A facile synthesis of 2h-chromenes and 9-functionalized phenanthrenes through reactions between α,β-unsaturated compounds and arynes

DOI: 10.1002/ejoc.201200042

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European Journal of Organic Chemistry p. 3507 - 3519 (2012)

Update date:2022-08-05

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Authors:

Zhang, Tiexin

Huang, Xian

Wu, Luling

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Article abstract of DOI:10.1002/ejoc.201200042

Facile syntheses of 2H-chromenes or 9-functionalized phenanthrenes under mild conditions in moderate to good yields have been developed. They each involve annulations of arynes with α,β-unsaturated compounds bearing different electron-withdrawing groups (EWGs). Depending on the natures of the different EWGs, the reactions proceed by different pathways: enals react with arynes through a tandem [2+2] cycloaddition/thermal electrocyclic ring-opening/6e-electrocyclization sequence to afford 2H-chromenes, whereas acyl-/ethoxycarbonyl-/cyano-substituted styrenes undergo Diels-Alder reactions with arynes followed by aromatization to afford 9-functionalized phenanthrenes. The scope, limitations, regioselectivities and mechanisms have been studied and are discussed in detail. Depending on the natures of different EWGs in α,β-unsaturated compounds, the reactions between arynes and α,β-unsaturated compounds proceed by different tandem pathways to afford either 2H-chromenes or 9-functionalized phenanthrenes in a selective manner, which is of potential pharmaceutical interest.

Full text of DOI:10.1002/ejoc.201200042

FULL PAPER

DOI: 10.1002/ejoc.201200042

A Facile Synthesis of 2H-Chromenes and 9-Functionalized Phenanthrenes

through Reactions between α,β-Unsaturated Compounds and Arynes

Tiexin Zhang,^[a]Xian Huang,^[a,b][‡]and Luling Wu*^[a]

Keywords: Arynes / Cyclization / Domino reactions / Chromenes / Phenanthrenes

Facile syntheses of 2H-chromenes or 9-functionalized phen-

anthrenes under mild conditions in moderate to good yields

have been developed. They each involve annulations of

arynes with α,β-unsaturated compounds bearing different

electron-withdrawing groups (EWGs). Depending on the na-

tures of the different EWGs, the reactions proceed by dif-

ferent pathways: enals react with arynes through a tandem

[2+2] cycloaddition/thermal electrocyclic ring-opening/6e-

electrocyclization sequence to afford 2H-chromenes,

whereas acyl-/ethoxycarbonyl-/cyano-substituted styrenes

undergo Diels–Alder reactions with arynes followed by aro-

matization to afford 9-functionalized phenanthrenes. The

scope, limitations, regioselectivities and mechanisms have

been studied and are discussed in detail.

Introduction

2H-Chromenes and their analogues constitute a signifi-

cant family of scaffolds found in naturally existing and arti-

ficial molecules and exhibit unique biological/pharmacolog-

ical activities^[1]and outstanding photochromic properties.^[2]

Ageratochromenes I and II (Figure 1a), for example, ini-

tially isolated from Ageratum houstonianum, are important

because of their insecticidal activities, including the abilities

to induce precocious metamorphosis.^[1c]Although 2H-

chromenes have attracted much synthetic interest,^[3]new ef-

ficient routes are still highly desirable.

Phenanthrenes, on the other hand, are the fundamental

building blocks of many organic compounds.^[4]PBT-1 (Fig-

ure 1b), well-known for its inhibition of the growth of can-

cer cells, is difficult to obtain because of the multi-step syn-

thesis of 9-carbonylphenanthrenes en route (Figure 1c).^[5]

New, concise constructions of 9-carbonylphenanthrenes

were thus essential for the rapid assembly of PBT-1 and its

analogues.

Figure 1. 2H-Chromenes and 9-functionalized phenanthrenes with

biological/pharmacological acivities.

years.^[8][2+2] Cycloadditions^[9,10]of arynes can provide

highly strained benzannulated four-membered rings,^[11]

which tend to undergo ring-opening to afford the important

intermediates A [Figure 2, Equation (a)] for further trans-

formations. In Suzuki’s pioneering contribution,^[6a,6f,9d]

[2+2] cycloadditions between arynes and alkenes afforded

stable benzocyclobutenes that were found to be hard to

isomerize to ortho-quinodimethanes^[12][Figure 2, Equa-

tion (a), X = C] by thermal electrocyclic ring-opening with-

out heating. [2+2] Cycloadditions between carbon–hetero-

atom double bonds and arynes have been much less widely

studied and are still challenging in relation to those between

alkenes and arynes. The heteroatom-containing [2+2] ad-

ducts tend, however, to undergo ring-opening at lower tem-

peratures, owing to their high ring strain, and can then be

trapped with subsequent reagents, which resulted in a tan-

dem strategy for facile construction of benzoheterocycles

[Figure 2, Equation (a), X = heteroatom]:^[10,13]trapping of

The reactions of highly reactive arynes^[6,7]have been ex-

tensively developed as powerful tools in organic synthesis.

The innovation of fluoride-induced in-situ generation of

arynes from silylaryl triflates under mild conditions has nat-

urally resulted in rapid progress in aryne chemistry in recent

[a] Department of Chemistry, Zhejiang University (Xixi Campus),

Hangzhou 310028, People’s Republic of China

Fax: +86-571-88807077

E-mail: wululing@zju.edu.cn

[b] State Key Laboratory of Organometallic Chemistry, Shanghai

Institute of Organic Chemistry, Chinese Academy of Sciences,

Shanghai 200032, People’s Republic of China

[‡] Prof. Huang passed away on March 6, 2010. He had been fully

in charge of this project. At this moment, Prof. Luling Wu is

helping in finishing all the projects with the assistance of Prof.

Shengming Ma

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201200042.

Eur. J. Org. Chem. 2012, 3507–3519

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the aryne–aldehyde [2+2] adduct with an additional aryne 6e-electrocyclization sequence [Figure 2, Equation (d)]. In

was reported by Yoshida [Figure 2, Equation (b)],^[13g]dialk- the pioneering work of Heaney, tetrachlorobenzenediazon-

ylzinc reagents have been shown to be effective in trapping ium-2-carboxylate was employed as the aryne precursor in

the [2+2] adducts of formamide with arynes^[13c][Figure 2, reactions with cinnamaldehydes (40 equiv.), giving 2H-

Equation (c)], and enolates of esters^[13a]and ketenimine chromenes in 4–58% yields.^[14a]Here we report a facile syn-

anions^[13b]have very recently also been successfully utilized thesis of 2H-chromenes by the tandem protocol described

in [4+2] cycloadditions with the intermediates A.

above with use of α,β-unsaturated enals and arynes gener-

ated from silylaryl triflates under very mild conditions.

Interestingly, when the aldehyde functionality was changed

to ketone, ester or nitrile, the reactions proceeded through

a totally different aryne Diels–Alder/aromatization se-

quence to afford 9-functionalized phenanthrenes.

Results and Discussion

Synthesis of 2H-Chromenes 3 by a Formal [2+2]

Cycloaddition/Thermal Electrocyclic Ring-Opening/6e-

Electrocyclization Sequence with Enals 1 and Arynes

Produced from o-(Trimethylsilyl)aryl Triflates 2

A preliminary experiment was conducted in acetonitrile

at 75 °C, with 3-(4-methoxyphenyl)propenal (1a, Table 1),

o-(trimethylsilyl)phenyl triflate (2a) and CsF in a ratio of

1:1.5:3. The reaction went to completion within 24 h

(Table 1, Entry 1) to afford the expected product 2-(4-meth-

oxyphenyl)-2H-chromene (3a, 40% yield), together with re-

covered 1a (25%). Efforts to optimize the reaction condi-

tions to improve the yield of 3a were then made. Mixed

solvents with different ratios of acetonitrile and toluene

were tested to control the rate of in-situ generation of aryne

Figure 2. [2+2] Cycloadditions of C=X with arynes and further

trapping reactions.

In view of these impressive results, we considered it from 2a (Entries 2–6). It was found that the reaction in

worthwhile to examine the feasibility of trapping formal MeCN/PhMe (1:4, v/v) afforded 3a in an improved yield of

aryne/C=O [2+2] adducts intramolecularly with alkenes to 51% with a 20% yield of 1a being recovered (Entry 5). The

furnish a tandem aryne [2+2] cycloaddition/ring-opening/ yield of 3a was not improved with more equivalents of

Table 1. Optimization of reaction conditions for the synthesis of 2-(4-methoxyphenyl)-2H-chromene (3a).^[a]

Entry

[equiv.]

CsF

[equiv.]

MeCN/PhMe

[v/v]

[°C]

Addition time of 2a^[b]Time of reaction^[c]Yield of 3a^[d]

Recovery of 1a^[d]

[h]

[%]

1.5

2.0

2.5

3.0

1:0

1:1

1:2

1:3

1:4

1:9

1:4

–

10.5

12.5

3.5

[a] The reaction was conducted with 1a (0.5 mmol), the specified amount of CsF and 2a in anhydrous solvent (5.0 mL). [b] When 2a was

added by microinfusion syringe pump, the addition rate of 2a was approximately 0.12 mmolh^–1. [c] Reaction times after addition of 2a.

[d] Isolated yields.

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Synthesis of 2H-Chromenes and 9-Functionalized Phenanthrenes

aryne (Entries 7, 8). Interestingly, though, when a solution corresponding 2,2-disubstituted 2H-chromenes in moderate

of aryne precursor 2a (2.5 equiv.) in MeCN/PhMe (1:4, v/ to good yields (Entries 7–11).

v, 2.5 mL) was added slowly by microinfusion syringe pump

We next investigated the tandem reactions of substituted

to a stirred mixture of 1a and CsF in MeCN/PhMe (1:4, arynes. Reactions utilizing 1i and symmetrical arynes (from

v/v, 2.5 mL) over 10.5 h, 93% of 1a could be converted to 2b and 2c) proceeded efficiently to give polysubstituted 2H-

afford 3a (53% yield) after additional stirring for 24 h (En- chromenes in yields of 77% and 98%, respectively (Table 2,

try 9). In order to consume all 2a, slow addition of 2a Entries 12, 13).

(3 equiv.) in MeCN/PhMe (1:4, v/v, 2.5 mL) by microin-

It should be noted that when (2-bornyliden)acetaldehyde

fusion syringe pump over 12.5 h was used, and the yield of (1m) was employed, the unsymmetrical bornylidene moiety

3a was improved to 59%. If the reaction was conducted at could be successfully introduced into the C2 position of the

a lower temperature or with a reduced amount of CsF, 2H-chromene scaffold stereoselectively, with the structure

lower yields of 3a and longer reaction times were observed of the resulting product 3o being determined by a 2D NOE

(Entries 11, 12).

experiment [Equation (1)].

With the optimized conditions to hand, the scope and

limitations of this process were then examined with various

enals 1 and aryne precursors 2. Typical results are summa-

rized in Table 2. Firstly, when β-aryl enals 1b–1f were em-

ployed, lower to good yields of the corresponding 2-aryl-

2H-chromenes 3b–3f could be obtained, indicating the re-

markable electronic effect of the substituents. Enals bearing

electron-donating groups on the β-aryl substituents gave

higher yields of products, probably due to the enhancement

of the nucleophilicities of the aldehyde groups by the elec-

(1)

To establish the regiochemistry of this protocol, the un-

tron-donating groups (Table 1, Entry 10 and Table 2, En- symmetrical 3-methoxy-substituted aryne (from 2d) was

tries 1, 2).^[13g]When α-methyl enal 1g was used, 3-methyl- employed in the reaction with 1i, leading to the formation

2H-chromene 3g was afforded in a lower yield (relative to of only one regioisomer – 3p – in 75% yield, as determined

that of Table 1, Entry 10) of 33%, which implied consider- by a 2D NOE experiment [Equation (2)]. The regioselecti-

able steric hindrance by the α-methyl group of 1g in the vity could be explained in terms of the electronic and

reaction. Secondly, β,β-disubstituted enals 1h–1l were found steric factors during the initial step of this reaction

also to participate smoothly in the reactions to afford the (Scheme 1).^[12a]

Table 2. Synthesis of 2H-chromenes through the reactions between enals 1 and symmetrical arynes.^[a]

Entry

R¹/R²/R³(1)

R⁴(2)/equiv. of 2

Time^[b][h]

Yield of 3^[c][%]

H/H/2-MeOC₆H₄(1b)

H/H/4-MeC₆H₄(1c)

H/H/C₆H₅(1d)

H/H/4-BrC₆H₄(1e)

H/H/4-FC₆H₄(1f)

H (2a)/3.0

H (2a)/4.0

H (2a)/4.5

H (2a)/3.0

H (2a)/3.7

H (2a)/3.0

4,5-Me₂(2b)/3.0

4,5-F₂(2c)/3.0

120

70 (3b)

66 (3c)

45 (3d)

34 (3e)

22 (3f)^[d]

33 (3g)

61 (3h)

80 (3i)

Me/H/4-MeOC₆H₄(1g)

H/4-MeOC₆H₄/4-MeOC₆H₄(1h)

H/C₆H₅/C₆H₅(1i)

H/C₆H₅/4-MeOC₆H₄(1j)

H/Me/3-MeOC₆H₄(1k)

H/Me/iBu (1l)

61 (3j)

52 (3k)

31 (3l)^[e]

77 (3m)

98 (3n)^[f]

H/C₆H₅/C₆H₅(1i)

[a] Reaction conditions: a solution of 2 (1.5 mmol) in MeCN/PhMe (1:4, v/v, 2.5 mL) was added by microinfusion syringe pump at 75 °C

to a stirred mixture of 1 (0.5 mmol) and CsF (3.0 mmol) in MeCN/PhMe (1:4, v/v, 2.5 mL) over 12.5 h. The reaction mixture was then

stirred for a specified time until the completion of the reaction. [b] Subsequent stirring time needed after slow addition of the solution

of 2 until completion of reaction. [c] Isolated yields. [d] The reaction was conducted at 85 °C. [e] A solution of 1l (0.5 mmol) in MeCN/

PhMe (1:4, v/v, 2.5 mL) was added by microinfusion syringe pump under N₂to a stirred mixture of 2a (1.5 mmol) and CsF (3.0 mmol)

in MeCN/PhMe (1:4, v/v, 2.5 mL) over 5 h and the stirring was then continued until the completion of reaction. [f] Conducted on a

0.3 mmol scale.

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Firstly, under the same reaction conditions as in Entry 10 in

Table 1, 1-(3-methoxyphenyl)-3-phenylpropenone (4a) was

employed to react with benzyne (from 2a). The expected

tandem reaction triggered by the formal aryne/C=O [2+2]

cycloaddition did not take place, however, probably due to

the increased steric hindrance of the ketone functionality in

4a relative to the aldehyde functionality of 1. Interestingly,

though, a sequential aryne Diels–Alder/aromatization reac-

tion with the styrene moiety of 4a was observed, providing

9-aroylphenanthrene 5a (41% yield) as the main product,

along with a 27% isolated yield of the byproduct 6a, pre-

sumably formed from the hydrogenation of 4a (Scheme 2).

Although aryne Diels–Alder reactions with cyclic dienes

have been extensively studied,^[15]sequential aryne Diels–Al-

der/aromatization reactions with acyclic dienes are still not

well developed.^[16]

(2)

Scheme 1. Steric and electronic factors in the initial formal [2+2]

cycloadditions between 1i and 3-methoxybenzyne (from 2d).

Synthesis of 9-Functionalized Phenanthrenes 5 by a Diels–

Alder/Aromatization Sequence with α,β-Unsaturated

Ketones/Esters/Nitriles 4 and Arynes Produced from

o-(Trimethylsilyl)aryl Triflates 2

Scheme 2. Reaction between 4a and aryne (from 2a).

On the basis of the reactions between the enals and the

arynes, we naturally sought to expand the scope of the reac-

To the best of our knowledge, sequential Diels–Alder/

tion to the synthesis of 4-substituted-2H-chromenes from dehydrogenation reactions between α,β-unsaturated com-

arynes and other α,β-unsaturated carbonyl compounds. pounds and arynes derived from silylaryl triflates have not

Table 3. Synthesis of 9-functionalized phenanthrenes 5 through the reactions between α,β-unsaturated ketones/ester/nitrile 4 and arynes.^[a]

Entry

EWG/R⁵(4)

R⁴(2)/equiv. of 2

Time [h]^[b]

Yield [%]^[c]

3-MeOC₆H₄CO/4-MeO (4b)

3-MeOC₆H₄CO/4-Me (4c)

2-MeOC₆H₄CO/4-Br (4d)

MeCO/4-MeO (4e)

H (2a)/3.0

49 (5b)

38 (5c)

35 (5d)

51 (5e)

52 (5f)

53 (5g)

0 (5h)

44 (6b)

37 (6c)^[d]

32 (6d)^[e]

41 (6e)

H (2a)/3.0

EtOCO/4-MeO (4f)

CN/4-MeO (4g)

NO₂/4-MeO(4h)

EtOCO/4-MeO (4f)

H (2a)/4.5

12 (6f)

H (2a)/4.5

16 (6g)

H (2a)/3.0

0 (6h)^[d,f]

trace (6f)^[d,g]

23 (6f)

4,5-Me₂(2b)/4.5

4,5-F₂(2c)/4.5

50 (5i)

55 (5j)

[a] Reactions were carried out on a 1.0 mmol scale under conditions similar to those of Entry 10 in Table 1. [b] Subsequent stirring time

after slow addition of the solution of 2 until completion of the reaction. [c] Isolated yields. [d] Conducted on a 0.5 mmol scale. [e] Con-

ducted on a 0.3 mmol scale. [f] Unknown mixtures were formed. [g] Formation of 6f was detected by H NMR examination of the crude

reaction mixture.

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Synthesis of 2H-Chromenes and 9-Functionalized Phenanthrenes

been researched, but might supply an efficient and mild me- 4a-D (Scheme 3) was prepared according to a literature

ans of access to 9-functionalized phenanthrenes en route to method.^[17]We then performed the reaction between 4a-D

PBT-1 derivatives.

and the aryne produced from 2a. The products 5a-D and

To test the scope and limitations of the sequential course, 6a-D were obtained in yields of 39% and 33%, respectively,

interactions between arynes and α,β-unsaturated com- and the corresponding ¹H NMR results showed that deute-

pounds bearing various electron-withdrawing groups rium incorporation at the C2 position of 6a-D was nearly

(EWGs) were examined. Some typical examples are listed 100% (Scheme 3; see the Experimental Section and the

in Table 3. When the EWGs were aroyl groups, compounds Supporting Information for details).

4 reacted smoothly with 2a to afford 9-aroylphenanthrenes

With the evidence of the deuterium incorporation shown

5 in moderate yields, together with the corresponding com- in Scheme 3 to hand, the mechanism of this reaction, espe-

pounds 6 in slightly lower yields (Table 3, Entries 1–3). A cially of the formation of 5 and 6, could be explained

similar result was obtained with 4e, bearing an acetyl group (Scheme 4). After the fluoride-induced 1,2-elimination in

(Entry 4). Not only keto groups, but also ester and nitrile 2a, the aryne 7 could be generated in situ. It could then

groups were tolerated in the reactions, producing modest undergo a Diels–Alder reaction with 4a-D to form the in-

yields of the corresponding 9-functionalized phenanthrenes termediate 8. Through the subsequent path A, the α proton

5 and much smaller amounts of compounds 6 (Entries 5, of the carbonyl group of 8 could be abstracted by the fluo-

6). However, the reaction between 2a and 4h, containing a ride anion, which would afford the anionic intermediate 9.

nitro group, was not effective, resulting only in unknown

mixtures (Entry 7). After screening of a number of α,β-un-

saturated compounds, we turned our attention to substi-

tuted arynes. 4,5-Dimethyl- and 4,5-difluoro-substituted

arynes (from 2b and 2c) performed well in the reactions to

afford 5i and 5j in moderate yields (Table 3, Entries 8, 9).

When the unsymmetrical 3-methoxy-substituted aryne

generated from 2d was employed to react with 4f, the re-

gioisomer 5k was formed exclusively in 22% yield [Equa-

tion (3)]. On the other hand, only trace amounts of 6f were

detected by H NMR spectroscopy of the crude products

of the reaction. The lower yield of 5k might be attributable

to steric hindrance caused by the 3-methoxy group of the

aryne during the reaction. The regiochemistry of the reac-

tion relating to the formation of 5k was determined by a

2D NOE experiment.

Scheme 4. Proposed mechanism for the formation of 5a-D and 6a-

(3)

A Michael addition could then occur between the deute-

rium anion generated from 9 and a second 4a-D molecule

to give the aromatization product 5a-D and anionic inter-

Mechanistic Studies

mediate 10,^[18]which might be driven by the aromatization

In order to study the mechanism of this reaction, based and the migration of the negatively charged centre of 9.

on the formation of 5 and 6, deuterium-labelled substrate After protonation of 10, 6a-D would be formed. However,

Scheme 3. Isotopic distribution reaction between 4a-D and aryne (from 2a).

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T. Zhang, X. Huang, L. Wu

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luted with acetone (20 mL) and filtered through a short pad of

silica gel to remove insoluble substances. After concentration of the

filtrates under vacuum, the residue was purified by flash

chromatography on silica gel to afford 3.

path B, by which the intermediate 8 might be dehydro-

genized directly, probably by a single-electron transfer pro-

cess, to afford 5a-D, cannot be ruled out completely.^[19]

The fact that the yields of 5 are higher than those of 6

was consistent with this hypothesis. In some cases, com-

pounds 6 are produced only in trace amounts [Table 3, En-

try 8 and Equation (3)]. In view of the possibility of arynes

acting as the dehydrogenation reagents of intermediate 8,

GC-MS experiments were performed on the supernatants

of the reaction mixtures of Scheme 3 and Table 3, but

path C was not supported, because no signals of the corre-

sponding deuteriobenzene/benzene/o-xylene/o-F₂-benzene

products could be observed.^[20]This can be viewed as cir-

cumstantial evidence for path B.

2-(4-Methoxyphenyl)-2H-chromene (3a): The General Procedure

with 1a (0.082 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a

(0.449 g, 1.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF

(0.464 g, 3.05 mmol) afforded 3a^[25](0.070 g, 59%) as a clear oil

{purified by flash chromatography [gradient eluents: petroleum

ether/dichloromethane (20:1, v/v) containing triethylamine (3‰),

then petroleum ether/ethyl acetate (80:1, v/v) containing triethyl-

amine (3‰)]; R_f= 0.47 [TLC eluent: petroleum ether/ethyl acetate

(40:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃): δ = 7.37 (d, J = 8.8 Hz,

2 H), 7.08 (td, J₁= 8.8, J₂= 1.6 Hz, 1 H), 7.00 (dd, J₁= 7.2, J₂=

1.2 Hz, 1 H), 6.89–6.82 (m, 3 H), 6.75 (d, J = 8.0 Hz, 1 H), 6.54

(dd, J₁= 9.6, J₂= 0.8 Hz, 1 H), 5.86–5.85 (m, 1 H), 5.77 (dd, J₁

= 9.6, J₂= 3.4 Hz, 1 H), 3.78 (s, 3 H) ppm. ¹³C NMR (90 MHz,

CDCl₃): δ = 55.2, 76.7, 113.9, 116.0, 121.0, 121.3, 124.0, 124.9,

Conclusions

126.5, 128.6, 129.4, 132.8, 153.0, 159.7 ppm. IR (neat): ν = 2933,

We have developed facile and mild syntheses of 2H-

chromenes and 9-functionalized phenanthrenes starting

from commercially available or easily prepared α,β-unsatu-

rated compounds and aryne precursors in the presence of

CsF. The reaction pathways largely depend on the nature

2835, 1606, 1511, 1484, 1456, 1303, 1247, 1204, 1173, 1109, 1033,

955, 830, 801, 754, 692 cm^–1. MS (70 eV, EI): m/z (%) = 238 (100.0)

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

238.0997.

2-(2-Methoxyphenyl)-2H-chromene (3b): The General Procedure

of the EWGs of the α,β-unsaturated compounds: enals and with 1b (0.081 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a

(0.444 g, 1.48 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF

(0.462 g, 3.04 mmol) afforded 3b^[26](0.083 g, 70%) as a clear oil

{purified by flash chromatography [gradient eluents: petroleum

ether/dichloromethane (20:1, v/v) containing triethylamine (3‰),

then petroleum ether/ethyl acetate (80:1, v/v) containing triethyl-

amine (3‰)]; R_f= 0.52 [TLC eluent: petroleum ether/ethyl acetate

(40:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃): δ = 7.49 (d, J = 8.0 Hz,

1 H), 7.29–7.22 (m, 1 H), 7.10 (t, J = 7.8 Hz, 1 H), 6.98–6.80 (m,

5 H), 6.46 (d, J = 9.6 Hz, 1 H), 6.35–6.34 (m, 1 H), 5.78 (dd, J₁=

10.0, J₂= 3.6 Hz, 1 H), 3.84 (s, 3 H) ppm. ¹³C NMR (90 MHz,

arynes undergo a tandem [2+2] cycloaddition/thermal elec-

trocyclic ring-opening/6e-electrocyclization course, whereas

α,β-unsaturated ketones/esters/nitriles react with arynes

through a Diels–Alder/aromatization sequence, as is sup-

ported by the result of the isotopic distribution experiment.

The electronic effects of these reactions are remarkable; in

general, substrates bearing electron-donating groups on the

β-aryl substituents afforded higher yields of products. The

regiochemistry of the reaction with unsymmetrical arynes

has been examined, and the results could be explained by CDCl₃): δ = 55.5, 71.6, 110.6, 115.8, 120.8, 121.0, 121.3, 123.3,

125.0, 126.5, 127.7, 129.1, 129.2, 129.3, 153.6, 155.8 ppm. IR

electronic and/or steric factors. Further studies in this area

are being conducted in this laboratory.

(neat): ν = 2937, 1598, 1486, 1457, 1353, 1228, 1160, 1107, 1029,

955, 833, 749, 697, 633 cm^–1. MS (70 eV, EI): m/z (%) = 238 (100.0)

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

238.0995.

Experimental Section

2-(4-Methylphenyl)-2H-chromene (3c): The General Procedure with

1c (0.074 g, 0.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a

(0.599 g, 2.01 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF

(0.464 g, 3.05 mmol) afforded 3c^[26a](0.073 g, 66%) as a clear oil

{purified by flash chromatography [eluent: petroleum ether/dichlo-

romethane (20:1, v/v) containing triethylamine (3‰)]; R_f= 0.48

General Remarks: All H and ¹³C NMR spectra were measured in

CDCl₃or [D₆]acetone with a 400 MHz spectrometer and with TMS

as the internal standard. Chemical shifts are expressed in ppm, and

J values are given in Hz. Anhydrous solvents were distilled prior

to use: PhMe was distilled from sodium/benzophenone, and

CH₃CN was distilled from CaH₂. Reagents in the solid state were

used as received without further purification. Petroleum ether re-

fers to the fraction with boiling point in the 60–90 °C range. Melt-

ing points are uncorrected.

[TLC eluent: petroleum ether/ethyl acetate (40:1, v/v)]}. H NMR

(400 MHz, [D₆]acetone): δ = 7.33 (d, J = 8.0 Hz, 2 H), 7.17 (d, J

= 7.2 Hz, 2 H), 7.12–7.05 (m, 2 H), 6.84 (td, J₁= 7.6, J₂= 1.0 Hz,

1 H), 6.71 (d, J = 8.0 Hz, 1 H), 6.60 (dd, J₁= 11.0, J₂= 3.2 Hz, 1

H), 5.89–5.87 (m, 2 H), 2.30 (s, 3 H) ppm. ¹³C NMR (90 MHz,

[D₆]acetone): δ = 21.0, 77.2, 116.5, 121.8, 122.3, 124.3, 126.0, 127.3,

General Methods for Preparation of Starting Materials: The starting

materials 1a–1g,^[17]4a–4e,^[17]4a-D,^[17]4g,^[21a]4h,^[21b]1h–1j,^[22a–22c]

1m,^[22d]1k–1l,^[23]4f^[23a]and 2a–2d^[24]were prepared according to

literature procedures.

127.7, 129.8, 130.0, 138.6, 138.9, 154.0 ppm. IR (neat): ν = 2922,

2853, 1638, 1484, 1456, 1228, 1204, 1111, 1041, 786, 755 cm^–1. MS

(70 eV, EI): m/z (%) = 222 (100.0) [M]⁺. HRMS (EI): calcd. for

C₁₆H₁₄O [M]⁺222.1045; found 222.1049.

General Procedure for the Synthesis of 2H-Chromenes 3 (Except for

3l and 3o): A solution of 2 (1.5 mmol) in MeCN/PhMe [1:4 (v/v),

2.5 mL, anhydrous] was added by microinfusion syringe pump at

75 °C over 12.5 h to a mixture of 1 (0.5 mmol) and CsF (3.0 mmol)

in MeCN/PhMe [1:4 (v/v), 2.5 mL, anhydrous] in a dry Schlenk

tube. The resulting mixture was then stirred until completion of the

reaction (monitored by TLC). The reaction mixture was then di-

2-Phenyl-2H-chromene (3d): The General Procedure with 1d

(0.067 g, 0.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a (0.668 g,

2.24 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF (0.467 g,

3.07 mmol) afforded 3d^[27](0.047 g, 45%) as a clear oil {purified

by flash chromatography [gradient eluents: petroleum ether/dichlo-

3512

www.eurjoc.org

Eur. J. Org. Chem. 2012, 3507–3519

Synthesis of 2H-Chromenes and 9-Functionalized Phenanthrenes

romethane (20:1, v/v) containing triethylamine (3‰), then petro-

leum ether/ethyl acetate (80:1, v/v) containing triethylamine (3‰)];

R_f= 0.71 [TLC eluent: petroleum ether/ethyl acetate (40:1, v/v)]}.

152.3, 160.8 ppm. IR (neat): ν = 2980, 2902, 1608, 1511, 1485,

1404, 1247, 1176, 1052, 877, 755 cm^–1. MS (70 eV, EI): m/z (%) =

252 (33.9) [M]⁺, 237 (100.0). HRMS (EI): calcd. for C₁₇H₁₆O₂

¹H NMR (400 MHz, [D₆]acetone): δ = 7.48–7.46 (m, 2 H), 7.39– [M]⁺252.1150; found 252.1147.

7.30 (m, 3 H), 7.11 (td, J₁= 7.6, J₂= 1.2 Hz, 1 H), 7.07 (dd, J₁=

2,2-Bis(4-methoxyphenyl)-2H-benzopyran (3h): The General Pro-

7.4, J₂= 1.4 Hz, 1 H), 6.86 (td, J₁= 7.2, J₂= 1.2 Hz, 1 H), 6.74

(d, J = 8.0 Hz, 1 H), 6.61 (d, J = 9.6 Hz, 1 H), 5.96–5.94 (m, 1 H),

5.92 (dd, J₁= 9.6, J₂= 3.6 Hz, 1 H) ppm. ¹³C NMR (90 MHz,

[D₆]acetone): δ = 77.4, 116.4, 121.8, 122.3, 124.3, 125.9, 127.4,

cedure with 1h (0.134 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2a (0.449 g, 1.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.469 g, 3.08 mmol) afforded 3h^[28](0.105 g, 61%) as a

pale white solid; m.p. 92–94 °C {recrystallized from petroleum

ether/ethyl acetate (40:1, v/v) after purification by flash chromatog-

raphy [eluent: petroleum ether/ethyl acetate (40:1, v/v)]; R_f= 0.32

127.6, 128.9, 129.2, 130.1, 141.9, 154.0 ppm. IR (neat): ν = 2980,

2902, 1404, 1251, 1056, 893 cm^–1. MS (70 eV, EI): m/z (%) = 208

(100.0) [M]⁺. HRMS (EI): calcd. for C₁₅H₁₂O [M]⁺208.0888;

found 208.0885.

[TLC eluent: petroleum ether/ethyl acetate (40:1, v/v)]}. H NMR

(400 MHz, CDCl₃): δ = 7.32 (d, J = 9.2 Hz, 4 H), 7.09 (t, J =

7.8 Hz, 1 H), 6.97 (d, J = 7.6 Hz, 1 H), 6.88–6.79 (m, 6 H), 6.56

(d, J = 10.0 Hz, 1 H), 6.08 (d, J = 10.0 Hz, 1 H), 3.75 (s, 6 H) ppm.

¹³C NMR (90 MHz, CDCl₃): δ = 55.2, 82.1, 113.4, 116.4, 121.0,

121.1, 122.9, 126.4, 128.3, 129.2, 129.4, 137.3, 152.5, 158.8 ppm.

2-(4-Bromophenyl)-2H-chromene (3e): The General Procedure with

1e (0.105 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a

(0.673 g, 2.26 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF

(0.460 g, 3.03 mmol) afforded 3e (0.050 g, 34%) as a clear oil

{purified by flash chromatography [gradient eluents: petroleum

ether/dichloromethane (20:1, v/v) containing triethylamine (3‰),

then petroleum ether/dichloromethane (10:1, v/v) containing trieth-

ylamine (3‰)]; R_f= 0.68 [TLC eluent: petroleum ether/ethyl acet-

IR (neat): ν = 2955, 2835, 1607, 1508, 1484, 1454, 1303, 1248, 1173,

1112, 1059, 1031, 984, 946, 827, 768, 754 cm^–1. MS (70 eV, EI): m/z

(%) = 344 (84.7) [M]⁺, 237 (100.0). HRMS (EI): calcd. for

C₂₃H₂₀O₃[M]⁺344.1412; found 344.1418.

ate (40:1, v/v)]}. H NMR (400 MHz, [D₆]acetone): δ = 7.56 (dd,

2,2-Diphenyl-2H-benzopyran (3i): The General Procedure with 1i

(0.104 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a (0.548 g,

1.84 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF (0.459 g,

3.02 mmol) afforded 3i^[29](0.113 g, 80%) as a white solid; m.p. 84–

86 °C (ref.^[29]85–87 °C) {recrystallized from petroleum ether/ethyl

acetate (40:1, v/v) after purification by flash chromatography [elu-

ent: petroleum ether/ethyl acetate (20:1, v/v) containing triethyl-

amine (1‰)]}; R_f= 0.67 [TLC eluent: petroleum ether/ethyl acetate

J₁= 6.4, J₂= 1.6 Hz, 2 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.12 (td, J₁

= 7.8, J₂= 1.6 Hz, 1 H), 7.08 (dd, J₁= 7.6, J₂= 1.2 Hz, 1 H), 6.87

(td, J₁= 7.4, J₂= 1.0 Hz, 1 H), 6.75 (d, J = 8.0 Hz, 1 H), 6.64 (d,

J = 9.2 Hz, 1 H), 5.96–5.92 (m, 2 H) ppm. ¹³C NMR (90 MHz,

[D₆]acetone): δ = 76.5, 116.5, 122.0, 122.2, 122.4, 124.6, 125.4,

127.5, 129.6, 130.2, 132.3, 141.3, 153.7 ppm. IR (neat): ν = 2981,

2902, 1631, 1404, 1250, 1069, 893 cm^–1. MS (70 eV, EI): m/z (%) =

286 (9.6) [M(⁷⁹Br)]⁺, 288 (7.4) [M(⁸¹Br)]⁺, 208 (100.0). HRMS (EI):

calcd. for C₁₅H₁₁O⁷⁹Br [M]⁺285.9993; found 285.9996.

(40:1, v/v)]. H NMR (400 MHz, CDCl₃): δ = 7.42 (d, J = 7.6 Hz,

4 H), 7.32–7.21 (m, 6 H), 7.10 (t, J = 7.8 Hz, 1 H), 6.98 (d, J =

7.2 Hz, 1 H), 6.91 (d, J = 8.0 Hz, 1 H), 6.82 (t, J = 7.4 Hz, 1 H),

6.59 (d, J = 10.0 Hz, 1 H), 6.15 (d, J = 10.0 Hz, 1 H) ppm. ¹³C

NMR (90 MHz, CDCl₃): δ = 82.6, 116.5, 121.1, 121.2, 123.3, 126.6,

2-(4-Fluorophenyl)-2H-chromene (3f): The General Procedure with

1f (0.074 g, 0.49 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2a

(0.677 g, 2.27 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF

(0.455 g, 2.99 mmol) afforded 3f (0.025 g, 22%) as a clear oil

{purified by flash chromatography [eluent: petroleum ether/dichlo-

romethane (10:1, v/v) containing triethylamine (3‰)]; R_f= 0.49

127.0, 127.4, 128.1, 128.8, 129.5, 145.0, 152.5 ppm. IR (neat): ν =

3059, 1637, 1604, 1486, 1450, 1238, 1112, 1054, 988, 942, 755,

698 cm^–1. MS (70 eV, EI): m/z (%) = 284 (39.0) [M]⁺, 207 (100.0).

HRMS (EI): calcd. for C₂₁H₁₆O [M]⁺284.1201; found 284.1204.

[TLC eluent: petroleum ether/ethyl acetate (40:1, v/v)]}. H NMR

(400 MHz, [D₆]acetone): δ = 7.53–7.49 (m, 2 H), 7.16–7.07 (m, 4

H), 6.86 (td, J₁= 7.4, J₂= 1.0 Hz, 1 H), 6.73 (d, J = 8.0 Hz, 1 H),

6.64 (dd, J₁= 9.8, J₂= 0.6 Hz, 1 H), 5.97–5.96 (m, 1 H), 5.91 (dd,

J₁= 10.2, J₂= 3.8 Hz, 1 H) ppm. ¹³C NMR (90 MHz, [D₆]ace-

tone): δ = 76.6, 116.0 (d, J = 19.5 Hz), 116.6, 122.0, 122.3, 124.6,

125.7, 127.5, 129.8 (d, J = 6.9 Hz), 130.2, 138.1 (d, J = 2.8 Hz),

2-(4-Methoxyphenyl)-2-phenyl-2H-benzopyran (3j): The General

Procedure with 1j (0.119 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2a (0.449 g, 1.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.464 g, 3.05 mmol) afforded 3j (0.095 g, 61%) as a white

solid; m.p. 80–82 °C {recrystallized from petroleum ether/ethyl

acetate (10:1, v/v) after purification by flash chromatography [elu-

ent: petroleum ether/ethyl acetate (10:1, v/v)]; R_f= 0.70 [TLC elu-

ent: petroleum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR

(400 MHz, CDCl₃): δ = 7.42 (d, J = 7.6 Hz, 2 H), 7.34–7.28 (m, 4

H), 7.23 (t, J = 7.6 Hz, 1 H), 7.09 (t, J = 7.6 Hz, 1 H), 6.98 (d, J

= 7.2 Hz, 1 H), 6.89 (d, J = 7.6 Hz, 1 H), 6.83–6.79 (m, 3 H), 6.57

(d, J = 10.0 Hz, 1 H), 6.11 (d, J = 10.0 Hz, 1 H), 3.74 (s, 3 H) ppm.

¹³C NMR (90 MHz, CDCl₃): δ = 55.2, 82.3, 113.4, 116.4, 121.1,

123.1, 126.5, 126.8, 127.3, 128.0, 128.4, 129.0, 129.4, 137.0, 145.2,

153.8, 163.4 (d, J = 219.4 Hz) ppm. IR (neat): ν = 2982, 2903,

1738, 1602, 1508, 1456, 1409, 1232, 1157, 1063, 839, 758 cm^–1. MS

(70 eV, EI): m/z (%) = 226 (93.8) [M]⁺, 225 (100.0) [M – 1]⁺. HRMS

(EI): calcd. for C₁₅H₁₁OF [M]⁺226.0794; found 226.0797.

2-(4-Methoxyphenyl)-3-methyl-2H-benzopyran (3 g): The General

Procedure with 1g (0.088 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2a (0.449 g, 1.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.469 g, 3.08 mmol) afforded 3g (0.041 g, 33%) as a clear

oil {purified by flash chromatography [gradient eluents: petroleum

ether/dichloromethane (10:1, v/v) containing triethylamine (3‰),

then petroleum ether/dichloromethane (7:1, v/v) containing trieth-

ylamine (3‰)]; R_f= 0.39 [TLC eluent: petroleum ether/ethyl acet-

152.5, 158.9 ppm. IR (neat): ν = 2957, 1607, 1509, 1485, 1452,

1304, 1242, 1174, 1112, 1057, 1033, 986, 943, 830, 756, 700 cm^–1.

MS (70 eV, EI): m/z (%) = 314 (78.1) [M]⁺, 237 (100.0). HRMS

(EI): calcd. for C₂₂H₁₈O₂[M]⁺314.1307; found 314.1315.

ate (40:1, v/v)]}. H NMR (400 MHz, [D₆]acetone): δ = 7.31 (dd,

2-(3-Methoxyphenyl)-2-methyl-2H-chromene (3k): The General

Procedure with 1k (0.091 g, 0.51 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2a (0.456 g, 1.53 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.483 g, 3.17 mmol) afforded 3k (0.066 g, 52%) as an oil

{purification by flash chromatography [gradient eluents: petroleum

ether/dichloromethane (20:1, v/v) containing triethylamine (1‰),

J₁= 6.6, J₂= 2.7 Hz, 2 H), 7.02–6.98 (m, 2 H), 6.90–6.87 (m, 2

H), 6.81 (td, J₁= 7.2, J₂= 1.0 Hz, 1 H), 6.60 (dd, J₁= 8.0, J₂=

0.4 Hz, 1 H), 6.44 (s, 1 H), 5.67 (s, 1 H), 3.77 (s, 3 H), 1.71 (s, 3

H) ppm. ¹³C NMR (90 MHz, [D₆]acetone): δ = 19.8, 55.3, 80.8,

114.5, 116.1, 120.3, 121.5, 123.0, 126.3, 128.9, 129.6, 132.1, 133.8,

Eur. J. Org. Chem. 2012, 3507–3519

www.eurjoc.org

3513

T. Zhang, X. Huang, L. Wu

FULL PAPER

then petroleum ether/dichloromethane (10:1, v/v) containing trieth-

ylamine (1‰)]; R_f= 0.49 [TLC eluent: petroleum ether/ethyl acet-

ate (40:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃): δ = 7.23 (t, J =

8.0 Hz, 1 H), 7.13–7.15 (m, 3 H), 6.96 (d, J = 7.6 Hz, 1 H), 6.88

(d, J = 8.4 Hz, 1 H), 6.82 (t, J = 7.6 Hz, 1 H), 6.76 (dd, J₁= 8.6,

J₂= 1.8 Hz, 1 H), 6.43 (d, J = 9.6 Hz, 1 H), 5.91 (d, J = 9.6 Hz, 1

H), 3.77 (s, 3 H), 1.76 (s, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃):

δ = 29.3, 55.2, 78.6, 111.4, 112.3, 116.3, 117.5, 121.0, 121.2, 122.8,

1212, 1096, 1006, 750, 698 cm^–1. MS (70 eV, EI): m/z (%) = 314

(39.9) [M]⁺, 237 (100.0). HRMS (EI): calcd. for C₂₂H₁₈O₂[M]⁺

314.1307; found 314.1315.

General Procedure. Synthesis of 3l: A solution of 1l (0.062 g,

0.49 mmol) in MeCN/PhMe [1:4 (v/v), 2.5 mL, anhydrous] was

added by microinfusion syringe pump under dry nitrogen at 75 °C

over 5.0 h to a mixture of 2a (0.448 g, 1.50 mmol) and CsF

(0.466 g, 3.06 mmol) in MeCN/PhMe [1:4 (v/v), 2.5 mL, anhydrous]

in a dry Schlenk tube. The resulting mixture was then stirred for

24 h until completion of the reaction (monitored by TLC). The

reaction mixture was then diluted with acetone (20 mL) and filtered

through a short pad of silica gel to remove insoluble substances.

After concentration of the filtrates under vacuum, the residue was

dissolved in EtOH (5 mL). KF (0.061 g, 1.05 mmol), 18-crown-6

(0.533 g, 2.02 mmol) and KOH (water solution, 1 m, 1 mL) were

added to the solution. The mixture was stirred under reflux for

20 h to consume the TMS-containing compounds in the residue to

facilitate the following purification. The reaction mixture was

poured into brine (20 mL) and then extracted with diethyl ether

(3ϫ20 mL). The organic layers were combined, dried (MgSO₄) and

concentrated in vacuo. The residue was purified by flash

chromatography on silica gel to afford 3l^[30](0.031 g, 31%).

126.5, 129.2, 129.3, 129.5, 147.6, 152.9, 159.4 ppm. IR (neat): ν =

2987, 2901, 1730, 1605, 1511, 1453, 1406, 1394, 1252, 1167, 1066,

892, 758 cm^–1. MS (70 eV, EI): m/z (%) = 252 (61.8) [M]⁺, 237

(100.0). HRMS (EI): calcd. for C₁₇H₁₆O₂[M]⁺252.1150; found

252.1149.

6,7-Dimethyl-2,2-diphenyl-2H-chromene (3m): The General Pro-

cedure with 1i (0.104 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2b (0.491 g, 1.51 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.469 g, 3.08 mmol) afforded 3m (0.119 g, 77%) as a

white solid; m.p. 140–142 °C {recrystallized from petroleum ether/

ethyl acetate (40:1, v/v) after purification by flash chromatography

[eluent: petroleum ether/ethyl acetate (10:1, v/v)]; R_f= 0.68 [TLC

eluent: petroleum ether/ethyl acetate (40:1, v/v)]}. ¹H NMR

(400 MHz, CDCl₃): δ = 7.42 (d, J = 7.6 Hz, 4 H), 7.30 (t, J =

7.6 Hz, 4 H), 7.24–7.23 (m. 2 H), 6.75 (s, 1 H), 6.72 (s, 1 H), 6.55

(d, J = 9.6 Hz, 1 H), 6.07 (d, J = 9.6 Hz, 1 H), 2.16 (s, 3 H), 2.11

(s, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 18.8, 19.9, 82.4,

117.5, 118.6, 123.2, 127.0, 127.3, 127.4, 127.8, 128.0, 128.9, 138.1,

2-Methyl-2-(2-methylpropyl)-2H-chromene (3l): Clear oil [purified

by flash chromatography (eluent: petroleum ether); R_f= 0.47 (TLC

eluent: petroleum ether)]. ¹H NMR (400 MHz, CDCl₃): δ = 7.08

(td, J₁= 8.0, J₂= 1.2 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.80 (t,

J = 7.6 Hz, 1 H), 6.73 (d, J = 8.0 Hz, 1 H), 6.31 (d, J = 9.6 Hz, 1

H), 5.54 (d, J = 10.0 Hz, 1 H), 1.98–1.88 (m, 1 H), 1.65–1.54 (m,

2 H), 1.39 (s, 3 H), 0.96 (d, J = 6.8 Hz, 3 H), 0.93 (d, J = 6.4 Hz,

3 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 24.1, 24.4, 24.5, 27.2,

49.5, 78.9, 116.2, 120.4, 121.0, 122.3, 126.3, 129.0, 130.4,

145.2, 150.4 ppm. IR (neat): ν = 3060, 2971, 2919, 1619, 1493,

1448, 1411, 1259, 1224, 1178, 1099, 1052, 943, 890, 758, 698 cm^–1.

MS (70 eV, EI): m/z (%) = 312 (76.6) [M]⁺, 235 (100.0). HRMS

(EI): calcd. for C₂₃H₂₀O [M]⁺312.1514; found 312,1511.

6,7-Difluoro-2,2-diphenyl-2H-chromene (3n): The General Pro-

cedure with 1i (0.061 g, 0.29 mmol)/MeCN (0.3 mL)/PhMe

(1.2 mL), 2c (0.303 g, 0.91 mmol)/MeCN (0.3 mL)/PhMe (1.2 mL)

and CsF (0.286 g, 1.88 mmol) afforded 3n (0.091 g, 98%) as a white

solid; m.p. 100–102 °C {recrystallized from petroleum ether/ethyl

acetate (40:1, v/v) after purification by flash chromatography [elu-

ent: petroleum ether/ dichloromethane (10:1, v/v)]; R_f= 0.48 [TLC

eluent: petroleum ether/ethyl acetate (40:1, v/v)]}. ¹H NMR

(400 MHz, CDCl₃): δ = 7.38 (d, J = 7.2 Hz, 4 H), 7.33–7.22 (m, 6

H), 6.81–6.70 (m, 2 H), 6.50 (d, J = 9.6 Hz, 1 H), 6.16 (d, J =

10.0 Hz, 1 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 82.9, 106.1

(d, J = 18.4 Hz), 114.2 (dd, J₁= 17.2, J₂= 1.4 Hz), 117.3 (dd, J₁

= 6.0, J₂= 3.2 Hz), 122.0, 126.9, 127.7, 128.2, 129.3 (d, J = 3.3 Hz),

144.1, 145.2 (dd, J₁= 215.2, J₂= 11.8 Hz), 148.5 (dd, J₁= 8.9, J₂

153.0 ppm. IR (neat): ν = 3041, 2955, 2926, 2869, 1640, 1606, 1576,

1486, 1458, 1367, 1275, 1243, 1182, 1126, 1041, 946, 772, 751 cm^–1.

GC-MS (70 eV, EI): m/z (%) = 202 (9.6) [M]⁺, 145 (100.0). HRMS

(EI): calcd. for C₁₄H₁₈O [M]⁺202.1358; found 202.1360.

(1ЈR,2ЈR,4ЈR)-1Ј,7Ј,7Ј-Trimethylspiro[bicyclo[2.2.1]heptane-2,2Ј-

2H-chromene] (3o): Compound 3o was prepared similarly to 3l. The

General Procedure with 1m (0.091 g, 0.51 mmol)/MeCN (0.5 mL)/

PhMe (2.0 mL), 2a (0.452 g, 1.52 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL) and CsF (0.461 g, 3.03 mmol) afforded 3m (0.041 g, 32%)

as a clear oil [purified by flash chromatography (eluent: petroleum

ether); R_f= 0.75 (TLC eluent: petroleum ether)]. ¹H NMR

(400 MHz, CDCl₃): δ = 7.07 (td, J₁= 7.8, J₂= 1.4 Hz, 1 H), 6.94

(dd, J₁= 7.4, J₂= 1.4 Hz, 1 H), 6.81 (t, J = 8.2 Hz, 2 H), 6.35 (d,

J = 10.4 Hz, 1 H), 5.75 (d, J = 10.4 Hz, 1 H), 2.39–2.32 (m, 1 H,

C_6Ј-H_endo), 2.10 (dt, J₁= 14.0, J₂= 3.6 Hz, 1 H, C_3Ј-H_exo), 1.79–

1.71 (m, 3 H, C_5Ј-H_exo, C_3Ј-H_endo, C₄-H), 1.46–1.39 (m, 1 H, C_5Ј-

H_endo), 1.32 (td, J₁= 12.0, J₂= 5.2 Hz, 1 H, C_6Ј-H_exo), 0.98 (s, 3

H, C_8Ј-CH₃), 0.90 (s, 3 H, C_9Ј-CH₃), 0.81 (s, 3 H, C_10Ј-CH₃) ppm.

¹³C NMR (90 MHz, CDCl₃): δ = 12.2, 21.29, 21.35, 27.0, 29.1,

44.8, 46.1, 49.4, 55.3, 86.2, 116.1, 120.6, 122.5, 122.7, 125.8, 128.8,

= 2.2 Hz), 150.3 (dd, J = 222.2, J = 11.2 Hz) ppm. IR (neat): ν

= 2973, 2919, 1598, 1502, 1440, 1371, 1321, 1237, 1156, 1120, 1052,

976, 872, 810, 753, 697 cm^–1. MS (70 eV, EI): m/z (%) = 320 (69.3)

[M]⁺, 243 (100.0). HRMS (EI): calcd. for C₂₁H₁₄OF₂[M]⁺

320.1013; found 320.1010.

5-Methoxy-2,2-diphenyl-2H-chromene (3p): The General Procedure

with 1i (0.104 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL), 2e

(0.662 g, 2.02 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL) and CsF

(0.468 g, 3.08 mmol) afforded 3p (0.118 g, 75%) as an oil {purified

by flash chromatography [eluent: petroleum ether/dichloromethane

(10:1, v/v)]; R_f= 0.52 [TLC eluent: petroleum ether/ethyl acetate

(40:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃): δ = 7.43–7.40 (m, 4 H),

7.28–7.24 (m, 4 H), 7.19 (tt, J₁= 7.4, J₂= 1.2 Hz, 2 H), 7.00 (t, J

= 8.2 Hz, 1 H), 6.94 (d, J = 10.4 Hz, 1 H), 6.57 (d, J = 8.4 Hz, 1

H), 6.32 (d, J = 8.0 Hz, 1 H), 6.07 (d, J = 9.6 Hz, 1 H), 3.70 (s, 3

H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 55.4, 82.1, 103.3, 109.5,

130.9, 154.2 ppm. IR (neat): ν = 2989, 2952, 2926, 2869, 1634,

1606, 1572, 1483, 1454, 1389, 1309, 1273, 1250, 1206, 1179, 1152,

1114, 1082, 1035, 1003, 983, 924, 862, 838, 804, 768, 754, 742,

708 cm^–1. GC-MS (70 eV, EI): m/z (%) = 254 (14.8) [M]⁺, 144

(100.0). HRMS (EI): calcd. for C₁₈H₂₂O [M]⁺254.1671; found

254.1668.

Compounds 5 and 6 were prepared similarly to 3a.

(3-Methoxyphenyl)(9-phenanthrenyl)methanone (5a) and 1-(3-Meth-

oxyphenyl)-3-phenylpropan-1-one (6a): The General Procedure with

110.6, 118.08, 118.11, 127.0, 127.3, 128.0, 129.3, 145.0, 153.2, 4a (0.072 g, 0.30 mmol)/MeCN (0.3 mL)/PhMe (1.2 mL), 2a

155.3 ppm. IR (neat): ν = 2938, 1602, 1576, 1464, 1446, 1275, 1251, (0.270 g, 0.91 mmol)/MeCN (0.3 mL)/PhMe (1.2 mL) and CsF

3514

www.eurjoc.org

Eur. J. Org. Chem. 2012, 3507–3519

Synthesis of 2H-Chromenes and 9-Functionalized Phenanthrenes

(0.277 g, 1.82 mmol) afforded 5a (0.038 g, 41%) and 6a (0.019 g, 7.6 Hz, 2 H), 2.99 (t, J = 7.6 Hz, 2 H) ppm. ¹³C NMR (90 MHz,

27%).

CDCl₃): δ = 29.2, 40.6, 55.1, 55.2, 112.2, 113.8, 119.3, 120.5, 129.2,

129.4, 133.1, 138.2, 157.9, 159.7, 199.0 ppm. IR (neat): ν = 2935,

Compound 5a: White solid; m.p. 147–149 °C {recrystallized from

petroleum ether/ethyl acetate (10:1, v/v) after purification by flash

chromatography [eluent: petroleum ether/dichloromethane (7:1,

v/v), then petroleum ether/ethyl acetate (40:1, v/v)]; R_f= 0.48 [TLC

eluent: petroleum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR

(400 MHz, CDCl₃): δ = 8.75 (d, J = 8.4 Hz, 1 H), 8.72 (d, J =

8.4 Hz, 1 H), 8.11 (d, J = 8.8 Hz, 1 H), 7.88 (d, J = 7.6 Hz, 1 H),

7.85 (s, 1 H), 7.76–7.72 (m, 1 H), 7.69 (t, J = 7.8 Hz, 1 H), 7.63 (t,

J = 7.4 Hz, 1 H), 7.60–7.56 (m, 2 H), 7.42 (d, J = 7.6 Hz, 1 H),

7.33 (t, J = 8.0 Hz, 1 H), 7.16 (dd, J₁= 8.2, J₂= 2.6 Hz, 1 H), 3.84

(s, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 55.5, 114.0, 120.0,

122.7, 122.9, 123.6, 126.6, 127.1, 127.15, 127.19, 128.3, 129.1,

129.3, 129.46, 129.50, 130.0, 130.6, 131.3, 135.4, 139.6, 159.8,

2835, 1683, 1584, 1511, 1457, 1430, 1291, 1244, 1176, 1035, 994,

909, 876, 826, 776, 730, 685 cm^–1. MS (70 eV, EI): m/z (%) = 270

(97.2) [M]⁺, 121 (100.0).

(3-Methoxyphenyl)(3-methyl-9-phenanthrenyl)methanone (5c) and 1-

(3-Methoxyphenyl)-3-(4-methylphenyl)propan-1-one (6c): The Gene-

ral Procedure with 4c (0.127 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2a (0.444 g, 1.49 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.462 g, 3.04 mmol) afforded 5c (0.062 g, 38%) and 6c

(0.047 g, 37%).

Compound 5c: Oil {purified by flash chromatography [eluent: petro-

leum ether/ethyl acetate (40:1, v/v)]; R_f= 0.34 [TLC eluent: petro-

leum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃):

δ = 8.73 (d, J = 8.4 Hz, 1 H), 8.49 (s, 1 H), 8.14 (d, J = 8.4 Hz, 1

H), 7.82 (s, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.68–7.64 (m, 1 H),

7.58–7.54 (m, 2 H), 7.43 (t, J = 9.2 Hz, 2 H), 7.32 (t, J = 7.8 Hz,

1 H), 7.16–7.13 (m, 1 H), 3.83 (s, 3 H), 2.63 (s, 3 H) ppm. ¹³C

NMR (90 MHz, CDCl₃): δ = 22.3, 55.4, 114.0, 119.9, 122.4, 122.8,

123.5, 126.5, 126.9, 127.0, 127.9, 128.8, 129.4, 129.5, 130.2, 130.3,

197.6 ppm. IR (neat): ν = 2983, 2903, 1658, 1583, 1449, 1401, 1261,

1051, 895, 769 cm^–1. MS (70 eV, EI): m/z (%) = 312 (100.0) [M]⁺.

HRMS (EI): calcd. for C₂₂H₁₆O₂[M]⁺312.1150; found 312.1158.

Compound 6a:^[31]Oil {purified by flash chromatography [gradient

eluents: petroleum ether/dichloromethane (7:1, v/v), then petro-

leum ether/ethyl acetate (40:1, v/v)]; R_f= 0.50 [TLC eluent: petro-

leum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃):

δ = 7.54 (d, J = 7.6 Hz, 1 H), 7.49–7.48 (m, 1 H), 7.36 (t, J =

8.2 Hz, 1 H), 7.32–7.25 (m, 4 H), 7.23–7.19 (m, 1 H), 7.10 (dd, J₁

= 8.4, J₂= 2.0 Hz, 1 H), 3.85 (s, 3 H), 3.29 (t, J = 7.8 Hz, 2 H),

3.07 (t, J = 7.6 Hz, 2 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ =

30.2, 40.6, 55.4, 112.3, 119.6, 120.7, 126.1, 128.4, 128.5, 129.6,

131.4, 134.2, 138.4, 139.7, 159.7, 197.7 ppm. IR (neat): ν = 2942,

1657, 1583, 1451, 1429, 1365, 1302, 1264, 1208, 1117, 1039, 877,

808, 772, 699 cm^–1. MS (70 eV, EI): m/z (%) = 326 (26.6) [M]⁺, 302

(100.0). HRMS (EI): calcd. for C₂₃H₁₈O₂[M]⁺326.1307; found

326.1302.

138.3, 141.3, 159.9, 199.0 ppm. IR (neat): ν = 3028, 2943, 2836,

Compound 6c: Oil {purified by flash chromatography [eluent: petro-

leum ether/ethyl acetate (40:1, v/v)]; R_f= 0.36 [TLC eluent: petro-

leum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃):

δ = 7.52 (d, J = 7.6 Hz, 1 H), 7.48 (s, 1 H), 7.34 (t, J = 8.2 Hz, 1

H), 7.15–7.08 (m, 5 H), 3.84 (s, 3 H), 3.26 (t, J = 7.8 Hz, 2 H), 3.02

(t, J = 7.6 Hz, 2 H), 2.32 (s, 3 H) ppm. ¹³C NMR (90 MHz,

CDCl₃): δ = 21.0, 29.7, 40.7, 55.4, 112.2, 119.5, 120.6, 128.3, 129.2,

1685, 1595, 1489, 1455, 1431, 1290, 1256, 1194, 1167, 1041, 993,

771, 746, 698, 619 cm^–1. MS (70 eV, EI): m/z (%) = 240 (96.4)

[M]⁺, 135 (100.0). HRMS (EI): calcd. for C₁₆H₁₆O₂[M]⁺240.1150;

found 240.1155.

(3-Methoxy-9-phenanthrenyl)(3-methoxyphenyl)methanone (5b) and

1-(3-Methoxyphenyl)-3-(4-methoxyphenyl)propan-1-one (6b): The

General Procedure with 4b (0.268 g, 1.0 mmol)/MeCN (1.0 mL)/

PhMe (4.0 mL), 2a (0.898 g, 3.01 mmol)/MeCN (1.0 mL)/PhMe

(4.0 mL) and CsF (0.921 g, 6.06 mmol) afforded 5b (0.167 g, 49%)

and 6b (0.119 g, 44%).

129.5, 135.6, 138.1, 138.2, 159.8, 199.1 ppm. IR (neat): ν = 2924,

1684, 1584, 1515, 1485, 1453, 1430, 1359, 1289, 1254, 1191, 1166,

1110, 1041, 997, 876, 839, 811, 779, 719, 686, 648 cm^–1. MS (70 eV,

EI): m/z (%) = 254 (76.8) [M]⁺, 135 (100.0). HRMS (EI): calcd. for

C₁₇H₁₈O₂[M]⁺254.1307; found 254.1303.

Compound 5b: Oil {purified by flash chromatography [gradient el-

uents: petroleum ether/dichloromethane (7:1, v/v), then petroleum

ether/ethyl acetate (15:1, v/v)]; R_f= 0.25 [TLC eluent: petroleum

(3-Bromo-9-phenanthrenyl)(2-methoxyphenyl)methanone (5d) and 3-

(4-Bromophenyl)-1-(2-methoxyphenyl)propan-1-one (6d): The Gene-

ral Procedure with 4d (0.094 g, 0.30 mmol)/MeCN (0.3 mL)/PhMe

(1.2 mL), 2a (0.272 g, 0.91 mmol)/MeCN (0.3 mL)/PhMe (1.2 mL)

and CsF (0.282 g, 1.85 mmol) afforded 5d (0.041 g, 35%) and 6d

(0.031 g, 32%).

ether/ethyl acetate (10:1, v/v)]}. H NMR (400 MHz, CDCl₃): δ =

8.67 (d, J = 8.4 Hz, 1 H), 8.21 (d, J = 8.0 Hz, 1 H), 8.07 (d, J =

2.0 Hz, 1 H), 7.83 (s, 1 H), 7.80 (d, J = 8.8 Hz, 1 H), 7.67 (td, J₁

= 7.6, J₂= 1.0 Hz, 1 H), 7.59 (td, J₁= 7.8, J₂= 0.8 Hz, 1 H), 7.54

(dd, J₁= 2.2, J₂= 1.4 Hz, 1 H), 7.42 (d, J = 7.6 Hz, 1 H), 7.34 (t,

J = 7.8 Hz, 1 H), 7.27 (dd, J₁= 8.8, J₂= 2.8 Hz, 1 H), 7.17–7.14

(m, 1 H), 4.05 (s, 3 H), 3.85 (s, 3 H) ppm. ¹³C NMR (90 MHz,

CDCl₃): δ = 55.4, 55.5, 104.0, 114.0, 117.3, 119.7, 122.9, 123.5,

124.5, 126.67, 126.70, 127.3, 129.4, 129.7, 130.0, 131.1, 132.6,

Compound 5d: Oil {purified by flash chromatography [gradient el-

uents: petroleum ether/dichloromethane (10:1, v/v), then petroleum

ether/ethyl acetate (40:1, v/v)]; R_f= 0.17 [TLC eluent: petroleum

ether/ethyl acetate (40:1, v/v)]}. H NMR (400 MHz, CDCl₃): δ =

8.82 (s, 1 H), 8.63 (d, J = 7.6 Hz, 1 H), 8.51 (d, J = 8.6 Hz, 1 H),

7.78 (s, 1 H), 7.72–7.62 (m, 5 H), 7.55–7.51 (m, 1 H), 7.06 (t, J =

7.4 Hz, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 3.54 (s, 3 H) ppm. ¹³C

NMR (90 MHz, CDCl₃): δ = 55.7, 112.0, 120.6, 122.8, 123.0, 125.7,

126.7, 127.2, 127.9, 128.8, 129.4, 129.50, 129.53, 129.6, 130.1,

133.0, 140.0, 159.7, 160.0, 197.6 ppm. IR (neat): ν = 2921, 1654,

1616, 1505, 1455, 1373, 1296, 1248, 1218, 1176, 1041, 889, 838,

770, 684, 624 cm^–1. MS (70 eV, EI): m/z (%) = 342 (19.4) [M]⁺, 57

(100.0). HRMS (EI): calcd. for C₂₃H₁₈O₃[M]⁺342.1256; found

342.1254.

Compound 6b:^[32]Oil {purified by flash chromatography [gradient

eluents: petroleum ether/dichloromethane (7:1, v/v), then petro-

leum ether/ethyl acetate (15:1, v/v)]; R_f= 0.28 [TLC eluent: petro-

leum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃):

δ = 7.50 (d, J = 7.6 Hz, 1 H), 7.47 (s, 1 H), 7.32 (t, J = 7.8 Hz, 1

H), 7.15 (d, J = 8.4 Hz, 2 H), 7.07 (dd, J₁= 8.2, J₂= 2.6 Hz, 1 H),

6.82 (d, J = 8.4 Hz, 2 H), 3.81 (s, 3 H), 3.75 (s, 3 H), 3.22 (t, J =

131.1, 133.0, 133.4, 137.1, 158.6, 197.4 ppm. IR (neat): ν = 3010,

2937, 1657, 1596, 1485, 1461, 1405, 1298, 1246, 1164, 1117, 1059,

1019, 882, 858, 809, 755, 670 cm^–1. MS (70 eV, EI): m/z (%) = 390

(27.0) [M(⁷⁹Br)]⁺, 392 (28.3) [M(⁸¹Br)]⁺, 135 (100.0). HRMS (EI):

calcd. for C₂₂H₁₅O₂⁷⁹Br [M]⁺390.0255; found 390.0252.

Compound 6d: Oil {purified by flash chromatography [gradient el-

uents: petroleum ether/dichloromethane (10:1, v/v), then petroleum

Eur. J. Org. Chem. 2012, 3507–3519

www.eurjoc.org

3515

T. Zhang, X. Huang, L. Wu

FULL PAPER

ether/ethyl acetate (40:1, v/v)]; R_f= 0.21 [TLC eluent: petroleum

ether/ethyl acetate (40:1, v/v)]}. H NMR (400 MHz, CDCl₃): δ =

7.67 (dd, J₁= 7.6, J₂= 1.2 Hz, 1 H), 7.47–7.43 (m, 1 H), 7.39 (d,

J = 8.4 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.99 (t, J = 7.4 Hz, 1

Compound 6f:^[35]Oil {purified by flash chromatography [gradient

eluents: petroleum ether/dichloromethane (10:1 to 7:1, v/v)]; R_f=

0.38 [TLC eluent: petroleum ether/ethyl acetate (40:1, v/v)]}. ¹H

NMR (400 MHz, CDCl₃): δ = 7.11 (d, J = 8.4 Hz, 2 H), 6.82 (d,

H), 6.95 (d, J = 8.4 Hz, 1 H), 3.87 (s, 3 H), 3.27 (t, J = 7.6 Hz, 2 J = 8.8 Hz, 2 H), 4.12 (q, J = 7.0 Hz, 2 H), 3.78 (s, 3 H), 2.89 (t,

H), 2.97 (t, J = 7.8 Hz, 2 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ

= 29.8, 45.1, 55.5, 111.5, 119.6, 120.7, 128.1, 130.2, 130.3, 131.4,

J = 7.8 Hz, 2 H), 2.58 (t, J = 8.0 Hz, 2 H), 1.23 (t, J = 7.2 Hz, 3

H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 14.2, 30.1, 36.2, 55.2,

133.5, 140.7, 158.5, 201.1 ppm. IR (neat): ν = 3019, 2924, 2845, 60.3, 113.8, 129.2, 132.6, 158.0, 172.9 ppm. IR (neat): ν = 2981,

1662, 1592, 1481, 1431, 1398, 1358, 1296, 1272, 1243, 1181, 1111,

1730, 1612, 1512, 1461, 1372, 1297, 1244, 1176, 1106, 1035, 824,

1068, 1018, 981, 810, 759, 654 cm^–1. MS (70 eV, EI): m/z (%) = 318 705 cm^–1. MS (70 eV, EI): m/z (%) = 208 (100.0) [M]⁺.

(8.8) [M(⁷⁹Br)]⁺, 320 (8.8) [M(⁸¹Br)]⁺, 135 (100.0). HRMS (EI):

3-Methoxy-9-phenanthrenecarbonitrile (5g) and 3-(4-Methoxy-

phenyl)propanenitrile (6g): The General Procedure with 4g (0.159 g,

calcd. for C₁₆H₁₅O₂⁷⁹Br [M]⁺318.0255; found 318.0258.

1-(3-Methoxy-9-phenanthrenyl)ethanone (5e) and 4-(4-Methoxy-

phenyl)butan-2-one (6e): The General Procedure with 4e (0.177 g,

1.00 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL), 2a (0.892 g,

2.99 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL) and CsF (0.934 g,

6.14 mmol) afforded 5e (0.128 g, 51%) and 6e (0.074 g, 41%).

Compound 5e:^[33]Light yellow solid; m.p. 66–68 °C {recrystallized

from petroleum ether/ethyl acetate (10:1, v/v) after purification by

flash chromatography [gradient eluents: petroleum ether/dichloro-

methane (10:1, v/v), then petroleum ether/ethyl acetate (40:1, v/v)];

R_f= 0.32 [TLC eluent: petroleum ether/ethyl acetate (10:1, v/v)]}.

¹H NMR (400 MHz, CDCl₃): δ = 8.85–8.83 (m, 1 H), 8.59–8.57

(m, 1 H), 8.16 (s, 1 H), 7.97 (d, J = 2.0 Hz, 1 H), 7.82 (d, J =

8.8 Hz, 1 H), 7.65–7.63 (m, 2 H), 7.24 (dd, J₁= 8.4, J₂= 2.4 Hz,

1 H), 4.01 (s, 3 H), 2.78 (s, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃):

δ = 29.6, 55.5, 104.0, 117.3, 122.7, 124.4, 126.6, 127.0, 127.7, 128.8,

1.00 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL), 2a (1.344 g,

4.51 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL) and CsF (0.913 g,

6.01 mmol) afforded 5g (0.123 g, 53%) and 6g (0.025 g, 16%).

Compound 5g:^[36]Pale white solid; m.p. 116–118 °C {recrystallized

from petroleum ether/ethyl acetate (10:1, v/v) after purification by

flash chromatography [gradient eluents: petroleum ether/dichloro-

methane (7:1, v/v), then petroleum ether/ethyl acetate (40:1, v/v)];

R_f= 0.32 [TLC eluent: petroleum ether/ethyl acetate (10:1, v/v)]}.

¹H NMR (400 MHz, CDCl₃): δ = 8.59–8.57 (m, 1 H), 8.26–8.24

(m, 1 H), 8.14 (s, 1 H), 7.97 (d, J = 2.0 Hz, 1 H), 7.81 (d, J =

8.8 Hz, 1 H), 7.73–7.71 (m, 2 H), 7.28 (dd, J₁= 8.8, J₂= 2.8 Hz,

1 H), 4.04 (s, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 55.6,

104.1, 106.5, 117.8, 118.3, 123.0, 124.5, 126.1, 127.6, 128.1, 129.31,

129.34, 131.1, 133.6, 135.2, 160.9 ppm. IR (neat): ν = 3675, 2987,

2901, 1616, 1506, 1454, 1406, 1394, 1251, 1233, 1145, 1066, 897,

759 cm^–1. MS (70 eV, EI): m/z (%) = 233 (100.0) [M]⁺. HRMS (EI):

calcd. for C₁₆H₁₁NO [M]⁺233.0841; found 233.0838.

130.1, 131.3, 131.4, 131.8, 133.8, 160.4, 201.3 ppm. IR (neat): ν =

2924, 1667, 1614, 1523, 1504, 1453, 1439, 1374, 1293, 1218, 1176,

1158, 1036, 1020, 895, 817, 763, 620 cm^–1. MS (70 eV, EI): m/z (%)

= 250 (61.8) [M]⁺, 235 (100.0). HRMS (EI): calcd. for C₁₇H₁₄O₂

[M]⁺250.0994; found 250.1000.

Compound 6e:^[34]Oil {purified by flash chromatography [gradient

eluents: petroleum ether/dichloromethane (10:1, v/v), then petro-

leum ether/ethyl acetate (40:1, v/v)]; R_f= 0.36 [TLC eluent: petro-

leum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃):

δ = 7.09 (d, J = 8.4 Hz, 2 H), 6.81 (d, J = 8.4 Hz, 2 H), 3.76 (s, 3

H), 2.83 (t, J = 7.6 Hz, 2 H), 2.71 (t, J = 7.4 Hz, 2 H), 2.11 (s, 3

H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 28.8, 29.9, 45.3, 55.1,

Compound 6g:^[37]Oil {purified by flash chromatography [gradient

eluents: petroleum ether/dichloromethane (7:1, v/v), then petro-

leum ether/ethyl acetate (40:1, v/v)]; R_f= 0.38 [TLC eluent: petro-

leum ether/ethyl acetate (10:1, v/v)]}. ¹H NMR (400 MHz, CDCl₃):

δ = 7.14 (d, J = 8.4 Hz, 2 H), 6.86 (d, J = 8.4 Hz, 2 H), 3.78 (s, 3

H), 2.88 (t, J = 7.4 Hz, 2 H), 2.56 (t, J = 7.4 Hz, 2 H) ppm. ¹³C

NMR (90 MHz, CDCl₃): δ = 19.6, 30.6, 55.2, 114.2, 119.2, 129.2,

130.1, 158.7 ppm. IR (neat): ν = 2935, 2247, 1612, 1512, 1462,

1300, 1246, 1179, 1110, 1032, 913, 832, 808, 731, 700, 647 cm^–1.

GC-MS (70 eV, EI): m/z (%) = 161 (19.0) [M]⁺, 121 (100.0).

113.8, 129.1, 132.9, 157.8, 208.0 ppm. IR (neat): ν = 2935, 1712,

1611, 1583, 1511, 1443, 1361, 1299, 1243, 1178, 1159, 1109, 1034,

817, 742, 698 cm^–1. GC-MS (70 eV, EI): m/z (%) = 178 (48.1)

[M]⁺, 121 (100.0).

Ethyl 3-Methoxy-6,7-dimethyl-9-phenanthrenecarboxylate (5i): The

General Procedure with 4f (0.102 g, 0.49 mmol)/MeCN (0.5 mL)/

PhMe (2.0 mL), 2b (0.491 g, 1.51 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL) and CsF (0.461 g, 3.03 mmol) afforded 5i (0.075 g, 50%)

as a white solid; m.p. 116–118 °C recrystallized from petroleum

ether/ethyl acetate (40:1, v/v) after purification by flash chromatog-

raphy [eluent: petroleum ether/ethyl acetate (40:1, v/v)]; R_f= 0.31

[TLC eluent: petroleum ether/ethyl acetate (40:1, v/v)]. ¹H NMR

(400 MHz, CDCl₃): δ = 8.73 (s, 1 H), 8.35 (s, 1 H), 8.33 (s, 1 H),

7.96 (d, J = 2.0 Hz, 1 H), 7.83 (d, J = 8.8 Hz, 1 H), 7.21 (dd, J₁=

8.8, J₂= 2.4 Hz, 1 H), 4.49 (q, J = 7.0 Hz, 2 H), 4.03 (s, 3 H), 2.52

(s, 3 H), 2.49 (s, 3 H), 1.49 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR

(90 MHz, CDCl₃): δ = 14.4, 20.37, 20.38, 55.5, 60.8, 103.6, 116.7,

123.0, 123.3, 124.5, 126.6, 128.0, 128.5, 131.3, 131.4, 133.5, 135.6,

Ethyl 3-Methoxy-9-phenanthrenecarboxylate (5f) and Ethyl 3-(4-

Methoxyphenyl)propanoate (6f): The General Procedure with 4f

(0.207 g, 1.00 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL), 2a (1.345 g,

4.51 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL) and CsF (0.915 g,

6.02 mmol) afforded 5f (0.146 g, 52%) and 6f (0.025 g, 12%).

Compound 5f: Oil {purified by flash chromatography [gradient el-

uents: petroleum ether/dichloromethane (10:1 to 7:1, v/v), then pe-

troleum ether/ethyl acetate (40:1, v/v)]; R_f= 0.37 [TLC eluent: pe-

troleum ether/ethyl acetate (40:1, v/v)]}. ¹H NMR (400 MHz,

CDCl₃): δ = 8.99–8.97 (m, 1 H), 8.64–8.62 (m, 1 H), 8.44 (s, 1 H),

8.02 (d, J = 1.6 Hz, 1 H), 7.88 (d, J = 8.4 Hz, 1 H), 7.69–7.64 (m,

2 H), 7.26 (dd, J₁= 8.6, J₂= 2.2 Hz, 1 H), 4.50 (q, J = 7.2 Hz, 2

H), 4.04 (s, 3 H), 1.49 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR

(90 MHz, CDCl₃): δ = 14.4, 55.5, 61.0, 104.0, 117.3, 122.8, 123.9,

124.8, 126.4, 126.7, 127.4, 129.6, 130.1, 131.5, 132.2, 133.9, 160.4,

136.9, 160.1, 167.9 ppm. IR (neat): ν = 2922, 1709, 1617, 1508,

1455, 1363, 1296, 1220, 1177, 1102, 1041, 840 cm^–1. MS (70 eV, EI):

m/z (%) = 308 (100.0) [M]⁺. HRMS (EI): calcd. for C₂₀H₂₀O₃

[M]⁺308.1412; found 308.1411.

167.7 ppm. IR (neat): ν = 2921, 2854, 1709, 1617, 1507, 1453, 1375,

Ethyl 6,7-Difluoro-3-methoxy-9-phenanthrenecarboxylate (5j) and

1293, 1219, 1183, 1161, 1121, 1036, 959, 878, 812, 782, 624 cm^–1. Ethyl 3-(4-Methoxyphenyl)propanoate (6f): The General Procedure

MS (70 eV, EI): m/z (%) = 280 (100.0) [M]⁺. HRMS (EI): calcd.

with 4f (0.206 g, 1.00 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL), 2c

(1.510 g, 4.52 mmol)/MeCN (1.0 mL)/PhMe (4.0 mL) and CsF

for C₁₈H₁₆O₃[M]⁺280.1099; found 280.1097.

3516

www.eurjoc.org

Eur. J. Org. Chem. 2012, 3507–3519

Synthesis of 2H-Chromenes and 9-Functionalized Phenanthrenes

(0.921 g, 6.06 mmol) afforded 5j (0.174 g, 55%) and 6f (0.048 g,

23%).

H), 3.87 (s, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 55.3, 112.7,

119.1, 120.9, 121.9, 127.9 (t, J = 21.4 Hz), 128.3 (t, J = 21.4 Hz),

129.4, 129.9 (t, J = 21.9 Hz), 134.6, 139.4, 144.6, 159.8, 190.0 ppm.

Compound 5j: White solid; m.p. 139–142 °C {recrystallized from

chloroform after purification by flash chromatography [gradient el-

uents: petroleum ether/dichloromethane (7:1, v/v), then petroleum

ether/ethyl acetate (40:1, v/v)]; R_f= 0.35 [TLC eluent: petroleum

IR (neat): ν = 2939, 1661, 1584, 1485, 1454, 1429, 1344, 1303, 1272,

1247, 1195, 1157, 1021, 979, 859, 790, 765, 738, 717, 682 cm^–1. MS

(70 eV, EI): m/z (%) = 243 (100.0) [M]⁺. HRMS (EI): calcd. for

C₁₆H₉D₅O₂[M]⁺243.1308; found 243.1309.

ether/ethyl acetate (40:1, v/v)]}. H NMR (400 MHz, CDCl₃): δ =

Compounds 5a-D and 6a-D were prepared similarly to 5a and 6a.

8.97 (dd, J₁= 13.6, J₂= 8.8 Hz, 1 H), 8.48 (s, 1 H), 8.26 (dd, J₁=

12.6, J₂= 8.2 Hz, 1 H), 7.87 (d, J = 8.8 Hz, 1 H), 7.72 (s, 1 H),

7.27 (dd, J₁= 8.8, J₂= 2.4 Hz, 1 H), 4.48 (q, J = 7.2 Hz, 2 H),

4.03 (s, 3 H), 1.49 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR (90 MHz,

CDCl₃): δ = 14.4, 55.5, 61.2, 103.7, 110.1 (d, J = 15.9 Hz), 114.4

(3-Methoxyphenyl)(1,2,3,4-tetradeuteriophenanthren-9-yl)methan-

one (5a-D) and 3-Deuterio-1-(3-methoxyphenyl)-3-(2,3,4,5,6-penta-

deuteriophenyl)propan-1-one (6a-D): The General Procedure with

4a-D (0.192 g, 0.79 mmol)/MeCN (0.8 mL)/PhMe (3.2 mL), 2a

(0.718 g, 2.41 mmol)/MeCN (0.8 mL)/PhMe (3.2 mL) and CsF

(0.728 g, 4.79 mmol) afforded 5a-D (0.098 g, 39%) and 6a-D

(0.065 g, 33%).

(d, J = 17.8 Hz), 117.8, 122.0, 124.5, 126.9 (dd, J₁= 7.5, J₂

1.4 Hz), 127.4 (dd, J₁= 5.6, J₂= 1.2 Hz), 131.8, 133.0 (d, J =

2.6 Hz), 133.1 (d, J = 1.3 Hz), 149.6 (dd, J₁= 222.6, J₂= 13.0 Hz),

150.2 (dd, J₁= 222.0, J₂= 12.4 Hz), 160.6, 167.0 ppm. IR (neat):

Compound 5a-D: White solid; m.p. 149–151 °C {recrystallized from

petroleum ether/ethyl acetate (40:1, v/v) after purification by flash

chromatography [gradient eluents: petroleum ether/dichlorometh-

ane (15:1 to 10:1, v/v), then petroleum ether/ethyl acetate (40:1,

v/v)]; R_f= 0.41 [TLC eluent: petroleum ether/ethyl acetate (20:1,

v/v)]}. ¹H NMR (400 MHz, CDCl₃): δ = 8.74 (d, J = 8.0 Hz, 1 H),

8.11 (d, J = 8.4 Hz, 1 H), 7.85 (s, 1 H), 7.68 (t, J = 7.6 Hz, 1 H),

7.59–7.55 (m, 2 H), 7.42 (d, J = 7.6 Hz, 1 H), 7.32 (t, J = 7.8 Hz,

1 H), 7.15 (dd, J₁= 8.4, J₂= 2.4 Hz, 1 H), 3.83 (s, 3 H) ppm. ¹³C

NMR (90 MHz, CDCl₃): δ = 55.4, 113.9, 120.0, 122.3 (t, J =

21.2 Hz), 122.9, 123.6, 126.6, 126.6 (overlapped with previous peak,

t, J = 21.3 Hz), 127.1, 127.2, 127.5–128.2 (m), 128.8, 129.1, 129.3,

129.4, 129.9, 130.5, 131.2, 135.3, 139.5, 159.8, 197.7 ppm. IR

ν = 2920, 1706, 1616, 1541, 1509, 1456, 1428, 1362, 1294, 1213,

1134, 1103, 1043, 897, 844, 806 cm^–1. MS (70 eV, EI): m/z (%) =

316 (100.0) [M]⁺. HRMS (EI): calcd. for C₁₈H₁₄O₃F₂[M]⁺

316.0911; found 316.0909.

Compound 6f: Oil {purified by flash chromatography [gradient el-

uents: petroleum ether/dichloromethane (7:1, v/v), then petroleum

ether/ethyl acetate (40:1, v/v)]}; R_f= 0.38 [TLC eluent: petroleum

ether/ethyl acetate (40:1, v/v)]. ¹H NMR (400 MHz, CDCl₃): δ =

7.11 (d, J = 8.4 Hz, 2 H), 6.82 (d, J = 8.8 Hz, 2 H), 4.12 (q, J =

7.0 Hz, 2 H), 3.78 (s, 3 H), 2.89 (t, J = 7.8 Hz, 2 H), 2.58 (t, J =

8.0 Hz, 2 H), 1.23 (t, J = 7.2 Hz, 3 H) ppm.

Ethyl 3,5-Dimethoxy-9-phenanthrenecarboxylate (5k): The General

Procedure with 4f (0.103 g, 0.50 mmol)/MeCN (0.5 mL)/PhMe

(2.0 mL), 2e (0.739 g, 2.25 mmol)/MeCN (0.5 mL)/PhMe (2.0 mL)

and CsF (0.461 g, 3.03 mmol) afforded 5k (0.034 g, 22%) as a white

solid; m.p. 89–91 °C {recrystallized from petroleum ether/ethyl

acetate (20:1, v/v) after purification by flash chromatography [gra-

dient eluents: petroleum ether/ethyl acetate (40:1 to 20:1, v/v)]; R_f

(neat): ν = 2972, 2903, 1658, 1584, 1484, 1430, 1387, 1265, 1175,

1044, 894, 767, 685 cm^–1. MS (70 eV, EI): m/z (%) = 316 (100.0)

[M]⁺. HRMS (EI): calcd. for C₂₂H₁₂D₄O₂[M]⁺316.1401; found

314.1404.

Compound 6a-D: Oil {purified by flash chromatography [gradient

eluents: petroleum ether/dichloromethane (15:1 to 10:1, v/v)]; R_f=

0.43 [TLC eluent: petroleum ether/ethyl acetate (10:1, v/v)]}. ¹H

NMR (400 MHz, CDCl₃): δ = 7.53 (d, J = 7.6 Hz, 1 H), 7.48 (d,

J = 2.4 Hz, 1 H), 7.35 (t, J = 8.0 Hz, 1 H), 7.09 (dd, J₁= 8.2, J₂

= 2.0 Hz, 1 H), 3.84 (s, 3 H), 3.28 (d, J = 7.6 Hz, 2 H), 3.05 (t, J

= 7.6 Hz, 1 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ = 29.7 (t, J =

18.0 Hz), 40.4, 55.4, 112.2, 119.5, 120.6, 125.6 (t, J = 21.2 Hz),

128.0 (t, J = 21.6 Hz), 129.6, 138.2, 141.0, 159.8, 199.0 ppm. IR

= 0.37 [TLC eluent: petroleum ether/ethyl acetate (20:1, v/v)]}. H

NMR (400 MHz, CDCl₃): δ = 9.21 (d, J = 2.4 Hz, 1 H), 8.52 (dd,

J₁= 8.4, J₂= 0.8 Hz, 1 H), 8.36 (s, 1 H), 7.86 (d, J = 8.4 Hz, 1 H),

7.59 (t, J = 8.0 Hz, 1 H), 7.26 (dd, J₁= 8.8, J₂= 2.4 Hz, 1 H), 7.17

(d, J = 7.2 Hz, 1 H), 4.49 (q, J = 7.2 Hz, 2 H), 4.13 (s, 3 H), 4.01 (s,

3 H), 1.48 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (90 MHz, CDCl₃): δ

= 14.4, 55.3, 55.9, 61.0, 108.5, 110.6, 116.1, 119.1, 121.1, 124.4,

125.4, 127.3, 130.9, 131.9, 132.9, 133.4, 158.8, 159.8, 168.2 ppm.

(neat): ν = 2937, 2836, 2361, 2273, 1684, 1592, 1486, 1457, 1430,

1334, 1253, 1198, 1168, 1042, 873, 788, 686 cm^–1. MS (70 eV, EI):

m/z (%) = 246 (94.1) [M]⁺, 135 (100.0). HRMS (EI): calcd. for

C₁₆H₁₀D₆O₂[M]⁺246.1527; found 246.1524.

IR (neat): ν = 2982, 1710, 1613, 1572, 1457, 1434, 1408, 1362, 1255,

1217, 1193, 1142, 1036, 866, 808, 760 cm^–1. MS (70 eV, EI): m/z

(%) = 310 (100.0) [M]⁺. HRMS (EI): calcd. for C₁₉H₁₈O₄[M]⁺

310.1205; found 310.1209.

Supporting Information (see footnote on the first page of this arti-

cle): H and ¹³C NMR spectra of all the products.

Synthesis of 1-(3-Methoxyphenyl)-3-(2,3,4,5,6-pentadeuteriophenyl)-

prop-2-en-1-one (4a-D): Sodium hydroxide solution (10%, 2.1 mL)

was added dropwise to a cooled (0 °C), stirred solution of 2,3,4,5,6-

pentadeuteriobenzaldehyde (1.415 g, 12.73 mmol) and 1-(3-meth-

oxyphenyl)ethanone (1.912 g, 12.73 mmol) in ethanol (6.4 mL).

The reaction mixture was brought to room temperature and further

stirred overnight and was then neutralized by addition of dilute

hydrochloric acid and extracted with diethyl ether (3ϫ20 mL). The

combined extracts were washed with brine, followed by drying with

anhydrous magnesium sulfate. Filtration, concentration and col-

umn chromatography {gradient eluents: petroleum ether/ethyl acet-

ate (15:1 to 10:1, v/v); R_f= 0.34 [TLC eluent: petroleum ether/ethyl

acetate (10:1, v/v)]} afforded 4a-D (1.983 g, 64%) as an oil. ¹H

NMR (400 MHz, CDCl₃): δ = 7.81 (d, J = 16.0 Hz, 1 H), 7.60 (d,

J = 7.2 Hz, 1 H), 7.55 (d, J = 1.6 Hz, 1 H), 7.51 (d, J = 15.6 Hz,

1 H), 7.40 (t, J = 7.8 Hz, 1 H), 7.12 (dd, J₁= 8.0, J₂= 2.4 Hz, 1

Acknowledgments

We are grateful to the National Natural Science Foundation of

China (Project Nos. 20872127, 20732005 and J0830431), the

National Basic Research Program of China (973 Program,

2009CB825300), the CAS Academician Foundation of Zhejiang

Province, and the Fundamental Research Funds for the Central

Universities for financial support.

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Received: January 12, 2012

Published Online: May 11, 2012

Eur. J. Org. Chem. 2012, 3507–3519

www.eurjoc.org

3519

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A facile synthesis of 2h-chromenes and 9-functionalized phenanthrenes through reactions between α,β-unsaturated compounds and arynes

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