A dramatic substituent effect in silver(I)-catalyzed regioselective cyclization of ortho-alkynylaryl aldehyde oxime derivatives

Article abstract of DOI:10.1002/adsc.200800568

A dramatic substituent effect was found in the silver(I)-catalyzed cyclization reaction of ortho-alkynylaryl aldehyde oxime derivatives. When R is an alkyl group, the Ag(I)-catalyzed reaction in dimethylacetamide at 110°C (conditions A) affords isoquinoli

Full text of DOI:10.1002/adsc.200800568

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DOI: 10.1002/adsc.200800568
A Dramatic Substituent Effect in Silver(I)-Catalyzed
Regioselective Cyclization of ortho-Alkynylaryl Aldehyde
Oxime Derivatives
Hongyin Gaoa and Junliang Zhanga,b,*
a
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal
University, 3663 N. Zhongshan Road, Shanghai 200062, Peopleꢀs Republic of China
Fax : (+86)-021-6223-5039; e-mail: jlzhang@chem.ecnu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, Shanghai 200032, Peopleꢀs Republic of China
Received: September 15, 2008; Published online: December 19, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800568.
Abstract: A dramatic substituent effect was found
in the silver(I)-catalyzed cyclization reaction of
ortho-alkynylaryl aldehyde oxime derivatives. When
R is an alkyl group, the Ag(I)-catalyzed reaction in
dimethylacetamide at 1108C (conditions A) affords
isoquinolines in good to excellent yields, in contrast,
or Lewis acids would afford an intermediate pyrridini-
um 6 and subsequent transformations of which might
depend on the type of substituent R of 6 (Scheme 1).
We report herein that, under the catalysis of
AgOTf, the cyclization of 5 can regioselectively give
three different products, i.e., isoquinoline N-oxides,[7]
isoquinolines[8] or isoquinolin-1(2H)-ones.[9] The type
of the R group of the oximes controls the product se-
lectivity.
isoquinolin-1
to high yields under conditions B (dimethylform-
amide, room temperature) when R is an acetyl
ACHTUNGTRENNUNG(2H)-ones were produced in moderate
ACHTUNGTRENNUNG
group. A plausible mechanism was proposed for
this product selectivity control reaction (PSCR) by
subtle structure modification.
Initially, we tested the cyclization pattern of (E)-2-
(2-phenylethynyl)benzaldehyde O-allyl oxime 5a-
Allyl and (E)-2-(2-phenylethynyl)benzaldehyde O-
acetyl oxime 5a-Ac in the presence of catalytic
amounts of various catalysts (see Tables 1 and 2 in
the Supporting Information). After numerous at-
tempts, we were pleased to find that the cyclization
reaction of 5a-Allyl proceeds smoothly in DMA at
1108C under the catalysis of 5 mol% of AgOTf to
afford isoquinoline 7a in 93% yield (Conditions A),
Keywords: alkynes; cyclization; regioselectivity;
silver
The selective synthesis of different products from the whereas isoquinolin-1(2H)-one 8a was produced in
same starting materials by simple subtle structure the same yield from the corresponding (E)-2-(2-phe-
modification or catalyst selection is an interesting but nylethynyl)benzaldehyde O-acetyl oxime 5a-Ac in
often troublesome topic for chemists.[1] The chemistry DMF at room temperature (Conditions B), which
of ortho-alkynylaryl aldehydes 1 mediated with transi- verified our hypothesis that the R group of the oxime
tion metals, Lewis acids or electrophiles to generate a indeed controls the cyclization pattern (Scheme 2).
pyrylium intermediate 2 which then undergoes many
In order to study the scope of this transformation,
transformations to afford versatile useful organic various substituted ortho-alkynylaryl aldehyde O-
building blocks has been well studied[2] by several methyl or O-acetyl oximes 5 were studied and the re-
groups such as those of Yamamoto[3] and Barluenga.[4] sults are summarized in Table 1. Several points are
Recently, The cyclization of their imine analogues 3[2i] noteworthy: (1) isoquinolines could be obtained ex-
has been also developed by Larock,[5] leading to an clusively in good to excellent yields from the cyliza-
efficient synthesis of isoquinoline derivatives via the tion reaction of corresponding O-methyl oximes 5-Me
intermediate pyrridinium 4. During our exploration of under Conditions A; (2) the cyclization reaction of O-
novel product selectivity control reactions (PSCR),[6] acetyl oximes 5-Ac produces isoquinolin-1(2H)-ones
we envisaged that ortho-alkynylaryl aldehyde oxime in moderate to excellent yields under Conditions B;
derivatives 5 catalyzed by transition metal complexes (3) aryl, cyclohexenyl, alkyl groups can be introduced
Adv. Synth. Catal. 2009, 351, 85 – 88
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85

Hongyin Gao and Junliang Zhang
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Scheme 1.
Scheme 2. The substituent controls the product selectivity.
at the R1 position and tolerated; (4) a cyclopropyl answered. Thus, O-benzyl oxime 5a-Bn was prepared
group at R1 was kept untouched in both cases; (5) the and the cyclization reaction of which was studied
reaction of 5g-Ac gives 3-vinylisoquinoline 7g’ by (Scheme 4). It is interesting to find that one equiva-
elimination of one molecule of HOAc under Condi- lent of benzaldehyde was formed along with the prod-
tions A, whereas the normal cycloisomerization prod- uct 7a, which gives further information to help us un-
uct 8g without HOAc elimination was formed in 63% derstand the reaction mechanism.
yield under Conditions B (entries 13 and 14).
Based on the above results, one plausible mecha-
Furthermore, substrates 5j and 5k without an aro- nism of this Ag(I)-catalyzed regioselective cyclization
matic ring were prepared and tested for the purpose of ortho-alkynylaryl aldehyde oxime derivatives 5
of studying the effect of the aromatic ring leading to different products is depicted in Scheme 5.
(Scheme 3). We found that the cyclization reaction of Intermediate 6a was initially formed via AgOTf-medi-
5j-Me did not work so well under Conditions A and ated cyclization, which would undergo fragmentation
gives 3-phenyl-5,6,7,8-tetrahydroisoquinoline 7j[10] in of the methoxy group to give intermediate 9 and one
only 37% yield. A better yield (63%) could be given molecular of CH2O, when R is a methyl group. The
by using Ph3PAuOTf (generated in situ from subsequent protonation of intermediate 9 would
Ph3PAuCl/AgOTf) as catalyst [Eq. (4)]. Ph3PAuOTf afford the isoquinoline product. In contrast, the inter-
also showed better catalytic activity than AgOTf in mediate 6b would undergo a cycloisomerization reac-
the cyclization of 5k-Me leading to 2,5-diphenylpyri- tion to form intermediate 10 when R is an acetyl
dine 7k [Eq. (5)]. It is quite surprising to find that the group. Intermediate 10 would undergo protonation to
reactions of the corresponding O-acetyl oximes 5j-Ac afford 1-acetoxyisoquinoline 11, which could be iso-
and 5k-Ac are complicated under Conditions B or lated in very low yield under some screening condi-
other conditions even when using Ph3PAuOTf as cata- tions. Subsequent hydrolysis of 11 gives the final iso-
lyst.
Where the OMe group goes in the cyclization of O-
quinolin-1(2H)-ones 8.
In conclusion, we have developed an efficient
methyl oximes is the next question which should be Ag(I)-catalyzed regioslective cyclization reaction of
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A Dramatic Substituent Effect in Silver(I)-Catalyzed Regioselective Cyclization
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Table 1. Ag(I)-catalyzed regioselective cyclization of ortho-
alkynylaryl aldehyde oxime derivatives.
Scheme 4.
Entry R2/R1/R (5)
Condi- Time Yield[b]
tions[a] [h]
[%]
1
2
3
4
5
6
7
8
9
H/Ph/Me (5a-Me)
H/Ph/Ac (5a-Ac)
A
B
A
B
A
B
A
B
A
4
7a (84)
8a (93)
7b (81)
8b (80)
7c (76)
8c (78)
7d (72)
8d (91)
7e (85)
12
12
20
8
8
8
H/1-naphthyl/Me (5b-Me)
H/1-naphthyl/Ac (5b-Ac)
H/n-Bu/Me (5c-Me)
H/n-Bu/Ac (5c-Ac)
H/cyclopropyl/Me (5d-Me)
H/cyclopropyl/Ac (5d-Ac)
H/1-cyclohexenyl/Me (5e-
Me)
8
6
10
11
H/1-cyclohexenyl/Ac (5e-Ac)
H/Allyl-N(Ts)CH2/Me (5f-
Me)
B
A
10
10
8e (88)
7f (71)
12
H/Allyl-N(Ts)CH2/Ac (5f-
Ac)
B
20
8f (83)
Scheme 5. Plausible mechanism for the cyclization reaction.
13
14
15
16
17
18
H/AcOC2H4/Me (5g-Me)
H/AcOC2H4/Ac (5g-Ac)
MeO/Ph/Me (5h-Me)
MeO/Ph/Ac (5h-Ac)
A
B
A
B
A
B
24
10
12
10
36
7
7g’ (62)
8g (63)
7h (75)
8h (77)
7i (79)
8i (58)
tively, whereby the type of the R group of the oximes
controls the product selectivity. The scope, mecha-
nism, and synthetic applications of this transformation
are being investigated in this laboratory.
MeO/n-Bu/Me
ACHTUNGTRNE(NUNG 5i-Me)
MeO/n-Bu/Ac(5i-Ac)
AHCTUNGTRENNUNG
[a]
Conditions A: AgOTf (5 mol%), DMA, 1108C; Condi-
tions B: AgOTf (5 mol%), DMF, room temperature.
Yield is isolated yield.
[b]
Experimental Section
Typical Procedure for Ag(I)-Catalyzed Cyclization of
ortho-Alkynylaryl Aldehyde Oxime Derivatives
Synthesis of 7a under Conditions A: To a solution of (E)-2-
(2-phenylethynyl)benzaldehyde O-methyl oxime (117.5 mg,
0.50 mmol) in 3 mL DMA was added AgOTf (6.50 mg,
0.025 mmol) under argon protection, the mixture was stirred
at 1108C and the reaction was complete after 4 h as was de-
termined by TLC analysis. After cooling down to room tem-
perature, 15 mL of water were added and the mixture was
extracted with EtOAc three times. The combined organic
layers were washed with saturated brine solution and dried
over MgSO4. After filtration and evaporation, the residue
was purified by column chromatography on silica gel (hex-
AHCTUNGTRENNUNG
2-(2-phenylethynyl)benzaldehyde O-acetyl oxime (126.5 mg,
0.50 mmol) in 3 mL DMF was added AgOTf (6.50 mg,
0.025 mmol) under argon protection, the mixture was stirred
at room temperature and the reaction was complete after
12 h as was determined by TLC analysis. 15 mL of water
Scheme 3.
ortho-alkynylaryl aldehyde oxime derivatives 5 lead-
ing to isoquinolines or isoquinolin-1(2H)-ones, respec- were added and the mixture was extracted by EtOAc three
Adv. Synth. Catal. 2009, 351, 85 – 88
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Hongyin Gao and Junliang Zhang
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times. The combined organic layers were washed with satu-
rated brine solution and dried over MgSO4. After filtration
and evaporation, the residue was purified by column chro-
matography on silica gel (DCM:EtOAc=5:1) to afford 8a;
yield: 102.6 mg (93%).
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Supporting Information
1
Experimental details and copies of H/13C NMR spectra of
all new compounds are available as supporting information.
Acknowledgements
We are grateful to National Natural Science Foundation of
China (20702015) and Shanghai Municipal Committee of
Sciences and Technology (07pj14039) for financial support.
This work was also sponsored by Shanghai Shuguang Pro-
gram (07SG27) and Shanghai Leading Academic Discipline
Project (B409).
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