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

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.
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T. Zhang, X. Huang, L. Wu
FULL PAPER
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
2a
[equiv.]
CsF
[equiv.]
MeCN/PhMe
[v/v]
T
[°C]
Addition time of 2a[b] Time of reaction[c] Yield of 3a[d]
Recovery of 1a[d]
[h]
[h]
[%]
[%]
1
2
3
4
5
6
7
8
9
1.5
1.5
1.5
1.5
1.5
1.5
2.0
2.5
2.5
3.0
3.0
3.0
3
3
3
3
3
3
4
5
5
1:0
1:1
1:2
1:3
1:4
1:9
1:4
1:4
1:4
1:4
1:4
1:4
75
75
75
75
75
75
75
75
75
75
45
75
–
–
–
–
–
–
–
–
10.5
12.5
12.5
12.5
24
48
48
48
48
96
48
48
24
24
72
48
40
43
48
50
51
29
40
43
53
59
55
56
25
17
18
30
20
26
17
9
7
0
0
10
11
12
6
6
3.5
7
[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] [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
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)/4.5
H (2a)/4.5
H (2a)/3.0
H (2a)/3.0
H (2a)/3.7
H (2a)/3.0
H (2a)/3.0
H (2a)/3.0
4,5-Me2 (2b)/3.0
4,5-F2 (2c)/3.0
24
36
36
60
120
48
24
24
24
24
24
36
24
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)
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 N2 to 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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T. Zhang, X. Huang, L. Wu
FULL PAPER
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]
5
6
1
2
3
4
5
6
7
8
9
3-MeOC6H4CO/4-MeO (4b)
3-MeOC6H4CO/4-Me (4c)
2-MeOC6H4CO/4-Br (4d)
MeCO/4-MeO (4e)
H (2a)/3.0
H (2a)/3.0
48
48
48
48
48
48
24
36
36
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
H (2a)/3.0
EtOCO/4-MeO (4f)
CN/4-MeO (4g)
NO2/4-MeO(4h)
EtOCO/4-MeO (4f)
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-
1
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
1
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-
D.
(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).
Eur. J. Org. Chem. 2012, 3507–3519
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T. Zhang, X. Huang, L. Wu
FULL PAPER
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‰)]; Rf = 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‰)]; Rf = 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‰)]; Rf = 0.48
1
General Remarks: All H and 13C NMR spectra were measured in
CDCl3 or [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.
1
[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
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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‰)];
Rf = 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)]; Rf = 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.
1
[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‰)]; Rf = 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.
1
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‰)]}; Rf = 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.
1
(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‰)]; Rf = 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.
1
[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)]; Rf = 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‰)]; Rf = 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.
1
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
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3513

T. Zhang, X. Huang, L. Wu
FULL PAPER
then petroleum ether/dichloromethane (10:1, v/v) containing trieth-
ylamine (1‰)]; Rf = 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)]; Rf = 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); Rf = 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)]; Rf = 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); Rf = 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,
C6Ј-Hendo), 2.10 (dt, J1 = 14.0, J2 = 3.6 Hz, 1 H, C3Ј-Hexo), 1.79–
1.71 (m, 3 H, C5Ј-Hexo, C3Ј-Hendo, C4-H), 1.46–1.39 (m, 1 H, C5Ј-
Hendo), 1.32 (td, J1 = 12.0, J2 = 5.2 Hz, 1 H, C6Ј-Hexo), 0.98 (s, 3
H, C8Ј-CH3), 0.90 (s, 3 H, C9Ј-CH3), 0.81 (s, 3 H, C10Ј-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
˜
1
2
= 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)]; Rf = 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
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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)]; Rf = 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)]; Rf = 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)]; Rf = 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)]; Rf = 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)]; Rf = 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%).
1
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)]; Rf = 0.17 [TLC eluent: petroleum
1
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)]; Rf = 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
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3515

T. Zhang, X. Huang, L. Wu
FULL PAPER
ether/ethyl acetate (40:1, v/v)]; Rf = 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)]; Rf =
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,
1
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)];
Rf = 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)];
Rf = 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)]; Rf = 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)]; Rf = 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)]; Rf = 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)]; Rf = 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
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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)]; Rf = 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.
1
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)]; Rf = 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)]}; Rf = 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)]; Rf
(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)]; Rf =
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
1
= 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-
1
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); Rf = 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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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3517

T. Zhang, X. Huang, L. Wu
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Received: January 12, 2012
Published Online: May 11, 2012
Eur. J. Org. Chem. 2012, 3507–3519
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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