calcd for C H N O [M + H] , 203.0821; found, 203.0816.

11 11

Synthesis of Pyrrolo[1,2-α]quinoxalines. Optimized Condi-

tion. To a mixture of 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

56.4 mg), iron catalyst (0.018 mmol), trimethylamine N-oxide (0.036

mmol, 2.7 mg), and 50 mg molecular sieve (4 Å, powder), benzyl

alcohol 2a (0.9 mmol, 93 μL) and solvent (0.3 mL) were added in

O -charged borosilicate glass tubes. The reaction tube was sealed and

stirred at 160 °C in a heating block. After stirring for 24 h, the

reaction mixture was cooled to room temperature, diluted with DCM

(1 mL), and ﬁltered. Then, the reaction mixture was concentrated in

vacuo. The crude reaction mixture was analyzed using dimethyl

sulfone (0.03 mmol) as an internal standard. In the case of entry 5 in

Table 1, the residue was puriﬁed by ﬂash column chromatography on

silica gel, using hexane/EtOAc (50:1) as the eluent. After puriﬁcation,

EXPERIMENTAL SECTION

■

General Information. All commercially available reagents and

solvents (purchased from Sigma-Aldrich, TCI, Alfa-Aesar, and Acros)

were used without further puriﬁcation unless otherwise noted. All

reactions were carried out in an oven-dried round-bottom ﬂask or

sealed tube purchased from Fishcer Scientiﬁc (Fisherbrand disposable

borosilicate glass tubes with threaded end and Qorpak Green

Thermoset Cap with F217 and PTFE Liner). Reactions were

monitored by thin layer chromatography on a silica gel 60 F254

plate (Merck, Darmstadt, Germany) using UV illumination at 254 and

aa was obtained as a pale-yellow solid (66 mg, 90%). In the case of

entry 6 in Table 1, 3aa (50 mg, 68%) and 3aa′ (18 mg, 24%) were

obtained.

For 1 mmol Scale Reaction (Entry 11 in Table 1). To a mixture of

-(2-nitrophenyl)-1H-pyrrole 1a (1.0 mmol, 188.2 mg), Fe I (0.15

mmol), trimethylamine N-oxide (0.3 mmol, 22.5 mg), and 300 mg

molecular sieve (4 Å, powder), benzyl alcohol 2a (3.0 mmol, 309 μL)

and CPME (1 mL) were added in an O -charged Ace pressure tube.

65 nm (VL-4.LC, Vilber Lourmat, Eberhardzell, Germany). Column

chromatography was performed on silica gel (230−400 mesh;

Zeochem, Lake Zurich, Switzerland), using hexane and EtOAc as

The reaction tube was sealed and stirred at 160 °C in an oil bath.

After stirring for 40 h, the reaction mixture was cooled to room

temperature, diluted with DCM (3 mL), and ﬁltered. Then, the

reaction mixture was concentrated in vacuo. The residue was puriﬁed

by ﬂash column chromatography on silica gel, using hexane/EtOAc

eluents. Nuclear magnetic resonance ( H NMR, C NMR, and

NMR) spectra were measured on a JEOL JNM-ECZ400s [400 MHz

(

H), 100 MHz ( C), and 376 MHz ( F)] spectrometer. The

(

50:1) as the eluent. After puriﬁcation, 3aa was obtained as a pale-

yellow solid (181 mg, 96%).

-Phenylpyrrolo[1,2-a]quinoxaline (3aa). Pale-yellow solid; mp

chemical shifts are given in parts per million (ppm) on the delta (δ)

scale. The solvent peak was used as a reference value, for H NMR:

CDCl = 7.26 ppm; for C NMR: CDCl = 77.16 ppm. Coupling

5−86 °C; H NMR (400 MHz, CDCl ): δ 8.05 (dd, J = 8.0, 1.6 Hz,

constants (J) are expressed in hertz (Hz). All high-resolution mass

spectra (HR-MS) were acquired using a fast atom bombardment

FAB) ionization method on a JMS-700 MStation mass spectrometer

JEOL, Tokyo, Japan). Melting points were measured on a Buchi B-

40 melting point apparatus. Starting compounds 1a−1j were

1H), 8.01 (dd, J = 7.8, 1.8 Hz, 3H), 7.88 (d, J = 8.3 Hz, 1H), 7.44−

(

7.58 (m, 5H), 7.00 (t, J = 2.1 Hz, 1H), 6.90 (t, J = 3.4 Hz, 1H);

C{ H} NMR (100 MHz, CDCl ): δ 154.6, 138.6, 136.4, 130.4,

129.9, 128.7, 127.6, 127.3, 125.5, 125.4, 114.7, 114.1, 113.8, 108.8;

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HRMS (FAB) m/z: calcd for C H N [M + H] , 245.1079; found,

starting material. After column chromatography (hexane/EtOAc =

45.1075.

50:1), 3ae was obtained as a pale-yellow solid (30 mg, 38% yield for

-Phenyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (3aa′). Colorless

24 h; 62 mg, 80% yield for 40 h); mp 86−87 °C; H NMR (400

oil; H NMR (400 MHz, CDCl ): δ 7.48 (dd, J = 8.0, 1.6 Hz, 2H),

MHz, CDCl ): δ 8.06 (dd, J = 7.8, 1.8 Hz, 1H), 7.98 (q, J = 1.4 Hz,

.34−7.41 (m, 4H), 7.20 (t, J = 2.1 Hz, 1H), 6.98 (td, J = 7.6, 1.4 Hz,

H), 6.86 (td, J = 7.7, 1.2 Hz, 1H), 6.76 (dd, J = 7.8, 1.4 Hz, 1H),

.25 (t, J = 3.2 Hz, 1H), 5.58 (t, J = 1.6 Hz, 1H), 5.55 (s, 1H), 4.17 (s,

1H), 7.87 (dd, J = 7.8, 1.4 Hz, 1H), 7.79−7.82 (m, 2H), 7.41−7.53

(m, 3H), 7.34 (d, J = 7.3 Hz, 1H), 7.00 (dd, J = 3.9, 1.1 Hz, 1H), 6.89

(q, J = 2.3 Hz, 1H), 2.48 (s, 3H); C{ H} NMR (100 MHz, CDCl ):

H); ¹³C{1H} NMR (100 MHz, CDCl ): δ 141.5, 136.3, 130.1,

δ 154.7, 138.5, 136.4, 130.7, 130.3, 129.3, 128.5, 127.5, 127.3, 125.8,

125.6, 125.4, 114.7, 114.0, 113.7, 108.9, 21.7; HRMS (FAB) m/z:

28.8, 128.5, 128.4, 128.0, 125.6, 124.8, 119.5, 115.5, 114.9, 114.5,

10.3, 106.0, 56.3; HRMS (FAB) m/z: calcd for C H N [M] ,

calcd for C H N [M + H] , 259.1235; found, 259.1241.

18 15

46.1157; found, 246.1161.

General Procedure of Pyrrolo[1,2-α]quinoxalines. To a

mixture of 2-pyrrole nitroarene 1 (0.3 mmol), Fe I (0.018 mmol,

.5 mg), trimethylamine N-oxide (0.036 mmol, 2.7 mg), and 50 mg

4-(3-Fluorophenyl)pyrrolo[1,2-a]quinoxaline (3af). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 3-ﬂuorobenzyl alcohol 2f (0.9 mmol, 102 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

molecular sieve (4 Å, powder), alcohol 2 (0.9 mmol) and CPME (0.3

mL) were added in O -charged borosilicate glass tubes. The reaction

0:1), 3af was obtained as a white solid (50 mg, 63% yield for 24 h;

75 mg, 95% yield for 40 h); mp 103−105 °C; H NMR (400 MHz,

CDCl ): δ 8.04 (dd, J = 8.0, 1.6 Hz, 1H), 8.01 (q, J = 1.3 Hz, 1H),

tube was sealed and stirred at 160 °C in a heating block. After stirring

for 24 h, the reaction mixture was cooled to room temperature,

diluted with DCM (1 mL), and ﬁltered. Then, the reaction mixture

was concentrated in vacuo. The residue was puriﬁed by ﬂash column

chromatography on silica gel, using hexane/EtOAc (50:1) as the

eluent.

(

.88 (dd, J = 8.2, 1.3 Hz, 1H), 7.81 (dt, J = 7.7, 1.2 Hz, 1H), 7.73

ddd, J = 9.8, 2.4, 1.6 Hz, 1H), 7.45−7.56 (m, 3H), 7.23 (tdd, J = 8.4,

.6, 0.9 Hz, 1H), 7.00 (dd, J = 4.0, 1.3 Hz, 1H), 6.91 (dd, J = 4.1, 2.8

Hz, 1H); C{ H} NMR (100 MHz, CDCl ): δ 164.2 (d, J

C−F

45.3 Hz), 161.7 (d, J

= 245.3 Hz), 153.0 (d, J

= 2.9 Hz),

C−F

-(o-Tolyl)pyrrolo[1,2-a]quinoxaline (3ab). Following the general

procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg) and

-methylbenzyl alcohol 2b (0.9 mmol, 110 mg) were used as the

starting material. After column chromatography (hexane/EtOAc =

53.0 (d, J

= 2.9 Hz), 140.7 (d, J

.7 Hz), 136.1, 130.4, 130.3 (d, J

= 7.7 Hz), 140.6 (d, J

= 8.6 Hz), 130.2 (d, J

C−F

= 8.6

C−F

Hz), 127.9, 127.2, 125.5, 125.1, 124.4 (d, J

= 2.9 Hz), 124.4 (d,

= 21 Hz),

= 23 Hz), 114.9, 114.2,

C−F

J_C₋_F= 2.9 Hz), 116.9 (d, J

= 21 Hz), 116.7 (d, J

C−F

0:1), 3ab was obtained as a pale-yellow solid (34 mg, 44% yield for

4 h; 62 mg, 80% yield for 40 h); mp 105−106 °C; H NMR (400

15.9 (d, J

= 23 Hz), 115.7 (d, J

C−F

13.7, 108.6; F NMR (376 MHz, CDCl ): δ −112.47 ppm; HRMS

MHz, CDCl ): δ 8.04 (d, J = 8.0 Hz, 1H), 7.99 (s, 1H), 7.91 (d, J =

(FAB) m/z: calcd for C H FN [M + H] , 263.0985; found,

17 12 2

.4 Hz, 1H), 7.46−7.57 (m, 3H), 7.30−7.40 (m, 3H), 6.84−6.86 (m,

63.0983.

13 1

H), 6.58 (d, J = 2.8 Hz, 1H), 2.34 (s, 3H); C{ H} NMR (100

-(3-Methoxyphenyl)pyrrolo[1,2-a]quinoxaline (3ag). Following

MHz, CDCl ): δ 155.8, 137.6, 136.6, 136.2, 130.9, 130.3, 129.1,

the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

56.4 mg) and 3-methoxylbenzyl alcohol 2g (0.9 mmol, 112 μL) were

used as the starting material. After column chromatography (hexane/

29.0, 127.6, 127.4, 126.4, 125.8, 125.4, 114.6, 114.0, 113.8, 108.8,

9.9; HRMS (FAB) m/z: calcd for C H N [M + H] , 259.1235;

found, 259.1239.

EtOAc = 10:1), 3ag was obtained as a pale-yellow solid (51 mg, 62%

-(2-Fluorophenyl)pyrrolo[1,2-a]quinoxaline (3ac). Following the

yield for 40 h); mp 129−131 °C; H NMR (400 MHz, CDCl ): δ

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 2-ﬂuorobenzyl alcohol 2c (0.9 mmol, 97 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

.05 (dd, J = 7.8, 1.4 Hz, 1H), 7.99 (t, J = 1.4 Hz, 1H), 7.87 (d, J =

.3 Hz, 1H), 7.44−7.60 (m, 5H), 7.08 (dd, J = 7.8, 2.3 Hz, 1H), 7.02

q, J = 1.7 Hz, 1H), 6.89 (t, J = 3.2 Hz, 1H), 3.91 (s, 3H); C{ H}

(

0:1), 3ac was obtained as a white solid (65 mg, 83% yield for 24 h;

2 mg, 91% yield for 40 h); mp 124−127 °C; H NMR (400 MHz,

NMR (100 MHz, CDCl

): δ 159.9, 154.3, 139.9, 136.3, 130.4, 129.7,

27.6, 127.3, 125.5, 125.4, 121.2, 116.0, 114.7, 114.1, 113.8, 113.7,

CDCl ): δ 8.05 (dd, J = 8.0, 1.4 Hz, 1H), 7.98 (q, J = 1.3 Hz, 1H),

08.9, 55.5; HRMS (FAB) m/z: calcd for C H N O [M + H] ,

.89 (dd, J = 8.2, 1.3 Hz, 1H), 7.74 (td, J = 7.4, 1.6 Hz, 1H), 7.45−

75.1184; found, 275.1183.

4-(p-Tolyl)pyrrolo[1,2-a]quinoxaline (3ah). Following the general

.56 (m, 3H), 7.31−7.34 (m, 1H), 7.24−7.28 (m, 1H), 6.88 (dd, J =

.9, 2.8 Hz, 1H), 6.75−6.76 (m, 1H); C{ H} NMR (100 MHz,

procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg) and

4-methylbenzyl alcohol 2h (0.9 mmol, 110 mg) were used as the

starting material. After column chromatography (hexane/EtOAc =

50:1), 3ah was obtained as a pale-yellow solid (51 mg, 66% yield for

CDCl ): δ 161.5 (d, J

= 249.2 Hz), 159.0 (d, J

= 249.2 Hz),

C−F

150.6, 136.1, 131.3 (d, J

= 11.5 Hz), 131.2, 131.2 (d, J

= 11.5

C−F

Hz), 130.4, 128.0, 127.4, 126.3 (d, J

= 15.4 Hz), 126.2 (d, J

= 3.8 Hz), 124.5 (d, J

= 21.1 Hz), 114.7,

= 33.6 Hz), 108.7 (d, J

C−F

5.4 Hz), 125.9, 125.4, 124.5 (d, J

C−F

24 h; 56 mg, 72% yield for 40 h); mp 80−82 °C; H NMR (400

.8 Hz), 116.5 (d, J

14.1 (d, J

= 21.1 Hz), 116.3 (d, J

C−F

MHz, CDCl ): δ 8.04 (dd, J = 8.0, 1.2 Hz, 1H), 7.99 (q, J = 1.2 Hz,

= 33.6 Hz), 113.8 (d, J

C−F

1H), 7.87−7.92 (m, 3H), 7.48 (tdd, J = 15.3, 7.4, 1.2 Hz, 2H), 7.35

3.8 Hz), 108.6 (d, J

= 3.8 Hz); F NMR (376 MHz, CDCl ): δ

C−F 3

(d, J = 8.0 Hz, 2H), 7.00 (q, J = 1.6 Hz, 1H), 6.89 (q, J = 2.2 Hz, 1H),

−

112.99 ppm; HRMS (FAB) m/z: calcd for C H FN [M + H] ,

17 12 2

.46 (s, 3H); C{ H} NMR (100 MHz, CDCl ): δ 154.5, 140.0,

63.0985; found, 263.0992.

-(2-Methoxyphenyl)pyrrolo[1,2-a]quinoxaline (3ad). Following

the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

6.4 mg) and 2-methoxylbenzyl alcohol 2d (0.9 mmol, 124 mg) were

36.4, 135.8, 130.3, 129.4, 128.7, 127.4, 127.3, 125.5, 125.4, 114.6,

14.0, 113.7, 108.8, 21.6; HRMS (FAB) m/z: calcd for C H N [M

H] , 259.1235; found, 259.1238.

18 15

-(4-Fluorophenyl)pyrrolo[1,2-a]quinoxaline (3ai). Following the

used as the starting material. After column chromatography (hexane/

EtOAc = 10:1), 3ad was obtained as a yellow liquid (35 mg, 42%

yield for 40 h); H NMR (400 MHz, CDCl ): δ 8.06 (dd, J = 8.0, 1.8

Hz, 1H), 7.93 (q, J = 1.4 Hz, 1H), 7.86 (dd, J = 8.3, 1.5 Hz, 1H), 7.54

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 4-ﬂuorobenzyl alcohol 2i (0.9 mmol, 98 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

(

dd, J = 7.4, 1.8 Hz, 1H), 7.42−7.52 (m, 3H), 7.05−7.13 (m, 2H),

50:1), 3ai was obtained as a white solid (72 mg, 91% yield); mp 155−

.82 (q, J = 2.2 Hz, 1H), 6.60 (q, J = 1.8 Hz, 1H), 3.77 (s, 3H);

157 °C; H NMR (400 MHz, CDCl

): δ 7.99−8.04 (m, 4H), 7.89

C{ H} NMR (100 MHz, CDCl ): δ 157.4, 153.6, 136.3, 130.6,

(dd, J = 8.0, 1.2 Hz, 1H), 7.51−7.55 (m, 1H), 7.45−7.49 (m, 1H),

.21−7.26 (m, 2H), 6.97 (q, J = 1.6 Hz, 1H), 6.91 (t, J = 3.4 Hz, 1H);

30.3, 127.5, 126.6, 125.2, 120.8, 114.1, 113.8, 113.7, 111.6, 108.6,

5.7; HRMS (FAB) m/z: calcd for C H N O [M + H] , 275.1184;

C{1H} NMR (100 MHz, CDCl

): δ 165.2 (d, JC−F = 247.3 Hz),

found, 275.1183.

162.7 (d, JC−F = 247.3 Hz), 153.4, 136.3, 134.7 (d, JC−F = 3.8 Hz),

-(m-Tolyl)pyrrolo[1,2-a]quinoxaline (3ae). Following the general

procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg) and

-methylbenzyl alcohol 2e (0.9 mmol, 110 mg) were used as the

134.7 (d, J

= 3.8 Hz), 130.7 (d, J

= 6.6 Hz), 130.7 (d, J

C−F

6.6 Hz), 130.3, 127.7, 127.2, 125.5, 125.3, 115.9 (d, J

= 22.0 Hz),

C−F

115.6 (d, J

= 22.0 Hz), 114.9, 114.2, 113.8, 108.7; F NMR (376

C−F

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

MHz, CDCl ): δ −110.98 ppm; HRMS (FAB) m/z: calcd for

(400 MHz, CDCl ): δ 8.13 (d, J = 8.0 Hz, 2H), 8.02−8.06 (m, 2H),

C H FN [M + H] , 263.0985; found, 263.0986.

7.90 (dd, J = 8.1, 0.8 Hz, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.54−7.58

(m, 1H), 7.48 (td, J = 7.5, 1.1 Hz, 1H), 6.96−6.97 (m, 1H), 6.93 (dd,

-(4-Methoxyphenyl)pyrrolo[1,2-a]quinoxaline (3aj). Following

the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

6.4 mg) and 4-methoxylbenzyl alcohol 2j (0.9 mmol, 124 mg) were

J = 4.0, 2.6 Hz, 1H); C{ H} NMR (100 MHz, CDCl ): δ 153.0,

142.0, 136.2, 132.3 (q, J

= 33.5 Hz), 131.9 (q, J

= 33.5 Hz),

C−F

used as the starting material. After column chromatography (hexane/

131.6 (q, J

= 33.5 Hz), 131.3 (q, J

128.1, 127.3, 125.8 (q, J

= 3.8 Hz), 125.7 (q, J

275.9 Hz), 125.6, 125.1, 122.9 (d, J

113.9, 108.5; F NMR (376 MHz, CDCl ): δ −62.55 ppm; HRMS

(FAB) m/z: calcd for C H F N [M + H] , 313.0953; found,

= 33.5 Hz), 130.5, 129.1,

= 3.8 Hz), 125.7 (q, J

C−F

EtOAc = 10:1), 3aj was obtained as a pale-yellow solid (31 mg, 38%

= 3.8 Hz),

C−F

yield for 40 h); mp 112−114 °C; H NMR (400 MHz, CDCl ): δ

125.7 (q, J

= 3.8 Hz), 125.6 (d, J

= 275.9 Hz), 115.1, 114.4,

C−F

.97−8.04 (m, 4H), 7.86 (dd, J = 8.0, 1.6 Hz, 1H), 7.43−7.51 (m,

H), 7.07 (dt, J = 9.3, 2.5 Hz, 2H), 7.01 (dd, J = 4.1, 0.9 Hz, 1H),

.89 (dd, J = 3.7, 2.7 Hz, 1H), 3.90 (s, 3H); C{ H} NMR (100

C−F

MHz, CDCl ): δ 161.1, 153.9, 136.4, 131.2, 130.2, 130.1, 127.2,

313.0963.

27.1, 125.4, 125.3, 114.6, 114.0, 113.9, 113.6, 108.7, 55.5; HRMS

4-(Pyrrolo[1,2-a]quinoxalin-4-yl)benzonitrile (3ap). Following

the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

56.4 mg) and 4-cyanobenzyl alcohol 2p (0.9 mmol, 120 mg) were

used as the starting material. After column chromatography (hexane/

EtOAc = 50:1), 3ap was obtained as a yellow solid (47 mg, 58% yield

(

FAB) m/z: calcd for C H N O [M + H] , 275.1184; found,

75.1184.

18 15 2

-(4-(tert-Butyl)phenyl)pyrrolo[1,2-a]quinoxaline (3ak). Follow-

ing the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3

mmol, 56.4 mg) and 4-tert-butylbenzyl alcohol 2k (0.9 mmol, 148

mg) were used as the starting material. After column chromatography

for 24 h; 66 mg, 81% yield for 40 h); mp 227−229 °C; H NMR (400

MHz, CDCl ): δ 8.14 (d, J = 8.6 Hz, 2H), 8.03−8.05 (m, 2H), 7.92

(

hexane/EtOAc = 50:1), 3ak was obtained as a yellow liquid (47 mg,

(d, J = 8.6 Hz, 1H), 7.85 (d, J = 8.6 Hz, 2H), 7.58 (t, J = 7.0 Hz, 1H),

2% yield for 40 h); H NMR (400 MHz, CDCl ): δ 8.03−8.06 (m,

7.50 (t, J = 7.6 Hz, 1H), 6.94−6.95 (m, 2H); C{ H} NMR (100

H), 7.99 (t, J = 1.5 Hz, 1H), 7.95−7.97 (m, 2H), 7.87 (d, J = 7.7 Hz,

H), 7.56−7.58 (m, 2H), 7.49−7.52 (m, 1H), 7.44−7.47 (m, 1H),

MHz, CDCl ): δ 152.3, 142.8, 136.1, 132.6, 130.6, 129.5, 128.4,

127.3, 125.7, 124.9, 118.8, 115.3, 114.5, 113.9, 113.5, 108.4; HRMS

.04 (q, J = 1.8 Hz, 1H), 6.90 (t, J = 3.4 Hz, 1H), 1.40 (s, 9H);

(FAB) m/z: calcd for C H N [M + H] , 270.1031; found,

C{ H} NMR (100 MHz, CDCl ): δ 154.5, 153.2, 136.5, 135.8,

270.1032.

30.3, 128.4, 127.4, 127.3, 125.7, 125.5, 125.4, 114.6, 114.0, 113.7,

4-(Naphthalen-2-yl)pyrrolo[1,2-a]quinoxaline (3aq). Following

the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

56.4 mg) and 2-naphtalenemethanol 2q (0.9 mmol, 142 mg) were

used as the starting material. After column chromatography (hexane/

08.9, 35.0, 31.4; HRMS (FAB) m/z: calcd for C H N [M + H] ,

01.1705; found, 301.1706.

-(4-Chlorophenyl)pyrrolo[1,2-a]quinoxaline (3al). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 4-chlorobenzyl alcohol 2l (0.9 mmol, 128 mg) were used as

the starting material. After column chromatography (hexane/EtOAc =

EtOAc = 100:1), 3aq was obtained as a yellow solid (88 mg, 99%);

mp 107−109 °C; H NMR (400 MHz, CDCl

): δ 8.54 (s, 1H),

8.10−8.17 (m, 2H), 7.93−8.04 (m, 4H), 7.87 (dd, J = 7.9, 1.5 Hz,

1H), 7.46−7.60 (m, 4H), 7.09 (dd, J = 4.0, 1.3 Hz, 1H), 6.91 (dd, J =

3.9, 2.8 Hz, 1H); C{ H} NMR (100 MHz, CDCl ): δ 154.5, 136.5,

0:1), 3al was obtained as a pale-yellow solid (76 mg, 90% yield); mp

76−178 °C; H NMR (400 MHz, CDCl ): δ 8.03 (d, J = 8.0 Hz,

H), 7.96 (d, J = 8.5 Hz, 2H), 7.89 (d, J = 8.0 Hz, 1H), 7.45−7.56

136.0, 134.2, 133.3, 130.4, 128.9, 128.5, 128.5, 127.9, 127.7, 127.3,

(

m, 4H), 6.96 (d, J = 4.1 Hz, 1H), 6.91−6.92 (m, 1H); C{ H}

127.0, 126.5, 126.2, 125.7, 125.5, 114.8, 114.2, 113.8, 108.9; HRMS

NMR (100 MHz, CDCl ): δ 153.3, 137.1, 136.3, 136.0, 130.4, 130.1,

(FAB) m/z: calcd for C21

[M + H] , 295.1235; found,

29.0, 127.9, 127.3, 125.6, 125.3, 114.9, 114.3, 113.8, 108.6; HRMS

295.1237.

(FAB) m/z: calcd for C H ClN [M + H] , 279.0689; found,

4-(Pyridin-3-yl)pyrrolo[1,2-a]quinoxaline (3ar). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 3-pyridinemethanol 2r (0.9 mmol, 98 mg) were used as the

starting material. After column chromatography (hexane/EtOAc =

79.0695.

-(4-Bromophenyl)pyrrolo[1,2-a]quinoxaline (3am). Following

the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol,

6.4 mg) and 4-bromobenzyl alcohol 2m (0.9 mmol, 168 mg) were

10:1), 3ar was obtained as a yellow solid (63 mg, 85% yield for 40 h);

used as the starting material. After column chromatography (hexane/

EtOAc = 50:1), 3am was obtained as a white solid (90 mg, 93%

yield); mp 160−162 °C; H NMR (400 MHz, CDCl ): δ 8.02−8.04

mp 153−155 °C; H NMR (400 MHz, CDCl

): δ 9.25 (s, 1H), 8.76

(d, J = 4.9 Hz, 1H), 8.30 (d, J = 7.9 Hz, 1H), 8.02 (d, J = 7.9 Hz, 2H),

7.86 (d, J = 7.9 Hz, 1H), 7.44−7.54 (m, 3H), 6.97 (t, J = 2.1 Hz, 1H),

6.90 (t, J = 3.1 Hz, 1H); C{ H} NMR (100 MHz, CDCl ): δ 151.6,

(

m, 2H), 7.89−7.91 (m, 3H), 7.67−7.69 (m, 2H), 7.54 (t, J = 7.7 Hz,

H), 7.45−7.49 (m, 1H), 6.96 (dd, J = 4.1, 1.1 Hz, 1H), 6.92 (dd, J =

150.8, 149.6, 136.2, 134.4, 130.4, 128.1, 127.2, 125.6, 125.2, 123.6,

.8, 2.4 Hz, 1H); ¹C{ H} NMR (100 MHz, CDCl ): δ 153.2, 137.5,

36.2, 131.9, 130.4, 130.3, 127.8, 127.2, 125.5, 125.1, 124.3, 114.9,

14.2, 113.8, 108.6; HRMS (FAB) m/z: calcd for C H BrN [M +

115.1, 114.4, 113.8, 108.4; HRMS (FAB) m/z: calcd for C H N

[M + H] , 246.1031; found, 246.1036.

16 12

4-(Furan-2-yl)pyrrolo[1,2-a]quinoxaline (3as). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and furfuryl alcohol 2s (0.9 mmol, 78 μL) were used as the

starting material. After column chromatography (hexane/EtOAc =

H] , 323.0184; found, 323.0189.

-(4-Iodophenyl)pyrrolo[1,2-a]quinoxaline (3an). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 4-iodobenzyl alcohol 2n (0.9 mmol, 210 mg) were used as

the starting material. After column chromatography (hexane/EtOAc =

50:1), 3as was obtained as a yellow solid (60 mg, 86% yield); mp 99−

100 °C; H NMR (400 MHz, CDCl ): δ 8.01 (dd, J = 7.7, 1.5 Hz,

0:1), 3an was obtained as a pale-yellow solid (97 mg, 88% yield); mp

1H), 7.95 (q, J = 1.2 Hz, 1H), 7.82 (dd, J = 7.7, 1.5 Hz, 1H), 7.72 (d,

J = 1.8 Hz, 1H), 7.40−7.48 (m, 4H), 6.92 (q, J = 2.2 Hz, 1H), 6.64

29−130 °C; H NMR (400 MHz, CDCl ): δ 8.03−8.04 (m, 1H),

.01−8.02 (m, 2H), 7.87−7.90 (m, 3H), 7.75 (dt, J = 8.7, 2.1 Hz,

H), 7.52−7.56 (m, 1H), 7.47 (td, J = 7.7, 1.4 Hz, 1H), 6.96 (dd, J =

(q, J = 1.6 Hz, 1H); C{1H} NMR (100 MHz, CDCl ): δ 152.4,

144.6, 143.5, 135.8, 130.1, 127.5, 127.2, 125.4, 123.2, 114.6, 114.2,

.1, 1.4 Hz, 1H), 6.91 (dd, J = 4.1, 2.7 Hz, 1H); C{1H} NMR (100

113.7, 112.9, 112.1, 108.5; HRMS (FAB) m/z: calcd for C H N O

MHz, CDCl ): δ 153.3, 138.0, 137.8, 136.2, 130.4, 130.3, 127.8,

[M + H] , 235.0871; found, 235.0875.

27.2, 125.5, 125.0, 114.9, 114.2, 113.7, 108.5, 96.3; HRMS (FAB)

4-(Thiophen-2-yl)pyrrolo[1,2-a]quinoxaline (3at). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 2-thiophenemethanol 2t (0.9 mmol, 85 μL) were used as the

starting material. After column chromatography (hexane/EtOAc =

m/z: calcd for C H IN [M + H] , 371.0045; found, 371.0051.

-(4-(Triﬂuoromethyl)phenyl)pyrrolo[1,2-a]quinoxaline (3ao).

Following the general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a

0.3 mmol, 56.4 mg) and 4-(triﬂuoromethyl)benzyl alcohol 2o (0.9

(

50:1), 3at was obtained as a yellow solid (54 mg, 72% yield for 40 h);

mmol, 158 mg) were used as the starting material. After column

chromatography (hexane/EtOAc = 100:1), 3ao was obtained as a

yellow solid (77 mg, 82% yield for 24 h); mp 150−153 °C; H NMR

mp 116−118 °C; H NMR (400 MHz, CDCl ): δ 7.97−8.01 (m,

3H), 7.86−7.88 (m, 1H), 7.44−7.56 (m, 3H), 7.29 (t, J = 2.5 Hz,

1H), 7.23 (q, J = 2.9 Hz, 1H), 6.94 (q, J = 2.2 Hz, 1H); C{ H}

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

NMR (100 MHz, CDCl ): δ 147.4, 142.5, 135.9, 130.0, 128.8, 128.3,

used as the starting material. After column chromatography (hexane/

27.9, 127.5, 127.1, 125.4, 124.1, 114.8, 114.2, 113.6, 107.9; HRMS

EtOAc = 50:1), 3ca was obtained as a pale-yellow solid (56 mg, 68%

(FAB) m/z: calcd for C H N S [M + H] , 251.0643; found,

yield); mp 129−130 °C; H NMR (400 MHz, CDCl ): δ 7.99 (dd, J

= 7.6, 2.1 Hz, 2H), 7.94 (t, J = 1.2 Hz, 1H), 7.80 (d, J = 8.6 Hz, 1H),

7.50−7.57 (m, 4H), 7.14 (dd, J = 9.2, 3.1 Hz, 1H), 6.97 (d, J = 4.3

Hz, 1H), 6.87 (q, J = 2.2 Hz, 1H), 3.93 (s, 3H); C{ H} NMR (100

procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg) and

cinnamyl alcohol 2u (0.9 mmol, 121 mg) were used as the starting

material. After column chromatography (hexane/EtOAc = 50:1), 3au

MHz, CDCl ): δ 157.2, 154.6, 138.5, 137.3, 129.8, 128.6, 128.6,

125.1, 121.4, 116.6, 114.5, 114.3, 113.6, 111.3, 108.4, 55.7; HRMS

was obtained as a yellow solid (71 mg, 88% yield); mp 128−129 °C;

(FAB) m/z: calcd for C H N O [M + H] , 275.1184; found,

H NMR (400 MHz, CDCl ): δ 8.08 (d, J = 15.6 Hz, 1H), 8.00 (d, J

275.1188.

6.9 Hz, 1H), 7.97−7.97 (m, 1H), 7.86 (dd, J = 8.0, 1.6 Hz, 1H),

7-Chloro-4-phenylpyrrolo[1,2-a]quinoxaline (3da). Following the

general procedure, 1-(4-chloro-2-nitrophenyl)-1H-pyrrole 1d (0.3

mmol, 66 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

.70−7.72 (m, 2H), 7.41−7.55 (m, 5H), 7.36 (t, J = 7.3 Hz, 1H),

.12 (d, J = 3.2 Hz, 1H), 6.93 (dd, J = 3.7, 2.7 Hz, 1H); C{ H}

NMR (100 MHz, CDCl ): δ 149.9, 136.6, 136.5, 136.3, 129.9, 129.1,

28.9, 127.8, 127.4, 127.2, 126.2, 125.5, 123.3, 114.6, 113.9, 113.8,

50:1), 3da was obtained as a yellow solid (75 mg, 90% yield); mp

106.0; HRMS (FAB) m/z: calcd for C H N [M + H] , 271.1235;

154−155 °C; H NMR (400 MHz, CDCl ): δ 7.97−8.00 (m, 2H),

found, 271.1230.

7.95 (d, J = 8.7 Hz, 1H), 7.90 (q, J = 1.2 Hz, 1H), 7.84 (d, J = 2.3 Hz,

1H), 7.53−7.56 (m, 3H), 7.39 (dd, J = 8.5, 2.1 Hz, 1H), 7.00 (dd, J =

3.9, 1.1 Hz, 1H), 6.90 (q, J = 2.3 Hz, 1H); C{ H} NMR (100 MHz,

-(Phenylethynyl)pyrrolo[1,2-a]quinoxaline (3av). Following the

general procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4

mg) and 3-phenyl-2-propyn-1-ol 2v (0.9 mmol, 110 μL) were used as

CDCl ): δ 155.6, 138.2, 137.3, 130.5, 130.3, 129.7, 128.8, 128.8,

127.6, 126.0, 125.4, 115.1, 114.9, 114.6, 109.5; HRMS (FAB) m/z:

calcd for C H ClN [M + H] , 279.0689; found, 79.0685.

NMR (400 MHz, CDCl ): δ 8.01 (dd, J = 8.2, 1.4 Hz, 1H), 7.95 (q, J

4-Phenyl-7-(triﬂuoromethyl)pyrrolo[1,2-a]quinoxaline (3ea).

Following the general procedure, 1-(2-nitro-4-(triﬂuoromethyl)-

phenyl)-1H-pyrrole 1e (0.3 mmol, 77 mg) and benzyl alcohol 2a

(0.9 mmol, 93 μL) were used as the starting material. After column

chromatography (hexane/EtOAc = 100:1), 3ea was obtained as a

1.2 Hz, 1H), 7.85 (dd, J = 8.2, 0.9 Hz, 1H), 7.71−7.73 (m, 2H),

.39−7.56 (m, 5H), 7.15 (dd, J = 3.9, 1.1 Hz, 1H), 6.93 (q, J = 2.3

Hz, 1H); C{ H} NMR (100 MHz, CDCl ): δ 138.7, 136.0, 132.4,

30.1, 129.6, 128.5, 128.2, 127.3, 127.1, 125.5, 121.7, 114.6, 114.1,

13.7, 107.7, 93.2, 85.8; HRMS (FAB) m/z: calcd for C H N [M +

yellow solid (69 mg, 74% yield); mp 96−98 °C; H NMR (400 MHz,

H] , 269.1079; found, 269.1078.

-Phenethylpyrrolo[1,2-a]quinoxaline (3aw). Following the gen-

CDCl ): δ 8.34 (d, J = 0.9 Hz, 1H), 8.00−8.04 (m, 3H), 7.97 (d, J =

8.7 Hz, 1H), 7.74 (dd, J = 8.7, 1.8 Hz, 1H), 7.54−7.58 (m, 3H), 7.07

eral procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg)

and 3-phenyl-1-propanol 1w (0.9 mmol, 122 μL) were used as the

starting material. After column chromatography (hexane/EtOAc =

(d, J = 4.1 Hz, 1H), 6.96 (t, J = 3.4 Hz, 1H); C{ H} NMR (100

MHz, CDCl ): δ 155.9, 138.0, 136.1, 130.4, 129.4, 128.8 (d, J

C−F

8.6 Hz), 128.7 (d, J

= 8.6 Hz), 128.0 (q, J

= 3.8 Hz), 127.9

C−F

0:1), 3aw was obtained as a thick brown liquid (45 mg, 56% yield);

(q, J

= 3.8 Hz), 127.9 (q, J

= 3.8

C−F

H NMR (400 MHz, CDCl ): δ 7.91−7.96 (m, 2H), 7.84 (dd, J = 8.0,

Hz), 127.8, 127.5, 125.7, 125.5 (d, J

= 270.0 Hz), 124.0 (q, J

C−F C−F

.6 Hz, 1H), 7.49 (td, J = 7.7, 1.5 Hz, 1H), 7.44 (td, J = 7.4, 1.5 Hz,

= 3.8 Hz), 123.9 (q, JC−F = 3.8 Hz), 123.9 (q, JC−F = 3.8 Hz), 123.9

(q, JC−F = 3.8 Hz), 122.8 (d, JC−F = 270.0 Hz), 115.5, 115.1, 114.5,

H), 7.29−7.35 (m, 4H), 7.19−7.23 (m, 1H), 6.90 (dd, J = 3.9, 1.1

Hz, 1H), 6.84 (dd, J = 3.7, 2.7 Hz, 1H), 3.29−3.35 (m, 2H), 3.20−

110.0; F NMR (376 MHz, CDCl ): δ −61.83 ppm; HRMS (FAB)

.26 (m, 2H); ¹³C{ H} NMR (100 MHz, CDCl ): δ 156.4, 141.9,

m/z: calcd for C18H F N [M + H] , 313.0953; found, 313.0951.

12 3 2

36.1, 129.6, 128.6, 127.4, 127.2, 126.2, 126.0, 125.3, 125.0, 114.4,

8-Methyl-4-phenylpyrrolo[1,2-a]quinoxaline (3fa). Following the

general procedure, 1-(5-methyl-2-nitrophenyl)-1H-pyrrole 1f (0.3

mmol, 61 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

13.8, 113.7, 106.3, 37.7, 34.3; HRMS (FAB) m/z: calcd for

C H N [M + H] , 273.1392; found, 273.1398.

-Cyclohexylpyrrolo[1,2-a]quinoxaline (3ax). Following the gen-

eral procedure, 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg)

and cyclohexanemethanol 2x (0.9 mmol, 110 μL) were used as the

starting material. After column chromatography (hexane/EtOAc =

50:1), 3fa was obtained as a pale-yellow solid (30 mg, 38% yield); mp

76−77 °C; H NMR (400 MHz, CDCl ): δ 7.90 (dd, J = 7.6, 1.6 Hz,

2H), 7.86 (q, J = 1.2 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.57 (s, 1H),

7.41−7.47 (m, 3H), 7.17 (dd, J = 8.7, 1.8 Hz, 1H), 6.87 (dd, J = 3.9,

0:1), 3ax was obtained as a yellow solid (47 mg, 58% yield for 24 h;

6 mg, 81% yield for 40 h); mp 75−77 °C; H NMR (400 MHz,

1.1 Hz, 1H), 6.78 (q, J = 2.3 Hz, 1H), 2.46 (s, 3H); C{ H} NMR

CDCl ): δ 7.92 (t, J = 8.0 Hz, 2H), 7.81−7.83 (m, 1H), 7.39−7.47

(100 MHz, CDCl ): δ 153.6, 138.7, 138.1, 134.4, 130.1, 129.8, 128.7,

(m, 2H), 6.93 (d, J = 3.7 Hz, 1H), 6.84 (t, J = 3.4 Hz, 1H), 3.13 (t, J

128.7, 127.0, 126.7, 125.6, 114.4, 114.0, 113.8, 108.5, 22.0; HRMS

11.7 Hz, 1H), 2.02 (d, J = 12.8 Hz, 2H), 1.78−1.94 (m, 5H), 1.33−

(FAB) m/z: calcd for C H N [M + H] , 259.1235; found,

.54 (m, 3H); ¹³C{1H} NMR (100 MHz, CDCl ): δ 161.2, 136.3,

259.1225.

29.8, 127.3, 126.9, 125.7, 125.1, 114.1, 113.7, 113.3, 105.9, 43.7,

1.4, 26.7, 26.2; HRMS (FAB) m/z: calcd for C H N [M + H] ,

51.1548; found, 251.1551.

-Methyl-4-phenylpyrrolo[1,2-a]quinoxaline (3ba). Following

the general procedure, 1-(4-methyl-2-nitrophenyl)-1H-pyrrole 1b

0.3 mmol, 61 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were

8-Methoxy-4-phenylpyrrolo[1,2-a]quinoxaline (3ga). Following

the general procedure, 1-(5-methoxyl-2-nitrophenyl)-1H-pyrrole 1g

(0.3 mmol, 65 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were

used as the starting material. After column chromatography (hexane/

EtOAc = 50:1), 3ga was obtained as a yellow solid (39 mg, 47%

(

yield); mp 95−96 °C; H NMR (400 MHz, CDCl ): δ 7.98 (dt, J =

used as the starting material. After column chromatography (hexane/

8.1, 2.3 Hz, 3H), 7.89 (d, J = 1.4 Hz, 1H), 7.53 (q, J = 6.4 Hz, 3H),

7.29 (d, J = 2.7 Hz, 1H), 7.06 (dd, J = 9.1, 2.7 Hz, 1H), 6.97 (q, J =

1.8 Hz, 1H), 6.90 (q, J = 2.3 Hz, 1H), 3.97 (s, 3H); C{ H} NMR

EtOAc = 50:1), 3ba was obtained as a pale-yellow solid (50 mg, 64%

yield); mp 96−97 °C; H NMR (400 MHz, CDCl ): δ 7.66 (d, J =

.4 Hz, 1H), 7.44 (dd, J = 8.2, 1.8 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H),

.77 (t, J = 2.1 Hz, 2H), 6.35 (t, J = 2.1 Hz, 2H), 2.47 (s, 3H);

C{ H} NMR (100 MHz, CDCl ): δ 154.4, 138.7, 136.3, 135.2,

(100 MHz, CDCl ): δ 159.3, 152.0, 138.8, 131.6, 130.9, 129.6, 128.7,

128.0, 125.5, 121.8, 114.2, 114.2, 113.0, 109.6, 108.3, 97.7, 56.0;

HRMS (FAB) m/z: calcd for C H N O [M + H] , 275.1184; found,

18 15

30.2, 129.8, 128.7, 128.7, 125.4, 125.2, 114.5, 113.8, 113.5, 108.5,

275.1193.

21.2; HRMS (FAB) m/z: calcd for C H N [M + H] , 259.1235;

8-Chloro-4-phenylpyrrolo[1,2-a]quinoxaline (3ha). Following the

general procedure, 1-(5-chloro-2-nitrophenyl)-1H-pyrrole 1h (0.3

mmol, 66 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

50:1), 3ha was obtained as a pale-yellow solid (63 mg, 76% yield); mp

found, 259.1233.

-Methoxy-4-phenylpyrrolo[1,2-a]quinoxaline (3ca). Following

the general procedure, 1-(4-methoxyl-2-nitrophenyl)-1H-pyrrole 1c

0.3 mmol, 65 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were

(

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

https://pubs.acs.org/doi/10.1021/acs.joc.0c02145.

Article

87−189 °C; H NMR (400 MHz, CDCl ): δ 8.02 (t, J = 2.5 Hz,

(0.018 mmol, 7.5 mg), trimethylamine N-oxide (0.036 mmol, 2.7

mg), and 50 mg molecular sieve (4 Å, powder), benzyl alcohol 2a (0.9

H), 7.97−8.00 (m, 2H), 7.93 (q, J = 1.4 Hz, 1H), 7.77 (d, J = 8.7

Hz, 1H), 7.53−7.56 (m, 3H), 7.44 (dd, J = 8.7, 2.3 Hz, 1H), 7.01 (dd,

mmol, 93 μL) and CPME (0.3 mL) were added in O -charged

J = 3.9, 1.1 Hz, 1H), 6.90 (q, J = 2.3 Hz, 1H); C{ H} NMR (100

borosilicate glass tubes. The reaction tube was sealed and stirred at

160 °C using a heating block. After stirring for 24 h, only trace

amount of the 3aa was observed in TLC.

MHz, CDCl ): δ 154.6, 138.2, 134.9, 132.9, 131.5, 130.1, 128.7,

28.7, 127.8, 125.8, 125.4, 114.9, 114.6, 113.9, 109.3; HRMS (FAB)

m/z: calcd for C H ClN [M + H] , 279.0689; found, 279.0685.

Reaction between 1a and 2a′. To a mixture of 1-(2-nitrophenyl)-

1H-pyrrole 1a (0.3 mmol, 56.4 mg), Fe I (0.018 mmol, 7.5 mg),

trimethylamine N-oxide (0.036 mmol, 2.7 mg), and 50 mg molecular

sieve (4 Å, powder), benzaldehyde 2a′ (0.9 mmol, 92 μL) and CPME

-Methyl-4-phenylpyrrolo[1,2-a]quinoxaline (3ia). Following the

general procedure, 1-(2-methyl-6-nitrophenyl)-1H-pyrrole 1i (0.3

mmol, 61 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were used as

the starting material. After column chromatography (hexane/EtOAc =

(0.3 mL) were added in O -charged borosilicate glass tubes. The

0:1), 3ia was obtained as a pale-yellow solid (27 mg, 35% yield); mp

reaction tube was sealed and stirred at 160 °C in a heating block.

22−124 °C; H NMR (400 MHz, CDCl ): δ 8.38 (t, J = 1.5 Hz,

After stirring for 24 h, 3aa was not observed in TLC.

H), 7.92−8.00 (m, 3H), 7.50−7.57 (m, 3H), 7.30−7.37 (m, 2H),

Reaction between 1a′ and 2a′. To a mixture of 2-(1H-pyrrol-1-

yl)aniline 1a′ (0.3 mmol, 47.5 mg), Fe I (0.018 mmol, 7.5 mg),

trimethylamine N-oxide (0.036 mmol, 2.7 mg), and 50 mg molecular

sieve (4 Å, powder), benzaldehyde 2a′ (0.9 mmol, 92 μL) and CPME

.00 (q, J = 1.8 Hz, 1H), 6.87 (q, J = 2.2 Hz, 1H), 2.97 (s, 3H);

C{ H} NMR (100 MHz, CDCl ): δ 154.4, 131.1, 129.9, 128.8,

28.7, 127.6, 126.9, 125.4, 124.9, 120.5, 113.4, 108.4, 24.1; HRMS

FAB): m/z calcd for C H N [M + H] , 259.1235; found,

(

(0.3 mL) were added in O -charged borosilicate glass tubes. The

59.1229.

-Phenylpyrido[3,2-e]pyrrolo[1,2-a]pyrazine (3ja). Following the

general procedure, 3-nitro-2-(1H-pyrrol-1-yl)pyridine 1j (0.3 mmol,

7 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were used as the

starting material. After column chromatography (hexane/EtOAc =

reaction tube was sealed and stirred at 160 °C in a heating block.

After stirring for 24 h, the reaction mixture was cooled to room

temperature, diluted with DCM (1 mL), and ﬁltered. Then, the

reaction mixture was concentrated in vacuo. After puriﬁcation by ﬂash

column chromatography (hexane/EtOAc = 50:1), 3aa was obtained

as a pale-yellow solid (63 mg, 86% yield).

0:1), 3ja was obtained as a brown solid (60 mg, 82% yield); mp

44−146 °C; H NMR (400 MHz, CDCl ): δ 8.55 (dd, J = 4.8, 1.6

Reaction between 1a′ and 2a′ without Fe I. To a mixture of 2-

(

1H-pyrrol-1-yl)aniline 1a′ (0.3 mmol, 47.5 mg) and 50 mg

Hz, 1H), 8.48 (q, J = 1.4 Hz, 1H), 8.32 (dd, J = 8.0, 1.6 Hz, 1H),

molecular sieve (4 Å, powder), benzaldehyde 2a′ (0.9 mmol, 92

.99−8.02 (m, 2H), 7.55 (td, J = 5.1, 3.4 Hz, 3H), 7.46 (q, J = 4.3 Hz,

13 1

μL) and CPME (0.3 mL) were added in O -charged borosilicate glass

H), 7.07 (q, J = 1.8 Hz, 1H), 6.94 (dd, J = 3.7, 2.7 Hz, 1H); C{ H}

tubes. The reaction tube was sealed and stirred at 160 °C in a heating

block. After stirring for 24 h, the reaction mixture was cooled to room

temperature, diluted with DCM (1 mL), and ﬁltered. Then, the

reaction mixture was concentrated in vacuo. After puriﬁcation by ﬂash

column chromatography (hexane/EtOAc = 50:1), 3aa was obtained

as a pale-yellow solid (61 mg, 83% yield).

ASSOCIATED CONTENT

sı Supporting Information

■

The Supporting Information is available free of charge at

₁_H_a_n_d13C NMR spectra, results of catalyst screening,

and details for detection of intermediates (PDF)

-Methyl-4-phenyl-1H-pyrrolo[3,2-c]quinoline (3la). Following

the general procedure, 1-methyl-2-(2-nitrophenyl)-1H-pyrrole 1l

0.3 mmol, 61 mg) and benzyl alcohol 2a (0.9 mmol, 93 μL) were

used as the starting material. The reaction was proceeded at 170 °C

for 40 h. After column chromatography (hexane/EtOAc = 10:1 to

AUTHOR INFORMATION

■

(

Corresponding Author

Suckchang Hong − Research Institute of Pharmaceutical

Sciences, College of Pharmacy, Seoul National University, Seoul

08826, Republic of Korea; orcid.org/0000-0003-4975-

:1), 3la was obtained as a pale-yellow solid (41 mg, 53% yield); mp

29−130 °C; H NMR (400 MHz, CDCl ): δ 8.43 (d, J = 6.7 Hz,

H), 8.32 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 6.7 Hz, 2H), 7.62−7.64

192 ; Email: schong17@snu.ac.kr

(

m, 1H), 7.54−7.57 (m, 3H), 7.49−7.50 (m, 1H), 7.11 (d, J = 3.1 Hz,

13 1

H), 6.84 (d, J = 3.1 Hz, 1H), 4.30 (s, 3H); C{ H} NMR (100

Authors

MHz, CDCl ): δ 154.9, 144.9, 140.4, 135.0, 130.9, 129.8, 129.3,

Simin Chun − Research Institute of Pharmaceutical Sciences,

College of Pharmacy, Seoul National University, Seoul 08826,

Republic of Korea

Jiwon Ahn − Research Institute of Pharmaceutical Sciences,

College of Pharmacy, Seoul National University, Seoul 08826,

Republic of Korea

Ramachandra Reddy Putta − BK 21 Plus Project, College of

Pharmacy, Seoul National University, Seoul 08826, Republic of

Korea

Seok Beom Lee − Research Institute of Pharmaceutical Sciences,

College of Pharmacy, Seoul National University, Seoul 08826,

Republic of Korea

Dong-Chan Oh − Natural Products Research Institute, College

of Pharmacy, Seoul National University, Seoul 08826, Republic

of Korea; orcid.org/0000-0001-6405-5535

28.9, 128.7, 126.4, 125.5, 120.6, 120.3, 118.5, 103.2, 38.3; HRMS

(FAB) m/z: calcd for C H N [M + H] , 259.1235; found,

18 15 2

59.1239.

Transfer Hydrogenation of 1a with Secondary Alcohol 4. To

a mixture of 1-(2-nitrophenyl)-1H-pyrrole 1a (0.3 mmol, 56.4 mg),

Fe I (0.018 mmol, 7.5 mg), trimethylamine N-oxide (0.036 mmol, 2.7

mg), and 50 mg molecular sieve (4 Å, powder), benzhydrol 4 (0.9

mmol, 166 mg) and CPME (0.3 mL) were added in O -charged

borosilicate glass tubes. The reaction tube was sealed and stirred at

60 °C in a heating block. After stirring for 40 h, the reaction mixture

was cooled to room temperature, diluted with DCM (1 mL), and

ﬁltered. Then, the reaction mixture was concentrated in vacuo. The

crude reaction mixture was analyzed using dimethyl sulfone (0.03

mmol) as an internal standard.

Mechanistic Studies. Reaction between 1a′ and 2a. To a

mixture of 2-(1H-pyrrol-1-yl)aniline 1a′ (0.3 mmol, 47.5 mg), Fe I

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Complete contact information is available at:

Article

https://pubs.acs.org/10.1021/acs.joc.0c02145

Ketones via Iron-Catalyzed Isomerization −Methylation. Org. Lett.

019, 21, 7914 −7918. (g) Di Gregorio, G.; Mari, M.; Bartoccini, F.;

Piersanti, G. Iron-Catalyzed Direct C3-Benzylation of Indoles with

Benzyl Alcohols through Borrowing Hydrogen. J. Org. Chem. 2017,

Author Contributions

82, 8769−8775. (h) Bala, M.; Verma, P. K.; Sharma, U.; Kumar, N.;

The manuscript was written through contributions of all

authors. All authors have given approval to the ﬁnal version of

the manuscript.

Singh, B. Iron phthalocyanine as an efficient and versatile catalyst for

N-alkylation of heterocyclic amines with alcohols: one-pot synthesis

of 2-substituted benzimidazoles, benzothiazoles and benzoxazoles.

Green Chem. 2013, 15, 1687−1693.

Notes

The authors declare no competing ﬁnancial interest.

(4) (a) Deibl, N.; Kempe, R. General and Mild Cobalt-Catalyzed C-

Alkylation of Unactivated Amides and Esters with Alcohols. J. Am.

ACKNOWLEDGMENTS

Chem. Soc. 2016 , 138 , 10786 −10789. (b) Rosler, S.; Ertl, M.; Irrgang,

■

T.; Kempe, R. Cobalt-Catalyzed Alkylation of Aromatic Amines by

This work was supported by the National Research

Foundation of Korea (NRF) grant funded by the Korea

government (2018R1C1B6005607 and 2018R1A4A1021703)

and Creative-Pioneering Researchers Program through Seoul

National University (SNU).

Alcohols. Angew. Chem., Int. Ed. 2015, 54, 15046−15050.

(5) (a) Schlagbauer, M.; Kallmeier, F.; Irrgang, T.; Kempe, R.

Manganese-Catalyzed β -Methylation of Alcohols by Methanol. Angew.

Chem., Int. Ed. 2020 , 59 , 1485 −1490. (b) Reed-Berendt, B. G.;

Morrill, L. C. Manganese-Catalyzed N-Alkylation of Sulfonamides

Using Alcohols. J. Org. Chem. 2019 , 84 , 3715 −3724. (c) Liu, T.;

Wang, L.; Wu, K.; Yu, Z. Manganese-Catalyzed β -Alkylation of

Secondary Alcohols with Primary Alcohols under Phosphine-Free

Conditions. ACS Catal. 2018, 8, 7201 −7207. (d) Fertig, R.; Irrgang,

T.; Freitag, F.; Zander, J.; Kempe, R. Manganese-Catalyzed and Base-

Switchable Synthesis of Amines or Imines via Borrowing Hydrogen or

Dehydrogenative Condensation. ACS Catal. 2018, 8, 8525 −8530.

(e) Chakraborty, S.; Daw, P.; Ben David, Y.; Milstein, D. Manganese-

Catalyzed α -Alkylation of Ketones, Esters, and Amides Using

Alcohols. ACS Catal. 2018, 8, 10300−10305. (f) Elangovan, S.;

Neumann, J.; Sortais, J.-B.; Junge, K.; Darcel, C.; Beller, M. Efficient

and selective N-alkylation of amines with alcohols catalysed by

manganese pincer complexes. Nat. Commun. 2016, 7, 12641−12648.

REFERENCES

■

1) (a) Reed-Berendt, B. G.; Polidano, K.; Morrill, L. C. Recent

advances in homogeneous borrowing hydrogen catalysis using earth-

abundant first row transition metals. Org. Biomol. Chem. 2019 , 17 ,

595 −1607. (b) Corma, A.; Navas, J.; Sabater, M. J. Advances in

One-Pot Synthesis through Borrowing Hydrogen Catalysis. Chem.

Rev. 2018 , 118 , 1410 −1459. (c) Chelucci, G. Ruthenium and osmium

complexes in CC bond-forming reactions by borrowing hydrogen

catalysis. Coord. Chem. Rev. 2017 , 331 , 1 −36. (d) Huang, F.; Liu, Z.;

Yu, Z. C-Alkylation of Ketones and Related Compounds by Alcohols:

Transition-Metal-Catalyzed Dehydrogenation. Angew. Chem., Int. Ed.

016 , 55 , 862 −875. (e) Wang, Q.; Wanga, Q.; Yu, Z. Substitution of

alcohols by N-nucleophiles via transition metal-catalyzed dehydrogen-

ation. Chem. Soc. Rev. 2015, 44, 2305−2329. (f) Nandakumar, A.;

Midya, S. P.; Landge, V. G.; Balaraman, E. Transition-Metal-

Catalyzed Hydrogen-Transfer Annulations: Access to Heterocyclic

Scaffolds. Angew. Chem., Int. Ed. 2015, 54, 11022−11034.

(g) Pena-Lopez, M.; Piehl, P.; Elangovan, S.; Neumann, H.; Beller, M.

Manganese-Catalyzed Hydrogen-Autotransfer C-C Bond Formation:

α -Alkylation of Ketones with Primary Alcohols. Angew. Chem., Int. Ed.

6) (a) Bera, S.; Bera, A.; Banerjee, D. Nickel-catalyzed hydrogen-

016, 55, 14967−14971.

2) (a) Wang, D.; McBurney, R. T.; Pernik, I.; Messerle, B. A.

Controlling the selectivity and efficiency of the hydrogen borrowing

reaction by switching between rhodium and iridium catalysts. Dalton

borrowing strategy: chemo-selective alkylation of nitriles with

alcohols. Chem. Commun. 2020, 56 , 6850 −6853. (b) Balamurugan,

G.; Ramesh, R.; Malecki, J. G. Nickel(II)−N N O Pincer Type

Complex-Catalyzed N-alkylation of Amines with Alcohols via the

Hydrogen Autotransfer Reaction. J. Org. Chem. 2020, 85, 7125 −7135.

Trans. 2019, 48, 13989−13999. (b) Genc,

̧ S.; Arslan, B.; Gulcemal, S.;

Gunnaz, S.; Cetinkaya, B.; Gulcemal, D. Iridium(I)-Catalyzed C-C

and C-N Bond Formation Reactions via the Borrowing Hydrogen

Strategy. J. Org. Chem. 2019, 84, 6286−6297. (c) Hikawa, H.;

Imamura, H.; Kikkawa, S.; Azumaya, I. A borrowing hydrogen

methodology: palladium-catalyzed dehydrative N-benzylation of 2-

aminopyridines in water. Green Chem. 2018, 20, 3044−3049.

Hydrogen-Mediated N-Alkylation Reactions by a Well-Defined

Homogeneous Nickel Catalyst. ACS Catal. 2019, 9, 9051−9059.

(d) Yang, P.; Zhang, C.; Gao, W.-C.; Ma, Y.; Wang, X.; Zhang, L.;

Yue, J.; Tang, B. Nickel-catalyzed borrowing hydrogen annulations:

(

d) Wong, C. M.; Peterson, M. B.; Pernik, I.; McBurney, R. T.;

Messerle, B. A. Highly Efficient Rh(I) Homo- and Heterogeneous

Catalysts for C-N Couplings via Hydrogen Borrowing. Inorg. Chem.

017 , 56 , 14682 −14687. (e) Marichev, K. O.; Takacs, J. M.

Ruthenium-Catalyzed Amination of Secondary Alcohols using

Borrowing Hydrogen Methodology. ACS Catal. 2016 , 6 , 2205 −

210. (f) Wang, Q.; Wu, K.; Yu, Z. Ruthenium(III)-Catalyzed β -

Alkylation of Secondary Alcohols with Primary Alcohols. Organo-

metallics 2016, 35, 1251−1256.

3) (a) Pignataro, L.; Gennari, C. Recent Catalytic Applications of

access to diversified N-heterocycles. Chem. Commun. 2019, 55 , 7844 −

7847. (e) Das, J.; Singh, K.; Vellakkaran, M.; Banerjee, D. Nickel-

Catalyzed Hydrogen-Borrowing Strategy for α -Alkylation of Ketones

with Alcohols: A New Route to Branched gem-Bis(alkyl) Ketones.

Org. Lett. 2018, 20, 5587−5591. (f) Yang, P.; Zhang, C.; Ma, Y.;

Zhang, C.; Li, A.; Tang, B.; Zhou, J. S. Nickel-Catalyzed N-Alkylation

of Acylhydrazines and Arylamines Using Alcohols and Enantiose-

lective Examples. Angew. Chem., Int. Ed. 2017, 56, 14702−14706.

(7) (a) Ashouri, A.; Samadi, S.; Ahmadian, M.; Nasiri, B. Copper-

catalyzed synthesis of diarylamines using p-toluene sulfonamides and

benzhydrol derivatives under homogeneous borrowing hydrogen

conditions. C. R. Chim. 2020 , 23 , 47 −55. (b) Xu, Z.; Wang, D.-S.; Yu,

X.; Yang, Y.; Wang, D. Tunable Triazole-Phosphine-Copper Catalysts

for the Synthesis of 2-Aryl-1H-benzo[d]imidazoles from Benzyl

Alcohols and Diamines by Acceptorless Dehydrogenation and

Borrowing Hydrogen Reactions. Adv. Synth. Catal. 2017, 359,

3332−3340.

205. (b) Piarulli, U.; Fachini, S. V.; Pignataro, L. Enantioselective

Cyclopentadienone)iron Complexes. Eur. J. Org. Chem. 2020 , 3192 −

Reductions Promoted by (Cyclopentadienone)iron Complexes.

Chimia 2017 , 71 , 580 −585. (c) Quintard, A.; Rodriguez, J. Iron

Cyclopentadienone Complexes: Discovery, Properties, and Catalytic

Reactivity. Angew. Chem., Int. Ed. 2014, 53 , 4044 −4055. (d) Polidano,

K.; Williams, J. M. J.; Morrill, L. C. Iron-Catalyzed Borrowing

Hydrogen β -C(sp )-Methylation of Alcohols. ACS Catal. 2019, 9,

Williams, J. M. J.; Morrill, L. C. Iron-Catalyzed Borrowing Hydrogen

C-Alkylation of Oxindoles with Alcohols. ChemSusChem 2019, 12,

575−8580. (e) Dambatta, M. B.; Polidano, K.; Northey, A. D.;

(8) Knolker, H.-J.; Baum, E.; Goesmann, H.; Klauss, R.

Demetalation of Tricarbonyl(cyclopentadienone)iron Complexes

Initiated by a Ligand Exchange Reaction with NaOH-X-Ray Analysis

of a Complex with Nearly Square Planar Coordinated Sodium. Angew.

Chem., Int. Ed. 1999, 38, 2064−2066.

345−2349. (f) Latham, D. E.; Polidano, K.; Williams, J. M. J.;

Morrill, L. C. One-Pot Conversion of Allylic Alcohols to α -Methyl

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

9) (a) Casey, C. P.; Guan, H. An Efficient and Chemoselective Iron

Catalyst for the Hydrogenation of Ketones. J. Am. Chem. Soc. 2007 ,

29 , 5816 −5817. (b) Casey, C. P.; Guan, H. Cyclopentadienone Iron

probes for amyloid fibrils. Org. Biomol. Chem. 2011, 9 , 5137 −5148.

(b) C ̧arbas ,̧ B. B.; Kivrak, A.; Zora, M.; Onal, A. M. Synthesis of a

novel fluorescent and ion sensitive monomer bearing quinoxaline

Alcohol Complexes: Synthesis, Reactivity, and Implications for the

Mechanism of Iron-Catalyzed Hydrogenation of Aldehydes. J. Am.

Chem. Soc. 2009, 131, 2499−2507. (c) Coleman, M. G.; Brown, A.

N.; Bolton, B. A.; Guan, H. Iron-Catalyzed Oppenauer-Type

Oxidation of Alcohols. Adv. Synth. Catal. 2010 , 352 , 967 −970.

moieties and its electropolymerization. React. Funct. Polym. 2011, 71,

579 −587. (c) Carbas, B. B.; Kivrak, A.; Zora, M.; Onal, A. M.

Synthesis and electropolymerization of a new ion sensitive ethyl-

enedioxy-substituted terthiophene monomer bearing a quinoxaline

moiety. J. Electroanal. Chem. 2012, 677−680, 9−14. (d) Patil, B. N.;

Lade, J. J.; Vadagaonkar, K. S.; Chetti, P.; Chaskar, A. C. Pyrrolo[1,2-

a]quinoxaline-Based Bipolar Host Materials for Efficient Red

Phosphorescent OLEDs. ChemistrySelect 2018, 3, 10010−10018.

(e) Lade, J. J.; Patil, B. N.; Sathe, P. A.; Vadagaonkar, K. S.; Chetti, P.;

Chaskar, A. C. Iron Catalyzed Cascade Protocol for the Synthesis of

Pyrrolo[1,2-a]quinoxalines: A Powerful Tool to Access Solid State

Emissive Organic Luminophores. ChemistrySelect 2017, 2, 6811−

6817.

608. (b) Rawlings, A. J.; Diorazio, L. J.; Wills, M. C-N Bond

10) (a) Yan, T.; Feringa, B. L.; Barta, K. Iron catalysed direct

alkylation of amines with alcohols. Nat. Commun. 2014 , 5 , 5602 −

Formation between Alcohols and Amines using an Iron Cyclo-

pentadienone Catalyst. Org. Lett. 2015 , 17 , 1086 −1089. (c) Yan, T.;

Feringa, B. L.; Barta, K. Benzylamines via Iron-Catalyzed Direct

Amination of Benzyl Alcohols. ACS Catal. 2016, 6, 381−388.

d) Brown, T. J.; Cumbes, M.; Diorazio, L. J.; Clarkson, G. J.; Wills,

M. Use of (Cyclopentadienone)iron Tricarbonyl Complexes for C-N

Bond Formation Reactions between Amines and Alcohols. J. Org.

Chem. 2017, 82 , 10489 −10503. (e) Emayavaramban, B.; Sen, M.;

Sundararaju, B. Iron-Catalyzed Sustainable Synthesis of Pyrrole. Org.

Lett. 2017 , 19 , 6 −9. (f) Pan, H.-J.; Ng, T. W.; Zhao, Y. Iron-catalyzed

amination of alcohols assisted by Lewis acid. Chem. Commun. 2015 ,

(13) (a) Wang, C.; Li, Y.; Zhao, J.; Cheng, B.; Wang, H.; Zhai, H.

An environmentally friendly approach to pyrrolo[1,2-a]quinoxalines

using oxygen as the oxidant. Tetrahedron Lett. 2016, 57, 3908−3911.

(b) Verma, A. K.; Jha, R. R.; Sankar, V. K.; Aggarwal, T.; Singh, R. P.;

Chandra, R. Lewis Acid-Catalyzed Selective Synthesis of Diversely

Substituted Indolo- and Pyrrolo[1,2-a]quinoxalines and Quinoxali-

nones by Modified Pictet-Spengler Reaction. Eur. J. Org. Chem. 2011,

51 , 11907 −11910. (g) Yan, T.; Feringa, B. L.; Barta, K. Direct N-

6998 −7010. (c) Krishna, T.; Reddy, T. N.; Laxminarayana, E.; Kalita,

alkylation of unprotected amino acids with alcohols. Sci. Adv. 2017, 3,

No. eaao6494. (h) Bai, X.; Aiolfi, F.; Cettolin, M.; Piarulli, U.; Dal

Corso, A.; Pignataro, L.; Gennari, C. Hydrogen-Borrowing Amination

of Secondary Alcohols Promoted by a (Cyclopentadienone)iron

Complex. Synthesis 2019 , 51 , 3545 −3555. (i) Hofmann, N.; Hultzsch,

K. C. Switching the N-Alkylation of Arylamines with Benzyl Alcohols

to Imine Formation Enables the One-Pot Synthesis of Enantioen-

riched α -N-Alkylaminophosphonates. Eur. J. Org. Chem. 2019, 3105−

D. Copper-Catalyzed One-Pot Synthesis of Pyrrolo[1,2-a]quinoxaline

Derivatives from 1-(2-Aminophenyl)-pyrroles and Aldehydes. Chem-

istrySelect 2019 , 4 , 250 −253. (d) Preetam, A.; Nath, M. An eco-

friendly Pictet-Spengler approach to pyrrolo- and indolo[1,2-

a]quinoxalines using p-dodecylbenzenesulfonic acid as an efficient

Brønsted acid catalyst. RSC Adv. 2015 , 5 , 21843 −21853. (e) Allan, P.

N. M.; Ostrowska, M. I.; Patel, B. Acetic Acid Catalysed One-Pot

Synthesis of Pyrrolo[1,2-a]quinoxaline Derivatives. Synlett 2019 , 30 ,

3111. (j) Polidano, K.; Allen, B. D. W.; Williams, J. M. J.; Morrill, L.

148 −2152. (f) Huo, H.-r.; Tang, X.-Y.; Gong, Y.-f. Metal-Free

C. Iron-Catalyzed Methylation Using the Borrowing Hydrogen

Approach. ACS Catal. 2018, 8, 6440−6445. (k) Vayer, M.;

Morcillo, S. P.; Dupont, J.; Gandon, V.; Bour, C. Iron-Catalyzed

Reductive Ethylation of Imines with Ethanol. Angew. Chem., Int. Ed.

Synthesis of Pyrrolo[1,2-a]quinoxalines Mediated by TEMPO

Oxoammonium Salts. Synthesis 2018, 50, 2727−2740. (g) Kamal,

A.; Babu, K. S.; Kovvuri, J.; Manasa, V.; Ravikumar, A.; Alarifi, A.

Amberlite IR-120H: an efficient and recyclable heterogeneous catalyst

for the synthesis of pyrrolo[1,2-a]quinoxalines and 5 ′H-spiro-

018 , 57 , 3228 −3232. (l) Lator, A.; Gaillard, S.; Poater, A.; Renaud,

J.-L. Well-Defined Phosphine-Free Iron-Catalyzed N-Ethylation and

[

indoline-3,4 ′-pyrrolo[1,2-a]quinoxalin]-2-ones. Tetrahedron Lett.

015, 56, 7012−7015.

14) Pereira, M. d. F.; Thiery, V. One-Pot Synthesis of Pyrrolo[1,2-

N-Methylation of Amines with Ethanol and Methanol. Org. Lett.

(

018, 20, 5985−5990.

a]quinoxaline Derivatives via Iron-Promoted Aryl Nitro Reduction

11) (a) Desplat, V.; Geneste, A.; Begorre, M.-A.; Fabre, S. B.;

Brajot, S.; Massip, S.; Thiolat, D.; Mossalayi, D.; Jarry, C.; Guillon, J.

Synthesis of New Pyrrolo[1,2-a]quinoxaline Derivatives as Potential

Inhibitors of Akt Kinase. J. Enzyme Inhib. Med. Chem. 2008, 23, 648−

and Aerobic Oxidation of Alcohols. Org. Lett. 2012, 14, 4754−4757.

(

15) Rubio-Presa, R.; Pedrosa, M. R.; Fernandez-Rodríguez, M. A.;

Arnaiz, F. J.; Sanz, R. Molybdenum-Catalyzed Synthesis of Nitro-

genated Polyheterocycles from Nitroarenes and Glycols with Reuse of

658. (b) Aiello, F.; Carullo, G.; Giordano, F.; Spina, E.; Nigro, A.;

Garofalo, A.; Tassini, S.; Costantino, G.; Vincetti, P.; Bruno, A.; Radi,

M. Identification of Breast Cancer Inhibitors Specific for G Protein-

Coupled Estrogen Receptor (GPER)-Expressing Cells. ChemMed-

Chem 2017, 12, 1279−1285. (c) Guillon, J.; Cohen, A.; Gueddouda,

N. M.; Das, R. N.; Moreau, S.; Ronga, L.; Savrimoutou, S.;

Basmaciyan, L.; Monnier, A.; Monget, M.; Rubio, S.; Garnerin, T.;

Waste Reduction Byproduct. Org. Lett. 2017, 19, 5470−5473.

(16) Sun, Q.; Liu, L.; Yang, Y.; Zha, Z.; Wang, Z. Unexpected

activated carbon-catalyzed pyrrolo[1,2-a]quinoxalines synthesis in

water. Chin. Chem. Lett. 2019, 30, 1379−1382.

Azas, N.; Mergny, J.-L.; Mullie, C.; Sonnet, P. Design, synthesis and

antimalarial activity of novel bis {N-[(pyrrolo[1,2-a]quinoxalin-4-

yl)benzyl]-3-aminopropyl}amine derivatives. J. Enzyme Inhib. Med.

Chem. 2017, 32, 547−563. (d) Guillon, J.; Mouray, E.; Moreau, S.;

Mullie,

Ravanello, F.; Le-Naour, A.; Leg

Deleris, G.; Sonnet, P.; Grellier, P. New ferrocenic pyrrolo[1,2-

C.; Forfar, I.; Desplat, V.; Belisle-Fabre, S.; Pinaud, N.;

er, J.-M.; Gosmann, G.; Jarry, C.;

a]quinoxaline derivatives: Synthesis, and in vitro antimalarial activity-

Part II. Eur. J. Med. Chem. 2011, 46, 2310−2326. (e) Desplat, V.;

Moreau, S.; Gay, A.; Fabre, S. B.; Thiolat, D.; Massip, S.; Macky, G.;

Godde, F.; Mossalayi, D.; Jarry, C.; Guillon, J. Synthesis and

evaluation of the antiproliferative activity of novel pyrrolo[1,2-

a]quinoxaline derivatives, potential inhibitors of Akt kinase. Part II. J.

Enzyme Inhib. Med. Chem. 2010, 25, 204−215.

(12) (a) Gemma, S.; Colombo, L.; Forloni, G.; Savini, L.; Fracasso,

C.; Caccia, S.; Salmona, M.; Brindisi, M.; Joshi, B. P.; Tripaldi, P.;

Giorgi, G.; Taglialatela-Scafati, O.; Novellino, E.; Fiorini, I.;

Campiani, G.; Butini, S. Pyrroloquinoxaline hydrazones as fluorescent