Phosphine-Mediated Iterative Arene Homologation Using Allenes

Article abstract of DOI:10.1021/jacs.5b07403

A PPh₃-mediated multicomponent reaction between o-phthalaldehydes, nucleophiles, and monosubstituted allenes furnishes functionalized non-C₂-symmetric naphthalenes in synthetically useful yields. When the o-phthalaldehydes were reacted with 1,3-disubstituted allenes in the presence of PPh₂Et, naphthalene derivatives were also obtained in up to quantitative yields. The mechanism of the latter transformation is straightforward: aldol addition followed by Wittig olefination and dehydration. The mechanism of the former is a tandem γ-umpolung/aldol/Wittig/dehydration process, as established by preparation of putative reaction intermediates and mass spectrometric analysis. This transformation can be applied iteratively to prepare anthracenes and tetracenes using carboxylic acids as pronucleophiles.

Full text of DOI:10.1021/jacs.5b07403

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Communication
Phosphine-Mediated Iterative Arene Homologation Using Allenes
Kui Zhang, Lingchao Cai, Xing Jiang, Miguel A. Garcia-Garibay, and Ohyun Kwon
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b07403 • Publication Date (Web): 21 Aug 2015
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Journal of the American Chemical Society
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Phosphine-Mediated Iterative Arene Homologation Using Allenes
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Kui Zhang, Lingchao Cai, Xing Jiang, Miguel A. GarciaꢀGaribay, and Ohyun Kwon
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Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095ꢀ1569, United States
Supporting Information Placeholder
optimized reaction conditions featured PPh3 (1 equiv) as the
mediator, an oꢀphthalaldehyde (1 equiv), a nucleophile (2 equiv),
and ethyl allenoate (3 equiv) in CH CN at 0 °C.
ABSTRACT:
A
PPh ꢀmediated multicomponent reaction
3
between oꢀphthalaldehydes, nucleophiles, and monosubstituted
allenes furnishes functionalized non–C ꢀsymmetric naphthalenes
3
2
in synthetically useful yields. When the oꢀphthalaldehydes were
a, b
Table 1. Arene homologation using ethyl allenoate 3a
reacted with 1,3ꢀdisubstituted allenes in the presence of PPh Et,
2
CHO
naphthalene derivatives were also obtained, in up to quantitative
yields. The mechanism of the latter transformation is
straightforward: aldol addition followed by Wittig olefination and
dehydration. The mechanism of the former is a tandem γꢀ
umpolung/aldol/Wittig/dehydration process, established through
the preparation of putative reaction intermediates and mass
spectrometric analysis. This transformation can be applied
iteratively to prepare anthracenes and tetracenes when employing
carboxylic acids as pronucleophiles.
PPh
3
CO
Nu
2
Et
•
2
CO Et
R
+
NuH
+
R
CHO
CH
3
0 o
CN
C
2
3a
4
1
O
O
O
OEt
OEt
OAc
OEt
O
Ph
HN
O
4g 32%
92%c
4h 25%
O
S
70%c
O
X
O
O
4
4
a 84% (X = 4-Me)
b 88% (X = H)
Cl
Cl
OEt
X
OEt
O
4c 78% (X = 4-F)
4
4
4
d 70% (X = 3-Me)
e 60% (X = 4-OMe)
85% (X = 2,6-dichloro)
O
X
4k 76% (X = OPh)
l 75% (X = NHTs)
4i 99% (X = H)
4
f
4j 95% (X = 4-Br)
The reactivity of electronꢀdeficient allenes under the conditions
X
X
1
O
of phosphine catalysis has been investigated extensively. Many
X
Y
X
Y
reports have appeared of the reactions of monosubstituted allenes
OEt
OEt
OPh
Y
X
Y
2
3
OPh
&
with activated olefin and imine electrophiles to construct
carbocyclic and azacyclic compounds. In contrast, few examples
are known of the reactions between monosubstituted allenes and
aldehyde electrophiles under the influence of phosphine
Y
4n 50% (X = H, Y = NO
2
)
4m/4m' 92%
4
n' 46% (X = NO , Y = H)
2
Y
X
(
X, Y = H, Me)
2 2
4o/4o' 70% (X = CO Et, Y = CH OAc)
a
4
Reaction performed by adding 3a (1.5 mmol) in CH CN (8 mL)
3
via syringe pump (rate: 2 mL/h) at 0 °C to a solution of an oꢀ
phthalaldehyde (0.5 mmol), a nucleophile (1 mmol), and PPh
catalysts. In general, the union of an allenoate and an aldehyde in
the presence of a phosphine results in the formation of an olefin
5
3
through a Wittigꢀlike process. Interestingly, all such reports have
b
c
(
0.5 mmol) in CH CN (4 mL). Isolated yields. A sodium
3
described reactions between αꢀ or γꢀsubstituted allenoates and
aldehydes. In contrast, Wittig reactions involving simple
allenoates are rare. We are aware of only one example of the
formation of a pyrrolizine, as a minor product (6%), through
intramolecular Wittig olefination between ethyl allenoate (3a) and
carboxylate (1 mmol) was added.
Tables 1 and 2 reveal the scope of this threeꢀcomponent
cascade
reaction.
As
the
nucleophilic
component,
6
pyrroleꢀ2ꢀcarboxaldehyde. Herein, we report Wittig olefination
benzenesulfonamides bearing electronꢀwithdrawing or ꢀdonating
substituents generated the naphthalene derivatives 4a–f in high
yields. With acetic acid and benzoic acid as nucleophiles, the
efficiencies of the reactions were poor, giving low yields of the
naphthalene derivatives 4g and 4h, respectively. Adding an
equimolar amount of sodium acetate or sodium benzoate as a
between monosubstituted allenes and oꢀphthalaldehydes to give
highly functionalized naphthalenes and higherꢀorder acenes.
Functionalized naphthalenes are valuable building blocks for
the synthesis of many important small molecules (e.g.7,
pharmaceuticals, chiral reagents, liquid crystals, organic dyes).
Many recent syntheses of functionalized naphthalenes have
employed costly transition metals or have required several steps to
10
buffer improved the yields of 4g and 4h dramatically. When
using phenol and pꢀbromophenol as the nucleophiles, the
naphthalene derivatives 4i and 4j, respectively, were formed
quantitatively. Examining substituted phthalaldehydes, we found
that 4,5ꢀdichlorophthalaldehyde also participated in the reaction,
furnishing the naphthalene derivatives 4k and 4l in good yields.
Asymmetric 4ꢀmethylphthalaldehyde furnished the inseparable
isomers 4m and 4m´ in 92% yield. When using 4ꢀ
nitrophthalaldehyde, we separated the two isomers 4n and 4n´ in
8
prepare the starting materials. Our phosphineꢀmediated
multicomponent cascade reaction described herein—between oꢀ
phthalaldehydes, nucleophiles, and monosubstituted allenes—is
an efficient and mild method for synthesizing functionalized
naphthalenes from readily available starting materials.
We surveyed the reaction between ethyl allenoate (3a), oꢀ
phthalaldehyde (1a), and pꢀtoluenesulfonamide by varying the
phosphine (stoichiometric), the solvent, the ratio between the
11
5
0 and 46% yields, respectively. Lastly, the combination of
benzeneꢀ1,2,4,5ꢀtetracarbaldehyde and acetic acid resulted in the
expected anthracenes 4o and 4o´ in a combined yield of 70%.
1
2
9
reactants, the reaction temperature, and the concentration. The
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Page 2 of 20
a, b
PPh3
Table 2. Arene homologation using phthalaldehyde 1a
•
CO Et
PhO
CO2Et
PhO
CO2Et
2
PhOH
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
PPh3
B
PPh3
O
C
CHO
PPh
3
R
R
CHO
CHO
+
NuH
+
•
CO2Et
CH
0 o
3
CN
C
Nu
CHO
O
2
3
1a
4
OPh
4
i
O
O
O
PPh3
CO2Et
PPh3
CO Et
PhO
PhO
H2O
OEt
OBn
OBn
OAc
OH
2
CO2Et
OPh
O
O
OH
HN
O
O
HN
O
S
S
4r 34%
85%c
O
PPh3
4
a 84%
E
D
O
O
O
X
4
4
p 99% (X = 4-Me)
q 40% (X = 4-NO )
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Although
γꢀumpolung
addition/aldol
reaction/Wittig
TMS
O
olefination/dehydration is the likely course of events for the
phthalaldehydeꢀtoꢀnaphthalene conversion, we could not exclude
the alternative sequence of aldol/γꢀumpolung/Wittig/dehydration
(Scheme 2). In this scenario, the phosphonium dienolate A adds to
1a to form the phosphonium lactolate F. Deprotonation of phenol
by lactolate provides the phenoxide nucleophile, γꢀumpolung
addition of which yields the lactol ylide E, ready for
intramolecular Wittig olefination and eventual formation of the
naphthalene 4i.
O
O
HN
O
O
OPh
S
4s 87%
OPh
4
u 98%
O
4
t 73%
a
Reaction performed by adding 3 (1.5 mmol) in CH CN (8 mL)
via syringe pump (rate: 2 mL/h) at 0 °C to a solution of 1a (0.5
mmol), a nucleophile (1 mmol), and PPh (1 mmol) in CH CN (4
3
3
3
b
c
mL). Isolated yields. NaOAc (1 mmol) was added.
Scheme 2. Aldol/γꢀumpolung/Wittig/dehydration sequence
PPh
3
We further investigated the reaction scope by treating 1a with a
suite of allenes and nucleophiles (Table 2). The reaction of pꢀ
toluenesulfonamide and benzyl allenoate provided the
CHO
2
CO Et
PPh
3
CHO
•
CO
Et
2
CO Et
2
O
O
PPh
3
naphthalene
4p
quantitatively,
while
that
of
pꢀ
F
A
nitrobenzenesulfonamide produced 4q in only 40% yield,
presumably because of attenuated nucleophilicity. By adding
NaOAc as a buffer, the yield of the naphthalene 4r improved from
4 to 85%. The combinations of 2ꢀ(trimethylsilyl)ethyl butaꢀ2,3ꢀ
dienoate/pꢀtoluenesulfonamide and 2,6ꢀdimethylphenyl butaꢀ2,3ꢀ
dienoate/phenol produced the desired products 4s (87%) and 4t
PhOH
PPh
3
PPh
3
PhO
PhO
10
CO
2
Et
2
CO Et
3
4i
O
O
E
OH
G
OH
(
73%), respectively. The reaction of pentaꢀ3,4ꢀdienꢀ2ꢀone and
phenol gave the naphthalene 4u in 98% yield.
To establish the greater likelihood between the two possible
mechanisms, we prepared the phosphonium salt 5 (precursor to B)
and the lactol 6 (precursor to F). Mixing 5 with NaH (1 equiv)
and 1a (1 equiv) in toluene at room temperature for 4 h yielded
the naphthalene 4i in 70% isolated yield (eq 3). Because the
optimized conditions for the threeꢀcomponent reaction differed
from those of the reaction described above, we also ran the
coupling reaction between 1a, 1 equiv of phenol, 1 equiv of the
PhO
9
CO
2
Et
PhO
2
CO Et
PPh
3
PPh
3
B
PhOH (R=Ph)
PPh
3
α
PR3
(1)
(2)
γ
CO Et
•
2
CO Et
2
PhO
2
2
CO Et
β
PR
3
A
R'
R'CHO
CO Et
allenoate, 1 equiv of PPh , and 1 equiv of NaI as an additive (eq
3
product
O
PR
3
4). This reaction, in toluene at room temperature, went to
completion within 6 h and produced the naphthalene 4i in 69%
isolated yield. Alternatively, when we mixed the lactol allenoate 6
with PPh (1 equiv) and phenol (1 equiv) in toluene at room
temperature, we obtained the expected product 4i in 45% yield
within only 30 min (eq 5). A control reaction between 1a, phenol
While phosphineꢀcatalyzed γꢀumpolung additions of
nucleophiles to allenoates have been documented amply (eq
reactions between monosubstituted allenes and aldehydes
other than salicylaldehyde (derivatives) have been scarce.
1
0,13
3
1),
4
a–e
In
those limited examples, the phosphonium dienolate A has added
to the aldehyde at its γꢀcarbon (eq 2). Based on this prior
knowledge, we postulated a credible process involving a sequence
of γꢀumpolung addition, aldol reaction, Wittig olefination, and
dehydration (Scheme 1). Here, the ylide intermediate B from the
initial γꢀumpolung addition undergoes proton transfer to form the
phosphonium enolate C, which adds to 1a to form the lactolate D.
Upon proton transfer, the ylide E is formed and undergoes Wittig
olefination. Subsequent dehydration provides the naphthalene 4i.
Notably, only the γꢀumpolung addition product was obtained
when 1a was replaced with benzaldehyde, suggesting that the
phthalaldehyde plays a crucial role in the progression of the
cascade sequence by forming the lactol substructure. Indeed,
when we attempted to prepare the adduct between 1a and
allenoate, we isolated the corresponding lactol product (see
compound 6 in eq 5).
(
1 equiv), 3a (1 equiv), and PPh (1 equiv) in toluene at room
3
temperature resulted in 4i in 70% isolated yield after 6 h (eq 6).
Thus, the NaI additive in eq 4 had no effect on the coupling
reaction.
CHO
CO Et
2
I
PPh
3
NaH
+
(3)
PhO
2
CO Et
toluene, rt
OPh
CHO
4
h
5
4
i 70%yield
CHO
PPh3, NaI
CO
2
Et
OEt
+
PhOH
+
•
(4)
toluene, rt
6 h
OPh
CHO
O
4i 69% yield
CO Et
OH
2
PPh
3
O
+
PhOH
(5)
(6)
toluene, rt
0.5 h
OPh
4i 45% yield
6
•
CO
Et
2
CO Et
2
CHO
CHO
PPh3
toluene, rt
OEt
O
•
+
PhOH
+
OPh
Scheme 1. γꢀUmpolung/aldol/Wittig/dehydration sequence
6
h
4i 70% yield
2
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PPh
3
Although inconclusive, the experiments in eqs 3–6 hinted at the
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
following possibility. If the aldol reaction occurred before the
umpolung reaction, the rateꢀlimiting step for the scenario in
Scheme 2 would be the addition of the phosphonium dienolate A
to 1a because the conversion of the lactol 6 to the product took
only 30 min. If the umpolung addition were the first event of the
cascade reaction (i.e., Scheme 1), the conversion of the ylide B to
the phosphonium enolate C or the addition of the enolate C to 1a
CO Et
2
PPh
3
O
PPh
279
3
PhO
2
CO Et
CO
2
Et
O
O
PPh3
A 375
PPh
3
263
B 491
F 509
1
: TOF MS ES+
.61e5
293.1097
2
100
would likely be the slowest step. Indeed, the pK of the ylide B
a
3 min
263.0997
(
21 in DMSO) is lower than that of the enolate C (30 in
14
DMSO).
Thus, despite unfavorable thermodynamics, the
3
75.1516
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
phosphonium dienolate A is likely to be funneled into the ylide B
as a result of rapid protonation by acidic phenol and the
subsequent γꢀaddition.
294.1141
295.0722
3
76.1567
491.1766
492.1800 523.2016
377.1583
3
42.1001
587.1132
0
Consequently, we envisioned a reaction between an allenoate
and 1a in the absence of a pronucleophile. The presumed
intermediate F´, we deduced, might form the ylide H, which
should undergo facile intramolecular Wittig olefination and
dehydration to form the naphthalene 7a (eq 7). Delightedly, the
reaction between 1a, ethyl 2,3ꢀpentadienoate (1 equiv), and PPh3
1
: TOF MS ES+
4.21e5
3
75.1490
100
4
0 min
279.0921
293.1078
263.0977
(1 equiv) in toluene at room temperature for 50 min gave 7a in 75%
491.1738
3
76.1532
isolated yield (eq 8). This outcome not only provides an
alternative pathway for arene homologation but also discounts the
aldol–before–γꢀumpolung addition scenario. Considering that the
γꢀumpolung/Wittig/dehydration sequence of the lactol 6 took 30
min and the aldol/Wittig/dehydration sequence of 1a and ethyl
2
94.1119 342.1010
492.1775 523.2002
493.1807
579.1619
301.0724
343.1072 377.1583
580.1657
0
1
: TOF MS ES+
3.60e5
3
75.1516
100
4 h
2
,3ꢀpentadienoate (through intermediate F´) took 50 min, the
279.0952
293.1105
threeꢀcomponent arene homologation would have been complete
within 1 h if the reaction had occurred through the aldolꢀfirst route.
Therefore, the reaction likely proceeds through initial γꢀumpolung
addition, with the rateꢀlimiting step being not the aldol addition of
C to 1a but the conversion of the ylide B to the enolate C.
491.1775
3
76.1561
263.1016
294.1151
509.1890
557.1824
23.2052
5
295.1130 342.1019
377.1616407.1710 445.1012
375 400 425 450 475
525.2037
558.1854
0
250
m/z
275
300
325
350
500
525
550
575
600
PPh
3
PPh
3
CO
2
Et
2
CO Et
Figure 1. Highꢀresolution mass spectra recorded during the
CO
Et
2
Et
+
+
reaction of eq 6 (m/z values for [M + H] or [M + Na] ions)
O
O
O
(7)
(8)
a, b
F'
OH Ph
3
P
O
H
2
O
7a
Table 3. Twoꢀcomponent arene homologation
H
O
CO
2
CHO
CHO
PPh3
R3
CHO
CHO
PPh
Et
R3
+
•
CO Et
•
2
R1
2
R1
+
R2
rt, toluene
50 min
O
rt, toluene
7a 75%
30~45 min
1
7
R2
Monitoring the reaction with highꢀresolution mass spectrometry
HRMS) confirmed our suspicions. After a reaction time of 3 min
O
O
O
(
Cl
Cl
+
OEt
OEt
OEt
(
3
8.3% 4i formation), the HRMS trace displayed A ([M + H] , m/z
+
+
75.1514) and B ([M + Na] , m/z 491.1752), but no F ([M + H] ,
9
7a 97%
7b 100%
7c 100%
m/z 509.1882). Although the reaction progressed steadily with
the peak for B clearly present throughout, the peak corresponding
to the phosphonium lactolate F was barely evident after 40 min
O
O
O
OEt
OEt
OX
(37.5% 4i formation) and was clearly visible only after 4 h (63.2%
4
i formation), suggesting that γꢀaddition–first is the dominant
7d 95%
7e 96%
7f 93% (X = t-Bu)
g 97% (X = Bn)
reaction pathway.
7
a
Examination of a range of phosphines, solvents, and reaction
temperatures revealed that addition of γꢀsubstituted allenoates (2
Reaction performed with a dialdehyde (0.4 mmol), an allenoate
(0.8 mmol), and PPh Et (0.4 mmol) in toluene (4 mL) at room
2
b
equiv) to a mixture of a phthalaldehyde and PPh Et (1 equiv) in
temperature. Isolated yields.
2
toluene at room temperature was optimal for arene homologation
The utility of the multicomponent reaction is further
illustrated in the synthesis of the 2,3ꢀdisubstituted tetracene 11
(Scheme 3). Reduction of the ester groups of the naphthalene 4g
(Table 3). After stirring for 30 to 45 min, we obtained the desired
arenes 7a–g in excellent yields. 4,5ꢀDichlorophthalaldehyde was
converted quantitatively to the naphthalene 7b. When using
naphthaleneꢀ2,3ꢀdicarbaldehyde in this reaction, the anthracene 7c
was obtained in 100% isolated yield. Ethyl hexaꢀ2,3ꢀdienoate and
ethyl 4ꢀcyclopentylbutaꢀ2,3ꢀdienoate were produced the
naphthalenes 7d and 7e, respectively, as Eꢀstereoisomers. tertꢀ
Butyl pentaꢀ2,3ꢀdienoate and benzyl pentaꢀ2,3ꢀdienoate gave their
expected products 7f (93%) and 7g (97%), respectively.
yielded
a diol, which was oxidized to naphthaleneꢀ2,3ꢀ
dicarbaldehyde (8) with high efficiency. Repetition of the
annulation, reduction, and oxidation sequence provided
anthraceneꢀ2,3ꢀdicarbaldehyde (10), which underwent another
annulation to provide the tetracene 11. A variety of 2,3ꢀsubstituted
tetracenes should be readily obtainable from 11 through
functional group manipulation, with potential applications in solar
1
5
cells and lightꢀemitting materials.
3
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(
1) For selected reviews, see: (a) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem.
Scheme 3. Iterative synthesis of anthracene and tetracene
Res. 2001, 34, 535. (b) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009,
38, 3102. (c) López, F.; Mascareñas, J. L. Chem. Eur. J. 2011, 17, 418. (d)
Zhao, Q. Y.; Lian, Z.; Wei, Y.; Shi, M. Chem. Commun. 2012, 48, 1724.
e) Fan, Y. C.; Kwon, O. Chem. Commun. 2013, 49, 11588. (f) Wang, Z.;
Xu, X.; Kwon, O. Chem. Soc. Rev. 2014, 43, 2927.
(2) Selected examples: (a) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60,
2906. (b) Du, Y.; Lu, X.; Yu, Y. J. Org. Chem. 2002, 67, 8901. (c) Lu, X.;
Lu, Z.; Zhang, X. Tetrahedron 2006, 62, 457. (d) Henry, C. E.; Kwon, O.
Org. Lett. 2007, 9, 3069. (e) Lu, Z.; Zheng, S.; Zhang, X.; Lu, X. Org.
Lett. 2008, 10, 3267. (f) Guan, X.ꢀY.; Wei, Y.; Shi, M. Org. Lett. 2010,
12, 5024. (g) Hua, X.; Chai, Z.; Zheng, C. W.; Yang, Y. Q.; Liu, W.;
Zhang, J. K.; Zhao, G. Angew. Chem. Int. Ed. 2010, 49, 4467. (h) Han, X.;
Wang, Y.; Zhong, F.; Lu, Y. J. Am. Chem. Soc. 2011, 133, 1726. (i) Han,
X.; Wang, S.ꢀX.; Zhong, F.; Lu, Y. Synthesis 2011, 1859. (j) Zhao, Q.;
Han, X.; Wei, Y.; Shi, M.; Lu, Y. Chem. Commun. 2012, 48, 970.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
•
2
CO Et
CHO
CHO
•
CO
2
Et
CHO
CHO
NaOAc, HOAc
PPh
2%
1. LAH
OAc 2.Swern ox.
3
(
84%
9
4
g
8
CO Et
2
CO
2
Et
CHO
CHO
NaOAc, HOAc
PPh
85%
1. LAH
.Swern ox.
8%
OAc
2
3
6
9
10
•
2
CO Et
CO
2
Et
NaOAc, HOAc
PPh
72%
OAc
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
11
(
3) Selected examples: (a) Xu, Z.; Lu, X. Tetrahedron Lett. 1997, 38,
3
461. (b) Xu, Z.; Lu, X. J. Org. Chem. 1998, 63, 5031. (c) Mercier, E.;
Fonovic, B.; Henry, C. E.; Kwon, O.; Dudding, T. Tetrahedron Lett. 2007,
48, 3617. (d) Fang, Y. Q.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130,
5
660. (e) Gaun, X. Y.; Wei, Y.; Shi, M. J. Org. Chem. 2009, 74, 6343. (f)
Meng, X. T.; Huang, Y.; Chen, R. Y. Org. Lett. 2009, 11, 137. (g) Sun, Y.
W.; Guan, X. Y.; Shi, M. Org. Lett. 2010, 12, 5664. (h) Chen, X. Y.; Lin,
R. C.; Ye, S. Chem. Commun. 2012, 48, 1317. (i) Han, X.; Zhong, F.;
Wang, Y.; Lu, Y. Angew. Chem. Int. Ed. 2012, 51, 767. (j) Henry, C. E.;
Xu, Q.; Fan, Y. C.; Martin, T. J.; Belding, L.; Dudding, T.; Kwon, O. J.
Am. Chem. Soc. 2014, 136, 11890.
(
4) (a) Zhu, X. F.; Henry, C. E.; Wang, J.; Dudding, T.; Kwon, O. Org.
Lett. 2005, 7, 1387. (b) Dudding, T.; Kwon, O.; Mercier, E. Org. Lett.
2006, 8, 3643. (c) Zhu, X.ꢀF.; Schaffner, A.ꢀP.; Li, R. C.; Kwon, O. Org.
Lett. 2005, 7, 2977. (d) Creech, G. S.; Kwon, O. Org. Lett. 2008, 10, 429.
e) Creech, G. S.; Zhu, X. F.; Fonovic, B.; Dudding, T.; Kwon, O.
Tetrahedron 2008, 64, 6935. (f) Sun, Y. W.; Guan, X. Y.; Shi, M. Org.
Lett. 2010, 12, 5664.
(5) (a) He, Z. R.; Tang, V.; He, Z. J. Phosphorous Sulfur Silicon Relat.
Elem. 2008, 183, 1518. (b) Xu, S. L.; Zhou, L. L.; Zeng, S.; Ma, R. Q.;
Wang, Z. H.; He, Z. J. Org. Lett. 2009, 11, 3498. (c) Xu, S. L.; Zou, W.;
Wu, G. P.; Song, H. B.; He, Z. J. Org. Lett. 2010, 12, 3556. (d) Khong, S.
N.; Tran, Y. S.; Kwon, O. Tetrahedron 2010, 66, 4760. (e) Xu, S. L.;
Chen, R. S.; He, Z. J. J. Org. Chem. 2011, 76, 7528. (f) Jacobsen, M. J.;
Funder, E. D.; Cramer, J. R.; Gothelf, K. V. Org. Lett. 2011, 13, 3418. (g)
Qin, Z.; Ma, R.; Xu, S.; He, Z. J. Tetrahedron 2013, 69, 10424. For
exceptions, see: ref. (d); ref. (g); (h) Ma, R. Q.; Xu, S. L.; Tang, X. F.;
Wu, G. P.; He, Z. J. Tetrahedron 2011, 67, 1053.
Figure 2. Excitation (solid lines) and emission (dashed lines)
spectra of 4g (blue lines), 9 (green lines), and 11 (red lines).
(
We obtained fluorescence excitation and emission spectra for
compounds 4g, 9, and 11 (Figure 2). Stronger transitions appeared
in the range 250–300 nm, with weaker transitions in the range
3
00–500 nm. A bathochromic shift occurred upon proceeding
from 4g (326 nm) to 9 (358 nm) to 11 (450 nm). A bathochromic
shift also occurred in the fluorescence emissions from 4g to 9 to
1
1, with 0–0 transitions at 342, 406, and 495 nm, respectively.
The quantum yields for the substituted polyacenes 4g, 9, and 11
were 0.18, 0.65, and 0.15, respectively. These observations match
16
well with reported photophysical data of 2ꢀcarbonylpolyacenes.
In conclusion, we have developed a phosphineꢀmediated
multicomponent reaction between allenes, oꢀphthalaldehydes, and
(
6) Virieux, D.; Guillouzic, A. F.; Cristau, H. J. Tetrahedron 2006, 62,
710.
(7) (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons; WileyꢀVCH:
3
nucleophiles that provides non–C ꢀsymmetric naphthalene,
2
anthracene, and tetracene derivatives. A mechanistic investigation
involving the synthesis of putative intermediates and reaction
monitoring through HRMS revealed that this conversion occurs
New York, 1996. (b) Waston, M. D.; Fethtenkötter, A.; Müllen, K. Chem.
Rev. 2001, 101, 1267. (c) De Koning, C. B.; Rousseau, A. L.; van Otterlo,
W. A. L. Tetrahedron 2003, 59, 7.
(8) Selected examples: (a) Feng, C.; Loh, T. P. J. Am. Chem. Soc. 2010,
through
a
γꢀumpolung/aldol/Wittig/dehydration cascade.
A
1
32, 17710. (b) Fukutani, T.; Hirato, K.; Satoh, T.; Miura, M. J. Org.
combination of phthalaldehydes and 1,3ꢀdisubstituted allenes also
produces naphthalenes through an aldol/Wittig/dehydration
sequence. This arene homologation can also be applied iteratively
to prepare higherꢀorder acenes.
Chem. 2011, 76, 2867. (c) Kocsis, L. S.; Benedetti, E.; Brummond, K. M.
Org. Lett. 2012, 14, 4430. (d) Kang, D. L.; Kim, J.; Oh, S.; Lee, P. H.
Org. Lett. 2012, 14, 5636. (e) Geary, L. M.; Chen, T. Y.; Montgomery, T.
P.; Krische, M. J. J. Am. Chem. Soc. 2014, 136, 5920. (f) Pham, M. V.;
Cramer, N. Angew. Chem. Int. Ed. 2014, 53, 3484.
(9) See the Supporting Information for more details.
ASSOCIATED CONTENT
(10) Trost, B. M.; Li, C. J. J. Am. Chem. Soc. 1994, 116, 3167.
9
Supporting Information.
Experimental procedures and analytical data (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
(11) The structure of 4n´ was established using Xꢀray crystallography.
1
(12) The structures of 4o and 4o´ were identified using H NMR
spectroscopy. See the detailed information in the Supporting Information.
(13) Selected examples: (a) Cristau, H.ꢀJ.; Viala, J.; Christol, H.
Tetrahedron Lett. 1982, 23, 1569. (b) Lu, X.; Zhang, C. Synlett 1995, 645.
AUTHOR INFORMATION
(
c) Chen, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Org.
Chem. 1998, 63, 5631. (d) Smith, S. W.; Fu, G. C. J. Am. Chem. Soc.
2009, 131, 14231. (e) Chung, Y. K.; Fu, G. C. Angew. Chem. Int. Ed.
2009, 48, 2225. (f) Lundgren, R. J.; Wilsily, A.; Marion, N.; Ma, C.;
Chung, Y. K.; Fu, G. C. Angew. Chem. Int. Ed. 2013, 52, 2525.
Corresponding Author
ohyun@chem.ucla.edu
(
14)
Evans
D.
A.
Evans
pK
a
Table.
ACKNOWLEDGMENT
http://evans.harvard.edu/pdf/evans_pKa_table.pdf.
(15) (a) Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev. 2004,
04, 4891. (b) Anthony, J. E. Chem. Rev. 2006, 106, 5028. (c) Burdett, J.
The NIH (GM071779) is acknowledged for financial support.
1
J.; Bardeen, C. J. Acc. Chem. Res. 2013, 46, 1312.
16) Nehira, T.; Parish, C. A.; Jockusch, S.; Turro, N. J.; Nakanishi, K.;
Berova, N. J. Am. Chem. Soc. 1999, 121, 8681.
REFERENCES
(
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TOC Graphic
EWG
Nu
•
EWG
Nu
EWG
EWG
NuH
+
PPh
3
R
2
CHO
CHO
23 examples
up to 99% yield
PR
3
R2
R1
EWG
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EWG
R1
2
PPh Et
R2
examples
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PPh3
CO Et
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PPh3
63
O PPh3
279
PhO
CO Et
2
CO Et
2
O
PPh3
2
PPh3
A
375
B
491
F
509
O
ꢀ
1: TOF MS ES+
293.1097
2.61e5
1
1
1
00
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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9
0
ꢀꢁꢂꢃꢄ
263.0997
375.1516
294.1141
376.1567
377.1583
491.1766
295.0722
492.1800 523.2016
3
42.1001
587.1132
0
1: TOF MS ES+
375.1490
4.21e5
00
ꢅꢆꢁꢂꢃꢄ
279.0921
293.1078
2
63.0977
491.1738
376.1532
2
94.1119 342.1010
492.1775 523.2002
493.1807
579.1619
3
43.1072 377.1583
3
01.0724
580.1657
0
1: TOF MS ES+
375.1516
3.60e5
00
ꢅꢁꢇ
279.0952
2
93.1105
491.1775
376.1561
294.1151
509.1890
2
63.1016
5
57.1824
5
23.2052
3
42.1019
377.1616
407.1710 445.1012
295.1130
525.2037
558.1854
0
250
m/z
275
300
325
350
375
400
425
450
475
500
525
550
575 600
ꢀ
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6x5mm (300 x 300 DPI)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 18 of 20
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30x60mm (300 x 300 DPI)
ACS Paragon Plus Environment

Page 19 of 20
Journal of the American Chemical Society
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0x34mm (300 x 300 DPI)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 20 of 20
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ꢀ
ACS Paragon Plus Environment