belonging to a previously unattainable class of π-extended
fenestrane-type7 systems. We also herein describe the
synthesis of a second unique DBA topology (2) from a shared
precursor.
Scheme 1a
Figure 1. Target macrocycles 1 and 2.
There existed two main difficulties in the synthesis of
macrocycle 1 that had to be overcome for its successful
construction. The first obstacle was designing a system to
minimize the large amount of steric bulk crowding the central
ring of the precyclized material 3 (Scheme 1). The second
difficulty to surmount was the closure of all four rings around
the periphery of the DBA.
Our annulene syntheses typically take advantage of the
difference in reactivity of trimethylsilyl (TMS) vs triiso-
propylsilyl (TIPS) groups for protection of the alkynes to
be used for cross-coupling vs homocoupling. However, the
steric bulk from installing the necessary eight TIPS groups
around the central ring would be impossible to achieve in
this new system. The preparation of 3 instead relied upon
the use of the smaller TMS groups. Triyne 4 seemed to be
the ideal precursor for this synthesis, relying on only one
alkyne protecting group and a terminal alkyne that was easily
attached via the Stille reaction.
The synthesis proceeded by an initial triazene formation
from diiodoaniline 58 followed by cross-coupling of TMSA
to the iodo positions, giving 6 in 96% yield (Scheme 1).
Decomposition of the triazene and iodide substitution was
accomplished by heating in MeI at 140 °C. A Stille cross-
coupling of ethynyltributylstannane gave triyne 4 in 72%
yield. Sonogashira cross-coupling of 4 with 1,2,4,5-tetraiodo-
a Reagents and conditions: (a) (i) HCl, NaNO2, THF, MeCN,
H2O; (ii) piperidine, K2CO3, MeCN, H2O; (b) TMSA, Pd(PPh3)2Cl2,
CuI, iPr2NH, THF; (c) MeI, 140 °C; (d) Bu3SnCtCH, Pd(PPh3)4,
THF, reflux; (e) 1,2,4,5-tetraiodobenzene, Pd(PPh3)4, CuI, iPr2NH,
THF, reflux; (f) TBAF, THF; (g) Pd(dppe)Cl2, Pd(PPh3)2Cl2, CuI,
I2, iPr2NH, THF, 55 °C.
benzene required heating at reflux for 60 h to give the
precyclized polyyne 3 in 62%, which is a respectable 89%
per cross-coupling transformation. The TMS groups were
next removed with tetrabutylammonium fluoride (TBAF),
and the material was immediately subjected to cyclization.
No detectable annulene products were found from the Cu-
mediated Glaser coupling of 3, which gave only oligomeric
byproducts. To induce ring closure we turned to oxidative
Pd-catalyzed homocoupling.6,9 A distinct advantage of this
route is the ability to tailor the reactivity of the catalyst by
judicious choice of ligand. We have previously found that
the cis-bidentate ligand 1,2-diphenylphosphinoethane (dppe)
favorably forms 14-membered annulenes with the geometry
present in 1.6 We also determined Pd(PPh3)2Cl2 will satis-
factorily provide 15-membered DBAs, which are also present
in macrocycle 1. Initial closure of one ring should further
facilitate cyclization by optimizing the geometry of terminal
alkyne groups for subsequent ring closures. By using a
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