Syntheses of 2-Benzylbenzofuran Derivatives and 2-Aryl-nitrochroman Derivatives from Nitroalkene Precursors

DOI: 10.1002/ejoc.201600314

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Oxygen Heterocycles

Syntheses of 2-Benzylbenzofuran Derivatives and 2-Aryl-nitro-

chroman Derivatives from Nitroalkene Precursors

Chia-Yu Huang,*^[a][‡]Chun-Wei Kuo,*^[a][‡]Veerababurao Kavala,*^[a]and Ching-Fa Yao*^[a]

Abstract: Simple and straightforward methods for the synthe- alkenes by reactions with Grignard reagents followed by a Nef

sis of 2-benzylbenzofuran, 3-substituted 2-benzylbenzofuran, reaction and an acid-mediated cyclization in a one-pot process.

and 2-aryl-nitrochroman derivatives are described. Benzofurans The synthesis of chromans involved a Knoevenagel condensa-

were generated from nitroalkenes by reduction with NaBH₄fol- tion and the 1,4-diazabicyclo[2.2.2]octane (DABCO) assisted cy-

lowed by a Nef reaction and acid-mediated cyclization, whereas clization of ꢀ-(2-hydroxyphenyl)-nitroethanes and benzalde-

3-substituted 2-benzylbenzofurans were prepared from nitro- hydes, also in a one-pot process.

Introduction

MT₁and MT₂;^[5]and 656224 (D) is an inhibitor of bronchocon-

striction and antigen-induced dyspnea. It also inhibits the pro-

duction of leukotriene B4 in polymorphonuclear leukocytes,

which are involved in inflammation.^[6]

Benzofuran structures are ubiquitous in a wide variety of natu-

ral products and bioactive substances.^[1]In particular, 2-benzyl-

benzofuran derivatives, possess a variety of biological activi-

On the other hand, chroman (3,4-dihydro-2H-1-benzopyran)

ties.^[2]For example pteroside (Figure 1, A), a natural product is a common skeletal structure in natural products. For example,

extracted from the tree Pterocarpus marsupium, has antihyper- catechin, which is found in cacao beans, vascular bundles, and

glycemic activity and is important in the semisynthesis of bio- tea leaves, is a natural antioxidant used in antibacterial and

medical compounds.^[3]Further, 2-benzyl-3-biphenylylbenzo- tooth decay preventing drugs, and a large amount of function-

furan derivatives (Figure 1, B) exhibit potent protein tyrosine alized catechin derivatives can be found in nature.^[7]BW683C,

phosphatase inhibitor activity and also have antihyperglycemic which is a 2-arylchroman derivative, is a potential drug for the

activity,^[4]S24014 (C) is an agonist of the melatonin receptors reduction of the production of subviral particles of rhino-

Figure 1. 2-Benzylbenzofuran derivatives.

[a] Department of Chemistry, National Taiwan Normal University,

virus 1B (Figure 1).^[8]Although several protocols are available

88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, R.O.C.

E-mail: cheyaocf@ntnu.edu.tw

cheyaocf@yahoo.com.tw

http://www.chem.ntnu.edu.tw/people/bio.php?PID=39

for the synthesis of various benzofuran derivatives,^[9]the num-

ber of protocols for the synthesis of 2-benzylbenzofuran deriva-

tives remains limited.^[10]Recently, a few more synthetic meth-

[‡] These two authors contributed equally to this work.

ods for accessing 2-benzylbenzofuran derivatives from prop-

argyl alcohols such as 2-(3-aryl-1-hydroxyprop-2-yn-1-yl)phenol

Supporting information and ORCID(s) from the author(s) for this article are

available on the WWW under http://dx.doi.org/10.1002/ejoc.201600314.

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Figure 2. Synthetic methods for the preparation of 2-benzylbenzofuran derivatives.

Scheme 1. Synthetic strategies for the synthesis of 2-benzylbenzofuran derivatives.

and 1,3-diarylprop-2-yn-1-ol as starting materials (Figure 2) nitroethanes and benzaldehydes followed by a Michael addi-

have been reported.^[11]There are several reports on the synthe- tion reaction (Scheme 1).

sis of 2-arylchroman derivatives.^[12]However, to the best of our

knowledge, the only one report of the preparation of 2-aryl-nitro-

chroman derivatives is that of Kabalka et al.^[12a]Their approach

involved the reduction of nitrochromene derivatives with so-

Results and Discussion

To implement our plan for the synthesis of benzylbenzofuran

dium borohydride.

derivatives, we initially synthesized various ꢀ-phenyl-nitro

Most of the methods reported for the synthesis of benzyl-

benzofuran and benzopyran derivatives require special starting

materials or expensive catalysts. Hence, a simple, straightfor-

ward method for the synthesis of 2-benzylbenzofuran and 2-

arylbenzopyran derivatives from readily available starting mate-

rials would be highly desirable. We have been investigating

functionalized nitroalkenes and derivatives thereof for the past

few years.^[13]On the basis of our experience in this area, we

considered the possibility of developing a synthetic route for

the synthesis of 2-benzylbenzofuran derivatives from nitro-

alkene derivatives. Our synthetic route involved the Knoeven-

agel condensation of a ꢀ-phenyl-nitroethane and benzaldehyde

to produce a nitroalkene followed by NaBH₄reduction, a Nef

ethane derivatives 1 from the corresponding ꢀ-nitrostyrenes by

[14a]

reduction with either NaBH₄

or Hantzsch dihydropyr-

idine.^[14b]The ꢀ-phenyl-nitroethanes 1 were then treated with

different substituted salicylaldehydes 2 to furnish the corre-

sponding nitroalkenes 3 in the presence of KF and Me₂NH·HCl

(Table 1).^[14c]

This method afforded nitroalkenes in good yields, if the

salicylaldehyde was unsubstituted or had an electron-withdraw-

ing substituent. However, if the salicylaldehyde had an electron-

donating substituent, the corresponding nitroalkenes were pro-

duced in low yields.

After the successful preparation of various hydroxy-substi-

reaction, and cyclization to obtain 2-benzylbenzofurans. More- tuted nitroalkenes 3, we used the nitroalkene 3a as a model

over, the nitroalkene, on treatment with a Grignard regent fol- substrate and attempted the synthesis of 2-benzylbenzofuran

lowed by a Nef reaction and cyclization would be predicted to by literature cyclization procedures. Unfortunately, methods

lead to the formation of 3-substituted-2-benzylfuran derivatives with acids such as formic acid^[15a]and H₂SO₄,^[15b]bases such as

(Scheme 1). In addition, 2-aryl-nitrochromans could be obtained triethylamine (TEA) and 1,8-diazabicycloundec-7-ene (DBU), or

from the Knoevenagel condensation of ꢀ-(2-hydroxyphenyl)- other reagents such as copper bromide^[15c]and iodine/potas-

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Table 1. Syntheses of nitroalkene derivatives 3a–3s.

[a] Reaction conditions: 1 (2.5 mmol), 2 (2.6 mmol), KF (0.25 mmol), Me₂NH·HCl (5 mmol), toluene (5 mL), 110 °C, 12 h. [b] Isolated yields. [c] Recovered yields.

sium carbonate^[15d]failed to convert the nitroalkene into the the reaction mixture) at 80 °C. Furthermore, we executed all of

desired product. As a result, we proposed an alternative route the transformations in one pot. To our delight, the desired prod-

for the production of the benzofuran 6a from 3a. This route uct was obtained in 91 % yield in a one-pot process.

was based on work of Yue;^[9c]the nitroalkene 3a was reduced

After determination of the optimized reaction conditions, we

by NaBH₄to give the corresponding nitroalkane (4a), which applied them to the preparation of nitroalkenes 3b–3s to give

was subjected to Nef reaction conditions to furnish the ketone, the corresponding 2-benzylbenzofuran derivatives 6b–6s, and

followed by cyclization in the presence of an acid to give the the results are depicted in Table 2. A substrate with both aryl

corresponding 2-benzylbenzofuran. When the reaction was per- rings unsubstituted gave the corresponding product in excel-

formed at room temperature in the presence of NaOH and lent yield, whereas substrates containing an electron-withdraw-

H₂SO₄, the 2-benzylbenzofuran was produced in moderate yield ing group, such as a bromo or a nitro group, or a mild electron-

along with the intermediate ketone (5a; Scheme 2). To improve donating group, such as a methyl group, on aryl ring A afforded

the yield of the desired product, the temperature was increased the desired 2-benzylbenzofuran derivatives in good yields (6b–

to 80 °C to affect the cyclization. Unfortunately, the temperature 6e). Moreover, substrates containing strong electron-donating

increase did not improve the yield of the desired product. How- groups, such as a methoxy group, on aryl ring A produced the

ever, the yield of 6a was increased drastically when methanol desired products in moderate yields (6f, 6j, 6n, and 6r). In con-

was added to the reaction mixture (methanol may homogenize trast, substrates derived from 1-hydroxy-2-naphthaldehyde fur-

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Scheme 2. Synthesis of 2-benzylbenzofuran derivatives.

nished the corresponding benzylbenzofuran derivatives in ex- ucts. Furthermore, a substrate containing a thiophene moiety

cellent yields (6g, 6k, 6o, and 6s). The substituents on aryl also participated in this reaction to afford the corresponding

ring B did not significantly affect the yields of the desired prod- benzofurane derivative (6t) in 57 % yield.

Table 2. Syntheses of 2-benzylbenzofuran derivatives 6a–6s.

[a] Reaction conditions: (i) 3 (1 mmol), NaBH₄(4 mmol), silica gel (0.3 g), IPA (2 mL), DCM (10 mL), 0 °C to r.t., 30 min; (ii) 4, 5

then 6 H₂SO₄(8 mL), MeOH (30 mL), 0–80 °C, 2 h. [b] Isolated yields.

M NaOH (3 mL), r.t., 30 min,

M

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It was observed by us and others that the reactions of electron-withdrawing or an electron-donating group in the

nitroalkenes and Grignard reagents afforded high yields of nitroalkane part of the nitroalkene also provided the corre-

nitroalkanes, aci-nitro compounds, or carbonyl compounds.^[16]sponding 2-substituted 3-ethylbenzofuran derivatives (7i and

Hence, by taking advantage of this reaction, we treated the 7j; Table 3).

A proposed mechanism for the formation of 2-benzylbenzo-

furan is shown in Scheme 3. After the deprotonation of the

nitroalkane 4a, there are two plausible pathways to afford the

benzofuran 6a. In Path A, under a basic environment, the intra-

molecular attack of the phenoxide oxygen atom occurs to form

a dihydrobenzofuran intermediate, followed by the elimination

of nitric oxide and water. In contrast, Path B involves a conven-

tional Nef reaction: in the presence of an acid, the nitroate

forms ketone 5a, after which the phenol attacks the carbonyl

group to complete the cyclization,^[10e]and the subsequent de-

hydration of the dihydrobenzofuran furnishes the benzofuran

6a. To investigate the possibility of Path A, we examined the

reaction with nitroalkane 4a in an aqueous NaOH solution, fol-

lowed by treatment with an aqueous NH₄Cl solution. However,

only the starting material was recovered without the formation

of cyclized compounds; thus, Path B was confirmed as the only

reaction pathway.

nitroalkenes 3 with various Grignard reagents to obtain the cor-

responding C-alkylated nitroalkanes, which, when further sub-

jected to Nef reaction conditions, directly gave the correspond-

ing 3-substituted 2-benzylfuran derivatives. Under the present

conditions, the reactions of ethylmagnesium bromide or allyl-

magnesium bromide with the nitroalkene 3a afforded the cor-

responding 2-benzyl-3-ethylbenzofuran (7a) and 3-allyl-2-benz-

ylbenzofuran (7b) derivatives in good yields. The reactions of

isobutylmagnesium bromide and phenylmagnesium bromide

with nitroalkene 3a furnished the corresponding 2-benzyl-3-iso-

butylbenzofuran derivative (7c) and 2-benzyl-3-phenylbenzo-

furan (7d) in moderate to good yields. On the other hand, the

reaction of tBuMgBr failed to produce the desired 2-benzyl-3-

tert-butylbenzofuran (7f) under these conditions. We further

treated different substituted nitroalkenes with ethylmagnesium

bromide under the same reaction conditions. Substrates pos-

sessing an electron-withdrawing or electron-donating group in

the salicylaldehyde part of the nitroalkene produced the corre-

The 2-benzylbenzofuran derivatives shown in Table 2 are key

sponding 2-substituted 3-ethylbenzofuran derivatives (7g and precursors in the synthesis of various bioactive compounds.

7h) in moderate yields. Furthermore, substrates possessing an Herein, we synthesized N-[2-(2-benzylbenzofuran-3-yl)ethyl]-

Table 3. Syntheses of 2-benzylbenzofuran derivatives 7a–7l.

[a] Reaction conditions: (i) 3 (0.5 mmol), 3

M RMgX in THF/diethyl ether (1.5 mmol), diethyl ether (2 mL), –20 °C to r.t., 30 min; (ii) 4, 5 M NaOH (3 mL), r.t.,

30 min, then 6 H₂SO₄(8 mL), MeOH (30 mL), 0–80 °C, 2 h. [b] Isolated yields.

M

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benzaldehydes 12 followed by a Michael addition. To determine

suitable conditions for the preparation of the desired chroman

derivatives, we examined the reaction of (2-hydroxyphenyl)-

nitroethane (11a) and benzaldehyde (12a) as model substrates.

The initial reaction was conducted with KF and Me₂NH·HCl in

toluene at 110 °C. Under these conditions, we obtained a 49 %

yield of trans-2-aryl-nitrochroman 13a,^[12a]as the major prod-

uct, along with trace amounts of the nitroalkene 13a′

(Scheme 5).

Scheme 5. One-pot conditions for the synthesis 3a.

Encouraged by the initial results, we then concentrated on

optimizing this reaction (Table S1, Supporting Information).

First, we screened the solvents including DMSO and N,N-di-

methylformamide (DMF) and also performed the reaction under

solvent-free conditions. The reaction resulted in the production

of 39 % of the chroman and 25 % of the nitroalkene in DMF

and 22 and 21 % of the chroman and nitroalkene in DMSO,

respectively. Moreover, 52 % of the chroman was obtained un-

der solvent-free conditions, and the intermediate nitroalkene

was not detected in the reaction mixture. On the basis of these

results, we decided to optimize other parameters for this reac-

tion under neat conditions. We next varied the amount of benz-

aldehyde. Notably, the yield of the chroman was improved by

increasing the amount of benzaldehyde used in the reaction.

The optimum amount of benzaldehyde needed for the reaction

was 5 equiv. relative to the nitroalkane. We then optimized the

quantity of KF used in the reaction. The reaction produced the

best yield of chroman when 10 mol-% of KF was used as the

catalyst. On the other hand, in the absence of KF, a low yield of

the desired product along with detectable levels of the inter-

mediate were observed. Further, we examined different addi-

Scheme 3. Proposed mechanism for the conversion of the nitroalkane 4a into

the benzofuran 6a.

acetamide (10a), which is an analogue of S24014.^[17a]As de-

picted in Scheme 3, the 2-benzylbenzofuran 6a was treated

with 1,3,5-trioxane in concentrated HCl to add the chloromethyl

group to the 2-benzylbenzofuran under mild conditions.^[17b]

The chloromethyl compound 8a then underwent cyanation

with NaCN in dimethyl sulfoxide (DMSO) to furnish the cyano

compound 9a,^[17c]which was further reduced with LiAlH₄(LAH)

followed by Ac₂O amidation to give the desired benzofuran de-

rivative 10a in good yield (Scheme 4).

2-Aryl-nitrochromans

The synthesis of 2-aryl-nitrochroman involves the Knoevenagel tives such as tetrabutylammonium fluoride (TBAF), KHF₂, tetra-

condensation of (2-hydroxyphenyl)-nitroethanes 11 and various butylammonium bromide (TBAB), and cetyltrimethylammo-

Scheme 4. Synthesis of N-[2-(2-benzylbenzofuran-3-yl)ethyl]acetamide.

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Scheme 6. Proposed mechanism for the DABCO-catalyzed cyclization of 13a′ to 13a.

Table 4. Synthesis of 2-aryl-nitrochromans 13a–13x.

[a] Reaction conditions: 10 (0.5 mmol), 11 (0.75 mmol), KF (0.05 mmol), DABCO (0.25 mmol), Me₂NH·HCl (0.5 mmol), toluene (1 mL), 110 °C, 12 h. [b] Isolated

yields.

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nium bromide (CTAB). TBAF produced the chroman in lower Experimental Section

yield, whereas the others provided the intermediate as the ma-

jor product.

General Information: Reagents and solvents were purchased from

various commercial sources and used directly without any further

purification, unless otherwise stated. Column chromatography was

performed with 63–200 mesh silica gel. ¹H and ¹³C NMR spectra

were recorded at 400 and 100 MHz, respectively. Chemical shifts (δ)

are reported in ppm with tetramethylsilane (TMS) and chloroform

as internal standards, and coupling constants are expressed in Hz.

Melting points were recorded with an electrothermal capillary melt-

ing-point apparatus. HR mass spectra were recorded in the ESI-TOF

or EI+ mode. The starting ꢀ-phenyl-nitroethane derivatives were

After screening various parameters such as the solvent,

amounts of reagents, and various additives, a maximum yield

of 73 % was obtained after 12 h of reaction. Although we ob-

tained the desired product in a satisfactory yield, a large

amount of benzaldehyde was required to achieve this. Hence,

to solve this problem, we tuned the reaction conditions further.

In this regard, we utilized different base additives including TEA,

DBU, and 1,4-diazabicyclo[2.2.2]octane (DABCO) along with KF.

The use of TEA and DBU did not improve the reaction. However,

the reaction in the presence of DABCO produced the product

in good yield, even when only 1 equiv. of ꢀ-(2-hydroxyphenyl)-

nitroethane and 2 equiv. of benzaldehyde were used. On the

basis of this finding, we attempted to optimize the amount of

Me₂NH·HCl and DABCO required for the reaction (Table S2). The

reaction produced the chroman in equally good yield when

nitroalkane 10a was treated with 1.5 equiv. of 11a in the pres-

ence of 1 equiv. of Me₂NH·HCl, 50 mol-% of DABCO, and

10 mol-% of KF in toluene at 110 °C.

synthesized from ꢀ-nitrostyrene by previously reported methods

[16]

with NaBH₄

gents.

or Hantzsch dihydropyridine^[17]as the reducing rea-

General Procedure for Nitroalkenes 3a–3s: The nitroalkane deriv-

ative (2.5 mmol), substituted benzaldehyde (2.6 mmol,

1

2

1.04 equiv.), KF (0.25 mmol, 10 mol-%), and Me₂NH·HCl (5 mmol,

2 equiv.) were added to toluene (5 mL), and the resulting solution

was heated to 110 °C and stirred for 12 h. The reaction mixture was

then extracted with dichloromethane (DCM) and water, and the

DCM layer was separated, dried with anhydrous MgSO₄, and con-

centrated under vacuum to give the crude product, which was fur-

Further, the role of DABCO in this reaction can be explained thered purified by column chromatography with ethyl acetate/hex-

ane [ethyl acetate (EA)/hexane] as the eluent to yield the desired

product 3.

through the mechanism depicted in the Scheme 6.

These optimized conditions were applied to the synthesis

of various substituted 2-aryl-nitrochroman derivatives 13a–13x

from the corresponding functionalized ꢀ-(2-hydroxyphenyl)-

General Procedure for the Preparation of the 2-Benzylbenzofur-

ans 6a–6s: The nitroalkene derivative 3 (1 mmol) was dissolved in

nitroethane 10 and benzaldehyde 11 (Table 4). Most of the 2-propanol (IPA; 2 mL) and DCM (10 mL) with silica gel (0.3 g).

NaBH₄(0.15 g, 4 equiv.) was added slowly, and the resulting solu-

tion was stirred for 30 min. The reaction was then quenched with

reactions of ꢀ-(2-hydroxyphenyl)-nitroethanes and benzalde-

hydes furnished moderate to good yields of the corresponding

2-aryl-nitrochromans. Moreover, the reaction of 2-naphthalde-

hyde and ꢀ-(2-hydroxyphenyl)-nitroethane produced the corre-

sponding nitrochromans (13l, 13p, 13t, and 13x) in slightly

lower yields than those of the other substrates. This may be due

to steric effects. On the other hand, ꢀ-(2-hydroxy-1-naphthyl)-

nitroethane as a substrate resulted in good yields (13u–13w).

Interestingly, in all of the reactions, we obtained a single dia-

stereomer (trans).

aqueous 6

M HCl (1 mL) and the mixture extracted with DCM and

water. The DCM layer was separated, dried with anhydrous MgSO₄,

and concentrated under vacuum to give the crude product 4. The

crude product 4 was added to aqueous 5

resulting solution was stirred at room temperature for 30 min and

then slowly added to a vigorously stirred aqueous 6 H₂SO₄solu-

M NaOH (6 mL), and the

M

tion (15 mL) at 0 °C. The reaction vessel was removed from the

ice bath, and MeOH (30 mL) was added. The reaction mixture was

furthered heated to 80 °C for 2 h and then extracted with EA and

water. The EA layer was separated, dried with anhydrous MgSO₄,

and concentrated under vacuum to give the crude product, which

was furthered purified by column chromatography with EA/hexane

as the eluent to yield the desired product 6.

Conclusions

General Procedure for the Synthesis of the 2-Benzylbenzofur-

ans 6t–6w: The nitroalkene derivative 3 (0.5 mmol) was dissolved

in anhydrous THF (2 mL) under N₂, and the solution was then

We have successfully synthesized 2-benzylbenzofuran and 3-

substituted 2-benzylbenzofuran derivatives from nitroalkene

precursors. 2-Benzylbenzofurans were generated from nitro-

alkenes (ꢀ-phenyl-nitroethanes and salicylaldehydes) by reduc-

cooled to –20 °C. The alkyl/arylmagnesium bromide/chloride (3

M

diethyl ether/THF solution, 0.5 mL, 3 equiv.) was then added slowly

to the solution. After the addition, the reaction mixture was

tion with NaBH₄followed by a Nef reaction and acid-mediated warmed to room temperature and stirred for 30 min. The solvent

was removed under vacuum to give the crude product 4. The crude

product 4 was added to aqueous 5 NaOH (3 mL), and the solution

was stirred at room temperature for 30 min and then slowly added

to vigorously stirred aqueous 6 H₂SO₄(7 mL) at 0 °C. The reaction

mixture was removed from the ice bath, MeOH (10 mL) was added,

and the mixture was further heated to 80 °C for 2 h. The reaction

mixture was then extracted with EA and water, and the EA layer was

separated, dried with anhydrous MgSO₄, and concentrated under

vacuum to give the crude product, which was furthered purified by

column chromatography with EA/hexane as the eluent to yield the

desired product 6.

cyclization in a two-step reaction. 3-Substituted 2-benzylbenzo-

furan derivatives were produced from nitroalkenes, ꢀ-phenyl-

nitroethanes, and salicylaldehydes by treating them with Grig-

nard reagents followed by a Nef reaction and acid-mediated

cyclization in a one-pot process. The methods are simple and

can be used in conjunction with most types of functionalized

precursors. Further, a simple and easy method for accessing

nitrochromans was achieved in a diastereoselective manner. No

expensive chemicals were used in these reactions, which also

represent potential methods for large-scale syntheses.

M

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2-(2-Benzylbenzofuran-3-yl)acetonitrile

(9a):

1,3,5-Trioxane (400 MHz, CDCl₃): δ = 8.27 (s, 1 H), 7.66 (d, J = 2.2 Hz, 1 H), 7.34–

(10 mmol, 5 equiv.) was dissolved in concd. HCl (3 mL), and 2- 7.30 (m, 3 H), 7.27–7.25 (m, 1 H), 7.17 (d, J = 7.2 Hz, 2 H), 5.90 (s, 1

benzylbenzofuran (6a, 2 mmol) was added dropwise to the solu-

tion. The reaction mixture was stirred at room temperature for 24 h

and then extracted with diethyl ether and water. The diethyl ether

layer was washed several times with water, dried with anhydrous

MgSO₄, and concentrated under vacuum to give the crude product

8a. The crude product 8a was added to NaCN (2.2 mmol, 1.1 equiv.)

in DMSO (2 mL) at room temperature and allowed to react for 2 h.

The reaction mixture was extracted with EA and water, and the EA

layer was separated, dried with anhydrous MgSO₄, and concen-

trated under vacuum to give the pure product 9a as a yellow oil.

H), 4.16 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 152.0, 150.3,

136.0, 135.8, 131.7, 129.2, 128.9, 128.0, 127.4, 122.2, 113.0, 111.9,

33.3 ppm. HRMS (EI): calcd. for C₁₅H₁₁Br₂NO₃[M]⁺410.9106; found

410.9112.

4-Nitro-2-[(Z)-2-nitro-3-phenylprop-1-en-1-yl]phenol (3d): Yield:

435 mg, 58 %. Yellow solid. M.p. 93–94 °C. ¹H NMR (400 MHz, CDCl₃):

δ = 8.31 (s, 1 H), 8.21–8.17 (m, 2 H), 7.34–7.30 (m, 2 H), 7.27–7.23

(m, 2 H), 7.19 (d, J = 7.3 Hz, 2 H), 6.98 (d, J = 8.7 Hz, 1 H), 4.21 (s, 2

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 160.1, 152.5, 141.7, 135.7,

129.3, 128.3, 128.0, 127.5, 127.4, 126.0, 120.3, 116.4, 33.3 ppm.

HRMS (EI): calcd. for C₁₅H₁₂N₂O₅[M]⁺300.0746; found 300.0747.

N-[2-(2-Benzylbenzofuran-3-yl)ethyl]acetamide (10a): 2-(2-Benz-

ylbenzofuran-3-yl)acetonitrile (9a; 1 mmol) was dissolved in diethyl

ether (2 mL), and the solution was added to a slurry of LAH

(4 mmol, 4 equiv.) in diethyl ether (8 mL) at 0 °C. The reaction

mixture was then heated slowly to 30 °C and allowed to react for

4 h. After completion of the reaction, the mixture was cooled to

0 °C, and the reaction was quenched carefully with water (1 mL).

The solid that formed was removed by filtration, and the filtrate

was dried with anhydrous MgSO₄and concentrated under vacuum

to afford a yellow oil, which was diluted with DCM (1 mL); Ac₂O

(1.1 mmol, 1.1 equiv.) was added dropwise at 0 °C, and the reaction

mixture was then warmed to room temperature and stirred for 1 h.

The reaction mixture was extracted with DCM and water, and the

DCM layer was separated, dried with anhydrous MgSO₄, and con-

centrated under vacuum to give the crude product, which was fur-

thered purified by column chromatography with DCM/MeOH as

eluent to yield the desired product 10a.

4-Methyl-2-[(Z)-2-nitro-3-phenylprop-1-en-1-yl]phenol

(3e):

Yield: 511 mg, 76 %. Yellow solid. M.p. 110–112 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.43 (s, 1 H), 7.33–7.19 (m, 5 H), 7.10–7.06 (m,

2 H), 6.76 (d, J = 8.2 Hz, 1 H), 5.34 (s, 1 H), 4.21 (s, 2 H), 2.20 (s, 3 H)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 152.6, 150.3, 136.9, 132.6,

131.1, 130.7, 129.9, 129.0, 128.0, 127.0, 119.5, 116.1, 33.4, 20.7 ppm.

HRMS (EI): calcd. for C₁₆H₁₅NO₃[M]⁺269.1052; found 269.1058.

5-Methoxy-2-[(Z)-2-nitro-3-phenylprop-1-en-1-yl]phenol

(3f):

Yield: 214 mg, 30 %. Yellow solid. M.p. 129–131 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.54 (s, 1 H), 7.34–7.20 (m, 6 H), 6.56 (dd, J =

8.7, 2.3 Hz, 1 H), 6.42 (d, J = 2.3 Hz, 1 H), 5.51 (s, 1 H), 4.25 (s, 2 H),

3.79 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 163.2, 156.7, 148.0,

136.9, 130.9, 130.8, 129.1, 127.8, 127.0, 112.5, 107.5, 102.2, 55.7,

33.5 ppm. HRMS (EI): calcd. for C₁₆H₁₅NO₄[M]⁺285.1001; found

285.1000.

General Procedure for the Synthesis of 2-Aryl-nitrochromans

13a–13x: Nitroalkane derivative 10 (0.5 mmol), substituted salicyl-

aldehyde 11 (0.75 mmol, 1.5 equiv.), KF (0.05 mmol, 10 mol-%),

DABCO (0.25 mmol, 50 mol-%), and Me₂NH·HCl (0.5 mmol, 1 equiv.)

were added to toluene (1 mL), and the mixture was heated to

110 °C and stirred for 12 h. The reaction mixture was then extracted

with DCM and water, and the DCM layer was separated, dried with

anhydrous MgSO₄, and concentrated under vacuum to give the

crude product, which was dissolved in MeOH (1 mL); NH₂OH

(0.25 mmol, 0.5 equiv.) was added, and the mixture was stirred for

30 min; the reaction was monitored by TLC. After the disappearance

of the benzaldehyde, the reaction mixture was extracted with DCM

and water, and the DCM layer was separated, dried with anhydrous

MgSO₄, and concentrated under vacuum to give the crude product,

which was furthered purified by column chromatography with EA/

hexane as the eluent to yield the desired product 13.

1-[(Z)-2-Nitro-3-phenylprop-1-en-1-yl]naphthalen-2-ol

(3g):

Yield: 343 mg, 45 %. Yellow solid. M.p. 150–151 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.31 (s, 1 H), 7.84 (d, J = 8.7 Hz, 2 H), 7.72 (d,

J = 8.4 Hz, 1 H), 7.57–7.53 (m, 1 H), 7.46–7.42 (m, 1 H), 7.18–7.13

(m, 4 H), 7.04–7.02 (m, 2 H), 5.23 (s, 1 H), 3.93 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 154.4, 150.6, 136.0, 132.3, 131.8, 129.1, 128.9,

128.8, 128.7, 128.6, 128.0, 127.0, 124.6, 123.7, 117.9, 111.9, 34.1 ppm.

HRMS (EI): calcd. for C₁₉H₁₅NO₃[M]⁺305.1052; found 305.1057.

2-[(Z)-3-(4-Chlorophenyl)-2-nitroprop-1-en-1-yl]phenol

(3h):

Yield: 506 mg, 70 %. Yellow solid. M.p. 174–175 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.47 (s, 1 H), 7.34–7.22 (m, 5 H), 7.13 (d, J =

8.4 Hz, 1 H), 6.96–6.92 (m, 1 H), 6.87 (d, J = 8.0 Hz, 1 H), 5.20 (s, 1

H), 4.17 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 154.6, 149.9,

135.2, 133.0, 132.2, 131.3, 129.6, 129.3, 129.2, 121.6, 119.6, 116.3,

32.8 ppm. HRMS (EI): calcd. for C₁₅H₁₂ClNO₃[M]⁺289.0506; found

289.0511.

2-[(Z)-2-Nitro-3-phenylprop-1-en-1-yl]phenol (3a): Yield: 517 mg,

1

81 %. Yellow solid. M.p. 122–123 °C. H NMR (400 MHz, CDCl₃): δ =

4-Bromo-2-[(Z)-3-(4-chlorophenyl)-2-nitroprop-1-en-1-yl]phen-

ol (3i): Yield: 651 mg, 71 %. Yellow solid. M.p. 189–190 °C. H NMR

1

8.54 (s, 1 H), 7.37–7.27 (m, 5 H), 7.24 (d, J = 7.2 Hz, 2 H), 6.96–6.88

(m, 2 H), 5.70 (s, 1 H), 4.26 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 155.0, 150.0, 136.6, 132.2, 131.4, 129.5, 129.1, 127.9, 127.1, 121.3,

119.6, 116.3, 33.3 ppm. HRMS (EI): calcd. for C₁₅H₁₃NO₃[M]⁺

255.0895; found 255.0899.

(400 MHz, CDCl₃): δ = 8.29 (s, 1 H), 7.40 (dd, J = 8.6, 2.3 Hz, 1 H),

7.33 (d, J = 2.3 Hz, 1 H), 7.28 (d, J = 8.4 Hz, 2 H), 7.11 (d, J = 8.3 Hz,

2 H), 6.77 (d, J = 8.6 Hz, 1 H), 5.29 (s, 1 H), 4.13 (s, 2 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 153.5, 151.2, 134.8, 134.6, 133.2, 132.2,

129.6, 129.5, 129.3, 121.6, 118.0, 113.4, 32.8 ppm. HRMS (EI): calcd.

for C₁₅H₁₁BrClNO₃[M]⁺366.9611; found 366.9617.

4-Bromo-2-[(Z)-2-nitro-3-phenylprop-1-en-1-yl]phenol

(3b):

Yield: 641 mg, 77 %. Yellow solid. M.p. 176–177 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.23 (s, 1 H), 7.40–7.37 (m, 2 H), 7.33–7.30 (m,

2 H), 7.26–7.23 (m, 1 H), 7.17 (d, J = 7.0 Hz, 2 H), 6.77 (d, J = 8.3 Hz,

1 H), 5.30 (s, 1 H), 4.17 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

153.5, 151.7, 136.3, 134.5, 132.2, 129.2, 129.2, 128.0, 127.3, 121.7,

117.9, 113.4, 33.3 ppm. HRMS (EI): calcd. for C₁₅H₁₂BrNO₃[M]⁺

333.0001; found 332.9992.

2-[(Z)-3-(4-Chlorophenyl)-2-nitroprop-1-en-1-yl]-5-methoxy-

phenol (3j): Yield: 319 mg, 40 %. Yellow solid. M.p. 182–183 °C. H

1

NMR (400 MHz, [D₆]DMSO): δ = 8.56 (s, 1 H), 8.62 (s, 1 H), 7.39 (d,

J = 8.4 Hz, 2 H), 7.22 (d, J = 8.5 Hz, 3 H), 6.54 (d, J = 2.4 Hz, 1 H),

6.47 (dd, J = 8.8, 2.4 Hz, 1 H), 4.22 (s, 2 H), 3.74 (s, 3 H) ppm. ¹³C

NMR [100 MHz, (CD₃)₂SO]: δ = 163.2, 159.3, 145.1, 136.0, 131.3,

131.2, 130.1, 129.2, 128.7, 111.1, 106.5, 101.1, 55.3, 32.2 ppm. HRMS

(EI): calcd. for C₁₆H₁₄ClNO₄[M]⁺319.0611; found 319.0618.

2,4-Dibromo-6-[(Z)-2-nitro-3-phenylprop-1-en-1-yl]phenol (3c):

Yield: 914 mg, 89 %. Yellow solid. M.p. 118–119 °C. ¹H NMR

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1-[(Z)-3-(4-Chlorophenyl)-2-nitroprop-1-en-1-yl]naphthalen-2-

ol (3k): Yield: 509 mg, 60 %. Yellow solid. M.p. 117–118 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.32 (s, 1 H), 7.84 (d, J = 8.6 Hz, 2 H), 7.69 (d,

J = 8.3 Hz, 1 H), 7.57–7.54 (m, 1 H), 7.46–7.43 (m, 1 H), 7.14–7.10

(m, 3 H), 6.95 (d, J = 8.3 Hz, 2 H), 5.18 (s, 1 H), 3.89 (s, 2 H), 3.74 (s,

3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 153.9, 150.5, 134.6, 132.9,

132.3, 132.0, 130.0, 129.3, 129.2, 129.0, 128.8, 128.1, 124.7, 123.6,

117.9, 111.8, 33.6 ppm. HRMS (EI): calcd. for C₁₉H₁₄ClNO₃[M]⁺

339.0662; found 339.0656.

121.6, 117.9, 112.7, 30.6 ppm. HRMS (EI): calcd. for C₁₉H₁₄BrNO₃[M]⁺

383.0157; found 383.0167.

5-Methoxy-2-[(Z)-3-(naphthalen-1-yl)-2-nitroprop-1-en-1-yl]-

1

phenol (3r): Yield: 193 mg, 23 %. Yellow solid. M.p. 176–178 °C. H

NMR (400 MHz, CDCl₃): δ = 8.73 (s, 1 H), 8.04–8.01 (m, 1 H), 7.93–

7.91 (m, 1 H), 7.80 (d, J = 8.2 Hz, 1 H), 7.59–7.54 (m, 2 H), 7.42–7.38

(m, 1 H), 7.22 (dd, J = 7.1, 1.0 Hz, 1 H), 7.05 (d, J = 8.7 Hz, 1 H), 6.40

(d, J = 2.3 Hz, 1 H), 6.30 (dd, J = 8.8, 2.4 Hz, 1 H), 5.28 (s, 1 H), 4.67

(s, 2 H), 3.74 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 163.3,

156.8, 147.2, 134.2, 132.4, 131.9, 131.6, 130.9, 129.2, 127.9, 126.6,

126.2, 125.9, 123.8, 123.2, 112.5, 107.6, 102.2, 55.7, 31.2 ppm. HRMS

(EI): calcd. for C₂₀H₁₇NO₄[M]⁺335.1158; found 335.1164.

2-[(Z)-3-(4-Methoxyphenyl)-2-nitroprop-1-en-1-yl]phenol (3l):

Yield: 542 mg, 76 %. Yellow solid. M.p. 104–105 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.43 (s, 1 H), 7.31–7.28 (m, 2 H), 7.11 (d, J =

8.6 Hz, 2 H), 6.94–6.90 (m, 1 H), 6.88–6.83 (m, 3 H), 5.61 (s, 1 H),

4.15 (s, 2 H), 3.19 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 158.7,

154.8, 150.7, 132.0, 130.6, 129.7, 129.0, 128.6, 121.4, 119.8, 116.2,

114.5, 55.5, 32.5 ppm. HRMS (EI): calcd. for C₁₆H₁₅NO₄[M]⁺

285.1001; found 285.0999.

1-[(Z)-3-(Naphthalen-1-yl)-2-nitroprop-1-en-1-yl]naphthalen-2-

1

ol (3s): Yield: 595 mg, 67 %. Yellow solid. M.p. 186–188 °C. H NMR

(400 MHz, CDCl₃): δ = 8.41 (s, 1 H), 7.83–7.80 (m, 2 H), 7.76 (d, J =

8.4 Hz, 2 H), 7.66–7.64 (m, 2 H), 7.57–7.53 (m, 1 H), 7.45–7.36 (m, 2

H), 7.28 (d, J = 5.2 Hz, 2 H), 7.22–7.18 (m, 1 H), 7.09 (d, J = 8.9 Hz,

1 H), 5.24 (s, 1 H), 4.42 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

163.3, 156.8, 147.2, 134.2, 132.4, 131.9, 131.6, 130.9, 129.2, 127.9,

126.6, 126.2, 125.9, 123.8, 123.2, 112.5, 107.6, 102.2, 55.7, 31.2 ppm.

HRMS (EI): calcd. for C₂₃H₁₇NO₃[M]⁺355.1208; found 355.1204.

4-Bromo-2-[(Z)-3-(4-methoxyphenyl)-2-nitroprop-1-en-1-yl]-

phenol (3m): Yield: 744 mg, 82 %. Yellow solid. M.p. 167–169 °C.

¹H NMR (400 MHz, CDCl₃): δ = 8.29 (s, 1 H), 7.41 (s, 1 H), 7.36–7.33

(m, 2 H), 7.10 (d, J = 8.6 Hz, 2 H), 6.85–6.80 (m, 3 H), 4.11 (s, 2 H),

3.78 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 158.8, 154.7, 151.5,

134.4, 132.0, 129.5, 129.2, 128.4, 121.8, 118.0, 114.5, 112.5, 55.5,

32.5 ppm. HRMS (EI): calcd. for C₁₆H₁₄BrNO₄[M]⁺363.0106; found

363.0109.

2-(2-Nitro-3-phenylpropyl)phenol (4a): Yield: 636 mg, 99 %. Yel-

low oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.23 (m, 3 H), 7.18–7.06

(m, 4 H), 6.88–6.84 (m, 1 H), 6.70 (d, J = 8.0 Hz, 1 H), 5.30 (s, 1 H),

5.21–5.16 (m, 1 H), 3.35–3.23 (m, 3 H), 3.13 (dd, J = 14.4, 5.0 Hz, 1

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 153.8, 135.7, 131.3, 129.1,

128.9, 128.9, 127.5, 122.1, 121.1, 115.6, 89.6, 40.0, 35.2 ppm. HRMS

(EI): calcd. for C₁₅H₁₅NO₃[M]⁺257.1052; found 257.1053.

5-Methoxy-2-[(Z)-3-(4-methoxyphenyl)-2-nitroprop-1-en-1-yl]-

phenol (3n): Yield: 228 mg, 29 %. Yellow solid. M.p. 133–135 °C. ¹H

NMR (400 MHz, CDCl₃): δ = 8.49 (s, 1 H), 7.24 (d, J = 8.8 Hz, 1 H),

7.12 (d, J = 8.7 Hz, 2 H), 6.86–6.84 (m, 2 H), 6.47 (dd, J = 8.7, 2.4 Hz,

1 H), 6.41 (d, J = 2.4 Hz, 1 H), 5.33 (s, 1 H), 4.18 (s, 2 H), 3.80 (s, 3

H), 3.79 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 163.2, 158.7,

1-(2-Hydroxyphenyl)-3-phenylpropan-2-one (5a): Colorless solid.

1

M.p. 115–116 °C. H NMR (400 MHz, CDCl₃): δ = 7.35–7.29 (m, 3 H),

7.19–7.18 (m, 3 H), 7.05 (s, 1 H), 6.91 (d, J = 8.1 Hz, 2 H), 6.86–6.82

156.5, 148.6, 130.8, 130.4, 128.9, 128.8, 114.5, 112.5, 107.6, 102.1, (m, 1 H), 3.86 (s, 2 H), 3.76 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

55.7, 55.5, 32.6 ppm. HRMS (EI): calcd. for C₁₇H₁₇NNaO₅[M + Na]⁺

338.1004; found 338.1002.

δ = 155.2, 133.1, 130.9, 130.7, 129.6, 129.1, 128.9, 128.5, 127.4, 120.9,

117.5, 50.0, 44.7 ppm. HRMS (EI): calcd. for C₁₅H₁₄O₂[M]⁺226.0994;

found 226.0996.

1-[(Z)-3-(4-Methoxyphenyl)-2-nitroprop-1-en-1-yl]naphthalen-

2-ol (3o): Yield: 603 mg, 72 %. Yellow solid. M.p. 131–132 °C. ¹H

NMR (400 MHz, CDCl₃): δ = 8.24 (s, 1 H), 7.83 (d, J = 8.7 Hz, 2 H),

7.70 (d, J = 8.3 Hz, 1 H), 7.57–7.53 (m, 1 H), 7.45–7.41 (m, 1 H), 7.14

(d, J = 8.9 Hz, 1 H), 6.93 (d, J = 8.7 Hz, 2 H), 6.70–6.68 (m, 2 H), 5.26

(s, 1 H), 3.86 (s, 2 H), 3.71 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 163.2, 158.7, 156.5, 148.6, 130.8, 130.4, 128.9, 128.8, 114.5, 112.5,

107.6, 102.1, 55.7, 55.5, 32.6 ppm. HRMS (EI): calcd. for C₂₀H₁₇NO₄

[M]⁺335.1158; found 335.1151.

2-Benzylbenzofuran (6a): Yield: 189 mg, 91 %. Colorless oil. ¹H

NMR (400 MHz, CDCl₃): δ = 7.57 (d, J = 7.5 Hz, 1 H), 7.51 (d, J =

7.6 Hz, 1 H), 7.44–7.25 (m, 7 H), 6.46 (s, 1 H), 4.20 (s, 2 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 158.0, 155.2, 137.4, 129.1, 129.0, 128.8,

127.0, 123.6, 122.7, 120.6, 111.1, 103.6, 35.2 ppm. HRMS (EI): calcd.

for C₁₅H₁₂O [M]⁺208.0888; found 208.0889.

2-Benzyl-5-bromobenzofuran (6b): Yield: 232 mg, 81 %. Colorless

solid. M.p. 43–44 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.62 (d, J =

1.8 Hz, 1 H), 7.40–7.28 (m, 7 H), 6.35 (d, J = 0.8 Hz, 1 H), 4.13 (s, 2

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 159.5, 153.9, 137.0, 131.0,

129.1, 128.9, 127.1, 126.5, 123.3, 115.8, 112.6, 103.1, 35.2 ppm.

HRMS (EI): calcd. for C₁₅H₁₁BrO [M]⁺285.9993; found 285.9993.

2-[(Z)-3-(Naphthalen-1-yl)-2-nitroprop-1-en-1-yl]phenol (3p):

Yield: 511 mg, 67 %. Yellow solid. M.p. 163–165 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 8.68 (s, 1 H), 7.99–7.97 (m, 1 H), 7.92–7.90 (m,

1 H), 7.80 (d, J = 8.3 Hz, 1 H), 7.56–7.54 (m, 2 H), 7.43–7.39 (m, 1 H),

7.28–7.24 (m, 2 H), 7.14 (d, J = 7.8 Hz, 1 H), 6.85 (d, J = 8.2 Hz, 1 H),

6.79–6.75 (m, 1 H), 5.34 (s, 1 H), 4.66 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 154.9, 149.5, 134.2, 132.3, 132.3, 131.8, 131.7,

129.6, 129.2, 128.0, 126.6, 126.2, 125.9, 124.0, 123.2, 121.7, 119.8,

116.1, 30.9 ppm. HRMS (EI): calcd. for C₁₉H₁₅NO₃[M]⁺305.1052;

found 305.1047.

2-Benzyl-5,7-dibromobenzofuran (6c): Yield: 284 mg, 78 %. Color-

1

less oil. H NMR (400 MHz, CDCl₃): δ = 7.51 (s, 1 H), 7.38–7.29 (m, 5

H), 6.31 (s, 2 H), 4.14 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

160.7, 151.3, 136.5, 131.6, 129.2, 129.0, 128.9, 127.3, 122.5, 115.9,

104.5, 103.9, 35.1 ppm. HRMS (EI): calcd. for C₁₅H₁₀Br₂O [M]⁺

363.9098; found 363.9097.

4-Bromo-2-[(Z)-3-(naphthalen-1-yl)-2-nitroprop-1-en-1-yl]phen- 2-Benzyl-5-nitrobenzofuran (6d): Yield: 182 mg, 72 %. Colorless

ol (3q): Yield: 536 mg, 56 %. Yellow solid. M.p. 167–169 °C. ¹H NMR solid. M.p. 100–101 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.40 (d, J =

(400 MHz, CDCl₃): δ = 8.44 (s, 1 H), 7.99–7.97 (m, 1 H), 7.95–7.88 (m,

2 H), 7.78 (d, J = 8.3 Hz, 1 H), 7.57–7.51 (m, 2 H), 7.42–7.33 (m, 2 H),

7.24–7.22 (m, 1 H), 6.74 (d, J = 8.6 Hz, 1 H), 5.14 (s, 1 H), 4.62 (s, 2

H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 154.6, 150.5, 134.6, 134.2,

2.2 Hz, 1 H), 8.16 (d, J = 9.0, 2.4 Hz, 1 H), 7.47 (d, J = 9.0 Hz, 1 H),

7.38–7.28 (m, 5 H), 6.51 (s, 1 H), 4.15 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 161.8, 158.1, 144.3, 136.4, 129.4, 129.2, 129.1,

127.4, 119.8, 117.1, 111.4, 104.3, 35.3 ppm. HRMS (EI): calcd. for

132.0, 131.7, 130.5, 129.2, 128.1, 126.6, 126.1, 125.7, 124.3, 123.1, C₁₅H₁₁NO₃[M]⁺253.0739; found 253.0733.

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2-Benzyl-5-methylbenzofuran (6e): Yield: 184 mg, 83 %. Colorless

oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.39–7.28 (m, 7 H), 7.06 (d, J =

8.4 Hz, 1 H), 6.34 (s, 1 H), 4.13 (s, 2 H), 2.46 (s, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 158.1, 153.6, 137.6, 132.1, 129.1, 128.8, 126.9,

124.8, 120.5, 110.6, 103.3, 35.2, 21.5 ppm. HRMS (EI): calcd. for

7.59 (d, J = 1.7 Hz, 1 H), 7.32 (d, J = 1.7 Hz, 1 H), 7.31 (dd, J = 8.6,

1.9 Hz, 1 H), 7.22 (d, J = 8.6 Hz, 2 H), 6.89 (d, J = 8.6 Hz, 2 H), 6.30

(s, 1 H), 4.04 (s, 2 H), 3.81 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 160.1, 158.8, 153.9, 131.0, 130.1, 128.9, 126.4, 123.2, 115.7, 114.3,

112.5, 102.9, 55.5, 34.3 ppm. HRMS (EI): calcd. for C₁₆H₁₃BrO₂[M]⁺

316.0099; found 316.0097.

C

₁₆H₁₄O [M]⁺222.1045; found 222.1047.

6-Methoxy-2-(4-methoxybenzyl)benzofuran (6n): Yield: 190 mg,

71 %. Colorless solid. M.p. 92–94 °C. H NMR (400 MHz, CDCl₃): δ =

2-Benzyl-6-methoxybenzofuran (6f): Yield: 143 mg, 60 %. Color-

less oil. H NMR (400 MHz, CDCl₃): δ = 7.36–7.25 (m, 6 H), 6.99 (d,

1

7.32 (d, J = 8.4 Hz, 1 H), 7.21 (d, J = 8.6 Hz, 2 H), 6.96 (d, J = 2.0 Hz,

1 H), 6.86 (d, J = 8.6 Hz, 2 H), 6.81 (dd, J = 8.44, 2.4 Hz, 1 H), 6.27

(s, 1 H), 4.01 (s, 2 H), 3.82 (s, 3 H), 3.80 (s, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 160.1, 158.8, 153.9, 131.0, 130.1, 128.9, 126.4,

123.2, 115.7, 114.3, 112.5, 102.9, 55.5, 34.3 ppm. HRMS (EI): calcd.

for C₁₇H₁₆O₃[M]⁺268.1099; found 268.1096.

J = 2.1 Hz, 1 H), 6.84 (dd, J = 8.4, 2.2 Hz, 1 H), 6.32 (s, 1 H), 4.09 (s,

2 H), 3.83 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 157.6, 157.0,

156.1, 137.7, 129.1, 128.8, 126.9, 122.3, 120.6, 111.5, 103.2, 96.1, 55.9,

35.2 ppm. HRMS (EI): calcd. for C₁₆H₁₄O₂[M]⁺238.0994; found

238.0995.

2-Benzylnaphtho[2,1-b]furan (6g): Yield: 256 mg, 99 %. Colorless

solid. M.p. 85–86 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.04 (d, J =

8.2 Hz, 1 H), 7.91 (d, J = 8.1 Hz, 1 H), 7.65 (d, J = 8.9 Hz, 1 H), 7.59

(d, J = 8.9 Hz, 1 H), 7.55–7.51 (m, 1 H), 7.46–7.42 (m, 1 H), 7.31–7.26

(m, 5 H), 6.87 (s, 1 H), 4.21 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 157.3, 152.5, 137.7, 136.7, 130.5, 129.2, 128.9, 127.7, 127.0, 126.2,

124.5, 124.4, 124.1, 123.6, 112.4, 102.7, 35.4 ppm. HRMS (EI): calcd.

for C₁₉H₁₄O [M]⁺258.1045; found 258.1039.

2-(4-Methoxybenzyl)naphtho[1,2-b]furan (6o): Yield: 285 mg,

99 %. Colorless solid. M.p. 101–102 °C. ¹H NMR (400 MHz, CDCl₃):

δ = 8.07 (d, J = 7.6 Hz, 1 H), 7.94 (d, J = 8.1 Hz, 1 H), 7.68 (d, J =

9.0 Hz, 1 H), 7.62 (d, J = 9.0 Hz, 1 H), 7.58–7.54 (m, 1 H), 7.49–7.45

(m, 1 H), 7.30 (d, J = 8.6 Hz, 2 H), 6.92 (d, J = 8.6 Hz, 2 H), 6.87 (s, 1

H), 4.18 (s, 2 H), 3.84 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

158.7, 157.8, 152.5, 130.5, 130.2, 129.7, 128.9, 127.7, 126.2, 124.4,

124.3, 124.1, 123.6, 114.3, 112.4, 102.5, 55.5, 34.5 ppm. HRMS (EI):

calcd. for C₂₀H₁₆O₂[M]⁺288.1150; found 288.1152.

2-(4-Chlorobenzyl)benzofuran (6h): Yield: 225 mg, 93 %. Colorless

solid. M.p. 70–71 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.49 (d, J =

7.1 Hz, 1 H), 7.41 (d, J = 7.9 Hz, 1 H), 7.31–7.29 (m, 2 H), 7.25–7.17

(m, 4 H), 6.39 (s, 1 H), 4.08 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 157.3, 155.2, 135.9, 132.9, 130.5, 129.0, 128.9, 123.8, 122.8, 120.7,

111.1, 103.8, 34.6 ppm. HRMS (EI): calcd. for C₁₅H₁₁ClO [M]⁺

242.0498; found 242.0494.

2-(Naphthalen-1-ylmethyl)benzofuran (6p): Yield: 277 mg, 97 %.

Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.09–8.07 (m, 1 H), 7.92–

7.89 (m, 1 H), 7.83 (dd, J = 7.1, 2.3 Hz, 1 H), 7.53–7.49 (m, 2 H), 7.47–

7.41 (m, 4 H), 7.25–7.15 (m, 2 H), 6.26 (s, 1 H), 4.58 (s, 2 H) ppm. ¹³

C

NMR (100 MHz, CDCl₃): δ = 157.8, 155.0, 134.1, 133.3, 132.2, 129.1,

128.9, 128.0, 127.6, 126.4, 125.9, 125.8, 124.1, 123.6, 122.7, 120.6,

111.1, 103.9, 32.7 ppm. HRMS (EI): calcd. for C₁₉H₁₄O [M]⁺258.1045;

found 258.1037.

5-Bromo-2-(4-chlorobenzyl)benzofuran (6i): Yield: 294 mg, 92 %.

1

Yellow solid. M.p. 53–55 °C. H NMR (400 MHz, CDCl₃): δ = 7.60 (d,

J = 1.9 Hz, 1 H), 7.33–7.29 (m, 3 H), 7.28–7.27 (m, 1 H), 7.22 (d, J =

8.5 Hz, 2 H), 6.33 (s, 1 H), 4.07 (s, 2 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 158.8, 154.0, 135.4, 133.1, 130.9, 130.4, 129.1, 126.7,

123.4, 115.9, 112.6, 103.3, 34.6 ppm. HRMS (EI): calcd. for

5-Bromo-2-(naphthalen-1-ylmethyl)benzofuran (6q): Yield:

319 mg, 95 %. Colorless solid. M.p. 85–86 °C. ¹H NMR (400 MHz,

CDCl₃): δ = 8.04 (dd, J = 6.2, 3.5 Hz, 1 H), 7.91 (dd, J = 6.2, 3.5 Hz,

1 H), 7.84 (d, J = 7.9 Hz, 1 H), 7.54–7.42 (m, 5 H), 7.33–7.28 (m, 2 H),

6.19 (s, 1 H), 4.56 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 159.3,

153.7, 134.1, 132.8, 132.1, 131.0, 129.0, 128.2, 127.6, 126.5, 126.4,

126.0, 125.8, 124.0, 123.2, 115.8, 112.5, 103.5, 32.6 ppm. HRMS (EI):

calcd. for C₁₉H₁₃BrO [M]⁺336.0150; found 336.0146.

C

₁₅H₁₀BrClO [M]⁺319.9604; found 319.9610.

2-(4-Chlorobenzyl)-6-methoxybenzofuran (6j): Yield: 171 mg,

1

63 %. Colorless solid. M.p. 81–82 °C. H NMR (400 MHz, CDCl₃): δ =

7.34 (dd, J = 8.5 Hz, 1 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.22 (d, J = 8.6 Hz,

2 H), 6.96 (d, J = 2.0 Hz, 1 H), 6.83 (dd, J = 8.6, 2.3 Hz, 1 H), 6.31 (s,

1 H), 4.04 (s, 2 H), 3.83 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

157.7, 156.2, 156.1, 136.2, 132.8, 130.4, 128.9, 122.1, 120.7, 111.6,

103.5, 96.1, 55.9, 34.5 ppm. HRMS (EI): calcd. for C₁₆H₁₃ClO₂[M]⁺

272.0604; found 272.0605.

6-Methoxy-2-(naphthalen-1-ylmethyl)benzofuran (6r): Yield:

184 mg, 64 %. Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.09–

8.06 (m, 1 H), 7.90–7.88 (m, 1 H), 7.82–7.80 (m, 1 H), 7.52–7.42 (m,

4 H), 7.27 (d, J = 8.5 Hz, 1 H), 6.99 (d, J = 2.3 Hz, 1 H), 6.81 (dd, J =

8.6, 2.3 Hz, 1 H), 6.18 (s, 1 H), 4.54 (s, 2 H), 3.83 (s, 3 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 157.6, 156.7, 155.9, 134.1, 133.5, 132.2,

128.9, 127.9, 127.5, 126.4, 125.9, 125.8, 124.1, 122.3, 120.6, 111.5,

103.6, 96.1, 55.9, 32.6 ppm. HRMS (EI): calcd. for C₂₀H₁₆O₂[M]⁺

288.1150; found 288.1146.

2-(4-Chlorobenzyl)naphtho[1,2-b]furan (6k): Yield: 277 mg, 95 %.

Colorless solid. M.p. 100–101 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.05

(d, J = 8.2 Hz, 1 H), 7.92 (d, J = 8.2 Hz, 1 H), 7.67 (d, J = 8.8 Hz, 1

H), 7.59 (d, J = 8.8 Hz, 1 H), 7.57–7.52 (m, 1 H), 7.48–7.44 (m, 1 H),

7.33–7.26 (m, 4 H), 6.87 (s, 1 H), 4.18 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 157.7, 156.2, 156.1, 136.2, 132.8, 130.4, 128.9,

122.1, 120.7, 111.6, 103.5, 96.1, 55.9, 34.5 ppm. HRMS (EI): calcd. for

C₁₉H₁₃OCl [M]⁺292.0655; found 292.0664.

2-(Naphthalen-1-ylmethyl)naphtho[1,2-b]furan (6s): Yield:

305 mg, 99 %. Colorless solid. M.p. 164.165 °C. ¹H NMR (400 MHz,

CDCl₃): δ = 8.13–8.11 (m, 1 H), 7.97–7.91 (m, 3 H), 7.86–7.84 (m, 1

H), 7.67 (d, J = 8.9 Hz, 1 H), 7.63 (d, J = 8.9 Hz, 1 H), 7.54–7.42 (m,

6 H), 6.75 (s, 1 H), 4.68 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

157.0, 152.3, 134.2, 133.5, 132.2, 130.4, 129.0, 128.8, 128.0, 127.6,

127.6, 126.5, 126.1, 126.0, 125.8, 124.4, 124.4, 124.2, 123.6, 112.4,

103.0, 32.8 ppm. HRMS (EI): calcd. for C₂₃H₁₆O [M]⁺308.1201; found

308.1196.

2-(4-Methoxybenzyl)benzofuran (6l): Yield: 252 mg, 89 %. Color-

less solid. M.p. 62–63 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.51–7.49

(m, 1 H), 7.45–7.43 (m, 1 H), 7.28–7.19 (m, 4 H), 6.91 (d, J = 8.6 Hz,

2 H), 6.39 (s, 1 H), 4.09 (s, 2 H), 3.83 (s, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 158.7, 158.5, 130.1, 129.5, 129.0, 123.5, 122.7, 120.6,

114.2, 111.1, 103.3, 55.5, 34.3 ppm. HRMS (EI): calcd. for C₁₆H₁₄O₂

[M]⁺283.0994; found 283.0997.

2-(Thiophen-2-ylmethyl)benzofuran (6t): Yield: 112 mg, 52 %.

Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.52 (d, J = 7.4 Hz, 1

H), 7.46 (d, J = 7.9 Hz, 1 H), 7.28–7.20 (m, 3 H), 6.99 (s, 2 H), 6.50 (s,

5-Bromo-2-(4-methoxybenzyl)benzofuran (6m): Yield: 284 mg,

90 %. Colorless solid. M.p. 62–63 °C. H NMR (400 MHz, CDCl₃): δ = 1 H), 4.34 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 156.9, 155.1,

1

Eur. J. Org. Chem. 2016, 2720–2734

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2730

Full Paper

139.4, 128.9, 127.1, 126.3, 124.6, 123.8, 122.8, 120.8, 111.2, 103.5, 7.39 (m, 1 H), 7.25–7.18 (m, 4 H), 6.86 (d, J = 8.7 Hz, 2 H), 4.06 (s, 2

29.4 ppm. HRMS (EI): calcd. for C₁₃H₁₀OS [M]⁺214.0452; found H), 3.79 (s, 3 H), 2.73 (q, J = 7.6 Hz, 2 H), 1.28 (t, J = 7.6 Hz) ppm.

214.0454.

¹³C NMR (100 MHz, CDCl₃): δ = 158.5, 154.3, 152.2, 130.3, 129.6,

123.5, 122.2, 119.3, 117.1, 114.2, 111.1, 55.5, 31.9, 17.2, 14.9 ppm.

HRMS (EI): calcd. for C₁₈H₁₈O₂[M]⁺266.1307; found 266.1305.

2-Benzyl-3-ethylbenzofuran (7a): Yield: 80 mg, 68 %. Colorless oil.

¹H NMR (400 MHz, CDCl₃): δ = 7.55–7.52 (m, 1 H), 7.41–7.39 (m, 1

H), 7.33–7.20 (m, 7 H), 4.12 (s, 2 H), 2.74 (q, J = 7.6 Hz, 2 H), 1.28 (t,

J = 7.6 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 154.4, 151.8,

138.3, 129.5, 128.8, 128.7, 126.7, 123.5, 122.2, 119.3, 117.3, 111.1,

32.8, 17.2, 14.9 ppm. HRMS (EI): calcd. for C₁₇H₁₆O [M]⁺236.1201;

found 236.1201.

2-Benzyl-3-methyl-5-nitrobenzofuran (7k): Yield: 61 mg, 46 %.

1

Yellow oil. H NMR (400 MHz, CDCl₃): δ = 8.38 (d, J = 2.3 Hz, 1 H),

8.15 (dd, J = 9.0, 2.3 Hz, 1 H), 7.42 (dd, J = 9.0 Hz, 1 H), 7.34–7.31

(m, 2 H), 7.27–7.25 (m, 3 H), 4.12 (s, 2 H), 2.28 (s, 3 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 157.3, 156.0, 144.0, 137.1, 131.0, 129.5, 129.0,

128.7, 127.1, 119.8, 115.8, 112.1, 111.3, 32.9, 8.1 ppm. HRMS (EI):

calcd. for C₁₆H₁₃NO₃[M]⁺267.0895; found 267.0895.

2-Benzyl-3-allylbenzofuran (7b): Yield: 82 mg, 66 %. Colorless oil.

¹H NMR (400 MHz, CDCl₃): δ = 7.53 (d, J = 6.9 Hz, 1 H), 7.42 (d, J =

7.1 Hz, 1 H), 7.35–7.22 (m, 7 H), 6.06–5.96 (m, 1 H), 5.17 (dd, J =

17.0, 1.6 Hz, 1 H), 5.12 (dd, J = 10.0, 1.4 Hz, 1 H), 4.14 (s, 2 H), 3.49

(d, J = 6.1 Hz, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 154.4,

152.9, 138.0, 135.8, 129.6, 128.8, 126.8, 123.7, 122.3, 119.6, 116.1,

113.1, 111.1, 32.9, 28.2 ppm. HRMS (EI): calcd. for C₁₈H₁₆O [M]⁺

248.1201; found 248.1202.

2-(4-Methoxybenzyl)-3-methylbenzofuran (7l): Yield: 120 mg,

95 %. Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.44 (m, 1

H), 7.38–7.36 (m, 1 H), 7.23–7.16 (m, 4 H), 6.84 (d, J = 8.7 Hz, 2 H),

4.04 (s, 2 H), 3.78 (s, 3 H), 2.22 (s, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 158.5, 154.3, 152.7, 130.5, 130.3, 129.7, 123.6, 122.2,

119.1, 114.2, 111.0, 110.7, 55.5, 32.0, 8.2 ppm. HRMS (EI): calcd. for

C₁₇H₁₆O₂[M]⁺252.1150; found 252.1150.

2-Benzyl-3-isobutylbenzofuran (7c): Yield: 75 mg, 57 %. Colorless

1

oil. H NMR (400 MHz, CDCl₃): δ = 7.60–7.57 (m, 1 H), 7.47–7.44 (m,

2-(2-Benzylbenzofuran-3-yl)acetonitrile (9a): Yield: 411 mg, 83 %.

¹H NMR (400 MHz, CDCl₃): δ = 7.59–7.57 (m, 1 H), 7.45–7.43 (m, 1

H), 7.36–7.26 (m, 7 H), 4.18 (s, 2 H), 3.65 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 154.3, 154.2, 136.5, 129.1, 128.8, 127.8, 127.3,

124.8, 123.3, 118.7, 116.9, 111.5, 105.0, 33.1, 12.8 ppm. HRMS (EI):

calcd. for C₁₇H₁₃NO [M]⁺247.0997; found 247.0996.

1 H), 7.39–7.27 (m, 7 H), 4.17 (s, 2 H), 2.79 (q, J = 7.6 Hz, 2 H), 1.33

(t, J = 7.6 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 154.4, 151.8,

138.3, 129.5, 128.6, 128.8, 126.7, 123.5, 122.2, 119.3, 117.3, 111.1,

32.8, 17.2, 14.9 ppm. HRMS (EI): calcd. for C₁₉H₂₀O [M]⁺264.1514;

found 264.1514.

2-Benzyl-3-phenylbenzofuran (7d): Yield: 75 mg, 53 %. Colorless

solid. M.p. 79–81 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.60 (d, J =

7.6 Hz, 1 H), 7.54–7.45 (m, 5 H), 7.41–7.37 (m, 1 H), 7.33–7.22 (m, 7

H), 4.22 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 154.6, 152.8,

138.1, 132.7, 129.3, 129.1, 128.8, 128.7, 127.5, 126.8, 124.2, 122.9,

N-[2-(2-Benzylbenzofuran-3-yl)ethyl]acetamide (10a): Yield:

235 mg, 80 %. Colorless solid. M.p. 99–101 °C. ¹H NMR (400 MHz,

CDCl₃): δ = 7.51 (d, J = 6.4 Hz, 1 H), 7.42 (d, J = 7.6 Hz, 1 H), 7.32–

7.20 (m, 7 H), 5.40 (s, 1 H), 4.11 (s, 2 H), 3.50 (q, J = 6.4 Hz, 2 H),

2.91 (d, J = 6.4 Hz, 2 H), 1.74 (s, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 170.3, 154.5, 153.7, 138.1, 129.3, 129.0, 128.6, 126.9,

124.0, 122.7, 119.2, 112.6, 111.3, 39.4, 32.7, 24.0, 23.3 ppm. HRMS

(EI): calcd. for C₁₉H₁₉NO₂[M + H]⁺294.1494; found 294.1494.

120.0, 118.5, 114.6, 111.4, 33.1 ppm. HRMS (EI): calcd. for C₂₁H₁₆

O

[M]⁺284.1201; found 284.1201.

2-Benzyl-5-bromo-3-ethylbenzofuran (7g): Yield: 63 mg, 40 %.

Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.44 (m, 1 H), 7.61

(d, J = 1.7 Hz, 1 H), 7.31–7.22 (m, 7 H), 4.07 (s, 2 H), 2.66 (q, J =

7.6 Hz, 2 H), 1.23 (t, J = 7.6 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃):

δ = 153.4, 153.2, 137.8, 131.6, 128.9, 128.7, 126.9, 126.4, 122.1, 117.1,

115.4, 112.6, 32.8, 17.1, 14.8 ppm. HRMS (EI): calcd. for C₁₇H₁₅BrO

[M]⁺314.0306; found 314.0303.

(Z)-2-(2-Nitro-3-phenylallyl)phenol (13a′): Yellow solid. M.p. 103–

1

104 °C. H NMR (400 MHz, CDCl₃): δ = 8.30 (s, 1 H), 7.43–7.42 (m, 5

H), 7.16–7.12 (m, 1 H), 7.19 (d, J = 7.5 Hz, 1 H), 6.88–6.85 (m, 1 H),

7.80 (d, J = 8.0 Hz, 1 H), 5.06 (s, 1 H), 4.23 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 153.6, 149.8, 135.8, 132.3, 130.5, 130.0, 129.3,

128.7, 128.5, 123.0, 121.6, 116.0, 27.7 ppm. HRMS (EI): calcd. for

1

2,3-Dibenzylbenzofuran (7e): Yield: 41 mg, 28 %. Colorless oil. H

C

₁₅H₁₃NO₃[M]⁺255.0895; found 285.0902.

NMR (400 MHz, CDCl₃): δ = 7.41 (d, J = 8.2 Hz, 1 H), 7.32–7.20 (m,

12 H), 7.16–7.11 (m, 1 H), 4.16 (s, 2 H), 4.09 (s, 2 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 154.5, 153.4, 139.8, 137.9, 129.7, 128.8, 128.7,

128.6, 126.8, 126.4, 123.7, 122.4, 119.8, 114.3, 111.1, 33.0, 29.9 ppm.

HRMS (EI): calcd. for C₂₂H₁₈O [M]⁺298.1358; found 298.1357.

3-Nitro-2-phenylchroman (13a): Yield: 91 mg, 71 %. Colorless

1

solid. M.p. 176–177 °C. H NMR (400 MHz, CDCl₃): δ = 7.40 (s, 5 H),

7.21 (t, J = 7.7 Hz, 1 H), 7.16 (d, J = 7.4 Hz, 1 H), 7.01–6.96 (m, 2 H),

5.42 (d, J = 7.9 Hz, 1 H), 5.05 (ddd, J = 9.2, 8.0, 5.4 Hz, 1 H), 3.67

(dd, J = 16.2, 5.4 Hz, 1 H), 3.33 (dd, J = 16.2, 5.4 Hz, 1 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 153.5, 136.0, 129.7, 129.5, 129.2, 128.7,

127.0, 122.1, 117.9, 117.2, 84.2, 78.2, 30.0 ppm. HRMS (EI): calcd. for

C₁₅H₁₃NO₃[M]⁺255.0895; found 255.0901.

2-Benzyl-3-ethyl-5-methoxybenzofuran (7h): Yield: 49 mg, 37 %.

Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.35–7.23 (m, 6 H), 7.00

(d, J = 2.4 Hz, 1 H), 6.85 (dd, J = 8.8, 2.5 Hz, 1 H), 4.10 (s, 2 H), 3.89

(s, 3 H), 2.72 (q, J = 7.6 Hz, 2 H), 1.28 (t, J = 7.6 Hz, 3 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 155.8, 152.8, 149.4, 138.3, 130.1, 128.8,

128.7, 126.7, 117.5, 111.7, 111.5, 102.5, 56.2, 32.9, 17.2, 14.8 ppm.

HRMS (EI): calcd. for C₁₈H₁₈O₂[M]⁺266.1307; found 266.1307.

2-(3-Fluorophenyl)-3-nitrochroman (13b): Yield: 91 mg, 67 %.

Colorless solid. M.p. 135–136 °C. ¹H NMR (400 MHz, CDCl₃): δ =

7.40–7.35 (m, 1 H), 7.24–7.20 (m, 1 H), 7.18–7.06 (m, 4 H), 7.02–6.96

(m, 2 H), 5.42 (d, J = 7.9 Hz, 1 H), 5.03–4.98 (m, 1 H), 3.66 (dd, J =

16.2, 9.2 Hz, 1 H) 3.33 (dd, J = 16.2, 5.5 Hz, 1 H) ppm. ¹³C NMR

2-(4-Chlorobenzyl)-3-ethylbenzofuran (7i): Yield: 94 mg, 70 %.

Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.56 (d, J = 7.1 Hz, 1

H), 7.43 (d, J = 7.2 Hz, 1 H), 7.32–7.21 (m, 6 H), 4.10 (s, 2 H), 2.75 (q,

J = 7.4 Hz, 2 H), 1.31 (t, J = 7.6 Hz, 3 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 154.4, 151.2, 136.7, 132.5, 130.0, 129.4, 128.9, 123.7,

122.3, 119.4, 117.6, 111.2, 32.1, 17.2, 14.9 ppm. HRMS (EI): calcd. for

(100 MHz, CDCl₃): δ = 163.1 (J_C,F= 247.6 Hz), 153.1, 138.4 (J_C,F

=

7.2 Hz), 130.8 (J_C,F= 8.1 Hz), 129.5, 128.8, 122.7 (J_C,F= 2.8 Hz), 122.3,

117.7, 116.7 (J_C,F= 21.1 Hz), 114.1 (J_C,F= 22.8 Hz), 84.1, 77.4,

29.8 ppm. HRMS (EI): calcd. for C₁₅H₁₂NO₃F [M]⁺273.0801; found

273.0802.

C

₁₇H₁₅ClO [M]⁺270.0811; found 270.0812.

3-Ethyl-2-(4-methoxybenzyl)benzofuran (7j): Yield: 81 mg, 61 %.

Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.54–7.51 (m, 1 H), 7.41–

2-(4-Fluorophenyl)-3-nitrochroman (13c): Yield: 94 mg, 69 %. Col-

orless solid. M.p. 144–145 °C. H NMR (400 MHz, CDCl₃): δ = 7.41–

1

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7.38 (m, 2 H), 7.23–7.08 (m, 4 H), 7.02–6.94 (m, 2 H), 5.34 (d, J = 16.2, 9.4 Hz, 1 H), 3.33 (dd, J = 16.2, 5.4 Hz, 1 H), 2.36 (s, 3 H) ppm.

8.4 Hz, 1 H), 5.00 (ddd, J = 9.8, 8.4, 5.5 Hz, 1 H), 3.68 (dd, J = 16.1,

¹³C NMR (100 MHz, CDCl₃): δ = 153.6, 139.6, 132.9, 129.8, 129.5,

128.7, 127.0, 122.0, 117.9, 117.2, 84.3, 78.2, 30.2, 21.5 ppm. HRMS

9.8 Hz, 1 H), 3.36 (d, J = 16.1, 5.5 Hz, 1 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 164.7, 162.3, 153.4, 131.7 (d, J_C,F= 3.1 Hz), 129.2 (d, (EI): calcd. for C₁₆H₁₅NO₃[M]⁺269.1052; found 269.1047.

J_C,F= 79.0 Hz), 129.1, (d, J_C,F= 8.5 Hz), 122.3, 117.8, 117.2, 116.2 (d,

2-(4-Methoxyphenyl)-3-nitrochroman (13k): Yield: 78 mg, 55 %.

J

_C,F= 21.8 Hz), 84.4, 77.7, 30.4 ppm. HRMS (EI): calcd. for C₁₅H₁₂FNO₃

Colorless solid. M.p. 144–145 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.33

(d, J = 8.6 Hz, 2 H), 7.22–7.14 (m, 2 H), 7.00–6.91 (m, 4 H), 5.30 (d,

J = 8.4 Hz, 1 H), 5.06–5.00 (m, 1 H), 3.81 (s, 3 H), 3.67 (dd, J = 16.0,

9.9 Hz, 1 H), 3.36 (dd, J = 16.0, 5.5 Hz, 1 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 160.7, 153.7, 129.5, 128.6, 128.5, 127.8, 122.1, 118.0,

117.2, 114.6, 84.4, 78.1, 55.5, 30.5 ppm. HRMS (EI): calcd. for

[M]⁺273.0801; found 273.0805.

2-(2-Chlorophenyl)-3-nitrochroman (13d): Yield: 113 mg, 78 %.

Colorless solid. M.p. 104–106 °C. ¹H NMR (400 MHz, CDCl₃): δ =

7.44–7.42 (m, 1 H), 7.40–7.38 (m, 1 H), 7.34–7.27 (m, 2 H), 7.25–7.21

(m, 1 H), 7.14–7.13 (m, 1 H), 7.01–6.96 (m, 2 H), 6.16 (d, J = 5.4 Hz,

1 H), 5.26–5.22 (m, 1 H), 3.62 (dd, J = 16.7, 6.5 Hz, 1 H), 3.16 (dd,

J = 16.7, 5.1 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 152.9,

134.2, 132.5, 130.4, 130.3, 129.4, 128.7, 128.0, 127.5, 121.9, 117.1,

116.7, 80.7, 74.4, 27.5 ppm. HRMS (EI): calcd. for C₁₅H₁₂ClNO₃[M]⁺

289.0506; found 289.0504.

C

₁₆H₁₅NO₄[M]⁺285.1001; found 285.1002.

2-(Naphthalen-1-yl)-3-nitrochroman (13l): Yield: 72 mg, 47 %.

Colorless solid. M.p. 193–194 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.14

(d, J = Hz, 1 H), 7.92 (d, J = 8.2 Hz, 2 H), 7.88 (d, J = 8.2 Hz, 3 H),

7.62–7.53 (m, 1 H), 7.46–7.42 (m, 1 H), 7.18 (d, J = 7.3 Hz, 1 H), 7.04–

7.00 (m, 2 H), 6.42 (d, J = 6.0 Hz, 1 H), 5.41–5.37 (m, 1 H), 3.65 (dd,

J = 16.6, 7.3 Hz, 1 H), 3.23 (dd, J = 16.6, 5.2 Hz, 1 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 153.4, 134.3, 131.9, 130.3, 130.2, 129.6, 129.6,

128.9, 127.4, 126.3, 125.5, 125.2, 122.7, 122.1, 117.5, 117.1, 82.3, 75.7,

28.5 ppm. HRMS (EI): calcd. for C₁₉H₁₅NO₃[M]⁺305.1052; found

305.1054.

2-(3-Chlorophenyl)-3-nitrochroman (13e): Yield: 107 mg, 74 %.

Colorless solid. M.p. 140–141 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.42

(s, 1 H), 7.38–7.31 (m, 2 H), 7.27–7.20 (m, 2 H), 7.16–7.14 (m, 1 H),

7.02–6.96 (m, 2 H), 5.38 (d, J = 8.0 Hz, 1 H), 5.03–4.98 (m, 1 H), 3.66

(dd, J = 16.2, 9.4 Hz, 1 H), 3.34 (dd, J = 16.2, 5.4 Hz, 1 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 152.9, 137.8, 135.0, 130.2, 129.7, 129.3,

128.6, 127.0, 125.1, 122.1, 117.5, 117.0, 83.9, 29.8 ppm. HRMS (EI):

calcd. for C₁₅H₁₂ClNO₃[M]⁺289.0506; found 289.0505.

7-Methoxy-3-nitro-2-phenylchroman (13m): Yield: 94 mg, 66 %.

Colorless solid. M.p. 150–151 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.39

(s, 5 H), 7.03 (d, J = 8.4 Hz, 1 H), 6.58 (dd, J = 8.4, 2.5 Hz, 1 H), 6.51

(d, J = 2.5 Hz, 1 H), 5.41 (d, J = 7.9 Hz, 1 H), 5.02 (ddd, J = 9.0, 7.9,

5.4 Hz, 1 H), 3.77 (s, 3 H), 3.58 (dd, J = 15.9, 9.0 Hz, 1 H), 3.26 (dd,

J = 15.9, 5.4 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 159.9,

154.0, 135.8, 129.8, 129.4, 128.9, 126.8, 109.5, 109.2, 101.6, 84.1, 78.0,

55.4, 29.2 ppm. HRMS (EI): calcd. for C₁₆H₁₅NO₄[M]⁺285.1001;

found 285.1000.

2-(4-Chlorophenyl)-3-nitrochroman (13f): Yield: 98 mg, 68 %. Col-

1

orless solid. M.p. 153–154 °C. H NMR (400 MHz, CDCl₃): δ = 7.39–

7.33 (m, 4 H), 7.23–7.19 (m, 1 H), 7.15 (d, J = 7.5 Hz, 1 H), 7.01–6.94

(m, 2 H), 5.36 (d, J = 8.1 Hz, 1 H), 5.02–4.96 (m, 1 H), 3.66 (dd, J =

16.2, 9.7 Hz, 1 H), 3.34 (dd, J = 16.2, 5.3 Hz, 1 H) ppm. ¹³C NMR

(100 MHz, CDCl₃): δ = 153.3, 135.7, 134.4, 129.6, 129.4, 128.8, 128.5,

122.3, 117.8, 117.2, 84.2, 77.6, 30.1 ppm. HRMS (EI): calcd. for

C₁₅H₁₂ClNO₃[M]⁺289.0506; found 285.0505.

2-(4-Chlorophenyl)-7-methoxy-3-nitrochroman (13n): Yield:

118 mg, 74 %. Colorless solid. M.p. 132–133 °C. H NMR (400 MHz,

2-(2-Bromophenyl)-3-nitrochroman (13g): Yield: 105 mg, 63 %.

Colorless solid. M.p. 113–115 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.62

(d, J = 8.0 Hz, 1 H), 7.39–7.30 (m, 2 H), 7.25–7.21 (m, 2 H), 7.15–7.13

(m, 1 H), 7.01–6.96 (m, 1 H), 6.15 (d, J = 5.16 Hz, 1 H), 5.26–5.22 (m,

1 H), 3.62 (dd, J = 16.7, 6.2 Hz, 1 H), 3.15 (dd, J = 16.7, 5.1 Hz, 1 H)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 153.0, 135.8, 133.6, 130.6,

129.4, 128.8, 128.2, 128.1, 122.2, 121.9, 117.0, 116.7, 80.7, 76.4,

27.3 ppm. HRMS (EI): calcd. for C₁₅H₁₁BrNO₃[M]⁺333.0001; found

333.0005.

1

CDCl₃): δ = 7.39–7.32 (m, 4 H), 7.03 (d, J = 8.5 Hz, 1 H), 6.59 (dd, J =

8.5, 2.5 Hz, 1 H), 6.50 (d, J = 2.5 Hz, 1 H), 5.36 (d, J = 8.1 Hz, 1 H),

4.97 (ddd, J = 9.4, 8.1, 5.5 Hz, 1 H), 3.77 (s, 3 H), 3.58 (dd, J = 15.9,

9.4 Hz, 1 H), 3.27 (dd, J = 15.9, 5.5 Hz, 1 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 159.9, 153.8, 153.6, 135.5, 134.2, 129.8, 129.2, 128.3,

109.3, 101.6, 84.1, 55.4, 29.4 ppm. HRMS (EI): calcd. for C₁₆H₁₄ClNO₄

[M]⁺319.0611; found 319.0620.

4-(3-Nitrochroman-2-yl)phenol (13h): Yield: 98 mg, 72 %. Color-

less solid. M.p. 191–192 °C. H NMR (400 MHz, CDCl₃): δ = 7.29 (d,

7-Methoxy-2-(4-methoxyphenyl)-3-nitrochroman (13o): Yield:

118 mg, 75 %. Colorless solid. M.p. 123–124 °C. H NMR (400 MHz,

1

J = 8.6 Hz, 2 H), 7.22–7.14 (m, 2 H), 7.00–6.94 (m, 2 H), 6.85 (d, J =

8.6 Hz, 2 H), 5.29 (d, J = 8.4 Hz, 1 H), 5.01 (ddd, J = 9.8, 8.4, 5.5 Hz,

1 H), 4.85 (s, 1 H), 3.67 (dd, J = 16.1, 9.7 Hz, 1 H), 3.36 (dd, J = 16.1,

5.6 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 156.7, 153.6, 129.5,

128.8, 128.7, 128.1, 122.1, 117.9, 117.2, 116.0, 84.4, 78.1, 30.6 ppm.

HRMS (EI): calcd. for C₁₅H₁₃NO₄[M]⁺271.0845; found 271.0846.

CDCl₃): δ = 7.34–7.31 (m, 2 H), 7.03 (d, J = 8.3 Hz, 1 H), 6.94–6.89

(m, 2 H), 6.58 (dd, J = 8.4, 2.5 Hz, 1 H), 6.50 (d, J = 2.5 Hz, 1 H), 5.30

(d, J = 8.4 Hz, 1 H), 5.00 (ddd, J = 9.7, 8.4, 5.4 Hz, 1 H), 3.81 (s, 3 H),

3.77 (s, 3 H), 3.59 (dd, J = 15.7, 9.7 Hz, 1 H), 3.29 (dd, J = 15.7, 5.4 Hz,

1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 160.4, 159.9, 154.2, 129.8,

128.3, 127.5, 114.4, 109.6, 109.1, 101.6, 84.3, 77.9, 55.4, 55.3,

29.8 ppm. HRMS (EI): calcd. for C₁₈H₂₁NO₅[M]⁺315.1107; found

315.1111.

3-Nitro-2-(4-nitrophenyl)chroman (13i): Yield: 90 mg, 60 %. Color-

1

less solid. M.p. 165–166 °C. H NMR (400 MHz, CDCl₃): δ = 8.27 (d,

J = 8.7 Hz, 2 H), 7.61 (d, J = 8.7 Hz, 2 H), 7.24–7.16 (m, 2 H), 7.05–

6.97 (m, 2 H), 5.51 (d, J = 8.1 Hz, 1 H), 5.01 (ddd, J = 9.2, 8.1, 5.6 Hz,

1 H), 3.70 (dd, J = 16.3, 9.2 Hz, 1 H), 3.35 (dd, J = 16.3, 5.3 Hz, 1 H)

ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 152.9, 148.8, 142.9, 129.6,

129.0, 128.2, 124.4, 122.7, 117.5, 117.2, 84.1, 29.9 ppm. HRMS (EI):

calcd. for C₁₅H₁₂N₂O₅[M]⁺300.0746; found 300.0743.

7-Methoxy-2-(naphthalen-1-yl)-3-nitrochroman (13p): Yield:

94 mg, 56 %. Colorless solid. M.p. 157–158 °C. ¹H NMR (400 MHz,

CDCl₃): δ = 8.13 (d, J = 8.4 Hz, 1 H), 7.93–7.87 (m, 2 H), 7.63–7.52

(m, 3 H), 7.46–7.42 (m, 1 H), 7.06 (d, J = 8.4 Hz, 1 H), 6.61 (dd, J =

8.4, 2.5 Hz, 1 H), 6.56 (d, J = 2.5 Hz, 1 H), 6.42 (d, J = 5.9 Hz, 1 H),

5.39–5.34 (m, 1 H), 3.80 (s, 3 H), 3.57 (dd, J = 16.3, 6.9 Hz, 1 H), 3.15

(dd, J = 16.3, 5.2 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

160.0, 153.9, 134.0, 131.6, 130.1, 129.9, 129.3, 127.1, 126.1, 125.3,

124.9, 122.4, 109.1, 109.0, 101.5, 82.1, 75.5, 55.4, 27.6 ppm. HRMS

3-Nitro-2-(p-tolyl)chroman (13j): Yield: 87 mg, 65 %. Colorless

solid. M.p. 144–145 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.29 (d, J =

8.0 Hz, 2 H), 7.22–7.19 (m, 3 H), 7.15 (d, J = 7.5 Hz, 1 H), 7.00–6.95

(m, 2 H), 5.36 (d, J = 8.0 Hz, 1 H), 5.07–5.01 (m, 1 H), 3.66 (dd, J = (EI): calcd. for C₂₀H₁₇NO₄[M]⁺335.1158; found 335.1155.

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6-Bromo-3-nitro-2-phenylchroman (13q): Yield: 127 mg, 76 %.

121.7, 118.3, 114.4, 110.0, 84.6, 77.8, 55.3, 27.6 ppm. HRMS (EI):

Colorless solid. M.p. 146–147 °C. ¹H NMR (400 MHz, CDCl₃): δ = calcd. for C₂₀H₁₇NO₄[M]⁺335.1158; found 335.1160.

7.40–7.38 (m, 3 H), 7.37–7.35 (m, 2 H), 7.32–7.28 (m, 2 H), 6.86 (d,

3-(Naphthalen-1-yl)-2-nitro-2,3-dihydro-1H-benzo[f]chromene

J = 8.6 Hz, 1 H), 5.49 (d, J = 7.2 Hz, 1 H), 5.05–5.01 (m, 1 H), 3.61

(13x): Yield: 135 mg, 76 %. Colorless solid. M.p. 204–205 °C. ¹H NMR

(dd, J = 16.6, 8.4 Hz, 1 H), 3.25 (dd, J = 16.6, 5.4 Hz, 1 H) ppm. ¹³C

(400 MHz, CDCl₃): δ = 8.20 (d, J = 8.4 Hz, 1 H), 7.94–7.85 (m, 3 H),

7.80–7.76 (m, 2 H), 7.62–7.54 (m, 4 H), 7.47–7.40 (m, 2 H), 7.22 (d,

NMR (100 MHz, CDCl₃): δ = 152.3, 135.5, 131.8, 131.5, 129.5, 129.0,

126.5, 119.8, 118.8, 114.0, 83.2, 77.9, 28.7 ppm. HRMS (EI): calcd. for

J = 9.0 Hz, 1 H), 6.48 (d, J = 6.3 Hz, 1 H), 5.60–5.55 (m, 1 H), 3.97

C₁₅H₁₂BrNO₃[M]⁺333.0001; found 333.0003.

(dd, J = 16.7, 6.9 Hz, 1 H), 3.50 (dd, J = 16.7, 5.6 Hz, 1 H) ppm. ¹³C

NMR (100 MHz, CDCl₃): δ = 151.0, 134.0, 132.2, 131.2, 130.3, 130.1,

129.6, 129.3, 129.2, 128.8, 127.2, 127.1, 126.1, 125.3, 125.0, 124.2,

122.5, 121.6, 118.2, 109.4, 82.3, 77.2, 75.3, 25.4 ppm. HRMS (EI):

calcd. for C₂₃H₁₇NO₃[M]⁺355.1208; found 355.1213.

6-Bromo-2-(4-chlorophenyl)-3-nitrochroman (13r): Yield:

159 mg, 86 %. Colorless solid. M.p. 167–168 °C. H NMR (400 MHz,

1

CDCl₃): δ = 7.39–7.36 (m, 2 H), 7.32–7.28 (m, 4 H), 6.85 (d, J = 8.6 Hz,

1 H), 5.42 (d, J = 7.6 Hz, 1 H), 4.97 (ddd, J = 8.8, 7.6, 5.4 Hz, 1 H),

3.62 (dd, J = 16.6, 8.8 Hz, 1 H), 3.27 (dd, J = 16.6, 5.4 Hz, 1 H) ppm.

¹³C NMR (100 MHz, CDCl₃): δ = 152.1, 135.6, 133.9, 131.8, 131.6,

129.3, 128.0, 119.6, 118.8, 114.3, 83.2, 29.0 ppm. HRMS (EI): calcd.

for C₁₅H₁₁BrClNO₃[M]⁺368.9611; found 368.9612.

Acknowledgments

Financial support from the Ministry of Science and Technology

of the Republic of China (MOST 103-2113-M-003-008-MY3), the

National Taiwan Normal University (103-07-C), and the Instru-

mentation Centre at National Taiwan Normal University is grate-

fully acknowledged. The authors are grateful to Mr. Ting-Shen

Kuo, Hsiu-Ni Huang, Mei-Ling Chen, and Chiu-Hui He for provid-

ing single-crystal X-ray, MS, HRMS, and NMR data.

6-Bromo-2-(4-methoxyphenyl)-3-nitrochroman (13s): Yield:

1

129 mg, 71 %. Colorless solid. M.p. 158–159 °C. H NMR (400 MHz,

CDCl₃): δ = 7.30–7.28 (m, 4 H), 6.93–6.90 (m, 2 H), 6.84 (d, J = 8.4 Hz,

1 H), 5.35 (d, J = 7.8 Hz, 1 H), 5.01 (ddd, J = 9.0, 7.8, 5.4 Hz, 1 H),

3.81 (s, 3 H), 3.62 (dd, J = 16.4, 9.0 Hz, 1 H), 3.28 (dd, J = 16.4, 5.4 Hz,

1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 160.5, 152.5, 131.8, 131.4,

128.1, 127.2, 119.9, 118.8, 114.4, 113.9, 83.4, 77.9, 55.3, 29.4 ppm.

HRMS (EI): calcd. for C₁₇H₁₈BrNO₄[M]⁺363.0106; found 363.0103.

Keywords: Nitroalkenes · Oxygen heterocycles · Nef

reaction · Synthesis design · Cyclization

6-Bromo-2-(naphthalen-1-yl)-3-nitrochroman (13t): Yield:

132 mg, 69 %. Colorless solid. M.p. 182–183 °C. H NMR (400 MHz,

1

CDCl₃): δ = 8.10 (d, J = 84 Hz, 1 H), 7.94–7.87 (m, 2 H), 7.64–7.54

(m, 2 H), 7.47–7.41 (m, 2 H), 7.35 (dd, J = 8.7, 2.4 Hz, 1 H), 7.30 (d,

J = 2.4 Hz, 1 H), 6.91 (d, J = 8.7 Hz, 1 H), 6.52 (d, J = 5.2 Hz, 1 H),

5.37–5.32 (m, 1 H), 3.56 (dd, J = 17.0, 6.1 Hz, 1 H), 3.11 (dd, J = 17.0,

5.1 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 152.2, 134.0, 131.9,

131.7, 131.4, 130.1, 129.7, 129.4, 127.3, 126.2, 125.3, 124.5, 122.1,

119.3, 118.5, 113.9, 81.2, 75.5, 27.0 ppm. HRMS (EI): calcd. for

C₁₉H₁₄BrNO₃[M]⁺383.0157; found 383.0149.

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2-Nitro-3-phenyl-2,3-dihydro-1H-benzo[f]chromene (13u): Yield:

1

111 mg, 73 %. Colorless solid. M.p. 188–189 °C. H NMR (400 MHz,

CDCl₃): δ = 7.83 (d, J = 8.0 Hz, 1 H), 7.77–7.72 (m, 2 H), 7.58–7.54

(m, 1 H), 7.46–7.41 (m, 6 H), 7.18 (d, J = 9.0 Hz, 1 H), 5.49 (d, J =

8.1 Hz, 1 H), 5.24–5.18 (m, 1 H), 3.89 (dd, J = 16.3, 9.0 Hz, 1 H), 3.67

(dd, J = 16.3, 5.8 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

151.1, 135.5, 132.2, 129.5, 129.1, 129.0, 128.7, 127.2, 126.9, 124.3,

121.7, 118.3, 109.9, 84.4, 77.9, 27.0 ppm. HRMS (EI): calcd. for

C₁₉H₁₅NO₃[M]⁺305.1052; found 305.1046.

3-(4-Chlorophenyl)-2-nitro-2,3-dihydro-1H-benzo[f]chromene

(13v): Yield: 132 mg, 78 %. Colorless solid. M.p. 181–182 °C. ¹H NMR

(400 MHz, CDCl₃): δ = 7.84 (d, J = 7.8 Hz, 1 H), 7.77–7.72 (m, 2 H),

7.59–7.55 (m, 1 H), 7.47–7.43 (m, 1 H), 7.4 (s, 4 H), 7.16 (d, J = 9.0 Hz,

1 H), 5.43 (d, J = 8.3 Hz, 1 H), 5.18–5.12 (m, 1 H), 3.88 (dd, J = 16.3,

9.2 Hz, 1 H), 3.69 (dd, J = 16.3, 5.9 Hz, 1 H) ppm. ¹³C NMR (100 MHz,

CDCl₃): δ = 150.9, 135.6, 134.0, 132.1, 129.5, 129.3, 129.2, 128.8,

128.4, 127.3, 124.4, 121.7, 118.2, 109.9, 84.4, 27.7 ppm. HRMS (EI):

calcd. for C₁₉H₁₄ClNO₃[M]⁺339.0662; found 339.0663.

3-(4-Methoxyphenyl)-2-nitro-2,3-dihydro-1H-benzo[f]chromene

(13w): Yield: 117 mg, 70 %. Colorless solid. M.p. 186–187 °C. ¹H

NMR (400 MHz, CDCl₃): δ = 7.83 (d, J = 8.0 Hz, 1 H), 7.77–7.71 (m,

2 H), 7.58–7.54 (m, 1 H), 7.45–7.41 (m, 1 H), 7.40–7.36 (m, 2 H), 7.15

(d, J = 9.0 Hz, 1 H), 6.96–6.92 (m, 2 H), 5.38 (d, J = 8.5 Hz, 1 H),

5.21–5.15 (m, 1 H), 3.87 (dd, J = 16.2, 9.4 Hz, 1 H), 3.82 (s, 3 H), 3.71

(dd, J = 16.2, 5.9 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ =

160.5, 151.3, 132.2, 129.5, 129.0, 128.7, 128.4, 127.3, 127.2, 124.3,

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Received: March 14, 2016

Published Online: April 28, 2016

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Syntheses of 2-Benzylbenzofuran Derivatives and 2-Aryl-nitrochroman Derivatives from Nitroalkene Precursors

DOI: 10.1002/ejoc.201600314

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