DOI: 10.1002/chem.201504085
Communication
&
Annulation
Aerobic Dimerization of Enediyne Compounds: Construction of
Naphthalene Frameworks
Dongxu Wang, Fei Ling, Xiang Liu, Zexiang Li, and Cheng Ma*[a]
a complementary alternate to this reductive cycloaromatization
Abstract: The first bimolecular oxygenative annulation of
of enediynes, we have recently reported a formal Pd/Cu-cata-
enediyne compounds leading to naphthalene frameworks
lyzed aerobic [4+2] cross-benzannulation of readily accessible
has been developed by using Pd(OAc)2 as the catalyst in
enediyne–imides 1 and internal alkynes using a directing
the presence of NaI under O2 (1 atm). This reaction provid-
group strategy to overcome the innate cycloisomerization ten-
ed efficient access to a class of symmetric core-annulated
dency of enediyne subunits.[11,12] In the light of this result,
naphthalenes by the homoannulation of enediyne–imides.
herein we present a novel dimerization approach for the con-
Intriguingly, the crossover annulation of enediyne–imides
struction of naphthalene frameworks through a nucleophilic-
and other functionalized enediynes could also be ach-
directing-group-triggered, PdII-catalyzed, intermolecular aero-
ieved by the same catalytic system, resulting in the forma-
bic oxidative annulation of 3-functionalized enediynes by
tion of several unsymmetrical naphthalene derivatives.
using molecular O2 (1 atm) as the oxygen source and reoxidant
Preliminary mechanistic investigation using 18O isotopic la-
in the presence of NaI (Scheme 1).[13]
belling and radical scavengers indicated that radical
oxygen incorporation cascades might be involved in this
conversion.
Selective synthesis of polysubstituted polycyclic aromatic hy-
drocarbons (PAHs) is of great interest because of their increas-
ing application in materials science and supramolecular
chemistry.[1] During the past decade, significant progress has
been achieved in PAH synthesis by transition-metal-catalyzed
reactions, which predominately utilize benzenoid substrates
for the synthesis of naphthalene frameworks.[2] For instance,
various transition-metal-catalyzed cyclization reactions, includ-
ing the [4+2] benzannulation of a given aryl substrate with al-
Scheme 1. Aerobic annulation cascades of enediyne compounds.
kynes,[3b–l] are among the most efficient tools for the construc-
tion of condensed aromatics.[3] Meanwhile, using a late-stage
diversification strategy, several promising protocols have re-
cently been developed based upon a transition-metal-cata-
lyzed CÀH functionalization, which provides an expedient
access to diversely substituted PAHs.[4] Despite these impres-
sive advances, given recent rising demands for core-substitut-
ed and core-annulated naphthalene derivatives,[5] novel syn-
thetic methods, particularly those enabling the regioisomer-
free formation of functionalized naphthalene compounds,
remain highly desirable.[6]
Fuelled by the sustained progress in the Bergman reaction[7]
and the Schreiner–Pascal cyclization,[8] the cycloaromatization
of benzenoid enediynes has emerged as a promising approach
for the generation of aromatic products in recent years.[9,10] As
The initial assays were triggered by the finding of trace
amounts of naphthalene derivative 2a as mixtures of a pair of
diastereoisomers (d.r.=1:1) when subjecting enediyne–imide
1a to Pd(OAc)2 (10 mol%) in DMF at 258C in air (Table 1).
While elevating the reaction temperature to 608C gave 2a in
23% yield under O2 (1 atm), the addition of CuBr2 sharply im-
proved the yield of 2a to 52% (entries 1 and 2). Further explo-
ration of the additives revealed that alkali halide salts could
also promote this PdII-catalyzed aerobic transformation[14] of
1a to 2a (entries 3–5). An extra addition of stoichiometric
amounts of 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO; 2 equiv)
decreased the reaction rate but had little effect on the yield
(entry 6), suggesting that a radical reaction might be involved.
In the presence of NaI, both PdCl2 and Pd(acac)2 showed the
catalytic activity but led to a lower yield (entries 7 and 8).
Switching the solvent to DMSO or DMA reduced the yield of
2a (entries 9 and 10). Furthermore, it was found that molecular
sieves (3 ) promoted the formation of 2a (entry 11; 81%
yield). In contrast, only a trace amount of 2a was observed
[a] D. Wang, F. Ling, X. Liu, Z. Li, Prof. Dr. C. Ma
Department of Chemistry, Zhejiang University
20 Yugu Road, Hangzhou 310027 (China)
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2016, 22, 124 – 128
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