cyclization of o-terphenyls under severe acidic and/or
oxidative conditions.6 However, since many functional
groups cannot tolerate such harsh reaction conditions,
the scope of this triphenylene synthesis is limited. More
recently, transition-metal catalyst-based approaches have
attracted much attention as they offer synthetic routes that
are highly efficient and compatible with various functional
groups.7,8 Nomura and Miura have reportedtwo examples
of substituted triphenylenes via the palladium-catalyzed
annulation of o-dibromobenzenes with o-phenybenzyl
alcohols.9 Larockalsoreported the synthesisofsubstituted
triphenylenes by the palladium-catalyzed annulation of
o-iodobiphenyls with in situ generated arynes.10 These
methods have the potential to significantly expand the sub-
strate scope, but drawbacks remain: (1) the reaction with
arynes lacks regioselectivity and as a result gives rise to a
mixture of regioisomers; and (2) the starting substrates are
often difficultto prepare. Herein, we report the synthesis of
highly functionalized triphenylenes, including previously
inaccessible unsymmetrical triphenylenes. These syntheses
proceed via palladium-catalyzed annulation of o-iodobi-
phenyls with o-bromobenzyl alcohols which are readily
prepared and also air- and moisture-stable. The reaction
involves the decarbonylative cross-coupling of aryl iodides
with tertiary benzylic alcohols and the subsequent intra-
molecular cyclization catalyzed by a palladium/phosphine
complex.11
(entry 1). However, the yields of 3a further decreased when
the corresponding chloride 2b and iodide 2c were used in
place of 2a (entries 2 and 3). The use of aryl triflate 1b or
aryl chloride 1c in the reaction with 2a gave no product
3a at all (entries 4 and 5). Of the systems screened the
combination of o-iodobiphenyl (1d) and o-bromobenzyl
alcohol 2a proved to be the best (entry 6).
Table 1. Effect of Halide in Palladium-Catalyzed Annulation
Reaction of 1 with 2a
entry
X1
X2
yield (%)b
1
2
3
4
5
6
Br (1a)
Br (1a)
Br (1a)
OTf (1b)
Cl (1c)
I (1d)
Br (2a)
Cl (2b)
I (2c)
15
<1
2
Br (2a)
Br (2a)
Br (2a)
0
0
26
a Conditions: 1 (0.25 mmol), 2 (0.3 mmol), Pd(dba)2 (0.0125 mmol),
PPh3 (0.05 mmol), and Cs2CO3 (0.6 mmol) in toluene (1 mL). b Deter-
mined by the 1H NMR analysis of the crude mixture using bromoform as
an internal standard.
We initially investigated the effect of halides in the
annulation of o-halobiphenyls 1 with o-halobenzyl alco-
hols 2 (Table 1).12 When the reaction was conducted with
o-bromobiphenyl (1a) and o-bromobenzyl alcohol 2a, the
desired triphenylene (3a) was obtained in 15% yield
Various palladium/phosphine combinations were then
screened as the potential catalysts using the best substrate
combination (Table 1, entry 6), and the results are sum-
marized in Table 2. Electron-deficient triarylphosphines
gave better results than electron-rich phosphines, suggest-
ing an accelerated CꢀH metalation process (entries 1ꢀ3).
Similar trends have been observed in other palladium-
catalyzed CꢀH functionalizationreactions.13 Trialkylpho-
sphines such as PCy3 (Cy = cyclohexyl) or PnBu3, triphe-
nylphosphite P(OPh)3, and bidentate ligands such as
DPPE (1,2-bis(diphenylphosphino)ethane) or DPPF
(1,10- bis(diphenylphosphino)ferrocene) were much less
active. The best ratio of palladium to ligand was 1 to 2,
although at the lower end of this range precipitation of a
palladium black was observed (entry 4). In the presence of
Pd(II) precursors such as Pd(OAc)2, PdCl2, or PdCl2-
(NCMe)2, the reaction proceeded well (entries 5ꢀ7).
Finally, PdCl2(NCPh)2 provided 3a in 81% yield (entry 8).
In the case that the product 3a was obtained in low yield, the
intermediate 4a and the homocoupled product 511a were
€
(6) For examples, see:(a)Kivala, M.; Wu, D.;Feng, D.;Li, C.;Mullen,
K. In Synthesis of Polymers; Schulter, D., Hawker, C. J., Sakamoto, J., Eds.;
Wiley-VCH: New York, 2012; pp 373ꢀ420. (b) Jørgensen, K. B. Molecules
2010, 15, 4334. (c) King, B. T.; Kroulık, J.; Robertson, C. R.; Rempala, P.;
Hilton, C. L.; Korinek, J. D.; Gortari, L. M. J. Org. Chem. 2007, 72, 2279.
(d) Mallory, F. B.; Mallory, C. W. Org. React. 1984, 30, 1.
(7) For reviews, see: (a) Ackermann, L. Chem. Rev. 2011, 111, 1315.
(b) Bras, J. L.; Muzart, J. Chem. Rev. 2011, 111, 1170. (c) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147. (d) Sehnal, P.; Taylor,
R. J. K.; Fairlamb, I. J. S. Chem. Rev. 2010, 110, 824. (e) Xu, L.-M.; Li,
B.-J.; Yang, Z.; Shi, Z.-J. Chem. Soc. Rev. 2010, 39, 712. (f) Daugulis, O.;
Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074. (g) Catellani,
M.; Motti, E.; Della Ca’, N. Acc. Chem. Res. 2008, 41, 1512. (h) Minatti,
~
A.; Muniz, K. Chem. Soc. Rev. 2007, 36, 1142. (i) D’Souza, D. M.;
€
Muller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095.
(8) Palladium-catalyzed [2 þ 2 þ 2] trimerization of arynes: (a) Cant,
A. A.; Roberts, L.; Greaney, M. F. Chem. Commun. 2010, 46, 8671. (b)
Nagao, I.;Shimizu, M.;Hiyama, T. Angew. Chem., Int.Ed. 2009, 48, 7573.
(9) Terao, Y.; Wakui, H.; Nomoto, M.; Satoh, T.; Miura, M.;
Nomura, M. J. Org. Chem. 2003, 68, 5236.
(10) (a) Liu, Z.; Larock, R. C. J. Org. Chem. 2007, 72, 223. (b) Xie, C.;
Zhang, Y.; Huang, Z.; Xu, P. J. Org. Chem. 2007, 72, 5431. (c) Jayanth,
T. T.; Cheng, C.-H. Chem. Commun. 2006, 894. (d) Liu, Z.; Zhang, X.;
Larock, R. C. J. Am. Chem. Soc. 2005, 127, 15716.
(11) Similar annulation has been reported to provide the benzochro-
menes. (a) Mahendar, L.; Krishna, J.; Reddy, A. G. K.; Ramulu, B. V.;
Satyanarayana, G. Org. Lett. 2012, 14, 628. (b) Motti, E.; Della Ca’, N.;
Xu, D.; Piersimoni, A.; Bedogni, E.; Zhou, Z.-M.; Catellani, M. Org.
Lett. 2012, 14, 5792.
(12) It is of note that the annulating reagents o-halobenzyl alcohols 2
actually need only a single step to prepare. Commercially available
o-halobenzoate esters were treatedwithGrignard reagents toyield tertiary
benzylic alcohols 2 quantitatively. When a methyl group was installed as a
substituent at the benzylic position of 2, the palladium-catalyzed dec-
arbonylative coupling reaction yielded a stoichiometric amount of acet-
one, which is easily separable from the target triphenylene 3.
1
detected by the H NMR and GC-MS analyses. We con-
firmed that the reaction of the isolated 4a proceeded under
the optimized conditions to afford 3a quantitatively.
A plausible mechanism is shown in Scheme 1, based on
the detected intermediate, 2-bromo-o-terphenyl (4a). Oxi-
dative addition of o-iodobiphenyl (1d) occurs to give an
(13) (a) Hitce, J.; Retailleau, P.; Baudoin, O. Chem.;Eur. J. 2007,
13, 792. (b) Yanagisawa, S.; Sudo, T.; Noyori, R.; Itami, K. J. Am.
Chem. Soc. 2006, 128, 11748. (c) Campeau, L.-C.; Parisien, M.; Leblanc,
M.; Fagnou, K. J. Am. Chem. Soc. 2004, 126, 9186.
B
Org. Lett., Vol. XX, No. XX, XXXX