Angewandte
Communications
Chemie
Arenes
Transition-Metal-Free Synthesis of Homo- and Hetero-1,2,4-Triaryl
Benzenes by an Unexpected Base-Promoted Dearylative Pathway
Mohammad Rehan, Sanjay Maity, Lalit Kumar Morya, Kaushik Pal, and Prasanta Ghorai*
Abstract: An unprecedented approach for the synthesis of
homo- and hetero-1,2,4-triaryl benzenes has been developed
using a simple base-mediated reaction of either a-aryl cin-
namyl alcohols or a,g-di-aryl propanones. The salient feature
of this strategy involves the sequential hydride transfer,
regiospecific condensation, regiospecific dearylation, and
aromatization under metal-free reaction conditions. The syn-
thesis of unsymmetrically substituted triphenylenes by oxida-
tive coupling of the synthesized 1,2,4-triaryl benzenes has also
been demonstrated.
T
he development of novel transition-metal-free organic
transformations has been a growing interest in modern
chemistry for the reasons of cost, safety, and environmental
concerns.[1] Because of this demand, to date, a wide variety of
highly efficient and selective transition-metal-free synthetic
approaches have been developed.[2] The development of
transition-metal-free cascade reactions remains an attractive
strategy for efficient synthesis of complex molecular archi-
tectures.[3]
Scheme 1. Synthesis of 1,2,4-triaryl benzenes.
The synthesis of multiply substituted aromatic compounds
is an issue of great interest in pharmaceutical, as well as in
materials science. The [2+2+2] cyclotrimerization of alkynes
catalyzed by transition metals is an elegant chemical trans-
formation for the single-step construction of such compounds
(Scheme 1a).[4] After the pioneering work by Reppe in
1948,[5] a large number of transition-metal catalysts were
developed for the same reaction.[4] Two major problems
associated with these methods are: first is the formation of
a mixture of regioisomers (homo-1,2,4- and 1,3,5-triaryl
benzenes; Scheme 1a) by homo-cyclotrimerizations of termi-
nal alkynes. Secondly, the crossed-cyclotrimerization of
different alkynes in an intermolecular fashion, without
tethering of the starting materials, leads to a mixture of 37
isomers (Scheme 1b). The first problem is solved in many
cases, and results in either the preference for the homo-1,3,5-
or homo-1,2,4-substitution pattern, thereby reducing the
number of possible products.[6] However, the use of different
alkynes and consequently the regio- and chemoselective
synthesis of hetero-1,2,4-trisubstituted benzenes still remains
an unsolved problem.[7] Herein, we report a transition-metal-
free synthesis of both homo- and hetero-1,2,4-triaryl benzenes
from homo- and hetero-a-aryl cinnamyl alcohols, respectively
(Scheme 1c). The salient features of this method are that it is
1) transition-metal-free, 2) operationally simple, 3) employs
readily available and inexpensive starting materials, and
4) provides either homo- or hetero-1,2,4-triaryl benzenes in
a regiospecific manner. The most notable finding is that an
unprecedented dearylative aromatization occurs in the pres-
ence of a simple KOH/DMSO system.[8] The KOH/DMSO
system itself is utilized in various cross-coupling reactions,
however, the current reactivity is unprecedented in the
literature.[9]
Serendipity plays an important role in the discovery of
new reactions. In this particular case, when a solution of a-
phenyl cinnamyl alcohol (1a) was treated with KOtBu in
DMSO at 1008C, the formation of the 1,2,4-triaryl benzene 3a
was observed (Table 1, entry 1). Encouraged by this result,
the screening of various bases, such as Na2CO3, K2CO3,
Cs2CO3, DBU, DMAP, pyridine, pipyridine, Et3N, LiOH,
NaOH, NaH, and KOH (entries 2–7) was carried out, and
interestingly, KOH provided the best result (83% of 3a was
isolated; entry 7). Carrying out the reaction employing KOH
in other solvents such as DMF, 1,4-dioxane, Et2O, THF,
MeOH, and EtOAc at various temperatures, the reactivity
remained less effective compared to using DMSO at 1008C
(see the Supporting Information for details).
[*] M. Rehan, S. Maity, L. K. Morya, K. Pal, Dr. P. Ghorai
Department of Chemistry
Next we focused on the synthesis of homo-1,2,4-triaryl
arenes from homo-a-aryl cinnamyl alcohols (Scheme 2).
Substrates with electron-donating groups, including p-Me
(3b), o-Me (3c), p-tBu (3d), and p-MeO (3e), and electron-
withdrawing groups such as p-Cl (3 f), p-Br (3g), p-F (3h),
Indian Institution of Science education and Research Bhopal
Bhopal By-pass Road, Bhouri, Bhopal 462066 (India)
E-mail: pghorai@iiserb.ac.in
Supporting information for this article can be found under:
7728
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 7728 –7732