AuBr3-catalyzed [4 + 2] benzannulation between an enynal unit and enol

Article abstract of DOI:10.1021/ja0477367

The reaction of enynals 1, including o-alkynylbenzaldehydes, and carbonyl compounds 2 in the presence of a catalytic amount of AuBr₃ in 1,4-dioxane at 100 °C gave the functionalized aromatic compounds 3 in high yields. The AuBr₃-catalyzed formal [4 + 2] benzannulation proceeds most probably through the coordination of the triple bond of 1 to AuBr₃, the formation of a pyrylium auric ate complex via the nucleophilic addition of the carbonyl oxygen atom, the reverse electron demand-type Diels-Alder addition of the enols, derived from 2, to the auric ate complex, and subsequent dehydration and bond rearrangement. Similarly, the AuBr₃-catalyzed reactions of 1 with acetal compounds afforded the corresponding aromatic compounds in good yields. Copyright

Full text of DOI:10.1021/ja0477367

Published on Web 05/27/2004
AuBr3-Catalyzed [4 + 2] Benzannulation between an Enynal Unit and Enol
Naoki Asao,* Haruo Aikawa, and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku UniVersity, Sendai 980-8578, Japan
Received April 19, 2004; E-mail: asao@mail.tains.tohoku.ac.jp, yoshi@yamamoto1.chem.tohoku.ac.jp
Table 1. AuBr3-Catalyzed Benzannulation between
o-Alkynylbenzaldehydes 1a-b and Carbonyl Compounds 2a
The Diels-Alder reaction is one of the most powerful synthetic
tools for the construction of various six-membered cyclic com-
pounds.1 Numerous studies on the normal electron demand-type
reaction between diene systems and carbonyl compounds have been
carried out. In such reactions, the carbon-oxygen double bond of
carbonyl compounds acts as a 2π system in the hetero-Diels-Alder
reaction with various 4π systems (type a in Scheme 1). However,
1
2
entry
1
R
2
R
R
ratio (3:5)b
yield (%)c
to the best of our knowledge, there is no report on reverse electron
demand-type cycloaddition between a 4π system and an enol de-
rived from an aldehyde and ketone (type b).2 In this paper, we report
an unprecedented [4 + 2] benzannulation between the enynal unit
1, including o-(alkynyl)benzaldehydes, and carbonyl compounds
2, in which the hetero-Diels-Alder reaction (type b) becomes a
key step; the AuBr3-catalyzed reaction of 1 with 2 gave 3, through
the pyrylium intermediate and hetero-Diels-Alder intermediate, in
good to high yields (Scheme 2).
1
1a
1a
1a
1a
1a
1a
1b
Ph
Ph
Ph
Ph
Ph
Ph
C4H9
2a
2b
2c
2d
2e
2f
Ph
CH3
H
H
H
H
3a:5a
87:13
97:3
90
87
81
81
56
45
71
2d,e
3
3b:5b
3c:5c
3d:5d
3e:5e
3f:5f
C5H11
99:<1
80:20
82:18
99:<1
99:<1
4f
5g
6
iPr
-(CH2)4-
BnO
CH3
H
H
7d
2b
3g:5g
a Reaction was performed using 1a,b (1 equiv) and 2a-f (1.2 equiv) in
the presence of AuBr3 (10 mol %) in 1,4-dioxane at 100 °C within 3 h
unless otherwise noted. b Determined by 1H NMR. c Combined isolated
yield. d Performed with 5 equiv of 2b. e Reaction was carried out at 80 °C.
f Reaction was carried out in the presence of 30 mol % AuBr3. g Reaction
was carried out in the presence of 20 mol % AuBr3.
Scheme 1
result suggested that the benzannulation in (ClCH2)2 would not
proceed through the [4 + 2] cycloaddition between 1a and 4a but
would proceed instead through 1a and 2a. Indeed, when the reaction
of 1a with 2a was carried out under the same conditions mentioned
above (Cu(OTf)2, (ClCH2)2, 50 °C), 3a was obtained in 43% yield
together with 5a in 37% yield (eq 2).
Scheme 2
Optimization experiments revealed that the use of AuBr3 catalyst
(10 mol %) in 1,4-dioxane at 100 °C gave 3a selectively in 78%
yield accompanied by 5a in 12% yield.8,9 The results of the AuBr3-
catalyzed benzannulation of 1 using various kinds of carbonyl
compounds 2 are summarized in Table 1.
The reaction proceeded well even with sterically bulky aldehydes
such as 3-methyl-butanal 2d, although an increased amount of
catalyst was needed (entry 4). Cyclohexanone 2e was usable as a
starting material, and the corresponding six-membered annulated
naphthalene 3e was obtained in a moderate yield (entry 5). Not
only simple alkyl and aryl substituents but also an alkoxy group
can be introduced into the naphthalene skeleton; the reaction of 1a
with benzyloxyacetaldehyde 2f gave 3f as the sole product (entry
6). The benzannulation of 1b, having a butyl group at the terminal
position of alkyne, with 2b gave 3g in 71% yield (entry 7). In every
case, we did not detect the regioisomers of 3; in all cases, R1 was
at the C-3 position and R2 was at the C-2 position.
Not only the benzaldehyde derivatives but also an R,â-unsatur-
ated aldehyde underwent the benzannulation.10 The reaction of the
enynal 1c with propanal 2b in the presence of Au catalyst proceeded
smoothly, and the corresponding [4 + 2] adduct 3h was obtained
in 70% yield along with the formation of 6a in 12% yield (eq 3).
Recently, we reported a novel synthetic method of naphthalene
derivatives via the Lewis acid-catalyzed benzannulation between
o-(alkynyl)benzaldehydes 1 and enolethers 4 (eq 1).3,4The reaction
proceeded smoothly in THF in the presence of Cu(OTf)2 catalyst
to give the corresponding naphthalene products in high yields.5,6
While optimizing the reaction of 1a (R ) Ph) with â-methoxy-
styrene 4a (R′ ) Ph), we accidentally used (ClCH2)2 as a solvent
instead of THF. Very interestingly, we observed that 4a was
consumed immediately at room temperature while 3a (R, R′ ) Ph)
was not produced at this stage. Then, 3a was produced gradually
by heating the reaction mixture at 50 °C. Accordingly, the reaction
was monitored carefully by GC-mass and NMR spectroscopy, and
we found that phenylacetaldehyde 2a (R1 ) Ph, R2 ) H) was
formed from 4a in situ at a very early stage of the reaction.7 This
9
7458
J. AM. CHEM. SOC. 2004, 126, 7458-7459
10.1021/ja0477367 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
reaction between 1c and 12b proceeded smoothly to give 3l in 51%
yield together with small amounts of 6b (8%) (eq 6).
We are now in a position to synthesize functionalized aromatic
compounds from enynals and carbonyl compounds in good to high
yields. The reaction most probably proceeds through the reverse
electron demand-type Diels-Alder reaction between the pyrylium
4π system 8 and enol 2π system 9. Further studies to elucidate the
precise mechanism of this reaction and to extend the scope of
synthetic utility are in progress in our laboratory.
Supporting Information Available: Spectroscopic and analytical
data for 3a-l and the representative procedure for the synthesis of 3c
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
References
A plausible mechanism for the present benzannulation is shown
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in Scheme 3.3,4 The coordination of the triple bond of 1a to AuBr3
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deficient alkyne would form the ate complex 8.11 The reverse elec-
tron demand-type Diels-Alder reaction of 8 with the enol 9, derived
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11 through 10. The subsequent bond rearrangement, as shown in
11 with arrows, would afford the naphthyl ketone derivative 3b
and regenerate AuBr3.12 It is worth mentioning that when the reac-
tion of 1a with 2b was carried out in the presence of 3 Å MS under
conditions similar to those mentioned in Table 1, the chemical yield
of 3b was dramatically decreased and only trace amounts of 3b
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reaction medium, would play an important role for the keto-enol
tautomerization between 2b and 9 in Scheme 3.13,14 The reaction
is not likely to proceed well without water due to the lack of the
generation of enol form 9.
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3i was obtained in 68% yield together with 5i in 5% yield.
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12b. Even without external addition of water, the corresponding
products 3j and 3k were obtained in 61 and 52% yields, respectively
(eq 5). This result clearly shows that 12b can be used as a masked
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acetaldehyde in the [4 + 2] benzannulation. Furthermore, the
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