Rhenium-catalyzed α-alkylation of enol acetates with alcohols or ethers

Rhenium-catalyzed α-alkylation of enol acetates with alcohols or ethers

Accepted Manuscript Rhenium-catalyzed α-alkylation of enol acetates with alcohols or ethers Rui Umeda, Yuuki Takahashi, Takaaki Yamamoto, Hideki Iseki...

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Accepted Manuscript Rhenium-catalyzed α-alkylation of enol acetates with alcohols or ethers Rui Umeda, Yuuki Takahashi, Takaaki Yamamoto, Hideki Iseki, Issey Osaka, Yutaka Nishiyama PII:

S0022-328X(18)30671-5

DOI:

10.1016/j.jorganchem.2018.09.010

Reference:

JOM 20567

To appear in:

Journal of Organometallic Chemistry

Received Date: 30 July 2018 Revised Date:

10 September 2018

Accepted Date: 17 September 2018

Please cite this article as: R. Umeda, Y. Takahashi, T. Yamamoto, H. Iseki, I. Osaka, Y. Nishiyama, Rhenium-catalyzed α-alkylation of enol acetates with alcohols or ethers, Journal of Organometallic Chemistry (2018), doi: https://doi.org/10.1016/j.jorganchem.2018.09.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Rhenium-Catalyzed α-Alkylation of Enol Acetates with Alcohols or Ethers Rui Umeda,a Yuuki Takahashi,a Takaaki Yamamoto,a Hideki Iseki,a Issey Osaka,b and Yutaka Nishiyama*a a

Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan

b

Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Imizu,

Key Words: rhenium, enol acetate, alcohol, ether, carbonyl compound

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Toyama 939-0398, Japan

Abstract: When alcohols were treated with enol acetate in the presence of a catalytic amount of a rhenium complex, ReBr(CO)5, the carbon-carbon bond formation of the alcohols and enol acetate smoothly

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proceeded to give the corresponding ketones and aldehyde in moderate to good yields. For the reaction of allylic alcohols, γ,δ-unsaturated carbonyl compounds were obtained in good yields. When ethers were used

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instead of alcohols as the alkylated agent, two alkyl moieties on the ethers were utilized on the reaction.

1. Introduction

The α-alkylation of carbonyl compounds is one of the useful synthetic methods of α-alkyl substituted carbonyl compounds, and various α-alkylation methods of carbonyl compounds have been reported [1]. Although the reaction of enolates and enamines with electrophiles is widely used for the synthesis of

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α-alkylated carbonyl compounds, the direct use of an alcohol as an electrophile remains a problem in organic transformations, due to the poor leaving ability of the hydroxyl unit and the decomposition of the catalysts and active intermediates.

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Recently, transition metal- or Lewis acid-catalyzed α-alkylation methods of carbonyl compounds using alcohols have been developed [2-5]. Alternative approaches via the transition metal catalytic dehydrogenation of alcohols has been described [6,7]. Furthermore, it is reported that a Lewis acid, such

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as [IrCl(cod)]2 [8], InI3 [9], GaBr3 [9], La(OTf)3 [10] and Hf(OTf)3 [10], can be used as a catalyst for the synthesis of α-alkyl substituted carbonyl compounds by the reaction of alcohols and enol acetates. However, there are some drawbacks of these methods using alcohols as a carbon source; (i) limitation of the substrates, (ii) instability of catalyst under a moist or air condition, (iii) the strong basic or acidic conditions, and (iii) the use of small excess amounts of the reagent. It was disclosed that a rhenium complex, such as ReX(CO)5 (X = Br and Cl), serves as an air and moisture-tolerant catalyst for organic reactions instead of various Lewis acid catalysts [11,12].

Very

recently, our group has successfully demonstrated the rhenium-catalyzed coupling reaction of alcohols and enol acetates [13,14]. In the continuation of this work, we wish to report the full details on the synthesis of α-alkylated carbonyl compounds and γ,δ-unsaturated ketones by the rhenium complex-catalyzed coupling

reaction of various alkyl and allylic alcohols and enol acetates. In addition, we will show the results of the ACCEPTED MANUSCRIPT reaction of enol acetates and ethers instead of alcohols as the alkylated agent (Scheme 1).

R1 OH

OAc + R

1

R

O

O

cat.

ReBr(CO)5

2

1

R

R3

R3

1

2

R

R

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Scheme 1.

2. Results and Discussion

Initially, we have chosen 1-phenylethanol (1a) and isopropenyl acetate (2a) as the model starting materials

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to explore the optimized reaction conditions and investigated the effects of the rhenium complex catalyst, reaction temperature, and solvent on the reaction (Table 1). When 1a was allowed to react with 2a in the

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presence of a catalytic amount of ReBr(CO)5 (5 mol%) in a 1,2-dichloroethane solvent at 80 °C for 5 h, the coupling reaction of 1a and 2a smoothly proceeded to give 4-phenyl-2-pentanone (3a) in 88% yield (entry 1). No reaction took place in the absence of the rhenium complex (entry 2) [15]. At the lower reaction temperature (60 °C), the yield of 3a slightly decreased (entry 3). Even when toluene and THF were used as the solvent, the reaction smoothly proceeded (entries 4 and 5). In the case of acetonitrile, 3a was not formed at all (entry 6). The most promising reaction yield was obtained when the reaction was performed in

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1,2-dichloroethane (entry 1). When ReCl(CO)5 was used instead of ReBr(CO)5 as the catalyst, 1a was coupled with 2a to give 3a in 53% yield (entry 7). In the case of other rhenium complexes, such as Re2(CO)10, Re2O7, ReCl5, and CH3ReO3, no formation of 3a was observed (entries 8-11).

1a

OH +

OAc

O

cat.

Re complex

AC C

Ph

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Table 1. Reaction of 1-phenylethanol (1a) with isopropenyl acetate (2a)a

Ph

solvent

2a

3a

entry

catalyst

solvent

temp (ºC)

yield (%)b

1

ReBr(CO)5

CH2ClCH2Cl

80

88 (72)

2

none

CH2ClCH2Cl

80

0

3

ReBr(CO)5

CH2ClCH2Cl

60

52

4

ReBr(CO)5

toluene

80

58

ReBr(CO)5

THF

6

ReBr(CO)5

CH3CN

80

0

7

ReCl(CO)5

CH2ClCH2Cl

80

53

8c

Re2(CO)10

CH2ClCH2Cl

80

0

9c

Re2O7

CH2ClCH2Cl

80

0

10

ReCl5

CH2ClCH2Cl

80

0

11

CH3ReO3

CH2ClCH2Cl

80

0

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80 56 ACCEPTED MANUSCRIPT

5

Reaction conditions: 1a (0.3 mmol), 2a (0.3 mmol), Re catalyst (5 mol%), solvent (2 mL), 5 h.

b

GC yield. The number in parenthesis shows the isolated yield.

Re catalyst (2.5 mol%).

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c

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a

Under the optimal reaction conditions, various alcohols were allowed to react with isopropenyl acetate (2a) in the presence of a catalytic amount of ReBr(CO)5, and these results are shown in Table 2. The 1-aryl substituted ethanols bearing electron-donating groups on the aromatic ring, such as 1-(4-methylphenyl)and 1-(4-methoxyphenyl)ethanol, gave the corresponding 4-aryl substituted 2-pentanones, 3b and 3c, in 84

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and 80% yields, respectively (entries 2 and 3). The 1-(3-methylphenyl)- and 1-(2-methylphenyl)ethanol produced the 4-(3-methylphenyl)- and 4-(2-methylphenyl)-2-pentanone, 3d,e, in 62 and 57% yields (entries 4 and 5). An electron withdrawing group, such as chlorine, substituted 1-aryl ethanol resulted in a significant drop in the yield of the ketone 3f (entry 6). In the case of 1-(4-nitrophenyl)-1-ethanol, 3g was

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not formed and 1-(4-nitrophenyl)ethyl acetate, which was a transesterficated product, was obtained in 82% yield (entry 7). 4-Phenyl-2-hexanone, 4,4-diphenyl-2-butanone, and 4,4,4-triphenyl-2-butanone, 3h-j, were prepared

by the coupling reaction

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also

between

1-phenyl-1-propanol,

diphenylmethanol,

or

triphenylmethanol and 2a (entries 8-10). The preparation of the 4-naphthyl substituted 2-pentanones, 3k,l, was successfully achieved using the rhenium catalytic system (entries 11 and 12). Similarly, 4-methoxybenzyl

alcohol,

a

primary

alcohol,

was

coupled

with

2a

to

form

4-(4-methoxyphenyl)-2-butanone (3m) in 56% yield; however, in the case of benzyl alcohol, 4-phenyl-2-butanone, 3n, was not formed at all (entries 13 and 14).

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Table 2. Reaction of alcohols 1 with isopropenyl acetate (2a)a

CH2ClCH2Cl

1

entry

ReBr(CO)5

+

OH

R1

cat.

2a

R2 3

yield (%)b

alcohol

OH

X X = H (1a)

72 (3a)

2

X = 4-CH3 (1b)

84 (3b)

3

X = 4-CH3O (1c)

4

X = 3-CH3 (1d)

5

X = 2-CH3 (1e)

6

X = 4-Cl (1f)

7

X = 4-NO2 (1g)

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1

80 (3c)

62 (3d) 57 (3e)

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38 (3f) 0 (3g)

R

R = C2H5 (1h)

9

R = Ph (1i)

10

Ph Ph OH (1j) Ph

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8

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Ph OH

11

OH (1k)

12

29 (3h)

83 (3i) 78 (3j)

63 (3k)

63 (3l) OH

13

(1l)

OH CH3O

O

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R2

OAc

SC

R1

(1m)

56 (3m)

14 a

0 (3n) ACCEPTED MANUSCRIPT

OH (1n)

Reaction conditions: alcohol 1 (0.3 mmol), 2a (0.3 mmol), ReBr(CO)5 (5 mol%), CH2ClCH2Cl (2 mL),

at 80 ºC for 5 h. bIsolated yield. Next, 1-phenylethanol (1a) was treated with various types of enol acetates, and these results are shown in Table 3. The yields of the products from the reaction of 1a and enol acetates derived from acetophenones

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with the electron withdrawing group were higher than those of the reaction with the electron donating group substituted ones (entries 1-5). 2-(1-Phenylethyl)cyclohexanone (4g) was also formed by the reaction of 1a and cyclohexenyl acetate 2g (entry 6). Similarly, the enol acetate 2h, which was prepared from an aldehyde, gave the corresponding α-alkylated aldehyde 4h (entry 7). The treatment of 1a and the mixture of

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E- and Z-isomers 2i (E/Z = 1.5/1.0) gave a mixture of regioisomers 4i (syn/anti = 1.0/1.5). It is interesting to note that when the mixture of the E- and Z-isomers 2i (E/Z = 1.0/7.2) was used as the enol acetate, the

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distribution of products 4i (syn/anti = 1.0/1.3) was almost the same (entries 8 and 9).

Table 3. Reaction of 1-phenylethanol (1a) with enol acetates 2a +

OH

R1

1a

entry

R2

cat.

ReBr(CO)5

CH2ClCH2Cl

2

yield (%)b

enol acetate OAc

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X

X = H (2b)

57 (4b)

2

X = 4-CH3 (2c)

48 (4c)

3

X = 4-CH3O (2d)

9 (4d)

4

X = 4-Cl (2e)

81 (4e)

5

X = 4-NO2 (2f)

65 (4f)

AC C

1

6

58 (4g)

OAc (2g)

7

OAc

O

(2h)

32 (4h)

R2

Ph

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Ph

OAc

1

R 4

n-C10H21

ACCEPTED MANUSCRIPT

OAc

43c (4i)

8 E / Z = 1.5 / 1.0 9

23d (4i)

E / Z = 1.0 / 7.2 a

Reaction conditions: 1a (0.2 mmol), enol acetate 2 (0.4 mmol), ReBr(CO)5 (5 mol%), CH2ClCH2Cl (5

b c

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mL), at 80 ºC for 5 h. Isolated yield.

Syn / anti = 1.0 / 1.5 Syn / anti = 1.0 / 1.3

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d

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In order to determine the possibility of the synthesis of γ,δ-unsaturated ketones by the rhenium-catalyzed coupling reaction of the allylic alcohols and isopropenyl acetate (2a), various allylic alcohols 5 were treated with 2a in the presence of a catalytic amount ReBr(CO)5, and these results are shown in Table 4. When 1,3-diphenyl-1-propene-3-ol (5a) was reacted with one equivalent amount of 2a in the presence of ReBr(CO)5 catalyst, (E)-4,6-diphenyl-5-hexene-2-one (6a), the γ,δ-unsaturated ketone, was formed in 46% yield. The yield of 6a was improved by using two equivalent amounts of 2a (entry 1). The 1,3-diaryl

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substituted allylic alcohols bearing a methyl group on the both aromatic rings, 1,3-di(4-methylphenyl)-, 1,3-di(3-methylphenyl)-, and 1,3-di(2-methylphenyl)-1-propene-3-ol, 5b-d, gave the corresponding (E)-4,6-diaryl-5-hexene-2-ones, 6b-d, in 82, 73, and 70% yield, respectively (entries 2-4). The introduction of a methoxy group on both aromatic rings caused a decrease in the yield of the γ,δ-unsaturated carbonyl

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compound, 6e, due to the preparation of various by-products (entry 5). For the reaction of 1,3-di(4-chlorophenyl)-1-propene-3-ol (5f), which has an electron withdrawing group on both aromatic

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rings, di(4-chlorophenyl)-5-hexene-2-one (6f) was formed in 90% yield (entry 6). Similarly, the cyclic allylic alcohol, such as cyclohexene-3-ol (5g), coupled with 2a to give 1-(cyclohex-2-enyl)-2-propanone (6g) in 45% yield (entry 7). Similarly, 1,3-diphenylprop-1-en-3-ol (4a) was coupled with various enol acetals to give the corresponding γ,δ-unsaturated ketones in 83-93 % yields (Table 5).

Table 4. Reaction of allylic alcohols 5 with isopropenyl acetate (2a)a OH R

R 5

+

OAc

cat.

CH2ClCH2Cl 2a

O

ReBr(CO)5 R

R 6

alcohol

b yield (%) ACCEPTED MANUSCRIPT

1

R = Ph (5a)

96 (6a)

2

R = 4-CH3C6H4 (5b)

82 (6b)

3

R = 3-CH3C6H4 (5c)

73 (6c)

4

R = 2-CH3C6H4 (5d)

70 (6d)

5

R = 4-CH3OC6H4 (5e)

18 (6e)

6

R = 4-ClC6H4 (5f)

90 (6f)

7

OH a

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entry

45 (6g)

(5g)

Reaction conditions: alcohol 5 (0.2 mmol), 2a (0.4 mmol), ReBr(CO)5 (5 mol%), CH2ClCH2Cl (5 mL),

at 80 ºC for 5 h. Isolated yield.

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b

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Table 5. Reaction of 1,3-diphenyl-1-propene-3-ol- (5a) with enol acetates 2a

O

Ph

Ph

+

OAc Ar

5a

ReBr(CO)5

CH2ClCH2Cl

2

6

yield (%)b

entry

enol acetate

1

Ar = Ph (2b)

2

Ar = 4-CH3C6H4 (2c)

3

Ar = 4-CH3OC6H4 (2d)

4

Ar = 4-ClC6H4 (2e)

91 (6k)

5

Ar = 4-NO2C6H4 (2f)

85 (6l)

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93 (6h)

AC C

a

Ar Ph

Ph

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OH

cat.

89 (6i)

83 (6j)

Reaction conditions: 5a (0.2 mmol), enol acetate 2 (0.4 mmol), ReBr(CO)5 (5 mol%), CH2ClCH2Cl (5

mL), at 80 ºC for 5 h. b

Isolated yield.

Next, the reaction of 1,3-diaryl substituted allylic alcohols, in which two different aryl groups were substituted at the C1 and C3 positions of the allyl alcohol, and 2a was investigated (Scheme 2). When 3-(4-methylphenyl)-1-phenyl-1-propene-3-ol (7a) was used as an allylic alcohol, γ,δ-unsaturated ketones

were formed in 60% yield with the mixture of (E)-4-(4-methylphenyl)-6-phenyl-5-hexene-2-one (8a) and ACCEPTED MANUSCRIPT (E)-6-(4-methylphenyl)-4-phenyl-5-hexene-2-one (8a’) (8a : 8a’ = 1.6 : 1.0).

For the reaction of

1-(4-methylphenyl)-3-phenyl-1-propene-3-ol (7b), the coupling products, 8a and 8a’, were obtained with almost same ratio as that of the reaction of 7a. The reaction of various 1,3-diaryl substituted allylic alcohols bearing different two aryl moieties also gave a mixture of 4,6-diaryl substituted 5-hexene-2-ones. It is interesting to note that the distribution of the two isomers was almost the same for the various 1,3-diaryl

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substituted allylic alcohols. It was found that the carbon-carbon bond formation was preferentially occurred at the carbon adjacent to the electron rich aryl group. For the reaction of 1-aryl-2-butene-1-ol and 1-aryl-1-butene-3-ol, in which aryl and methyl groups are substituted on the allyl alcohol, 2a was predominantly coupled at the carbon adjacent to the methyl group.

In order to determine the reasons for the preparation of the mixture of two isomers by the reaction of substituted

allylic

alcohols

bearing

different

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1,3-diaryl

aryl

groups,

3-(4-methylphenyl)-1-phenyl-1-propene-3-ol (7a) or 1-(4-methylphenyl)-3-phenyl-1-propene-3-ol (7b) was

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treated with the ReBr(CO)5 catalyst at 80 ºC, and the reaction was monitored by their 1H-NMR spectra. Within 10 min, the isomerization of the allylic alcohols by the 1,3-transposition of the hydroxyl group was observed and the mixture of 7a and 7b was formed.[16] Based on these results, it was suggested that isomerization of allylic alcohol by the 1,3-transposition of the hydroxyl group easily occurred in the

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presence of ReBr(CO)5 to form the mixture of allylic alcohols.

OH +

ACCEPTED MANUSCRIPT

OAc

O

O

cat.

ReBr(CO)5 (5 mol%) +

2a (0.4 mmol)

7a (0.2 mmol)

CH2ClCH2Cl (5 ml) OH +

8a

80 oC, 5h

2a

8a' 60% (8a : 8a'= 1.6 : 1.0) 62% (8a : 8a' = 1.6 : 10.)

OH +

OAc

O

cat.

ReBr(CO)5 (5 mol%)

O

CH2ClCH2Cl (5 ml) OH

O

8b

80 oC, 5h

2a

O

8b'

SC

+

O

+

2a (0.4 mmol)

7c (0.2 mmol)

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(0.4 mmol)

7b (0.2 mmol)

34% (8b: 8b' = 3.0 : 1.0)

O

35% (8b : 8b'= 3.1 : 1.0)

OH

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(0.4 mmol)

7d (0.2 mmol)

OAc

+

cat.

O

O

ReBr(CO)5 (5 mol%)

Cl 7e (0.2 mmol)

2a (0.4 mmol)

CH2ClCH2Cl (5 ml) OH

80 oC, 5h

Cl

Cl 8c

8c' 74% (8c : 8c' = 1.0 : 1.8) 73% (8c : 8c' = 1.0 : 1.8)

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2a

+

+

Cl

(0.4 mmol)

7f (0.2 mmol)

OH

OAc

+

O

O

cat.

ReBr(CO)5 (5 mol%)

7g (0.2 mmol)

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Cl

OH

CH2ClCH2Cl (5 ml) 80 oC, 5h

2a

AC C

+ Cl

+

2a (0.4 mmol)

Cl

Cl 8d

8d' 72% (8d : 8d' = 1.0 : 2.0) 74% (8d : 8d' = 1.0 : 2.0)

(0.4 mmol)

7h (0.2 mmol) OH

+

OAc

O

O cat.

ReBr(CO)5 (5 mol%)

7i (0.2 mmol)

+

2a (0.8 mmol) CH2ClCH2Cl (5 ml)

OH +

2a

80 oC, 5h

8e

8e' 76% (8e : 8e' = 1.0 : 2.1) 75% (8e : 8e' = 1.0 : 2.3)

7j (0.2 mmol)

(0.8 mmol)

ACCEPTED MANUSCRIPT OH

7k (0.2 mmol)

2a ReBr(CO)5 (5 mol%)

(0.8 mmol)

7l (0.2 mmol)

+

CH2ClCH2Cl (5 mL) 80 oC, 5 h

OH +

O

O

2a

8f 69% (8f : 8f' = 1.0 : 1.8)

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+

(0.8 mmol)

8f'

67% (8f : 8f' = 1.0 : 1.8) OH 2a

Cl 7m 0.2 mmol)

ReBr(CO)5 (5 mol%)

(0.8 mmol)

CH2ClCH2Cl (5 mL) 80 oC, 5 h

OH 2a

+

8g 84% (8g : 8g' = 1.0 : 4.2)

Cl 7n (0.2 mmol)

Cl

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+

O

O

SC

+

(0.8 mmol)

Cl 8g'

81% (8g : 8g' = 1.0 : 4.2)

Scheme 2

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To obtain the information about the reaction pathway, the time-dependence of the products was followed by GC measurement at the appropriate time intervals (Fig. 1). The GC analysis of the reaction products showed that di(1-phenylethyl) ether (9a) was formed as the main product at an early stage of the reaction.[17] The yield of 9a then gradually decreased and the yields of 3a and α-methylbenzyl acetate

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(10a) increased. The acetate 10a was gradually converted into 3a. In fact, when di(1-phenylethyl) ether (9a) (0.3 mmol) was treated with two equivalent amounts of 2a (0.6 mmol) in the presence of the ReBr(CO)5 catalyst, 4-phenyl-2-pentanone (3a) was formed in 77% yield (0.47 mmol) (Scheme 3). The

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conversion of 10a into 3a was also achieved by the rhenium catalyst. Based on these results, it was suggested that both 9a and 10a were intermediates during the coupling reaction. On the other hand, in the case of 1,3-diphenyl-1-propen-3-ol, the intermolecular dehydration product was not observed on the time-dependence of the products

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ACCEPTED MANUSCRIPT

CH2ClCH2Cl (2 mL) at 80 ºC for 6 h

cat.

O

Ph

ReBr(CO)5 (5 mol%)

2a

CH2ClCH2Cl (5 ml)

O Ph

cat.

+

O

ReBr(CO)5 (5 mol%)

2a

77% (0.47 mmol)

3a

CH2ClCH2Cl (5 ml) (0.3 mmol)

80 °C, 5h

85% (0.25 mmol)

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10a (0.3 mmol)

Scheme 3.

80 °C, 5h

(0.6 mmol)

9a (0.3 mmol)

3a

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Ph

+

SC

Figure 1. Time-dependence curves for the Re-catalyzed reaction of 1a (0.3 mmol) with 2a (0.3 mmol) in

Based on the above observations, the plausible reaction pathways for the rhenium-catalyzed reaction are

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shown in Scheme 4 and 5. First, the decarbonylation of ReBr(CO)5 to form ReBr(CO)4, which is the coordinative unsaturated 16-electron complex, is the first step of the catalytic reaction [18]. In the case of 1-phenyl-1-ethanol 1a, the C-O bond of di(phenylethyl) ether (9a), which is in situ formed by the

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intermolecular dehydration of 1a, is activated by coordinating of the rhenium species to increase the positive charge on the α-methylbenzyl group. The addition of the activated coordinating rhenium species to the C=C double bond of enol acetate 2a followed by the deacetoxylation then gave the corresponding ketone 3a and α-methylbenzyl acetate (10a) [19]. The reaction of 10a with 1a easily occurred in the presence of the rhenium catalyst to afford 3a.

On the other hand, in the case of

1,3-diphenyl1-propen-3-ol, the coordinating of the rhenium species to the oxygen atom of allylic alcohol followed by the C-O bond cleavage of alcohol to form the corresponding allylic cation. The reaction of cation with 2a easily occurred to afford the corresponding γ,δ-unsaturated carbonyl compounds 3.

ReBr(CO)5 MANUSCRIPT ACCEPTED O

O

+

Ph

Ph 3a

O 10a

- CO/∆

ReBr(CO)4

Ph

OH 1a H2O

OReBr(CO)4

Ph

OAc

O

ReBr(CO)4

SC

Ph

OAc 2a

Scheme 4.

ReBr(CO)5 + AcOH

- CO/∆

+ CO

ReBr(CO)4

TE D

R

R

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OReBr(CO)4

Ph

O

6

R

(HO)ReBr(CO)4

AC C

R

EP

OAc

R

OAc

Ph

RI PT

Ph

+ CO

R

R

OH R

5

ReBr(CO)4 OH

R

R

(HO)ReBr(CO)4

2a

Scheme 5.

Based on the result of the reaction of bis(1-phenylethyl) ether (9a) with isopropenyl acetate (2a) shown in Scheme 3, it is suggested that both alkyl groups of the ether were efficiently used for the synthesis of the

α-alkylated ketones by the reaction of ethers and enol acetates. We then investigated the use of ether as a ACCEPTED MANUSCRIPT carbon source for the synthesis of ketones by the reaction of isopropenyl acetate (2a) (Scheme 6). When bis[1-(4-methoxyphenyl)ethyl] ether was allowed to react with 1a, both 1-(4-methoxyphenyl)ethyl groups were also introduced to 1a and 2-(4-methoxyphenyl)-2-pentanone was formed in 0.38 mmol (63% based on 2a). In the case of bis(diphenylmethyl) ether, the corresponding ketone was formed in good yield. On the other hand, when di(4-methoxyphenylmethyl)ether was used as an alkylated reagent, the yield of the ketone

cat.

O O (0.3 mmol)

O

80 °C, 5h

cat.

ReBr(CO)5 (5 mol%)

2a

+

Ph

3i

CH2ClCH2Cl (5 ml)

(0.3 mmol)

80 °C, 5h

(0.6 mmol)

cat.

ReBr(CO)5 (5 mol%)

+

(0.6 mmol)

3m

80 °C, 5h

(0.23 mmol)

AC C

EP

Scheme 6.

3. Conclusion

(0.49 mmol)

CH2ClCH2Cl (5 ml)

O (0.3 mmol)

2a

TE D

O O

(0.38 mmol)

SC

(0.6 mmol)

Ph Ph Ph

3c

CH2ClCH2Cl (5 ml)

M AN U

O

ReBr(CO)5 (5 mol%)

2a

+

RI PT

was low.

In summary, we have now developed a novel catalytic ability of the rhenium complex for the carbon-carbon formation of alcohols and enol acetates giving the corresponding carbonyl and γ,δ-unsaturated carbonyl compounds. Furthermore, for the rhenium-catalyzed system, ethers were also utilized as the alkylated source. utilized on the reaction.

4. Experimental section 4.1. General

In particular, in the case of ethers, both alkyl units of the ethers were

FT-IR spectra were recorded on a JASCO FT/IR-4100 instrument. 1H-NMR spectra were recorded at 400 ACCEPTED MANUSCRIPT MHz and

13

C-NMR spectra at 100 MHz on JEOL a JNM-ECS-400 or a JEOL JNM-AL400. Chemical

shifts were reported in ppm relative to tetramethylsilane or residual solvent as the internal standard. GLC mass spectral analyses were performed on a Shimadozu GCMS-QP5050A with CBP-M25-025. High mass spectral analyses were performed on a JEOL JMS-T200GC and 7890B GC with HP-5 system. Preparative HPLC separation was undertaken with a JAI LC-908 chromatograph using 600 mm X 20 mm JAIGEL-1H

RI PT

and 2H GPC columns with CHCl3 as an eluent. ReBr(CO)5, ReCl(CO)5, MeReO3, Re2(CO)10, ReCl5 and Re2O7 were commercially available and were used without further purification. Alcohols (1a-1h, 1k, and 1l) and allyl alcohols were prepared by the reduction of the corresponding ketones and α,β-unsaturated carbonyl compounds.

α,β-Unsaturated carbonyl compounds were prepared by the Aldol condensation of

SC

corresponding ketones and aldehydes. Enol acetates (2a-2g) were prepared by the reaction of the corresponding ketones and 1a. Enol acetal (2i) was prepared by the reaction of the corresponding aldehyde and acetic acid anhydride. Other chemical agents were obtained commercially and were purified if

M AN U

necessary by distillation.

4.2. Procedure

4.2.1. General procedure for rhenium-catalyzed reaction of alcohol 1 with enol acetate 2 A 1,2-dichloroethane (2.0 mL) solution of alcohol 1 (0.3 mmol), enol acetate 2 (0.3 mmol), and ReBr(CO)5

TE D

(5 mol%) was stirred under an atmosphere of nitrogen at 80 ºC for 5 h. After the reaction was complete, H2O was added to the reaction mixture and extracted with ethyl acetate. The organic layer was dried with MgSO4. The resulting mixture was filtered, and the filtrate was concentrated. Purification of the residue by silica gel column chromatography afforded carbonyl compounds. Further purification was carried out by

EP

recyclable preparative HPLC, if necessary. The structures of the products were assigned by their 1H and 13

C-NMR, and mass spectra. The product was characterized by comparing its spectral data with those of

AC C

authentic sample or previous reports 3a [20], 3b [21], 3c [21a], 3e [22], 3f [21a, 23], 3h [24], 3i [25], 3j [26], 3k [22], 3l [27], 3m [28], 4b [24], 4d [29], 4g [21a,30], 4h [31], 6a [32], 6g [21a], 6h [33], 8e [34], and 8e’ [35]. The structures of the products (3d, 4c, 4e, 4f, 4i, 6b, 6c, 6d, 6e, 6f, 6i, 6j, 6k, 6l, 8a, 8a’, 8b, 8b’, 8c, 8c’, 8d, 8d’, 8f, 8f’, 8g, and 8g’) were assigned by their 1H and 13C NMR, IR, and high resolution mass spectra analysis.

4.2.2. Procedure for rhenium-catalyzed reaction of isopropenyl acetate (2a) with ether in Scheme6 A 1,2-dichloroethane (2.0 mL) solution of isopropenyl acetate (2a) (0.6 mmol), corresponding ether (0.3 mmol) and ReBr(CO)5 (5 mol%) was stirred under an atmosphere of nitrogen at 80 ºC for 5 h. After the

reaction was complete, H2O was added to the reaction mixture and extracted with ethyl acetate. The organic ACCEPTED MANUSCRIPT layer was dried with MgSO4. The resulting mixture was filtered, and the filtrate was concentrated. Purification of the residue by silica gel column chromatography afforded the corresponding ketone 3. The product was characterized by comparing its spectral data with those of authentic sample. The product was characterized by comparing its spectral data with those of authentic sample or previous reports 3a [20], 3c [21a], 3i [24], and 3m [28].

RI PT

4.2.3. Procedure for rhenium-catalyzed reaction of isopropenyl acetate (2a) with 1-phenylethyl acetate (10a)

A 1,2-dichloroethane (2.0 mL) solution of isopropenyl acetate (2a) (0.3 mmol), 1-phenylethyl acetate (10a) (0.3 mmol) and ReBr(CO)5 was stirred under an atmosphere of nitrogen at 80 ºC for 5 h. After the reaction

SC

was complete, H2O was added to the reaction mixture and extracted with ethyl acetate. The organic layer was dried with MgSO4. The resulting mixture was filtered, and the filtrate was concentrated. Purification of the residue by silica gel column chromatography afforded 4-phenylpentan-2-one (3a). The product (3a) was

M AN U

characterized by comparing its spectral data with those of authentic sample [20].

3d: 1H-NMR (400 MHz, CDCl3) δ 1.26 (d, J = 6.8 Hz, 3H), 2.07 (s, 3H), 2.34 (s, 3H), 2.65 (dd, J = 16.0, 8.0 Hz, 1H), 2.75 (dd, J = 16.4, 6.4 Hz, 1H), 3.27 (ddq, J = 6.8, 8.0, 6.4 Hz, 1H), 6.83-7.02 (m, 3H), 7.19 (t, J = 7.6 Hz, 1H).

13

C-NMR (100 MHz, CDCl3) δ 21.4, 22.0, 30.5, 35.4, 52.0, 123.7, 127.0, 127.5, 128.4,

138.0, 146.1, 207.9. IR (KBr) 704, 784, 1159, 1268, 1360, 1606, 1718, 2872, 2926, 2961 cm-1. MS: m/z

TE D

Calcd. for C12H16O: 176.1201; Found: 176.1193.

4c: 1H-NMR (400 MHz, CDCl3) δ 1.33 (d, J = 6.8 Hz, 3H), 2.40 (s, 3H), 3.15 (dd, J = 16.0, 8.4 Hz, 1H), 3.26 (dd, J = 16.0, 5.6 Hz, 1H), 3.49 (ddq, J = 6.8, 8.4, 5.6 Hz, 1H), 7.17-7.32 (m, 7H), 7.83 (d, J = 8.4 Hz, 2H). 13C-NMR (100 MHz, CDCl3) δ 21.6, 21.8, 35.6, 46.9, 126.2, 126.8, 128.2, 128.5, 129.2, 134.7, 143.7,

EP

146.7, 198.7. IR (KBr) 700, 761, 808, 1180, 1269, 1407, 1452, 1606, 1683, 2925, 2963, 3028 cm-1. MS: m/z Calcd. for C17H18O: 238.1358; Found: 238.1348.

AC C

4e: 1H-NMR (400 MHz, CDCl3) δ 1.34 (d, J = 6.8 Hz, 3H), 3.15 (dd, J = 16.4, 8.0 Hz, 1H), 3.27 (dd, J = 16.4, 5.6 Hz, 1H), 3.49 (ddq, J = 6.8, 8.0, 5.6 Hz, 1H), 7.18-7.32 (m, 5H), 7.41 and 7.85 (AA’BB’, JAB = 8.8 Hz, 4H).

13

C-NMR (100 MHz, CDCl3) δ 21.8, 35.5, 46.9, 126.3, 126.8, 128.5, 128.8, 129.5, 135.4,

139.4, 146.3, 197.8. IR (KBr) 700, 760, 817, 990, 1092, 1201, 1270, 1399, 1589, 1687, 1945, 2927, 2964, 3028, 3061 cm-1. MS (EI): 258 (M+). Calcd for C16H15ClO, 258.0811; Found 258.0835. 4f: 1H-NMR (400 MHz, CDCl3) δ 1.37 (d, J = 7.2 Hz, 3H), 3.22 (dd, J = 16.8, 7.6 Hz, 1H), 3.35 (dd, J = 16.8, 6.0 Hz, 1H), 3.50 (ddq, J = 7.2, 7.6, 6.0 Hz, 1H), 7.15-7.32 (m, 5H), 8.03 and 8.28 (AA’BB’, JAB = 8.4 Hz, 4H).

13

C-NMR (100 MHz, CDCl3) δ 21.9, 35.6, 47.5, 123.8, 126.5, 126.8, 128.6, 129.0, 141.5,

145.8, 150.2, 197.5. IR (KBr) 701, 744, 764, 855, 1197, 1318, 1346, 1525, 1604, 1693, 2928, 2964, 3028, 3082, 3107cm-1. MS (EI): 269 (M+). Calcd for C16H15NO3, 269.1052; Found 269.1083.

1 4i (mixture of isomers: syn/anti = 1.0/1.5): H-NMRMANUSCRIPT (400 MHz, CDCl3) δ 0.85-0.89 (m, 3H), 1.15-1.32 (m, ACCEPTED

19H), 1.41-1.63 (m, 2H), 2.42-2.46 (m, 1H), 2.96 (dt, J = 16.8, 7.2 Hz, 0.56H), 3.09 (quint, J = 7.2 Hz, 0.44H), 7.15-7.34 (m, 5H), 9.48 (d, J = 3.2 Hz, 0.44 H), 9.59 (d, J = 4.0 Hz, 0.56H). 13C-NMR (100 MHz, CDCl3) δ 14.1, 18.5, 18.6, 20.3, 20.9, 22.7, 26.7, 27.1, 27.3, 27.8, 29.28, 29.33, 29.38, 29.43, 29.52, 29.54, 29.59, 29.63, 29.7, 31.9, 40.00, 40.02, 41.9, 52.8, 58.0, 58.6, 126.5, 126.6, 127.4, 127.5, 128.5, 128.6, 143.9, 144.0, 205.3, 205.5. IR (KBr) 700, 763, 1726, 2854, 2925, 3029 cm-1. MS (EI): 288 (M+). Calcd for

RI PT

C20H32O, 288.2453; Found C, 288.2435. 6b: 1H-NMR (400 MHz, CDCl3) δ 2.09 (s, 3H), 2.30 (s, 3H), 2.31 (s, 3H), 2.85-2.96 (m, 2H), 4.05-4.10 (m, 1H), 6.24 (dd, J = 16.0, 6.8 Hz, 1H), 6.33 (d, J = 16.0 Hz, 1H), 7.06-7.23 (m, 8H).

13

C-NMR (100 MHz,

CDCl3) δ 21.0, 21.1, 30.7, 43.6, 49.5, 126.1, 127.4, 129.1, 129.3, 129.6, 131.5, 134.3, 136.1, 137.0, 140.0,

SC

207.2. IR (KBr) 668, 794, 967, 1158, 1356, 1416, 1513, 1716, 2922, 3024 cm-1. MS: m/z Calcd. for C20H22O: 278.1671; Found: 278.1678.

M AN U

6c: 1H-NMR (400 MHz, CDCl3) δ 2.09 (s, 3H), 2.30 (s, 3H), 2.33 (s, 3H), 2.86-2.97 (m, 2H), 4.00-4.05 (m, 1H), 6.28 (dd, J = 16.0, 6.0 Hz, 1H), 6.35 (d, J = 16.0 Hz, 1H), 6.99-7.06 (m, 4H), 7.11-7.22 (m, 4H). 13

C-NMR (100 MHz, CDCl3) δ 21.3, 21.4, 30.7, 43.9, 49.3, 123.4, 124.5, 126.8, 127.4, 128.0, 128.3, 128.4,

128.5, 129.8, 132.2, 137.0, 137.9, 138.2, 142.9, 207.0. IR (KBr) 694, 774, 964, 1159, 1359, 1489, 1604, 1717, 2920, 3026 cm-1. MS: m/z Calcd. for C20H22O: 278.1671; Found: 278.1670. 6d: 1H-NMR (400 MHz, CDCl3) δ 2.12 (s, 3H), 2.25 (s, 3H), 2.42 (s, 3H), 2.88-3.01 (m, 2H), 4.33 (q, J =

TE D

7.2 Hz, 1H), 6.10 (dd, J = 16.0, 7.6 Hz, 1H), 6.51 (d, J = 16.0 Hz, 1H), 7.09-7.21 (m, 7H), 7.32-7.34 (m, 1H). 13C-NMR (100 MHz, CDCl3) δ 19.6, 19.7, 30.7, 39.6, 48.9, 125.5, 125.9, 126.1, 126.2, 126.4, 127.1, 127.9, 130.1, 130.6, 133.3, 135.1, 135.9, 136.3, 140.9, 207.0. IR (KBr) 749, 966, 1158, 1355, 1460, 1489,

EP

1601, 1653, 1718, 2922, 3019 cm-1. MS: m/z Calcd. for C20H22O: 278.1671; Found: 278.1681. 6e: 1H-NMR (400 MHz, CDCl3) δ 2.10 (s, 3H), 2.84-2.95 (m, 2H), 3.19 (s, 6H), 4.00 (q, J = 7.2 Hz, 1H), 6.16 (dd, J = 16, 6.8 Hz, 1H), 6.29 (d, J = 8.4 Hz, 1H), 6.83 (q, J = 8.4 Hz, 4H), 7.17 (d, J = 8.8 Hz, 2H),

AC C

7.25 (d, J = 8.8 Hz, 2H). 13C-NMR (100 MHz, CDCl3) δ 30.4, 42.9, 49.3, 54.9, 55.0, 113.6, 113.7, 127.1, 128.3, 128.7, 129.6, 130.3, 134.9, 158.0, 158.7, 206.9. IR (KBr) 523, 546, 832, 967, 1033, 1112, 1175, 1249, 1301, 1357, 1418, 1422, 1464, 1510, 1608, 1700, 1716, 2835, 2957, 2999 cm-1. MS: m/z Calcd. for C20H22O3: 310.1569; Found: 310.1550. 6f: 1H-NMR (400 MHz, CDCl3) δ 2.11 (s, 3H), 2.87-2.98 (m, 2H), 4.05 (dd, J = 16, 7.4 Hz, 1H), 6.22-6.32 (m, 2H), 7.16-7.31 (m, 8H).

13

C-NMR (100 MHz, CDCl3) δ 30.4, 42.8, 48.8, 127.3, 128.4, 128.6, 128.8,

128.9, 132.2, 132.4, 132.8, 135.3, 141.0, 206.0. IR (KBr) 504, 539, 667, 670, 720, 827, 967, 1013, 1092, 1158, 1232, 1359, 1405, 1491, 1593, 1699, 1718, 1897, 2891, 3028 cm-1. MS: m/z Calcd. for C18H16Cl2O: 318.0578; Found: 318.0562.

6i: 1H-NMR (400 MHz, CDCl3) δ 2.38 (s, 3H), 3.40-3.52 (m, 2H), 4.27-4.32 (m, 1H), 6.35-6.44 (m, 2H), ACCEPTED MANUSCRIPT 7.14-7.32 (m, 10H), 7.84 (d, J = 8.4 Hz, 2H). 13C-NMR (100 MHz, CDCl3) δ 21.6, 43.9, 44.3, 126.2, 126.5, 127.2, 127.7, 128.2, 128.4, 128.6, 129.2, 130.0, 132.7, 134.6, 137.2, 143.3, 143.8, 197.7. IR (KBr) 697, 744, 809, 965, 1180, 1493, 1606, 1685, 3027 cm-1. MS: m/z Calcd. for C24H22O: 326.1671; Found: 326.1675. 6j: 1H-NMR (400 MHz, CDCl3) δ 3.39-3.49 (m, 2H), 3.83 (s, 3H), 4.26-4.32 (m, 1H), 6.35-6.45 (m, 2H),

RI PT

6.89-6.91 (m, 2H), 7.14-7.31 (m, 10H), 7.92 (d, J = 8.4 Hz, 2H). 13C-NMR (100 MHz, CDCl3) δ 44.0, 44.1, 55.4, 113.7, 126.2, 126.5, 127.1, 127.7, 127.7, 128.4, 128.6, 129.9, 130.2, 130.3, 132.7, 137.2, 143.4, 163.4, 196.6. IR (KBr) 801, 947, 1074, 1205, 1505, 1963, 2570, 2889, 3026 cm-1. m.p. 114-115 ºC. MS: m/z Calcd. for C24H22O2: 342.1620; Found: 342.1617.

SC

6k: 1H-NMR (400 MHz, CDCl3) δ 3.44 (dd, J = 6.4, 2.8 Hz, 2H), 4.24-4.30 (m, 1H), 6.39 (t, J = 2.0 Hz, 2H), 7.15-7.31 (m, 10H), 7.39 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 9.2 Hz, 2H). 13C-NMR (100 MHz, CDCl3) δ

M AN U

43.9, 44.3, 126.1, 126.6, 127.2, 127.6, 128.4, 128.6, 128.8, 129.4, 130.1, 132.3, 135.3, 137.0, 139.4, 143.0, 196.8. IR (KBr) 698, 745, 818, 967, 1087, 1196, 1396, 1447, 1487, 1588, 1685, 3025, 3054 cm-1. MS: m/z Calcd. for C23H19ClO: 346.1124; Found: 346.1127.

6l: 1H-NMR (400 MHz, CDCl3) δ 3.53 (d, J = 7.2 Hz, 2H), 4.25-4.30 (m, 1H), 6.40 (t, J = 2.0 Hz, 2H), 7.17-7.32 (m, 10H), 8.04 (m, J = 8.8 Hz, 2H), 8.26 (d, J = 8.8 Hz, 2H). 13C-NMR (100 MHz, CDCl3) δ 43.9, 45.0, 123.8, 126.2, 126.8, 127.4, 127.6, 128.4, 128.7, 129.0, 130.4, 131.8, 136.8, 141.4, 142.6, 150.2, 196.7.

TE D

IR (KBr) 700, 745, 987, 1227, 1348, 1452, 1598, 1700, 3024 cm-1. m.p. 99-100 ºC. MS: m/z Calcd. for C23H19NO3: 357.1364; Found: 357.1371.

Mixture of 8a and 8a’ (8a : 8a’ = 1.6:1.0): 1H-NMR (400 MHz, CDCl3) δ 2.09 (s, 3H), 2.30 (s, 1.2H),

EP

2.31 (s, 1.8H), 2.86-2.97 (m, 2H), 4.01-4.08 (m, 1H), 6.23-6.39 (m, 2H), 7.06–7.32 (m, 9H). 13C-NMR (100 MHz, CDCl3) δ 21.0, 21.1, 30.7, 43.5, 43.9, 49.4, 126.1, 126.2, 126.6, 127.2, 127.4, 127.6, 128.4, 128.6, 129.1, 129.3, 129.6, 129.7, 131.2, 132.5, 134.2, 136.2, 137.0, 137.1, 139.8, 143.0, 206.9, 207.0. IR (KBr)

AC C

700, 802, 1018, 1262, 1356, 1513, 1718, 2927, 3025 cm-1. MS: m/z Calcd. for C19H20O: 264.1514; Found: 264.1509, 264.1511.

Mixture of 8b and 8b’ (8b : 8b’ = 3.1:1.0): 1H-NMR (400 MHz, CDCl3) δ 2.10 (s, 3H), 2.86-2.99 (m, 2H), 3.79 (s, 3H), 4.08-4.00 (m, 1H), 6.17 (dd, J = 16.0, 7.2 Hz, 2H), 6.27-6.37 (m, 1.7H), 6.83 (dd, J = 16.0, 8.8 Hz, 2H), 7.16-7.32 (m, 8H).

13

C-NMR (100 MHz, CDCl3) δ 29.6, 30.6, 30.7, 43.1, 43.9, 49.5,

55.1, 55.2, 113.8, 114.0, 126.2, 126.6, 127.2, 127.3, 127.6, 128.4, 128.5, 128.6, 129.3, 129.6, 129.8, 130.1, 132.6, 134.8, 137.1, 143.1, 158.2, 159.0, 207.0, 207.1. IR (KBr) 694, 753, 829, 966, 1033, 1111, 1158, 1176, 1251, 1301, 1359, 1419, 1450, 1464, 1608, 1716, 2852, 2924, 3033 cm-1. MS: m/z Calcd. for C19H20O2: 280.1463; Found: 280.1460, 280.1459.

1 ACCEPTED Mixture of 8c and 8c’ (8c : 8c’ = 1.0:1.8): H-NMRMANUSCRIPT (400 MHz, CDCl3) δ 2.10 (s, 3H), 2.86-2.99 (m, 2H),

4.05-4.12 (m, 1H), 6.24-6.37 (m, 2H), 7.17-7.33 (m, 9H). 13C-NMR (100 MHz, CDCl3) δ 29.6, 30.7, 43.0, 43.8, 49.1, 49.2, 126.2, 126.7, 127.3, 127.4, 127.6, 128.4, 128.5, 128.6, 128.7, 129.0, 130.2, 131.7, 132.3, 132.8, 133.0, 135.5, 136.8, 141.4, 142.6, 206.4, 206.7. IR (KBr) 700, 750, 822, 965, 1012, 1091, 1158, 1357, 1405, 1452, 1491, 1599, 1718, 3026, 3058 cm-1. MS: m/z Calcd. for C18H17ClO: 284.0968; Found: 284.0960.d

RI PT

Mixture of 8d and 8d’ (8d : 8d’ = 1.0:2.0): 1H-NMR (400 MHz, CDCl3) δ 2.07 (s, 3H), 2.28 (s, 1H), 2.30 (s, 2H), 2.88-2.90 (m, 2H), 3.99-4.03 (m, 1H), 6.17-6.33 (m, 2H), 7.05-7.26 (m, 8H). 13C-NMR (100 MHz, CDCl3) δ 20.9, 21.0, 30.5, 43.0, 43.4, 49.0, 49.1, 126.0, 127.2, 127.3, 128.2, 128.4, 128.6, 128.9, 129.1, 129.3, 129.6, 130.0, 130.6, 132.1, 132.6, 133.2, 133.9, 135.5, 136.2, 137.1, 139.5, 141.5, 206.3, 206.7. IR

SC

(KBr) 668, 819, 967, 1014, 1091, 1156, 1363, 1404, 1491, 1513, 1539, 1560, 1700, 1715, 1717, 1894, 2919, 3028 cm-1. MS: m/z Calcd. for C19H19ClO: 298.1124; Found: 284.1108, 298.1114.

M AN U

Mixture of 8f and 8f’ (8f : 8f’ = 1.0:1.5): 1H-NMR (400 MHz, CDCl3) δ 1.11 (d, J = 6.8 Hz, 3H), 1.63 (d, J = 6.4 Hz, 2H), 2.07 (s, 1H), 2.14 (s, 2H), 2.31 (s, 2H), 2.32 (s, 3H), 2.44 (dd, J = 16.0, 7.6 Hz, 1H), 2.56 (dd, J = 16.0, 6.4 Hz, 1H), 2.75-2.82 (m, 1H), 2.84-2.89 (m, 1H), 3.78-3.81 (m, 0.4H), 5.44-5.54 (m, 1H), 6.07 (dd, J = 16.0, 7.2 Hz, 1H), 6.35 (d, J = 16.0 Hz, 1H), 7.06-7.13 (m, 4H), 7.19-7.26 (m, 2H). 13C-NMR (100 MHz, CDCl3) δ 8.6, 17.8, 20.2, 21.0, 29.6, 30.5, 30.6, 32.9, 43.5, 46.3, 49.7, 50.7, 125.9, 127.2, 128.4, 129.1, 129.2, 133.4, 133.5, 134.5, 136.8, 140.6, 207.8, 208.2. IR (KBr) 802, 967, 1160, 1359, 1453, 1513,

TE D

1716, 1917, 2026, 2924, 2956 cm-1. MS: m/z Calcd. for C14H18O: 202.1358; Found: 202.1357, 202.1359. Mixture of 8g and 8g’ (8g : 8g’ = 1.0:4.0): 1H-NMR (400 MHz, CDCl3) 1H-NMR (400 MHz, CDCl3) δ 1.11 (d, J = 6.8 Hz, 12H), 1.64 (t, J = 6.0 Hz, 3H), 2.08 (s, 3H), 2.14 (s, 13H), 2.46 (dd, J = 16.0, 6.8 Hz,

EP

4H), 2.56 (dd, J = 16.0, 6.8 Hz, 4H), 2.72-2.80 (m, 2H), 2.82-2.92 (m, 4H), 3.82 (dd, J = 14, 6.8 Hz, 1H), 5.40-5.55 (m, 2H), 6.11 (dd, J = 16.0, 7.2 Hz, 4H), 6.33 (d, J = 16 Hz, 4H), 7.12 (d, J = 8.8 Hz, 2H), 13

C-NMR (100 MHz, CDCl3) δ 17.8, 20.0, 29.6, 30.5, 30.6, 32.7, 43.0, 43.8, 49.3,

AC C

7.25-7.26 (m, 20H).

50.4, 126.2, 126.6, 127.2, 127.2, 127.4, 127.5, 128.4, 128.5, 128.5, 128.6, 128.8, 129.9, 132.2, 132.5, 132.9, 135.2, 135.8, 137.0, 142.8, 206.8, 207.6. IR (KBr) 699, 746, 807, 967, 1012, 1090, 1159, 1232, 1358, 1406, 1452, 1491, 1699, 1716, 1917, 2021, 2924, 3026, cm-1. MS: m/z Calcd. for C13H15ClO: 222.0811; Found: 222.0820. References 1. For recent reviews of the α-alkylation of carbonyl compounds, see: (a) J. Mlynarski, B. Gut, B. Chem. Soc. Rev. 41 (2012) 587-596; (b) P. H.-Y. Cheong, C. Y.;Legault, J. M. Um, N. Celebi-Olcum, K. N. Houk, Chem. Rev. 111 (2011) 5042-5137; (c) G. Casiraghi, L. Battistini, C. Curti, G. Rassu, F. Zanardi, Chem. Rev. 111 (2011) 3076-3154; (d) C. Palomo, M. Oiarbide, J. M.

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of propynyl alcohols and several nucleophiles, such as 1,3-diketones, β-keto ester, thiols, alcohols and silyl enol ethers under mild conditions to afford the corresponding coupling products in moderate to good yields. However, in the case of ReBr(CO)5 as the catalyst, the reaction did not

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proceeded. See; Ref. 3b.

15. Although the reaction of 1a and 2a was carried out in the presence of a catalytic amount of AcOH, the yield of 3a was very low (5 %).

1,3-transpotion of hydroxyl group.

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16. It has already reported the rhenium oxide-mediated isomerization of allylic alcohols by the See: Y. Xie, P. F. Floreancig, Angew. Chem. Int. Ed. 52

(2013) 625-628.

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Acknowledgments

This work was financially supported by the MEXT-Supported Program for Grant-in-Aid for Scientific

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ACCEPTED MANUSCRIPT

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Highlights

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and enol acetates smoothly proceeded.

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A new catalytic ability of rhenium complex is described. A new method of the α-alkylation is developed. A rhenium-catalyzed carbon-carbon bond formation of the benzylic and allylic alcohols