Novel and rapid palladium-assisted 6π electrocyclic reaction affording 9,10-dihydrophenanthrene and its analogues

Article abstract of DOI:10.1021/ol801882t

(Equation Presented) A novel methodology for the synthesis of 9,10-dihydrophenanthrene and its analogues has been developed via a palladium-assisted 6π electrocyclic reaction followed by formaldehyde elimination.

Full text of DOI:10.1021/ol801882t

ORGANIC
LETTERS
2
008
Vol. 10, No. 21
795-4797
Novel and Rapid Palladium-Assisted 6π
Electrocyclic Reaction Affording
4
9,10-Dihydrophenanthrene and Its
Analogues
Rathin Jana, Indranil Chatterjee, Shubhankar Samanta, and Jayanta K. Ray*
†
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
jkray@chem.iitkgp.ernet.in
Received August 12, 2008
ABSTRACT
A novel methodology for the synthesis of 9,10-dihydrophenanthrene and its analogues has been developed via a palladium-assisted 6π
electrocyclic reaction followed by formaldehyde elimination.
The extraordinary C-C bond-forming ability of palladium
vigorous. Trost synthesized polycyclic molecules via a
pallladium-catalyzed electrocyclic process. Recently, a
7
places it among the most versatile and useful metals in
1
organic synthesis. Among these, polycyclic aromatic and
palladium-catalyzed electrocyclization strategy for the syn-
8
heteroaromatic hydrocarbons have been widely studied for
thesis of fused bicyclic and tricyclic rings has been reported.
2
their unique properties in material science. Heck first
In this letter, we report a novel and rapid convenient
approach to the synthesis of substituted 9,10-dihydrophenan-
threne along with its analogues by a palladium-catalyzed 6π
electrocyclic reaction. Recently, we described the palladium-
catalyzed intramolecular Heck reaction by ꢀ-H elimination
reported the synthesis of 9,10-diphenylphenanthrene from
2
-iodobiphenyl and diphenyl acetylene by a palladium-
3
catalyzed annulation process; however, the yield was 14%.
Later, Larock improved the product yield by changing the
reaction condition and also synthesized fused polycycles
4
9
or C-H activation to afford a polycyclic pyran moiety. We
5
by 1,4-palladium migration followed by C-H activation.
were planning to apply this reaction for the synthesis of a
bicyclicpyran ring, but surprisingly we obtained 9,10-
dihydrophenanthrene in good yield (Scheme 1).
Fagnou synthesized 9,10-dihydophenanthrene by a direct
6
arylation process, but the reaction condition was more
†
Dedicated to Professor Miguel Yus, University of Alicante, Spain, on
his 60th birthday.
(
1) Tsuji, J. Transition metal reagents and catalysts: InoVation in organic
synthesis; Wiley: New York, 2002.
2) For reviews, see:(a) Watson, M. D.; Fethtenkotter, A.; Mullen, K.
Chem. ReV. 2001, 101, 1267. (b) Chandrasekhar, S. Liq. Cryst. 1993, 14,
. (c) Chandrasekhar, S.; Kumar, S. Sci. Spectra 1997, 8, 66. (d) P e´ rez, D.;
Scheme 1
(
3
Guiti a´ n, E. Chem. Soc. ReV. 2004, 33, 274. (e) Buess, C. M.; Lawson, D. D.
Chem. ReV. 1960, 60, 313. (f) Watson, M.; Fechtenk o¨ tter, A.; M u¨ llen, K.
Chem. ReV. 2001, 101, 1267.
(
3) Wu, G.; Rheingold, A. L.; Geib, S. J.; Heck, R. F. Organometallics
1
987, 6, 1941.
4) Larock, R. C.; Doty, M. K.; Tian, Q.; Zenner, J. M. J. Org. Chem.
997, 62, 7536.
5) Campo, M. A.; Huong, Q.; Yao, T.; Tian, Q.; Larock, R. C. J. Am.
Chem. Soc. 2003, 125, 11506.
(
The convergent approach involved preparation of the
cyclic precursors 4(a-j) which were efficiently synthesized
starting from vinylbromoaldehydes, as per Scheme 2.
1
(
10.1021/ol801882t CCC: $40.75
Published on Web 10/02/2008
 2008 American Chemical Society

Scheme 2
a
Table 2. Palladium-Catalyzed Electrocyclic Reaction
2
When we treated substrate 4a with Pd(OAc) (10 mol %),
Cs CO (2 equiv), PPh (0.5 equiv), and TBAC(1 equiv), in
2 3 3
DMF solvent, followed by heating at 85-90 °C for 1.5-2
h, the unexpected product 5a was obtained in 70% yield. A
fused aromatic ring resulted from cleavage of the pyran ring
present in the substrate followed by ring closure and
aromatization. The reaction was then attempted by changing
the base and solvent to optimize the reaction conditions. The
results are summarized in Table 1.
In acetonitrile (Table 1; entries 4, 5, 6, and 8), yield was
poor; however, in DMF, yields were improved with both
Cs
2
CO
3
and NaOAc (Table 1; entries 1 and 7).
a
Table 1. Optimization Studies
a
b
2 3
Reagent and conditions: 4(a-j) (1equiv), Pd(OAc) (10 mol %), PPh
entry
base
solvent
temp (°C)
yield (%)
(
0.5 equiv), Cs2CO3 (2 equiv), n-Bu4NCl (1 equiv), DMF (6-7 mL), heated
at 85-90 °C. Isolated yield obtained after column chromatography.
b
1
2
3
4
5
6
7
8
a
Cs2CO3
Na2CO3
K2CO3
Cs2CO3
Na2CO3
K2CO3
DMF
DMF
DMF
CH3CN
CH3CN
CH3CN
DMF
90
90
90
85
85
80
90
85
70
62
61
35
30
33
68
33
Finally, we concluded that our optimization conditions were
10 mol % of Pd(OAc)
2 3
, 0.5 equiv of PPh , and 2 equiv of
Cs CO in DMF solvent heated at 85-90 °C for 1.5-2 h.
2
3
NaOAc
NaOAc
We next examined the scope of this reaction with different
substituted 2-(1-bromo-3,4-dihydro-napthenen-2-yl)-3,6-di-
hydro-2H-pyran, 2-(2-bromo-3,4-dihydro-napthenen-1-yl)-
3,6 dihydro-2H-pyran, 4-bromo-3-(3,6-dihydro-2H-pyran-2-
yl)-2H-chromene, and 2-(2-bromo-acenaphthylen-yl)-3,6-
CH3CN
All the reactions were carried out in the presence of Pd(OAc)2 (10
mol %), PPh3 (0.5 equiv), and n-Bu4NCl (1 equiv). All the reactions were
carried out in the presence of 2 equiv of base.
b
4796
Org. Lett., Vol. 10, No. 21, 2008

Scheme 4
Scheme 3. Proposed Mechanism for the Formation of
a
9
,10-Dihydrophenanthrene
generate alkenyl palladium(II) intermediate (A) via oxidative
addition of the Pd(0) to the substrate, which then coordinates
with oxygen to generate the intermediate (B). This undergoes
proton abstraction followed by rearrangement to afford a
nine-membered cyclic Pd-O complex (C). This complex
involves a 6π electrocyclic reaction forming complex (D),
followed by formaldehyde extrusion to afford 9,10-dihydro-
phenanthrene. The plausible mechanism of the reaction is
outlined below (Scheme 3).
From the above cycle, it can be assumed that the oxo-
palladium complex (B) decomposes to the nine-membered
cyclic Pd-O complex (C) by H elimination. Next, we
thought that the introduction of two methyl groups instead
of 2H could lead to a situation where further H-elimination
is impossible and hence the reaction will stop. This hypoth-
esis was found to be valid with the experimental results. The
substrate 2-(2-bromo-3,4-dihydro-naphthalen-1-yl)-3,3-di-
methyl-3,6-dihydro-2H-pyran did not react under similar
conditions (Scheme 4).
In summary, we have developed a novel and efficient
methodology for the synthesis of 9,10-dihydrophenanthrene
and its analogue by the palladium-catalyzed 6π electrocyclic
reaction. This methodology will also be helpful to synthesize
highly substituted phenanthrene derivatives providing an
efficient route to a wide variety of substituted polycyclic
aromatics from readily available starting materials.
a
Steric interaction of complex (E) in substrate 4a.
dihydro-2H-pyran (Table 2) to obtain overall good yield in
each case. This process represents a very powerful new tool
for the preparation of 9,10-dihydrophenanethrene and its
analogues from vinyl bromoaldehydes 1(a-h). In the case
of substrates 4(g-i), a slightly better result than substrates
4
(a-f) was observed. This is presumably due to the fact that
in later cases the complex formed (E) interacted with the
adjacent benzene ring (peri-interaction), but such an interac-
tion was absent in the former cases (Scheme 3).
The reaction mechanism presumely involves a 6π elec-
trocyclic reaction followed by formaldehyde elimination. The
catalytic cycle involves initial oxidation of the Pd(0) to
Acknowledgment. We thank DST, New Delhi, for
providing financial support. R. Jana and S. Samanta thank
CSIR, New Delhi, for their fellowships.
(
6) Campeau, L. C.; Parisien, M.; Leblanc, M.; Fagnou, K. J. Am. Chem.
Supporting Information Available: Detailed experimen-
tal procedures and spectral data for all the compounds
1(a-h), 2(a-i), 3(a-j), 4(a-j), 5(a-j), and 6(b-d). This
material is available free of charge via the Internet at
http://pubs.acs.org.
Soc. 2004, 126, 9186.
(
(
7) Trost, B. M.; Shi, Y. J. Am. Chem. Soc. 1992, 114, 791.
8) (a) Kan, S. B. J.; Anderson, E. Org. Lett. 2008, 10, 2323. (b) Tamber,
U. K.; Kano, T.; Zepernick, J. F.; Stoltz, B. M. Tetrahedron Lett. 2007, 48,
3
1
45. (c) Wang, F.; Tong, X.; Cheng, J.; Zhang, Z. Chem.-Eur. J. 2004,
0, 5338. (d) Von Zezschwitz, P.; Petry, F.; De Meijere, A. Chem.-Eur.
J. 2001, 7, 4035.
(
9) Jana, R.; Samanta, S.; Ray, J. K. Tetrahedron Lett. 2008, 49, 851.
OL801882T
Org. Lett., Vol. 10, No. 21, 2008
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