Organic Letters
Letter
promoted by I-,10 Br-,11 S-,16 Se-,12 B-,13 and Si-based
electrophiles (Scheme 1c);14 we envisaged that by design of
the alkyne substrates, the annulative cyanoarylation of the
carbon−carbon triple bond might be favored at the expense of
the chlorocyanation (Scheme 1d). In this Letter, the feasibility
of this hypothesis is demonstrated, and the application of the
newly developed method to the synthesis of cyano-substituted
phenanthrenes, dihydronaphthalenes, and dibenzocyclohepta-
1,3,5-trienes of different substitution patterns is described. The
prevalence of the nitrile moiety in natural products,15
pharmaceuticals,16 agrochemicals,17 dyes,18 and high-perform-
ance materials19 anticipates a broad range of applications for
the protocol described herein.
regioselective attack of the [CN]+ unit and seem to be critical
for obtaining high yields of the corresponding phenanthrenes
(Scheme 2). In fact, the reaction fails when the akyne moieties
Scheme 2. Scope of the Electrophilic Cyanation of 1-(Aryl)-
a
2-etynylbenzenes toward Phenanthrenes
Employing biphenyl 3a as the model substrate, its reaction
with thioimidazolium salt 1 in the presence of a range of Lewis
acids was evaluated. Only starting material was recovered when
AlCl3 was used as the promoter, whereas Al(TfO)3, Yb(TfO)3,
and BF3·OEt3 induced the formation of phenanthrene product
5a with excellent conversion (Table 1, entries 1−4).
Table 1. Reaction Optimization
a
entry
Lewis acid (equiv)
conv. (%)
additive
4a/5a
1
2
3
4
5
6
7
8
9
AlCl3 (1.0)
n.r.
Al(TfO)3 (1.0)
Yb(TfO)3 (1.0)
BF3·OEt3 (1.0)
BCl3 (1.0)
B(C6F5)3 (1.0)
BCl3 (1.0)
>95
>95
>95
>95
>95
n.r.
only 5a
only 5a
only 5a
1:1
1:1
b
DIPEA
b
BCl3 (1.0)
BCl3 (1.2)
78
95
6
b d
,
only 4a
only 4a
c
6
a
b
Conversions were determined by NMR. 6 = 2,6-di-tert-butylpyr-
c
d
idine, 1.0 equiv. Isolated yield. 1.2 equiv.
Interestingly, both BCl3 and B(C6F5)3 were able to enroll 1
in the desired cyclization, and cyano-substituted phenanthrene
4a could be obtained for the first time, albeit as an equimolar
mixture with 5a (Table 1, entries 5 and 6). Because the
annulation from 3a to 4a generates stoichiometric amounts of
protons and acids are known to catalyze the formation of 5a
from 3a, organic bases were incorporated in the reaction
mixture in an attempt to quench that reaction pathway.20
Interestingly, whereas DIPEA completely suppresses any
cyclization, much bulkier 2,6-di-tert-butylpyridine seems not
to interfere with the Lewis acid promoter, allowing the
conversion of 3a toward 4a in a selective manner (Table 1,
entries 7 and 8). Finally, increasing the amount of BCl3 up to
1.2 equiv substantially improved the conversion; the isolation
of 4a with an excellent (95%) yield was possible under these
conditions (Table 1, entry 9).
a
Standard conditions were used in all cases: 3a−n (1 equiv), 1 (1.2
equiv), 2,6-di-tert-butylpyridine (1.2 equiv), DCM, rt, 1 h.
are alkyl- or −NTs-substituted. In these cases, products of
alkyne chlorocyanation such as 7−9 are obtained. Contrarily,
there is relative tolerance regarding the substitution pattern at
the arene undergoing substitution. Even substrate 3c,
decorated with a strong electron-withdrawing −CF3 group,
affords the desired phenanthrene 4c in acceptable yield. The
cyclization has been successfully extended to substrates bearing
condensed arene moieties affording cyano-substituted [4]- and
[5]helicenes 4i−m. In all cases the use of 2,6-di-tert-
butylpyridine is essential to suppress the noncyanative
cyclization.
The connectivity of phenanthrene derivatives 4i and 4k and
chloroacrylonitrile 9 was confirmed by the X-ray analysis; their
structures are depicted in Figure 1 (for 4i and 9) and the
Encouraged by the results obtained in the synthesis of
phenanthrenes from o-alkynyl biaryls, the cyclization of 1,4-
Having identified the optimal reaction conditions, the scope
and limitations of the new transformation were explored. As
expected from a cyclization proceeding through a carbocationic
intermediate, electron-rich substituents at the alkyne termini,
such as p-anisyl 3a,c−e,i or thioalkyl/aryl 3g,h, facilitate the
B
Org. Lett. XXXX, XXX, XXX−XXX