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10.1002/adsc.202000591
Advanced Synthesis & Catalysis
Vinylalkyne deivative 1j was also amenable to this
aminoaromatization to afford product 3j in 61% yield
(entry 9). The scope of substrates was further
expanded with additional C(4)-substituents (X = Cl
and Me) at the bridging benzene of 1,2-
bis(alkynyl)benzene 1k-1l, producing compounds 3k-
3l in 80-88 % yields (entries 10-11). For diynes 1m-
1n bearing C-(5) substituents (Y=Cl and Me), their
gold-catalyzed reactions furnished 1-amino-2-
napthaldehydes 3m-3n in 73-77 % yields (entries 12-
13).
12 % yield, and a doubly annulated indole product 6
in 72 % (eq. 7)[15-a,b]. We believe that the superior
reactivity of Au-π prop-1-yn-3-ol (1a) and its siloxy
derivative 1o toward anthranils, as compared to 3-
methyl-1-propynol (1p) and 1-butun-4-ol (1r) is due
to the greater electron-withdrawing power of prop-1-
yn-3-ol. Without this alcohol, diyne 1s followed the
formation of indole according to
a
known
pathway.[15b]
Table 3. Reactions on various substituted Benzisoxazoles
[a]1a = 0.17 M. 2 = 3.0 equiv. L = P(t-Bu)2(o-biphenyl).
Scheme
1
demonstrates
chemical
[b]Product yields are reported after purification from a silica
functionalizations of some resulting products 3.
Treatment of two representatives 3a (R = Ph) and 3h
(R = n-Bu) with p-toulenesulfonic acid (20 mol %) in
hot toluene (80 0C, 3 h) afforded polyaromatic
derivatives 5a (R = Ph) and 5b (R = n-butyl) in 68-
71% yields. Compound 3a was further reduced by
gel column. DCE = 1,2-dichloroethane.
We also assess the reaction generality with various
anthranils 2b-2d under standard conditions; the
results are provided in Table 3. We tested the
reactions of anthranils 2b-2d bearing various C(4)-
substituents (R1 = Cl, Br and Me), further affording 1-
amino-2- napthaldehydes 4b-4d in 59-83 % yields
(entries 1-3). In the case of C(5)-substituted
anthranils 2e-2g (R2 = Cl, Br and Me), their resulting
products 4e-4g were obtained in satisfactory yields
(78-82 %, entries 4-6); the molecular structure of
compound 4f was determined with x-ray diffraction.
We prepared anthranils 2h-2i with a methyl and
phenyl substituent at the nitroxy ring, (R3= Me and
Ph), delivering 1-amino-2-napthaldehydes 4h and 4i
efficiently (entries 7-8).
To clarify the role of a free hydroxyl group on the
reaction chemoselectivity, we prepared diyne 1o
bearing a siloxy-protected but-1-ynol, that still
yielded the aminocyclization product 3a in 77% yield
(eq 5). This information indicates that a free alcohol
is not crucial to affect this aminocyclization reactivity.
We also prepared diyne 1p bearing a 2-methylprop-1-
yn-3-ol and siloxy protected 2-methylprop-1-yn-3-ol,
diyne 1q which yielded only the cycloisomerization
product 1p’ in 41% yield (eq 5).We tested the
reaction on diyne 1r bearing a but-1-yn-4-ol that
delivered only the cycloisomerization product 1r’
(89 %, eq 6); its molecular structure was
characterized by X-ray diffraction.[12] We prepared
diyne 1s to check the reaction generality towards
anthranil 2a in standard reaction condition, we
obtained the self cycloisomerization product 1s‘ in
Scheme 1. Functionalizations with 1-amino-
nathaldehyde derivatives 3.
NaBH4 in THF to deliver a diol compound 5c in 94%
yield. Treatment of compound 3c (R = 4-MeOC6H4)
0
with NaH in hot DMSO (100 C, 6 h) enabled an
unexpected deamination reaction, producing an
phenol derivative 5d in 81 % of which H and 13C
1
NMR are identical to an authentic sample reported in
the literature[13,14]. If MeI (4.0 equiv) was present in
this NaH-promoted deamination reaction, a methyl
phenoxy product 5e was obtained in 88% yield. The
mechanism of formation of compounds 5d and 5e are
not difficult to elucidate.[14]
We
postulate
a
mechanism
for
the
aminocyclizations of bis(alkynyl)benzenes 1 with
anthranils (Scheme 2); the reactions begin with the
3
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