Dehydrative thiolation of allenols: Indium vs gold catalysis

Article

pubs.acs.org/joc

Dehydrative Thiolation of Allenols: Indium vs Gold Catalysis

S. Webster, P. C. Young, G. Barker, G. M. Rosair, and A.-L. Lee*

Institute of Chemical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, United Kingdom

S

* Supporting Information

ABSTRACT: Intermolecular additions of thiols to allenols via formal S_N2′ selectivity to produce functionalized dienes are

described. Although this dehydrative reaction was initially developed using gold(I) catalysis, indium(III) proves to be a far

superior catalyst in terms of selectivity and substrate scope.

Within this context, we have recently developed gold-catalyzed

intermolecular etheriﬁcation (NuH = ROH)⁶and thioether-

iﬁcation (NuH = RSH)⁷reactions which are highly regio-

selective (formal S_N2′; see eq 1, Scheme 1). Our next challenge

was to extend this intermolecular dehydrative method to allenols 3,

which would produce functionalized dienes 4useful building

blocks in organic synthesis⁸(eq 2, Scheme 1). However, this

dehydrative mode^3a,9of gold-catalyzed reaction with allenols has no

literature precedent,^10,11presumably due to the well-documented

propensity for allenols to undergo cyclization instead¹²(eq 3,

Scheme 1). We herein report our investigations toward this aim

and present the ﬁrst formal S_N2′ intermolecular additions to

allenols using a variety of thiols as nucleophiles. The optimal

Lewis acid catalyst to emerge from our investigations turns out

to be InCl₃, and a comparison between catalysis by Au(I) and

that by In(III) for this reaction is also presented.

INTRODUCTION

■

The use of gold catalysis in organic synthesis has expanded

rapidly over recent years, mainly due to functional group com-

patibility, ease of handling, and the wide array of reactions that

can be carried out under mild conditions.¹Addition of hetero-

atoms to carbon−carbon π bonds (e.g., alkynes, allenes, and

alkenes) in particular has been greatly facilitated by develop-

ments in gold catalysis, by virtue of the latter’s excellent

π-Lewis acidity.²More recently, gold-catalyzed dehydrative

transformations of allylic alcohols 1 have emerged as mild

and selective methods for allylations (eq 1, Scheme 1).^3,4The

Scheme 1. Previous Work on Allylic Alcohols (Eq 1), Our

Current Aim with Allenols (Eq 2), and Literature Known

Cyclizations (Eq 3)

RESULTS AND DISCUSSION

■

We initiated this project using allenol 3a, which is readily

accessed in one step from the corresponding alkynol using a

modiﬁcation of Lee’s procedure.¹³During our initial screens

using 3a as a model allenol, we found that p-nitrothiophenol

successfully acts as a nucleophile, despite thiol’s ability to

reduce the activity of gold catalysts.¹⁴⁻¹⁶The reaction was not

selective, however, and our initial results using gold(I) catalysis

provided a complex mixture of several diﬀerent products.

Following extensive optimization (see the Supporting In-

formation), Echavarren’s catalyst 8 was found to be optimal,

producing a ∼1:1 mixture of only formal S_N2′:S_N2 products

4a:6a in 55% combined yield after 10 min of microwave

heating at 70 °C (Table 1, entry 1). Despite our best eﬀorts

including a ligand and counterion screen on the gold catalyst,

the selectivity could not be improved. For example, another

commonly used catalyst, PPh₃AuNTf₂, in fact produces mainly

beneﬁt of such a gold-catalyzed method is that neither the allylic

alcohol nor the incoming nucleophile needs to be activated

(the former with a leaving group or the latter with a base, for

example), producing only water as a byproduct. Therefore,

unlike many traditional transition-metal-based allylating reac-

tions,⁵additives and preactivation are usually not required.

Received: November 20, 2014

Published: December 18, 2014

1703

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

Table 1. Lewis Acid Screen

a

entry

Lewis acid

4:6:7

yield of 4a (%)

yield of 6a (%)

b

c

1

2

Au(I) catalyst 8

PPh₃AuNTf₂

1:1:0

1:1:5

1:0:0

25

30

d

ND

e

f

3

NaAuCl₄·2H₂O

5

b

4

Au(III) catalyst 9

InCl₃

no reaction

10:0:1

c

5

47

c

6

7

InI₃

5:0:1

31

c

In(OTf)₃

Yb(OTf)₃

Sc(OTf)₃

Ga(OTf)₃

FeCl₃

3:0:2

44

e

f

8

1:0:1

10

e

f

9

1:1:0

8

e

f

10

5:0:1

32

11

12

13

14

complex mixture

1:0:2

c

ZnI₂

10

c

AgSbF₆

PtCl₂

1:1:0

7

no reaction

a

b

1

Determined using H NMR analysis of the crude reaction. The structures of catalysts 8 and 9 are as follows:

c

d

e

f

1

Isolated yields. ND = not determined. Incomplete conversion. Yield determined using H NMR analysis with dimethyl sulfone as the internal

standard.

unwanted product 7a (a result of conjugate addition as well as

formal S_N2, Table 1, entry 2).

alkyne. Triene 4p is also successfully formed from 3p albeit in a

modest 38% yield (entry 16). Tertiary alcohol 3q reacts well to

produce 4q in quantitative yield (entry 17). It should be noted

that lowering the InCl₃catalyst loading from 5 to 1 mol % and

increasing the scale of the reaction from 0.105 to 0.57 mmol of

3 is not detrimental to the reaction (4c still formed in 96%

yield, entry 2, Table 2). The crystal structure of 4a conﬁrms the

E,E stereochemistry indicated by NOESY analysis for this series

of dienes (Figure 1).

In an attempt to improve the selectivity of the reaction, a

Lewis acid screen was carried out next (Table 1). While many

other catalysts including Pt(II), Au(III), Ag(I), and Fe(III)

fared worse than gold(I), to our delight, the soft Lewis

17

acid InCl₃showed excellent selectivity (1:0 4a:6a, entry 5).

Other water-stable Lewis acids¹⁸were also capable catalysts

(entries 6−10),¹⁹but InCl₃produced by far the best selectivity

and yield for 4a. Thus, InCl₃was chosen as the optimal catalyst

for further investigation.²⁰Advantages of InCl₃include lower

cost (cf. gold(I) catalysts), nontoxic nature, lower hetero-

philicity (readily tolerates S, for example), and air and water

stability.^17b,e

Next, allenols without an ester substituent (3r,s, R′ = H;

n

3t−3v, R′ = Pr) were evaluated to ascertain if the ester group

is necessary for good reactivity/selectivity (entries 18−22).

These substrates are generally less reactive and require higher

temperature (90 °C) and longer times for good conversions.

Nevertheless, when R′ = H, the desired dienes 4r and 4s are

produced in good 72−91% yields, proving that the ester sub-

stituent is not necessary (entries 18 and 19).²¹When R′ is an

alkyl group (3t,u), the reaction works equally well with electron-

rich and electron-poor R substituents (3t,u, 77−88%, entries 20

and 21). Finally, 3u, with two Ph substituents and R′ = ⁿPr, also

reacts smoothly (4v, 59%, entry 22). However, unlike 4a−4s,

dienes with R′ = alkyl (4t, 4u, and 4v) are formed in poor EE:EZ

ratio (2:1 to 1:1). This could be linked to the fact that 4t, 4u,

and 4v were found not to be conﬁgurationally stable, with the

EE:EZ ratio changing over time.

With these results in hand, an allenol substrate scope was

carried out (Table 2). First, the substituent on the aryl ring was

varied (3a−3j, entries 1−10). Allenols with electron-rich aryl

substituents (including O- and N-alkyl substitutions, ortho,

meta, and para) 3b−3f reacted very eﬃciently to produce the

desired dienes 4b−4f in good to excellent yields (68−96%,

entries 1−5), with the exception of the 1,3-benzodioxole

derivative 4g (47%, entry 6). Slightly electron-withdrawing aryls

still give good selectivity (4h, 93%; 4i, 49%; entries 8 and 9),

but very electron-withdrawing substituted allenols do not react

under these conditions (4j, entry 10). Pleasingly, replacing the

aryl group with heterocycles still produces good yields of 4k,l

(79−84%, entries 11 and 12). Alkyl R groups on the allenol are

Gold(I) catalyst 8 was also evaluated alongside InCl₃for

several of these transformations. First, conditions were reoptimized

for 3a under gold catalysis. A temperature of 70 °C for 30 min

provided the best yields, albeit with a poor selectivity of 1:1

4a:6a (38% 4a, 34% 6a, entry 7, Table 2).²²Using these condi-

tions, transformation of 3f to 4f also occurred but with a poor

selectivity (5:2 4f:6f, entry 5). Gold catalysis fared even worse

with a selection of other substrates. The use of gold(I) catalysis

t

also tolerated, with Bu substitution (4n, 80%, entry 14) per-

forming better than n-alkyl substitution (4m, 42%, entry 13).

Next, chemoselectivity was probed by investigating an allenol

with a pendant alkyne (3o, entry 15) and pendant alkene (3p,

entry 16). Gratifyingly, 3o reacts chemoselectively to produce

ynediene 4o (85%, entry 15) with no reaction observed at the

1704

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

resulted in either a complex mixture of products (entries 1, 14,

and 18) or no reaction (entries 10 and 15). Therefore, in all of

the cases evaluated, regioselectivities or yields are signiﬁcantly

worse with Au(I) compared to InCl₃.

above the boiling point of chloroform.²⁴The reaction can alter-

natively be carried out in a robust sealed tube under conven-

tional heating, but we chose microwave heating as it is more

practical from a safety viewpoint (for temperatures above the

boiling point of solvents) and the isolated yields are also

improved. For example, when the reaction in Table 2, entry 2,

It should be noted that microwave heating²³was adopted for

ease of use and to readily heat the InCl₃-catalyzed reaction

Table 2. Allenol Substrate Scope

1705

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

Table 2. continued

a

b

Isolated yields. A 0.07 mmol scale of ArSH and 0.105 mmol of 3. Same result when repeated with only 1 mol % InCl₃, 0.36 mmol scale of ArSH.

c

d

e

f

g

At 90 °C, 20 min. Catalyst 8 (5 mol %), 70 °C, 30 min, sealed tube. Complex mixture of products. At 90 °C, 30 min. Recovered starting

h

i

j

k

l

m

material. At 90 °C for 60 min. Product 7 also observed in 31% yield. 4r:6r = 5:1. At 90 °C, 18 h, sealed tube. EE:EZ = 2:1. E:Z = 1:1.

is repeated under conventional heating, 4c is obtained in 76%

isolated yield after 10 min as well as a longer reaction time of

30 min (vs 96% 4c using microwave heating).

Next, we proceeded to investigate the thiol nucleophile

scope using allenol 3b as a model substrate under InCl₃

catalysis (Table 3). Electron-withdrawing substituents on the

thiophenol perform much better than strongly electron-

donating ones (entries 1−3, 65−80%, vs entry 10, 52%). The

presence of acidic protons (phenol and carboxylic acid) on the

thiophenol though causes a severe drop in yield (29%, 9%,

entries 4 and 5) presumably because the H-bonding required in

the mechanism is disrupted (vide infra). Neutral and slightly

electron-donating substituents, including ortho-, meta-, and

para-substituted thiophenols, react well (entries 6−9). Next,

we evaluated the use of alkanethiols instead of thiophenols as

nucleophiles (entries 11−14). Although the yields were

moderate (40−52%), both primary (entries 11−13) and

secondary (entry 14) alkanethiols are suitable nucleophiles.

Furthermore, even the presence of furan (entry 12) and

carboxylic acid (entry 13) is tolerated, although the acidic

1706

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

Table 3. Thiol Nucleophile Scope

Figure 1. Crystal structure of 4a.

proton once again causes a slightly lower yield (40%). Finally,

thioacid nucleophiles were evaluated. These were competent

nucleophiles but surprisingly gave the opposite selectivity to

form formal S_N2 products 6bn and 6bo (entries 15 and 16;

isomerization of 6 to 4 does not occur, vide infra).

Next, several control reactions were carried out. First, the

reaction with 3a (entry 7, Table 2) was repeated in the absence

of any catalyst, and no reaction was observed after 10 min at

70 °C, thereby suggesting that the desired product 4a requires a

catalyst under these conditions. Second, the reaction with 3a

was repeated with InCl₃but in the absence of thiol nucleophile:

this also resulted in no reaction. In contrast, under gold catalysis

(8), 3a is consumed to give a complex mixture of products

(decomposition) in the absence of the thiol nucleophile. Finally, the

formal S_N2′ product 4a (from entry 7, Table 2) was resubjected to

the reaction conditions under both In(III) and Au(I) catalysis

(Scheme 2). No further reaction of 4a occurs under In(III) catalysis

conditions, but further reaction of 4a does occur under Au(I)

catalysis to yield a complex mixture of products. Therefore, the

superior performance of InCl₃vs gold(I) catalysis in the dehydrative

thiolation of allenols could in part be due to the better stability of

the diene products 4 in the presence of In(III) vs Au(I).

We have recently shown that the related gold(I)-catalyzed

thioetheriﬁcation reaction of allylic alcohols is under equili-

brium control.⁷It was therefore deemed judicious to also study

the behavior of the product 6a (formal S_N2 product in Table 1)

under the reaction conditions (Scheme 3). Under gold(I)

catalysis, 6a isomerizes to 4a, but the proportion of 4a to 6a

remains stagnant at 1:1 even after 16 h. This ratio reﬂects the

observed ratio of products in entry 1, Table 1, as well as entry 7,

Table 2. Under InCl₃catalysis, however, 6a converts fully to 4a

over time. Full isomerization is much faster in the presence of 1

equiv of thiol (5 min vs 3 h).

The eﬀect of temperature was also investigated for substrates

which require higher temperatures (90 °C vs 70 °C, Table 2)

for good selectivity. For example, under standard conditions

(70 °C, 10 min), 1:1 4d:6d is produced from 3d, and a higher

temperature of 90 °C changes the selectivity to 4d only

(Scheme 4). At a lower temperature of 35 °C, the selectivity

swings slightly toward 6d: 1:1.3 4d:6d (Scheme 4).

a

b

Isolated yields. A 0.07 mmol scale of RSH and 0.105 mmol of 3. At

c

d

e

90 °C, 60 min. Coelutes with starting material. dr = 1:2. dr = 1:0.6.

facilitated by H-bonding²⁸(I). Elimination of the catalyst and

water (II) then furnishes the diene product 4. In path b, the

indium catalyst activates the alcohol and direct displacement by

thiol (III) produces the formal S_N2 product 6,²⁹which then

undergoes isomerization to 4 via IV and V. At higher tempera-

tures, either the reaction proceeds directly through path a or

high temperatures facilitate the isomerization (IV → V → 4)

via path b to produce the excellent selectivity for 4. It is possible

With these results in mind, plausible mechanisms are presented

in Scheme 5. InCl₃has been shown to activate both soft C−C

multiple bonds²⁵and the O-center,²⁶so two possible pathways

are presented. In path a, the indium catalyst²⁷activates the

allene toward nucleophilic attack by thiol, presumably

1707

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

Scheme 2. Resubjection of 4a to the Reaction Conditions

(Both In and Au)

Scheme 6. Crossover Experiment

Scheme 3. Resubjection of 6a to the Reaction Conditions

(Both In and Au)

CONCLUSION

■

In conclusion, we have successfully developed an intermolec-

ular formal S_N2′ addition of thiols to allenols, and InCl₃turned

out to be far superior to Au(I) as a catalyst for this dehydrative

reaction. Control reactions indicate that the latter is at least in

part due to better stability of the diene products 4 in the

presence of In(III) vs Au(I). The indium-catalyzed reaction has

a wide substrate scope, with thiophenols and alkanethiol

nucleophiles producing excellent formal S_N2′ selectivity, while

thioacid nucleophiles result in formal S_N2 selectivity.

Mechanistic studies suggest that the regioselectivity is under

equilibrium control and is determined by the thermodynamic

stability of the products.

Scheme 4. Eﬀect of Temperature on Regioselectivity

EXPERIMENTAL SECTION

■

Synthesis of Allenol Substrates 3. General Procedure A (When

Triethylamine is Required). To the propargylic alcohol (1.30 mmol,

1 equiv) were added dry MeCN (1 M), CuI (5 mol %), and EDA

(1.30 mmol, 1 equiv). The reaction was stirred at 25 °C overnight

under argon. The reaction mixture was ﬁltered through a plug of glass

wool and washed with diethyl ether. Solvent was removed on a rotary

evaporator, and the resulting crude mixture was dissolved in dry DCM

(0.2 M) before Et₃N (1.2 equiv) was added. The resulting mixture was

stirred at 0 °C for 1 h. Removal of solvent by rotary evaporator

followed by column chromatography (hexane/ethyl acetate) yielded

allenic alcohol 3 as the product.¹³

General Procedure B (When Triethylamine is Not Required). To

the propargylic alcohol (1.30 mmol, 1 equiv) were added dry MeCN

(1 M), CuI (5 mol %), and EDA (1.30 mmol, 1 equiv). The reaction

was stirred at 25 °C overnight under argon. The reaction mixture was

ﬁltered through a plug of glass wool and washed with diethyl ether.

Solvent was removed on a rotary evaporator, and the resulting crude

mixture was puriﬁed by column chromatography (hexane/ethyl

acetate) to give allenic alcohol 3 as the product.¹³

Scheme 5. Plausible Mechanism

Note: In our hands, the one-pot procedure described by Sabbasani

et al.¹³was sometimes low yielding and/or resulted in no reaction.

Where this was the case, omitting triethylamine from the ﬁrst step

greatly improved the yields (see general procedures A and B above). In

some cases, triethylamine was found to be unnecessary to form 3

(procedure B); in others, it was added in a second separate step as

described above (procedure A) to isomerize any unwanted alkyne

isomer to the allene 3.

that both pathways operate, with the favored pathway being

dependent on the substituents on the substrates.

Ethyl 5-Hydroxy-5-phenylpenta-2,3-dienoate (3a).¹³General

procedure A was followed using 1-phenylprop-2-yn-1-ol to yield the

title product 3a as a yellow oil and a 1:1.4 mixture of diastereomers

(415 mg, 1.90 mmol, 93%): puriﬁed by column chromatography

(eluent hexane/ethyl acetate, 10:1 to 3:1); R_f0.38 (3:1 hexane/ethyl

acetate); ν_max/cm⁻¹3400 br (OH), 2982 (C−H), 1961 (CC,

allene), 1694 (CO), 1493, 1450, 1421 (Ar C−C), 1156 (C−O−C),

In addition, crossover experiments support the possibility of

path b: when 6a (formal S_N2 product in Table 1) is resubjected

to the reaction conditions but with a diﬀerent thiol (R²SH)

present, isomerization to 4 occurs with incorporation of the

external thiophenol (eq 1, Scheme 6). Similarly, when 4a

(formal S_N2′ product in Table 1) is resubjected to the reaction

conditions with thiol R²SH present, incorporation of this

external thiol is observed (eq 2), supporting the reversible

nature of the process, as indicated in Scheme 6.

1

748, 698 (m-C₆H₅); H NMR (300 MHz, CDCl₃) δ 7.44−7.49 (m,

2H + 2H′), 7.28−7.41 (m, 3H + 3H′), 5.89 (m, 1H + 1H′), 5.78 (m,

1H + 1H′), 5.41 (m, 1H + 1H′), 4.20 (m, 2H + 2H′), 2.43 (br s, 1H′,

minor), 2.36 (br s, 1H, major), 1.30 (m, 3H + 3H′); ¹³C NMR (75.5

1708

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

MHz, CDCl₃), δ 211.5 (C, minor), 211.4 (C, major), 165.9 (C,

minor), 165.7 (C, major), 141.8 (C, major + minor), 128.6 (CH,

minor), 128.5 (CH, major), 128.2 (CH, minor), 128.0 (CH, major),

126.4 (CH, minor), 126.1 (CH, major), 100.4 (CH, minor), 100.2

(CH, major), 90.8 (CH, major + minor), 71.5 (CH, minor), 71.4 (CH,

major), 61.3 (CH₂, minor), 61.1 (CH₂, major), 14.2 (CH₃, major +

minor).

C−C), 1252 (C−O−C), 1157 (C−O); ¹H NMR (300 MHz, CDCl₃)

δ 7.33 (t, 2H + 2H′, J = 8.5 Hz), 6.72 (d, 2H + 2H′, J = 8.2 Hz), 5.87

(m, 1H + 1H′), 5.70−5.84 (m, 1H + 1H′), 5.35 (m, 1H), 5.28 (m,

1H′), 4.14−4.27 (m, 2H + 2H′), 2.95 (s, 6H), 2.94 (s, 6H′), 2.35 (m,

1H + 1H′), 1.26−1.35 (m, 3H + 3H′); ¹³C NMR (75.5 MHz, CDCl₃)

δ 211.33 (C), 211.26 (C), 165.8 (C), 165.6 (C), 150.7 (C), 150.6 (C),

129.48 (C), 129.42 (C), 127.6 (CH), 127.2 (CH), 112.5 (CH), 112.4

(CH), 100.5 (CH), 100.3 (CH), 91.0 (CH), 90.7 (CH), 71.3 (2 ×

CH), 61.04 (CH₂), 60.98 (CH₂), 40.59 (CH₃), 40.57 (CH₃), 14.3

(2 × CH₃); found (FTMS + pNSI) [M + H]⁺262.1441, C₁₅H₂₀NO₃

requires 262.1438.

Ethyl 5-(3,4-Dimethoxyphenyl)-5-hydroxypenta-2,3-dienoate

(3b).¹³General procedure B was followed using 1-(3,4-

dimethoxyphenyl)prop-2-yn-1-ol to yield product 3b as a yellow oil

and a 1:1 mixture of diastereomers (325 mg, 0.90 mmol, 90%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate, 10:1

to 7:1 to 5:1 to 3:1 to 2:1); R_f0.29 (3:1 hexane/ethyl acetate);

ν_max/cm⁻¹3474 br (OH), 2980 (C−H), 2836 (C−H), 1961 (CC,

allene), 1711 (CO), 1593, 1513, 1463, 1415 (Ar C−C), 1256

Ethyl 5-(4-tert-Butylphenyl)-5-hydroxypenta-2,3-dienoate (3f).

General procedure A was followed using 1-(4-(tert-butyl)phenyl)-

prop-2-yn-1-ol to yield product 3f as a yellow oil and a 1:1 mixture of

diastereomers (236 mg, 0.86 mmol, 63%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 7:1 to 5:1); R_f0.63

(hexane/ethyl acetate, 3:1); ν_max/cm⁻¹3400 br (OH), 2962 (C−H),

1960 (CC, allene), 1713 (CO), 1509, 1463, 1408 (Ar C−C),

1

(C−O−C), 1138 (C−O); H NMR (300 MHz, CDCl₃) δ 7.00 (m,

2H), 6.85 (d, 1H, J = 8.2 Hz), 5.88 (m, 1H), 5.78 (m, 1H), 5.36 (m,

1H), 4.20 (q, 2H, J = 7.1 Hz), 3.91 (s, 3H), 3.88 (s, 3H), 2.47 (br s,

1H), 1.28 (m, 3H); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.4 (C), 211.1

(C), 165.6 (C), 165.4 (C), 149.2 (C), 149.1 (C), 149.0 (C), 148.9

(C), 134.3 (C), 134.2 (C), 118.8 (CH), 118.5 (CH), 111.0 (CH),

110.9 (CH), 109.6 (CH), 109.3 (CH), 100.4 (CH), 100.2 (CH), 91.2

(CH), 90.8 (CH), 71.3 (CH), 71.2 (CH), 61.1 (CH₂), 61.0 (CH₂),

56.0 (2 × CH₃), 14.2 (2 × CH₃).

1

1254 (C−O−C), 1157 (C−O); H NMR (300 MHz, CDCl₃) δ 7.39

(m, 4H + 4H′), 5.83−5.92 (m, 1H + 1H′), 5.77−5.80 (m, 1H), 5.74−

5.77 (m, 1H′), 5.37−5.43 (m, 1H), 5.31−5.37 (m, 1H′), 4.11−4.27

(m, 2H + 2H′), 3.07 (d, 1H′, J = 4.0 Hz), 2.96 (d, 1H, J = 4.1 Hz),

1.26−1.35 (m, 12H + 12H′); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.42

(C), 211.40 (C), 165.9 (C), 165.6 (C), 151.1 (C), 151.0 (C), 138.8

(C), 138.7 (C), 126.2 (CH), 125.9 (CH), 125.6 (CH), 125.5 (CH),

100.4 (CH), 100.2 (CH), 90.8 (CH), 90.7 (CH), 71.3 (CH), 71.2

(CH), 61.2 (CH₂), 61.1 (CH₂), 34.60 (C), 34.58 (C), 31.3 (2 ×

CH₃), 14.2 (2 × CH₃); found (FTMS + pNSI) [M + Na]⁺297.1458,

C₁₇H₂₂O₃Na requires 297.1461.

Ethyl 5-Hydroxy-5-(2,4-dimethoxyphenyl)penta-2,3-dienoate

(3c). General procedure A was followed using 1-(2,4-dimethoxyphenyl)-

prop-2-yn-1-ol to yield product 3c as a yellow oil and a 1:1 mixture of

diastereomers (337 mg, 1.21 mmol, 89%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 5:1 to 3:1); R_f0.40 (3:1

hexane/ethyl acetate); ν_max/cm⁻¹3400 br (OH), 3012 (C−H), 2836

(C−H), 1961 (CC, allene), 1704 (CO), 1588, 1505, 1464, 1416

(Ar C−C), 1260 (C−O−C), 1156 (C−O); ¹H NMR (300 MHz,

CDCl₃) δ 7.84 (d, 1H, J = 9.1 Hz), 7.27 (d, 1H′, J = 9.2 Hz), 6.42−

6.49 (m, 2H + 2H′), 5.99 (t, 1H, J = 6.0 Hz), 5.90 (t, 1H′, J = 6.0 Hz),

5.66−5.73 (m, 1H + 1H′), 5.52 (m, 1H + 1H′), 4.09−4.21 (m, 2H +

2H′), 3.81 (s, 3H + 3H′), 3.78 (s, 3H + 3H′), 3.31 (d, 1H, J = 6.4 Hz),

3.15 (d, 1H′, J = 6.4 Hz), 1.21−1.29 (m, 3H + 3H′); ¹³C NMR (75.5

MHz, CDCl₃) δ 211.4 (C), 211.3 (C), 165.8 (C), 165.6 (C), 160.8

(C), 160.7 (C), 157.7 (C), 157.6 (C), 128.3 (CH), 128.0 (CH), 122.5

(2 × C), 104.34 (CH), 104.25 (CH), 99.8 (CH), 99.6 (CH), 98.7

(2 × CH), 90.7 (CH), 90.5 (CH), 67.7 (CH), 67.2 (CH), 60.9 (CH₂),

60.8 (CH₂), 55.43 (CH₃), 55.39 (CH₃), 14.23 (2 × CH₃), 14.21

(2 × CH₃); found (FTMS + pNSI) [M + Na]⁺301.1040, C₁₅H₁₈O₅Na

requires 301.1046.

Ethyl 5-(Benzo[d][1,3]dioxol-5-yl)-5-hydroxypenta-2,3-dienoate

(3g). General procedure A was followed but on a smaller scale using

1-(benzo[d][1,3]dioxol-5-yl)prop-2-yn-1-ol (191.3 mg, 1.09 mmol,

1 equiv), CuI (10.2 mg, 0.05 mmol, 0.05 equiv), EDA (0.14 mL,

1.31 mmol, 1.2 equiv), and MeCN (1.1 mL) to yield product 3g as a

yellow oil and a 1:0.8 mixture of diastereomers (178 mg, 0.68 mmol,

63%): puriﬁed by column chromatography (eluent hexane/ethyl

acetate, 3:1); R_f0.49 (3:1 hexane/ethyl acetate); ν_max/cm⁻¹3400 br

(OH), 2982 (C−H), 1961 (CC, allene), 1709 (CO), 1502, 1487,

1441 (Ar C−C), 1241 (C−O−C), 1158 (C−O); ¹H NMR (300

MHz, CDCl₃) δ 6.96−6.98 (m, 1H′, minor), 6.94−6.96 (m, 1H,

major), 6.89−6.92 (m, 1H′, minor), 6.86−6.89 (m, 1H, major), 6.77

(s, 1H, major), 6.75 (s, 1H′, minor), 5.94 (s, 2H′, minor), 5.93 (s, 2H,

major), 5.79−5.86 (m, 1H + 1H′), 5.71−5.79 (m, 1H + 1H′), 9.29−

9.35 (m, 1H, major), 5.23−5.29 (m, 1H′, minor), 4.12−4.24 (m, 2H +

2H′), 3.25 (d, 1H′, J = 4.2 Hz, minor), 3.19 (d, 1H, J = 4.3 Hz, major),

1.24−1.33 (m, 3H + 3H′); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.4 (C,

major), 211.3 (C, minor), 165.9 (C, minor), 165.6 (C, major), 147.9

(C, minor), 147.8 (C, major), 147.5 (C, minor), 147.3 (C, major),

135.9 (C, major), 135.8 (C, minor), 120.0 (CH, minor), 119.6 (CH,

major), 108.11 (CH, minor), 108.07 (CH, major), 107.1 (CH, minor),

106.9 (CH, major), 101.13 (CH₂, minor), 101.10 (CH₂, major), 100.4

(CH, minor), 100.2 (CH, major), 91.0 (CH, minor), 90.7 (CH,

major), 71.22 (CH, minor), 71.21 (CH, major), 61.3 (CH₂, minor),

61.2 (CH₂, major), 14.2 (CH₃, major + minor); found (FTMS +

pNSI) [M + Na]⁺285.0735, C₁₄H₁₄O₅Na requires 285.0733.

Ethyl 5-(4-Bromophenyl)-5-hydroxypenta-2,3-dienoate (3h).

General procedure B was followed using 1-(4-bromophenyl)prop-2-

yn-1-ol to yield product 3h as an orange solid and a 1:1 mixture of

diastereomers (212 mg, 0.71 mmol, 60%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 3:1); R_f0.38 (3:1

hexane/ethyl acetate); mp 66−71 °C; ν_max/cm⁻¹3400 br (OH), 2981

(C−H), 1962 (CC, allene), 1694 (CO), 1487, 1444 (Ar C−C),

1254 (C−O−C), 1159 (C−O); ¹H NMR (300 MHz, CDCl₃) δ 7.45−

7.51 (m, 2H + 2H′), 7.32−7.34 (m, 2H′), 7.28−7.32 (m, 2H), 5.80−

5.89 (m, 1H + 1H′), 5.73−5.78 (m, 1H + 1H′), 5.30−5.40 (m, 1H +

1H′), 4.11−4.25 (m, 2H + 2H′), 3.34 (d, 1H, J = 4.0 Hz), 3.17 (d,

1H′, J = 4.5 Hz), 1.17−1.41 (m, 3H + 3H′); ¹³C NMR (75.5 MHz,

CDCl₃) δ 211.5 (2 × C), 165.8 (C), 165.5 (C), 140.7 (C), 140.6 (C),

131.7 (CH), 131.6 (CH), 128.1 (CH), 127.9 (CH), 122.0 (C), 121.9

(C), 100.1 (CH), 99.8 (CH), 91.0 (CH), 90.9 (CH), 70.90 (CH),

Ethyl 5-Hydroxy-5-(4-methoxyphenyl)penta-2,3-dienoate (3d).

General procedure A was followed using 1-(4-methoxyphenyl)prop-

2-yn-1-ol to yield product 3d as a yellow oil and a 1:1 mixture of

diastereomers (278 mg, 1.24 mmol, 78%): puriﬁed by column chro-

matography (eluent hexane/ethyl acetate, 3:1); R_f0.33 (3:1 hexane/ethyl

acetate); ν_max/cm⁻¹3426 br (OH), 2982 (C−H), 1961 (CC,

allene), 1711 (CO), 1511, 1489, 1443 (Ar C−C), 1245 (C−O−C),

1

1171 (C−O); H NMR (300 MHz, CDCl₃) δ 7.36 (d, 2H, J = 8.8

Hz), 7.36 (d, 2H, J = 8.8 Hz), 6.87 (d, 2H, J = 8.6 Hz), 6.87 (d, 2H,

J = 8.7 Hz), 5.82−5.90 (m, 1H + 1H′), 5.74 (two overlapping t, 1H +

1H′, J = 5.7, 5.9 Hz), 5.36 (m, 1H), 5.30 (m, 1H), 4.12−4.25 (m,

2H + 2H′), 3.79 (s, 3H + 3H′), 3.28 (d, 1H, J = 3.6 Hz), 3.22 (d, 1H,

J = 3.8 Hz), 1.28 (m, 3H + 3H′); ¹³C NMR (75.5 MHz, CDCl₃) δ

211.40 (C), 211.39 (C), 165.9 (C), 165.8 (C), 159.5 (C), 159.4 (C),

134.0 (C), 133.9 (C), 127.8 (CH), 127.5 (CH), 114.0 (CH), 113.8

(CH), 100.5 (CH), 100.3 (CH), 90.8 (CH), 90.6 (CH), 71.0 (2 ×

CH), 61.2 (CH₂), 61.0 (CH₂), 55.3 (2 × CH₃), 14.2 (2 × CH₃);

found (FTMS + pNSI) [M + Na]⁺271.0936, C₁₄H₁₆O₄Na requires

271.0941.

Ethyl 5-(4-(Dimethylamino)phenyl)-5-hydroxypenta-2,3-dienoate

(3e). General procedure B was followed using 1-(4-(dimethylamino)-

phenyl)prop-2-yn-1-ol to yield product 3e as a red/orange oil and a

1:1 mixture of diastereomers (147 mg, 0.56 mmol, 39%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 3:1); R_f0.28

(3:1 hexane/ethyl acetate); ν_max/cm⁻¹3400 br (OH), 2981 (C−H),

1959 (CC, allene), 1710 (CO), 1521, 1477, 1444, 1413 (Ar

1709

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

70.86 (CH), 61.4 (CH₂), 61.2 (CH₂), 14.2 (2 × CH₃); found (FTMS +

pNSI) [M + Na]⁺318.9942, C₁₃H₁₃O₃BrNa requires 318.9940.

Ethyl 5-(4-Chlorophenyl)-5-hydroxypenta-2,3-dienoate (3i).¹³

General procedure B was followed using 1-(4-chlorophenyl)prop-2-

yn-1-ol to yield product 3i as a brown oil and a 1:0.95 mixture of

diastereomers (368 mg, 1.46 mmol, 94%); R_f0.33 (5:1 hexane/ethyl

acetate); ν_max/cm⁻¹3400 br (OH), 2982 (C−H), 1962 (CC,

allene), 1712 (CO), 1594, 1490, 1444 (Ar C−C), 1255 (C−O−C),

minor), 125.6 (CH, major), 124.9 (CH, minor), 124.8 (CH, major),

100.0 (CH, minor), 99.8 (CH, major), 91.31 (CH, major), 91.29 (CH,

minor), 67.6 (CH, major), 67.4 (CH, minor), 61.3 (CH₂, minor), 61.2

(CH₂, major), 14.2 (CH₃, major + minor); found (FTMS + pNSI)

[M + Na]⁺247.0401, C₁₁H₁₂O₃SNa requires 247.0399.

Ethyl 5-Hydroxydeca-2,3-dienoate (3m).¹³1-Octyn-3-ol (1.00 g,

7.92 mmol, 1 equiv) was dissolved in dry MeCN (20 mL). EDA

(0.87 mL, 8.32 mmol, 1.05 equiv), CuI (150.9 mg, 0.79 mmol, 10 mol %),

and Et₃N (1.1 mL, 7.92 mmol, 1.0 equiv) were added sequentially, and

the ﬂask was ﬂushed with Ar. MeCN (20 mL) was added, and the

reaction mixture was allowed to stir at 25 °C for 23 h. The solvent was

then removed on a rotary evaporator, and the resulting residue was

quenched with a saturated solution of NH₄Cl and extracted with ethyl

acetate. The organic layer was washed with brine and dried over

MgSO₄. Following removal of solvent on a rotary evaporator, the

crude mixture was puriﬁed by column chromatography (eluent

hexane/ethyl acetate, 4:1) to yield 3m as a yellow oil and a 1:1.2

mixture of diastereomers (310 mg, 1.46 mmol, 18%): R_f0.27 (4:1

hexane/ethyl acetate); ν_max/cm⁻¹3410 br (OH), 2930 (C−H), 1960

1

1159 (C−O); H NMR (300 MHz, CDCl₃) δ 7.30−7.40 (m, 4H +

4H′), 5.79 (m, 1H + 1H′), 5.83 (m, 1H + 1H′), 5.71−5.77 (m, 1H +

1H′), 4.14−4.24 (m, 2H + 2H′), 3.50 (br s, 1H, major), 3.31 (br s,

1H′, minor), 1.25−1.31 (m, 3H + 3H′); ¹³C NMR (75.5 MHz,

CDCl₃), δ 211.5 (C), 211.4 (C), 165.8 (C), 165.4 (C), 140.2 (C),

140.1 (C), 133.9 (C), 133.7 (C), 128.7 (CH), 128.6 (CH), 127.8

(CH), 127.5 (CH), 100.2 (CH), 100.0 (CH), 90.9 (CH), 90.8 (CH),

70.8 (2 × CH), 61.3 (CH₂), 61.2 (CH₂), 14.2 (2 × CH₃).

Ethyl 5-Hydroxy-5-(3-nitrophenyl)penta-2,3-dienoate (3j).¹³Gen-

eral procedure A was followed using 1-(3-nitrophenyl)prop-2-yn-1-ol

to obtain product 3j as a yellow oil and a 1:0.7 mixture of diastereomers

(11.8 mg, 0.04 mmol, 6%): puriﬁed by column chromatography

(eluent hexane/ethyl acetate, 3:1); R_f0.17 (3:1 hexane/ethyl acetate);

ν_max/cm⁻¹3422 br (OH), 2983 (C−H) 1963 (CC, allene), 1713

(CO), 1510 (NO₂), 1583, 1476, 1444 (Ar C−C), 1340 (NO₂),

1

(CC, allene), 1698 (CO), 1251 (C−O−C), 1159 (C−O); H

NMR (300 MHz, CDCl₃) δ 5.67−5.72 (m, 2H + 2H′, major + minor),

4.24−4.34 (m, 1H + 1H′), 4.19 (q, 2H′, J = 7.1 Hz, minor), 4.18 (q,

2H, J = 7.1 Hz, major), 2.46 (br s, 1H, minor), 2.31, (br s, 1H, major),

1.55−1.71 (m, 2H + 2H′), 1.24−1.49 (m, 9H + 9H′), 0.84−0.93 (m,

3H + 3H′); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.2 (C, minor), 211.0

(C, major), 166.0 (C, minor), 165.8 (C, major), 100.03 (CH, minor),

99.96 (CH, major), 90.2 (CH, major), 90.0 (CH, minor), 69.44 (CH,

major), 69.39 (CH, minor), 61.1 (CH₂, minor), 61.0 (CH₂, major),

37.2 (CH₂, major), 37.1 (CH₂, minor), 31.6 (CH₂, major + minor),

24.9 (CH₂, major + minor), 22.6 (CH₂, major + minor), 14.2 (CH₃,

major + minor), 14.0 (CH₃, major + minor).

1

1255 (C−O−C), 1178 (C−O); H NMR (300 MHz, CDCl₃) δ 8.41

(br t, 1H, J = 1.7 Hz), 8.31 (dt, 1H, J = 12.7, 1.7 Hz), 8.11−8.20 (m,

2H), 7.85−7.91 (m, 1H), 7.75−7.83 (m, 1H), 7.52 (q, 2H, J = 7.7

Hz), 5.84−5.91 (m, 1H, minor), 5.77 (td, 1H, J = 1.9 Hz, 6.0 Hz,

major), 5.54−5.61 (m, 1H, minor), 5.51 (m, 1H, major), 4.15−4.25

(m, 2H, major), 4.02−4.13 (m, 2H, minor), 3.78 (br s, 1H, minor),

3.70 (br s, 1H, major), 1.20−1.33 (m, 6H); ¹³C NMR (75.5 MHz,

CDCl₃), δ 211.6 (C, major + minor), 165.4 (C, minor), 165.2 (C,

major), 148.4 (C, major + minor), 143.7 (C, major), 143.6 (C, minor),

132.4 (CH, minor), 132.3 (CH, major), 129.6 (CH, minor), 129.5

(CH, major), 123.1 (CH, minor), 123.0 (CH, major), 121.4 (CH,

minor), 121.2 (CH, major), 99.7 (CH, minor), 99.3 (CH, major), 91.4

(CH, minor), 91.2 (CH, major), 70.8, (CH, major), 70.6 (CH,

minor), 61.5 (CH₂, minor), 61.4 (CH₂, major), 14.2 (CH₃, major +

minor).

Ethyl 5-Hydroxy-6,6-dimethylhepta-2,3-dienoate (3n). General

procedure A was followed using 4,4-dimethylpent-1-yn-3-ol to yield

product 3n as a pale yellow liquid and a 1:1.2 mixture of diastereomers

(360 mg, 1.81 mmol, 72%): puriﬁed by column chromatography

(eluent hexane/ethyl acetate, 10:1 to 5:1); R_f0.67 (3:1 hexane/ethyl

acetate); ν_max/cm⁻¹3434 br (OH), 2955, 2906 (C−H), 1960 (CC,

allene), 1715 (CO), 1252 (C−O−C), 1157 (C−O); ¹H NMR (300

MHz, CDCl₃) δ 5.61−5.75 (m, 2H + 2H′), 4.06−4.21 (m, 2H + 2H′),

3.87−4.00 (m, 1H +1H′), 2.80−2.87 (m, 1H′, minor), 2.69−2.78 (m,

1H, major), 1.19−1.28 (m, 3H + 3H′), 0.94 (s, 9H, major), 0.93 (s,

9H, minor); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.53 (C, major),

211.48 (C, minor), 166.3 (C, minor), 166.0 (C, major), 97.4 (CH,

minor), 96.8 (CH, major), 89.7 (CH, minor), 89.2 (CH, major), 77.3

(CH, minor), 77.2 (CH, major), 61.1 (CH₂, minor), 61.0 (CH₂,

major), 35.6 (C, minor), 35.5 (C, major), 25.4 (CH₃, major + minor),

14.2 (CH₃, major + minor); found (FTMS + pNSI) [M + Na]⁺

221.1148, C₁₁H₁₈O₃Na requires 221.1148.

Ethyl 5-(Furan-2-yl)-5-hydroxypenta-2,3-dienoate (3k).¹³General

procedure B was followed using 1-(furan-2-yl)prop-2-yn-1-ol to yield

product 3k as a yellow oil and a 1:1 mixture of diastereomers (299 mg,

1.44 mmol, 71%): puriﬁed by column chromatography (eluent

hexane/ethyl acetate, 3:1); R_f0.31 (3:1 hexane/ethyl acetate);

ν_max/cm⁻¹3399 br (OH), 2983 (C−H), 1964 (CC, allene), 1711

(CO), 1502, 1445, 1414 (Ar C−C), 1255 (C−O−C), 1159

1

(C−O); H NMR (300 MHz, CDCl₃) δ 7.33−7.37 (m, 1H + 1H′),

6.28−6.36 (m, 2H + 2H′), 5.88−5.99 (m, 1H + 1H′), 5.75 (dd, 1H,

J = 3.5, 2.4 Hz), 5.73 (dd, 1H′, J = 3.5, 2.5 Hz), 5.38 (td, 1H, J = 5.8,

2.4 Hz), 5.33 (m, 1H′), 4.10−4.20 (m, 2H + 2H′), 3.97 (d, 1H′,

J = 5.4 Hz), 3.90 (d, 1H, J = 5.7 Hz), 1.19−1.29 (m, 3H + 3H′); ¹³C

NMR (75.5 MHz, CDCl₃) δ 212.0 (C), 211.7 (C), 165.9 (C), 165.6

(C), 154.10 (C), 154.08 (C), 142.51 (CH), 142.49 (CH), 110.34

(CH), 110.32 (CH), 107.2 (CH), 107.1 (CH), 97.7 (CH), 97.6 (CH),

91.1 (CH), 90.9 (CH), 65.1 (CH), 64.9 (CH), 61.3 (CH₂), 61.2

(CH₂), 14.1 (2 × CH₃).

Ethyl 5-Hydroxy-7-phenylhepta-2,3-dien-6-ynoate (3o).¹³Gen-

eral procedure B was followed using 1-phenylpenta-1,4-diyn-3-ol to

yield product 3o as a yellow oil and a 1:1 mixture of diastereomers

(316 mg, 1.30 mmol, 82%): puriﬁed by column chromatography

(eluent hexane/ethyl acetate, 3:1); R_f0.36 (3:1 hexane/ethyl acetate);

ν_max/cm⁻¹3399 br (OH), 2981 (C−H), 2232 (CC), 1965 (CC,

allene), 1713 (CO), 1597, 1489, 1443 (Ar C−C), 1255 (C−O−C),

1

Ethyl 5-Hydroxy-5-(thiophene-2-yl)penta-2,3-dienoate (3l). Gen-

eral procedure A was followed using 1-(thiophene-2-yl)prop-2-yn-1-ol

to yield product 3l as a yellow oil and a 1:1.2 mixture of diastereomers

(71 mg, 0.32 mmol, 16%): puriﬁed by column chromatography

(eluent hexane/ethyl acetate, 4:1); R_f0.40 (3:1 hexane/ethyl acetate);

ν_max/cm⁻¹3400 br (OH), 2981 (C−H), 1962 (CC, allene), 1710

(CO), 1517, 1445, 1414 (Ar C−C), 1254 (C−O−C), 1159

1157 (C−O); H NMR (300 MHz, CDCl₃) δ 7.38−7.44 (m, 2H +

2H′), 7.26−7.36 (m, 3H + 3H′), 5.93−5.96 (m, 1H + 1H′), 5.81−5.87

(m, 1H + 1H′), 5.24−5.32 (m, 1H + 1H′), 4.19 (q, 2H′, J = 7.1 Hz),

4.18 (q, 2H, J = 7.1 Hz), 3.80−3.91 (m, 1H + 1H′), 1.26 (t, 3H′, J =

7.1 Hz), 1.25 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ

211.9 (C), 211.8 (C), 165.6 (C), 165.5 (C), 131.8 (2 × CH), 128.7

(2 × CH), 128.3 (2 × CH), 122.2 (2 × C), 98.5 (CH), 98.4 (CH),

91.7 (CH), 91.3 (CH), 87.2 (2 × C), 86.0 (C), 85.9 (C), 61.4 (CH₂),

61.3 (CH₂), 60.3 (CH), 60.0 (CH), 14.2 (2 × CH₃).

1

(C−O); H NMR (300 MHz, CDCl₃) δ 7.28−7.30 (m, 1H′, minor),

7.25−7.27 (m, 1H, major), 7.07−7.11 (m, 1H + 1H′), 6.96−7.02 (m,

1H + 1H′), 5.94−6.00 (m, 1H + 1H′), 5.77−5.82 (m, 1H + 1H),

5.57−5.67 (m, 1H + 1H′), 4.41−4.25 (m, 2H + 2H′), 3.26 (d, 1H′, J =

4.9 Hz, minor), 3.15 (d, 1H, J = 5.2 Hz, major), 1.24−1.33 (m, 3H +

3H′); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.5 (C, minor), 211.3 (C,

major), 165.7 (C, minor), 165.4 (C, major), 145.7 (C, major), 145.5

(C, minor), 126.82 (CH, major), 126.80 (CH, minor), 126.8 (CH,

(E)-Ethyl 5-Hydroxy-7-phenylhepta-2,3,6-trienoate (3p).¹³Gen-

eral procedure B was followed using (E)-1-phenylpent-1-en-4-yn-3-ol

to yield product 3p as a yellow oil and a 1:1 mixture of diastereomers

(388 mg, 1.59 mmol, 84%): puriﬁed by column chromatography

(eluent hexane/ethyl acetate, 4:1); R_f0.40 (4:1 hexane/ethyl acetate);

ν_max/cm⁻¹3399 br (OH), 2981 (C−H), 1960 (CC, allene), 1711

1710

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

1

(CO), 1494, 1447, 1414 (Ar C−C), 1253 (C−O−C), 1156

1444 (Ar C−C), 1246 (C−O−C); H NMR (400 MHz, CDCl₃) δ

7.32 (d, 2H, J = 8.9 Hz), 6.89 (d, 2H, J = 8.9 Hz), 5.33−5.44 (m, 2H),

5.16−5.21 (m, 1H), 3.81 (s, 3H), 2.07−2.10 (m, 1H), 1.98−2.07 (m,

2H), 1.38−1.51 (m, 2H), 0.87−0.97 (m, 3H); ¹³C NMR (100.6 MHz,

CDCl₃) 202.3 (C), 202.1 (C), 159.21 (C), 159.17 (C), 135.5 (C),

135.4 (C), 127.5 (CH), 127.4 (CH), 113.9 (CH), 113.8 (CH), 96.22

(CH), 96.15 (CH), 95.0 (CH), 94.7 (CH), 72.0 (CH), 71.8 (CH),

55.3 (2 × CH₃), 30.9 (CH₂), 30.8 (CH₂), 22.33 (CH₂), 22.30 (CH₂),

13.63 (CH₃), 13.61 (CH₃).

1

(C−O); H NMR (300 MHz, CDCl₃) δ 7.20−7.40 (m, 5H + 5H′),

6.68−6.72 (m, 1H′), 6.63−6.67 (m, 1H), 6.28 (d, 1H, J = 15.9 Hz),

6.26 (d, 1H′, J = 15.9 Hz), 5.79−5.87 (m, 1H + 1H′), 5.74−5.79 (m,

1H + 1H′), 4.96−5.06 (m, 1H + 1H′), 4.13−4.23 (m, 2H + 2H′), 3.60

(d, 1H′, J = 4.6 Hz), 3.47 (d, 1H, J = 5.0 Hz), 1.21−130 (m, 3H +

3H′); ¹³C NMR (75.5 MHz, CDCl₃) δ 211.7 (C), 211.4 (C), 165.9

(C), 165.8 (C), 136.3 (2 × C), 131.40 (CH), 131.38 (CH), 129.37

(CH), 129.32 (CH), 128.6 (2 × CH), 128.0 (2 × CH), 126.7 (2 ×

CH), 99.3 (CH), 99.2 (CH), 91.0 (CH), 90.5 (CH), 70.0 (CH), 69.8

(CH), 61.3 (CH₂), 61.2 (CH₂), 14.2 (2 × CH₃).

1-(4-Bromophenyl)hepta-2,3-dien-1-ol (3u). A ﬂask was charged

with 1-(4-bromophenyl)prop-2-yn-1-ol (207 mg, 0.98 mmol, 1 equiv),

freshly distilled butyraldehyde (0.14 mL, 1.57 mmol, 1.6 equiv), CuI

(36.2 mg, 0.10 mmol, 10 mol %), freshly distilled dibutylamine

(0.23 mL, 1.37 mmol, 1.4 equiv), and dry dioxane (2.8 mL, 0.34 M).

The resulting mixture was stirred at 130 °C for 18 h. The solvent

was then removed on a rotary evaporator. Puriﬁcation by column

chromatography (eluent hexane/ethyl acetate, 10:1 to5:1) yielded

product 3u as a yellow liquid and a 1:1 mixture of diastereomers

(164.4 mg, 0.62 mmol, 62%): R_f0.24 (10:1 hexane/ethyl acetate);

ν_max/cm⁻¹3334 (OH), 2957, 2928, 2870 (C−H), 1961 (CC,

allene), 1485, 1455, 1398 (Ar C−C); ¹H NMR (400 MHz, CDCl₃) δ

7.48 (d, 2H, J = 8.6 Hz), 7.27 (d, 2H, J = 8.6 Hz), 5.34−5.39 (m, 2H),

5.16−5.21 (m, 1H), 2.16 (br t, 1H, J = 2.6 Hz), 1.97−2.05 (m, 2H),

1.42 (sext, 2H, J = 7.4 Hz), 0.88−0.97 (m, 3H); ¹³C NMR (100.6

MHz, CDCl₃) 202.5 (C), 202.3 (C), 142.2 (C), 142.1 (C), 137.5

(CH), 131.5 (CH), 128.1 (CH), 127.9 (CH), 121.46 (C), 121.43 (C),

95.84 (CH), 95.76 (CH), 95.4 (CH), 95.1 (CH), 71.8 (CH), 71.6

(CH), 30.8 (CH₂), 30.7 (CH₂), 22.28 (CH₂), 22.26 (CH₂), 13.6 (2 ×

CH₃); found (FTMS + pAPCI) [M + H]⁺267.0375, C₁₃H₁₆BrO

requires 267.0379.

Ethyl 5-Hydroxy-5,5-diphenylpenta-2,3-dienoate (3q). General

procedure A was followed using 1,1-diphenylprop-2-yn-1-ol to yield

product 3q as a yellow oil (340 mg, 1.16 mmol, 97%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 15:1 to 10:1 to

5:1); R_f0.34 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹3433 br (OH),

2981 (C−H), 1963 (CC, allene), 1697 (CO), 1492, 1447, 1410

(Ar C−C), 1261 (C−O−C), 1162 (C−O); ¹H NMR (400 MHz,

CDCl₃) δ 7.43−7.52 (m, 2H), 7.44−7.47 (m, 2H), 7.27−7.37 (m,

6H), 6.31 (d, 1H, J = 6.1 Hz), 5.70 (d, 1H, J = 6.1 Hz), 4.14−2.24 (m,

2H), 2.86 (s, 1H), 1.31 (t, 3H, J = 7.1 Hz); ¹³C NMR (100.6 MHz,

CDCl₃) δ 211.0 (C), 165.4 (C), 145.0 (C), 144.9 (C), 128.24 (CH),

128.15 (CH), 127.8 (CH), 127.7 (CH), 126.8 (CH), 126.5 (CH),

104.9 (CH), 92.1 (CH), 78.4 (C), 61.1 (CH₂), 14.2 (CH₃); found

(FTMS + pNSI) [M + NH₄]⁺312.1597, C₁₉H₂₂O₃N requires 312.1594.

1-Phenylbuta-2,3-dien-1-ol (3r).³⁰A ﬂask was charged with

1-phenylprop-2-yn-1-ol (348 mg, 2.63 mmol, 1 equiv), paraformalde-

hyde (157 mg, 5.22 mmol, 2 equiv), CuI (305 mg, 1.60 mmol, 0.6

equiv), diisopropylamine (0.73 mL, 5.26 mmol, 2 equiv), and dry

dioxane (8.8 mL, 0.30 M). The resulting mixture was stirred at 115 °C

for 18 h. The reaction mixture was then cooled and ﬁltered through a

plug of silica (eluent hexane/ethyl acetate, 4:1, 200 mL). Following

removal of solvent on a rotary evaporator, the crude product was

puriﬁed by column chromatography (eluent hexane/ethyl acetate, 4:1)

to yield product 3r as a yellow oil (266 mg, 1.82 mmol, 76%): R_f0.32

(10:1 hexane/ethyl acetate); ν_max/cm⁻¹3338 br (OH), 3029 (C−H)

1953 (CC, allene); ¹H NMR (300 MHz, CDCl₃), δ 7.27−7.43 (m,

5H), 5.45 (q, 1H, J = 6.5 Hz), 5.23−5.31 (m, 1H), 4.90−4.96 (m,

2H), 2.44 (br s, 1H); ¹³C NMR (75.5 MHz, CDCl₃), δ 207.1 (C),

142.7 (C), 128.5 (CH), 127.7 (CH), 126.1 (CH), 95.2 (CH), 78.2

(CH₂), 71.9 (CH).

1,1-Diphenylhepta-2,3-dien-1-ol (3v).³¹A ﬂask was charged with

1,1-diphenylprop-2-yn-1-ol (206.5 mg, 0.99 mmol, 1 equiv), freshly

distilled butyraldehyde (0.14 mL, 1.58 mmol, 1.6 equiv), CuI

(39.4 mg, 20 mol %), freshly distilled dibutylamine (0.24 mL,

1.39 mmol, 1.4 equiv), and dry dioxane (3.0 mL, 0.34 M). The

resulting mixture was stirred at 150 °C for 26 h. The solvent was then

removed on a rotary evaporator. Puriﬁcation by column chromatog-

raphy (eluent hexane/ethyl acetate, 20:1 to 10:1) yielded product 3v

as a yellow liquid (50 mg, 0.19 mmol, 19%): R_f0.38 (10:1 hexane/

ethyl acetate); ν_max/cm⁻¹3455 (OH), 3059, 3025, 2958, 2930, 2871

1-(4-Chlorophenyl)-buta-2,3-diene-1-ol (3s).³¹A ﬂask was charged

with 1-(4-chlorophenyl)prop-2-yn-1-ol (191.1 mg, 1.15 mmol, 1.0

equiv), CuI (112.4 mg, 0.59 mmol, 0.5 equiv), paraformaldehyde

(84.9 mg, 2.83 mmol, 2.5 equiv), and dry dioxane (1.7 mL).

Diisopropylamine (0.3 mL, 2.07 mmol, 1.8 equiv) was added, and the

mixture was heated to reﬂux for 2 h under argon. The reaction mixture

was then allowed to cool to room temperature and ﬁltered (washed

with diethyl ether). Water (10 mL) was added, and the product was

extracted with diethyl ether. The organic layer was then dried with

MgSO₄and ﬁltered and the solvent removed using a rotary evaporator.

Puriﬁcation by column chromatography (eluent hexane/ethyl acetate,

5:1) yielded product 3s as a yellow liquid (60.1 mg, 0.33 mmol, 29%):

R_f0.50 (3:1 hexane/ethyl acetate); ν_max/cm⁻¹3333 (OH), 2886

(C−H), 1954 (CC, allene), 1490, 1406, 1344 (Ar C−C); ¹H NMR

(400 MHz, CDCl₃) δ 7.33 (s, 4H), 5.36−5.45 (m, 1H), 5.23−5.29 (m,

1H), 4.95−4.92 (m, 2H), 2.17 (d, 1H, J = 4.0 Hz); ¹³C NMR (100

MHz, CDCl₃) δ 207.2 (C), 141.3 (C), 133.5 (C), 128.7 (CH), 128.6

(CH), 95.0 (CH), 78.5 (CH₂), 71.3 (CH).

1

(C−H), 1962 (CC, allene), 1491, 1447 (Ar C−C); H NMR (400

MHz, CDCl₃) δ 7.42−7.46 (m, 4H), 7.29−7.35 (m, 4H), 7.24−7.27

(m, 2H), 5.91 (dt, 1H, J = 6.2, 2.9 Hz), 5.41 (q, 1H, J = 6.2 Hz)), 2.66

(s, 1H), 1.96−2.04 (m, 2H), 1.38 (sext, 2H, J = 7.4 Hz), 0.87 (t, 3H,

J = 7.4 Hz); ¹³C NMR (100.6 MHz, CDCl₃) δ 200.9 (C), 146.42 (C),

146.40 (C), 128.01 (CH), 127.99 (CH), 127.1 (CH), 126.8 (CH),

126.7 (CH), 126.7 (CH), 100.9 (CH), 97.1 (CH), 77.2 (C), 30.9

(CH₂), 22.7 (CH₂), 13.6 (CH₃).

Preparation of 1,3-Dienes 4. General procedure C: Using Au(I)

Catalysis. Allenol (0.070 mmol, 1 equiv) was added to a sealed tube

and dissolved in CDCl₃(0.35 mL). A solution of Au(I) catalyst 8

(5 mol %) and thiol (0.077 mmol, 1.1 equiv) in CDCl₃(0.15 mL) was

then added to the sealed tube and washed in with additional CDCl₃

(0.2 mL). The resulting mixture was heated at 70 °C for 30 min. The

mixture was allowed to cool before it was passed through a plug of

silica and washed with ether. The ﬁltrate was then concentrated on a

rotary evaporator. The products were puriﬁed by column chromatog-

raphy (hexane/ethyl acetate).

General procedure D: Using InCl₃Catalysis. InCl₃(5 mol %) and

thiol (0.07 mmol, 1 equiv) were added to a microwave tube and

dissolved in CHCl₃(0.35 mL). A solution of allenol (0.105 mmol,

1.5 equiv) in CHCl₃(0.15 mL) was added and washed in with

additional CHCl₃(0.2 mL). The tube was then sealed and placed in

the microwave and heated at 70 °C (external surface sensor), 300 W,

for 10 min. The mixture was allowed to cool before it was passed

through a plug of silica and washed with ether. The ﬁltrate was then

concentrated on a rotary evaporator. The products were puriﬁed by

column chromatography (hexane/ethyl acetate).

1-(4-Methoxyphenyl)hepta-2,3-dien-1-ol (3t).³¹A ﬂask was

charged with 1-(4-methoxyphenyl)prop-2-yn-1-ol (190.0 mg, 1.17 mmol,

1 equiv), freshly distilled butyraldehyde (0.17 mL, 1.87 mmol, 1.6 equiv),

CuI (25.5 mg, 0.10 mmol, 10 mol %), freshly distilled dibutylamine

(0.28 mL, 1.64 mmol, 1.4 equiv), and dry dioxane (3.8 mL, 0.34 M).

The resulting mixture was stirred at 130 °C for 18 h. The solvent

was then removed on a rotary evaporator. Puriﬁcation by column

chromatography (eluent hexane/ethyl acetate, 10:1) yielded product

3t as a yellow liquid and a 1:1 mixture of diastereomers (74.8 mg,

0.34 mmol, 29%): R_f0.24 (10:1 hexane/ethyl acetate); ν_max/cm⁻¹

3383 (OH), 2956, 2931, 2871 (C−H), 1961 (CC, allene), 1463,

1711

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

E,E stereochemistry for 4 was conﬁrmed by X-ray structure analysis

(4a) and NOESY where possible. The E,E stereochemistries for the

others were assigned by analogy with the rest in the series.

(CH₂, minor), 15.3 (CH₃, minor), 14.1 (CH₃, major); found (FTMS +

pAPCI) [M + H]⁺528.1251, C₂₅H₂₆N₃O₆S₂requires 528.1258.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((4-nitrophenyl)thio)-

penta-2,4-dienoate (4b). General procedure D was followed to obtain

product 4b as a yellow oil (23.3 mg, 0.06 mmol, 80%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 5:1); R_f0.25 (5:1

hexane/ethyl acetate); ν_max/cm⁻¹2935 (C−H alkyl), 1699 (CO), 1596

(CC diene), 1578, 1557 (Ar C−C), 1510 (NO₂), 1367 (NO₂), 1177

(C−O−C); ¹H NMR (300 MHz, CDCl₃) δ 8.25 (dd, 1H, J = 15.8, 0.8

Hz), 8.17 (d, 2H, J = 9.0 Hz), 7.52 (d, 2H, J = 9.0 Hz), 7.29 (d, 1H, J =

15.8 Hz), 7.06 (m, 2H), 6.82 (m, 1H), 5.92 (app t, 1H, J = 0.6 Hz), 4.21

(q, 2H, J = 7.1 Hz), 3.92 (s, 3H), 3.90 (s, 3H), 1.30 (t, 3H, J = 7.1 Hz);

¹³C NMR (75.5 MHz, CDCl₃), δ 165.0 (C), 150.6 (C), 149.9 (C), 149.2

(2E,4E)-Ethyl 3-((4-Nitrophenyl)thio)-5-phenylpenta-2,4-dienoate

(4a). Using Au(I) Catalysis. General procedure C was followed to yield

title product 4a as a yellow solid (9.5 mg, 0.03 mmol, 38%) and product 6a

as a yellow oil (8.2 mg, 0.02 mmol, 34%): puriﬁed by column chroma-

tography (eluent hexane/ethyl acetate, 80:1 to 70:1 to 50:1 to 25:1).

Using InCl₃. General procedure D was followed to yield title product

4a as a yellow solid (12 mg, 0.03 mmol, 49%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 80:1 to 70:1 to 50:1 to

25:1); R_f0.66 (5:1 hexane/ethyl acetate); mp 111−113 °C; ν_max/cm⁻¹

3097 (C−H), 2098 (C−H), 1703 (CO), 1614 (CC, diene conj),

1597 (CC, diene conj), 1576, 1561 (Ar C−C), 1518 (NO₂), 1340

(NO₂), 1192 (C−O−C); ¹H NMR (300 MHz, CDCl₃), δ 8.35 (dd, 1H,

J = 15.9 Hz, 0.8 Hz), 8.18 (d, 2H, J = 8.9 Hz), 7.54 (d, 2H, J = 8.9 Hz),

7.47−7.52 (m, 2H), 7.28−7.41 (m, 4H), 5.95 (app s, 1H), 4.21 (q, 2H, J =

7.1 Hz), 1.30 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃), 164.8

(C), 149.9 (C), 146.8 (C), 142.7 (C), 138.9 (CH), 135.7 (C), 131.0 (CH),

129.5 (CH), 128.8 (CH), 127.8 (CH), 124.4 (CH), 123.3 (CH), 121.1

(CH), 60.6 (CH₂), 14.3 (CH₃); found (FTMS + pAPCI) [M + H]⁺

356.0950, C₁₉H₁₈NO₄S requires 356.0951. E,E stereochemistry was

conﬁrmed by crystal structure analysis (Figure 1).

(C), 146.7 (C), 143.2 (C), 139.1 (CH), 130.7 (CH), 128.8 (C), 124.4

(CH), 122.1 (CH), 121.4 (CH), 120.4 (CH), 111.1 (CH), 109.7 (CH),

60.5 (CH₂), 55.97 (CH₃), 55.95 (CH₃), 14.2 (CH₃); found (FTMS +

pAPCI) [M + H]⁺416.1169, C₂₁H₂₂NO₆S requires 416.1162. E,E stereo-

chemistry was conﬁrmed by NOESY (δ 5.92 and 7.52):

Crystals were grown by vapor diﬀusion from CHCl₃−hexane.

Crystal data: C₁₉H₁₇NO₄S, M = 355.40, triclinic, a = 9.6997(7) Å, b =

9.9793(6) Å, c = 10.2055(7) Å, β = 73.565(4)°, U = 869.20(10) Å³,

T = 100 K, space group P1, Z = 2, μ(Mo Kα) = 0.210 mm⁻¹, 26793

̅

reﬂections measured, 7525 independent reﬂections (R_int= 0.0465).

The ﬁnal wR2 was 0.1146.

(2E,4E)-Ethyl 5-(2,4-Dimethoxyphenyl)-3-((4-nitrophenyl)thio)-

penta-2,4-dienoate (4c). General procedure D was followed to

yield product 4c as a yellow solid (27.9 mg, 0.07 mmol, 96%): puriﬁed

by column chromatography (eluent hexane/ethyl acetate, 5:1).

Repeated on a 0.36 mmol Scale with 1 mol % InCl₃. Thiol

(55 mg, 0.355 mmol, 1.0 equiv) and InCl₃(0.7 mg, 1 mol %) were

added to a microwave tube and dissolved in CHCl₃(1.6 mL). A

solution of allenol 3c (157 mg, 0.566 mmol, 1.5 equiv) in CHCl₃

(1 mL) was added to the microwave tube and washed in with CHCl₃

(1 mL). The reaction was heated at 70 °C in a microwave for 20 min

to yield product 4c as a yellow solid (142 mg, 0.34 mmol, 96% yield):

R_f0.36 (5:1 hexane/ethyl acetate); mp 126−128 °C; ν_max/cm⁻¹2938

(C−H), 1698 (CO), 1596 (CC, diene conj), 1515 (NO₂), 1556,

1463, 1438, 1419 (Ar C−C), 1337 (NO₂), 1159 (C−O−C); ¹H NMR

(300 MHz, CDCl₃) δ 8.28 (dd, 1H, J = 16.0, 0.8 Hz), 8.15 (d, 2H, J =

9.0 Hz), 7.67 (d, 1H, J = 16.0 Hz), 7.52 (d, 3H, J = 9.0 Hz), 6.38−6.51

(m, 2H), 5.89 (app s, 1H), 4.21 (q, 2H, J = 7.1 Hz), 3.82 (s, 3H), 3.81

(s, 3H), 1.29 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ

165.1 (C), 162.3 (C), 159.2 (C), 151.1 (C), 146.7 (C), 143.5 (C),

134.2 (CH), 131.0 (CH), 129.0 (CH), 124.5 (CH), 121.2 (CH),

119.3 (CH), 117.9 (C), 105.4 (CH), 98.4 (CH), 60.3 (CH₂), 55.6

(CH₃), 55.5 (CH₃), 14.3 (CH₃); found (FTMS + pAPCI) [M + H]⁺

416.1161, C₂₁H₂₂NO₆S requires 416.1162. E,E stereochemistry was

conﬁrmed by NOESY (δ 7.52 and 5.89):

Data for ethyl 5-((4-nitrophenyl)thio)-5-phenylpenta-2,3-dien-

oate (6a): R_f0.58 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹2979 (C−H),

1980 (CC, allene), 1698 (CO), 1613, 1596, 1575, (Ar C−C),

1

1513 (NO₂), 1336 (NO₂) 1215 (C−O−C); H NMR (300 MHz,

CDCl₃, dr = 1:1.4) δ 8.19 (d, 2H + 2H′, J = 9.1 Hz, major + minor),

8.11 (m, 1H + 1H′), 7.62 (d, 2H + 2H′, J = 9.1 Hz), 7.28−7.48 (m,

4H + 4H′), 6.04 (dd, 1H, J = 7.4, 6.1 Hz, major), 5.99 (dd, 1H′, J =

7.3, 6.1 Hz, minor), 5.71 (dd, 1H, J = 6.1, 2.2, Hz, major), 5.66 (dd,

1H, J = 6.1, 2.3 Hz, minor), 5.15 (dd, 1H, J = 7.3, 2.3 Hz, minor), 5.13

(dd, 1H, J = Hz, 7.3, 2.2 Hz, major), 4.16 (q, 2H + 2H′, J = 7.1 Hz),

1.26 (t, 3H + 3H′, J = 7.1 Hz); ¹³C NMR (100.6 MHz, CDCl₃) δ

212.6 (C, minor), 212.4 (C, major), 164.8 (C, major), 164.7 (C,

minor), 147.0 (C, major), 145.3 (C, major), 145.0 (C, minor), 144.1

(C, major), 137.8 (C, major), 137.7 (C, minor), 129.0 (CH, major),

128.9 (CH, minor), 128.5 (CH, major + minor), 127.9 (CH, major),

127.8 (CH, minor), 126.4 (CH, minor), 124.4 (CH, major), 123.9

(CH, major), 123.8 (CH, minor), 97.3 (CH, major), 97.1 (CH,

minor), 91.6 (CH, major), 91.3 (CH, minor, SCHCHCCH),

61.2 (CH₂, major), 61.1 (CH₂, minor), 49.9 (CH, minor), 49.4 (CH,

major), 14.2 (CH₃, major), 14.1 (CH₃, minor); found (FTMS +

pAPCI) [M + H]⁺356.0950, C₁₉H₁₈NO₄S requires 356.0951. Note:

this product decomposes within weeks.

Data for (Z)-ethyl 3,5-bis((4-nitrophenyl)thio)-5-phenylpent-3-

encate (7a): ν_max/cm⁻¹2923 (C−H), 1731 (CO), 1513 (NO₂),

1595, 1576, 1476, (Ar C−C), 1336 (NO₂) 1180 (C−O−C); ¹H NMR

(300 MHz, CDCl₃, E:Z = 1:0.3) δ 8.07 (d, 2H + 2H′, J = 8.9 Hz), 8.03

(d, 2H + 2H′, J = 8.0 Hz), 7.48 (d, 2H + 2H′, J = 9.0 Hz) 7.27−7.44

(m, 5H + 5H′), 7.20 (d, 2H + 2H′, J = 9.0 Hz), 6.56 (d, 1H, J = 10 Hz,

major, CHCS), 6.47 (1H′, d, J = 9.8 Hz, minor, CHCS), 5.66

(1H, d, J = 9.9 Hz, major), 5.35 (d, 1H′, J = 9.8 Hz, minor), 4.10 (q,

2H + 2H′, J = 7.1 Hz), 3.26 (s, 2H + 2H′), 1.17 (m, 3H + 3H′); ¹³C

NMR (100 MHz, CDCl₃) δ 169.3 (C, major), 168.8 (C, minor), 146.4

(C, major), 146.2 (C, minor), 146.2 (C, minor), 144.1 (C, major),

143.2 (C, minor), 142.1 (CH, major + minor), 138.9 (C, minor),

137.7 (C, major), 130.4 (CH, major + minor), 129.1 (CH, major +

minor), 128.4 (CH, minor), 128.3 (CH, major), 127.8 (CH, minor),

127.7 (CH, major), 126.8 (C, major + minor), 126.4 (CH, major +

minor), 124.4 (CH, major + minor), 124.2 (CH, minor), 124.1 (CH,

major), 123.9 (CH, major + minor), 65.8 (CH₂, minor), 61.3 (CH₂,

major), 51.7 (CH, major), 50.8 (CH, minor), 43.0 (CH₂, major), 38.2

(2E,4E)-Ethyl 5-(4-Methoxyphenyl)-3-((4-nitrophenyl)thio)penta-

2,4-dienoate (4d). General procedure D was followed with the

following modiﬁcation. The reaction was placed in a microwave at

90 °C for 20 min to yield product 4d as a yellow solid (26.3 mg, 0.068

mmol, 79%): puriﬁed by column chromatography (eluent hexane/

ethyl acetate, 10:1); R_f0.51 (5:1 hexane/ethyl acetate); mp 80−82 °C;

ν_max/cm⁻¹3096 (C−H), 2979 (C−H), 1699 (CO), 1596 (CC,

diene conj), 1509 (NO₂), 1558, 1476, 1463, 1442 (Ar C−C), 1337

1

(NO₂), 1184 (C−O−C); H NMR (300 MHz, CDCl₃) δ 8.26 (dd,

1H, J = 15.8, 0.9 Hz), 8.16 (d, 2H, J = 9.0 Hz), 7.52 (d, 2H, J = 9.0 Hz),

1712

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

7.46 (d, 2H, J = 8.4 Hz), 7.30 (d, 1H, J = 15.8 Hz), 6.87 (d, 2H, J = 8.4

Hz), 5.92 (app t, 1H, J = 0.7 Hz), 4.21 (q, 2H, J = 7.1 Hz), 3.82 (s, 3H),

1.30 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ 165.0 (C),

160.88 (C), 150.0 (C), 146.7 (C), 143.2 (C), 138.8 (CH), 130.8 (CH),

129.4 (CH), 128.5 (C), 124.4 (CH), 121.2 (CH), 120.3 (CH), 114.3

(CH), 60.5 (CH₂), 55.4 (CH₃), 14.3 (CH₃); found (FTMS + pAPCI)

[M + H]⁺386.1052, C₂₀H₂₀NO₅S requires 386.1057. E,E stereo-

chemistry conﬁrmed by NOESY (δ 7.52 and 5.92):

puriﬁed by column chromatography (eluent hexane/ethyl acetate, 7:1); R_f

0.44 (5:1 hexane/ethyl acetate); mp 122−125 °C; ν_max/cm⁻¹2980 (C−H),

1699 (CO), 1596 (CC, diene conj), 1517 (NO₂), 1559, 1502, 1487,

1

1446 (Ar C−C), 1338 (NO₂), 1177 (C−O−C); H NMR (300 MHz,

CDCl₃) δ 8.13−8.26 (m, 3H), 7.52 (d, 2H, J = 8.9 Hz), 7.24 (d, 1H, J =

15.8 Hz), 7.07 (d, 1H, J = 1.5 Hz), 6.94 (dd, 1H, J = 8.1, 1.6 Hz), 6.76 (d,

1H, J = 8.0 Hz), 5.98 (s, 2H), 5.92 (app s, 1H), 4.21 (q, 2H, J = 7.1 Hz),

1.30 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ 165.0 (C), 149.8

(C), 149.1 (C), 148.4 (C), 146.8 (C), 143.1 (C), 138.8 (CH), 130.8 (CH),

130.2 (C), 124.4 (CH), 123.8 (CH), 121.6 (CH), 120.5 (CH), 108.5 (CH),

106.5 (CH), 101.5 (CH₂), 60.5 (CH₂), 14.3 (CH₃); found (FTMS +

pAPCI) [M + H]⁺400.0854, C₂₀H₁₈NO₆S requires 400.0849. E,E stereo-

chemistry was conﬁrmed by NOESY (δ 7.52 and 5.29):

(2E,4E)-Ethyl 5-(4-(Dimethylamino)phenyl)-3-((4-nitrophenyl)-

thio)penta-2,4-dienoate (4e). General procedure D was followed to

yield product 4e as a red solid (25.8 mg, 0.06 mmol, 90%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 7:1); R_f0.44

(5:1 hexane/ethyl acetate); mp 146−149 °C; ν_max/cm⁻¹2980 (C−H),

1698 (CO), 1595 (CC, diene conj), 1520 (NO₂), 1554, 1476,

1444 (Ar C−C), 1338 (NO₂), 1164 (C−O−C); ¹H NMR (300 MHz,

CDCl₃) δ 8.21 (dd, 1H, J = 15.6, 0.7 Hz), 8.14 (d, 2H, J = 9.0 Hz),

7.49 (d, 2H, J = 9.0 Hz), 7.41 (d, 2H, J = 8.8 Hz), 7.29 (d, 1H, J = 15.6

Hz), 6.64 (d, 2H, J = 8.8 Hz), 5.90 (app s, 1H), 4.22 (q, 2H, J = 7.1 Hz),

3.00 (s, 6H), 1.30 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ

165.3 (C), 151.4 (C), 150.1 (C), 146.4 (C), 144.2 (C), 140.1 (CH), 130.2

(CH), 129.6 (CH), 124.3 (CH), 123.6 (CH), 119.1 (C), 119.1 (CH),

118.7 (CH), 60.3 (CH₂), 40.2 (CH₃), 14.3 (CH₃); found (FTMS +

pAPCI) [M + H]⁺399.1374, C₂₁H₂₃N₂O₄S requires 399.1373. E,E stereo-

chemistry was conﬁrmed by NOESY (δ 7.49 and 5.90):

(2E,4E)-Ethyl 5-(4-Bromophenyl)-3-((4-nitrophenyl)thio)penta-

2,4-dienoate (4h). General procedure D was followed with the

following modiﬁcation. The reaction was placed in a microwave at

90 °C for 20 min to yield product 4h as a yellow solid (28.1 mg, 0.06

mmol, 93%): puriﬁed by column chromatography (eluent hexane/

ethyl acetate, 10:1); R_f0.71 (5:1 hexane/ethyl acetate); mp:117−

120 °C; ν_max/cm⁻¹3065, 2980 (C−H), 1701 (CO), 1614 (CC,

diene conj), 1596 (CC, diene conj), 1515 (NO₂), 1566, 1556, 1485

(Ar C−C), 1336 (NO₂), 1174 (C−O−C); ¹H NMR (300 MHz,

CDCl₃) δ 8.36 (dd, 1H, J = 15.9, 0.8 Hz), 8.18 (d, 2H, J = 9.0 Hz),

7.53 (d, 2H, J = 9.0 Hz), 7.47 (d, 2H, J = 8.5 Hz), 7.36 (d, 2H, J = 8.5

Hz), 7.25 (d, 1H, J = 15.9 Hz), 5.94 (app s, 1H), 4.20 (q, 2H, J = 7.1

Hz), 1.30 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ 164.8

(C), 149.7 (C), 147.0 (C), 142.4 (C), 137.4 (CH), 134.6 (C), 132.0

(CH), 131.3 (CH), 129.2 (CH), 124.5 (CH), 123.9 (CH), 123.6 (C),

121.3 (CH), 60.7 (CH₂), 14.3 (CH₃); found (FTMS + pAPCI) [M + H]⁺

434.0057, C₁₉H₁₇NO₄SBr requires 434.0056. E,E stereochemistry was

conﬁrmed by NOESY (δ 7.53 and 5.94):

(2E,4E)-Ethyl 5-(4-tert-Butylphenyl)-3-((4-nitrophenyl)thio)penta-

2,4-dienoate (4f). General procedure D was followed to yield product

4f as a yellow solid (18.8 mg, 0.05 mmol, 68%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 25:1 to 10:1); R_f0.70

(5:1 hexane/ethyl acetate); mp 112−114 °C; ν_max/cm⁻¹2962 (C−H),

1703 (CO), 1598 (CC, diene conj), 1517 (NO₂), 1565, 1476,

1410 (Ar C−C), 1338 (NO₂), 1176 (C−O−C); ¹H NMR (300 MHz,

CDCl₃) δ 8.32 (dd, 1H, J = 15.8, 0.8 Hz), 8.17 (d, 2H, J = 9.0 Hz),

7.52 (d, 2H, J = 9.0 Hz), 7.44 (d, 2H, J = 8.4 Hz), 7.36 (d, 2H, J = 8.4

Hz), 7.31 (d, 1H, J = 15.8 Hz), 5.97 (app s, 1H), 4.22 (q, 2H, J = 7.1

Hz), 1.26−1.35 (m, 12H); ¹³C NMR (75.5 MHz, CDCl₃) δ 164.9 (C),

153.1 (C), 149.8 (C), 146.7 (C), 143.1 (C), 139.1 (CH), 133.0 (C),

130.8 (CH), 127.7 (CH), 125.8 (CH), 124.4 (CH), 122.5 (CH), 121.0

(CH), 60.6 (CH₂), 34.8 (C), 31.2 (CH₃), 14.3 (CH₃); found (FTMS +

pAPCI) [M + H]⁺412.1573, C₂₃H₂₆NO₄S requires 412.1577. E,E

stereochemistry was conﬁrmed by NOESY (δ 7.52 and 7.31):

(2E,4E)-Ethyl 5-(4-Chlorophenyl)-3-((4-nitrophenyl)thio)penta-

2,4-dienoate (4i). General procedure D was followed with the

following modiﬁcation. The reaction was placed in a microwave at

90 °C for 30 min to yield product 4i as a yellow solid (14.3 mg, 0.04

mmol, 49%): puriﬁed by column chromatography (eluent hexane/

ethyl acetate, 7:1); R_f0.64 (5:1 hexane/ethyl acetate); mp 107−110 °C;

ν_max/cm⁻¹2981 (C−H), 1703 (CO), 1616 (CC, diene conj), 1596

(CC, diene conj), 1517 (NO₂), 1569, 1489, 1476 (Ar C−C), 1339

(NO₂), 1187 (C−O−C); ¹H NMR (300 MHz, CDCl₃) δ 8.23 (dd, 1H,

J = 15.9, 0.9 Hz), 8.11 (d, 2H, J = 9.0 Hz), 7.46 (d, 2H, J = 9.0 Hz), 7.37

(d, 2H, J = 8.4 Hz), 7.17−7.28 (m, 3H), 5.87 (app s, 1H), 4.14 (q, 2H,

J = 7.1 Hz), 1.23 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ

164.8 (C), 149.7 (C), 147.0 (C), 142.1 (C), 137.3 (CH), 135.3 (C),

134.2 (C), 131.2 (CH), 129.2 (CH), 129.1 (CH), 124.5 (CH), 123.8

(CH), 121.2 (CH), 60.7 (CH₂), 14.3 (CH₃); found (FTMS + pAPCI)

[M + H]⁺390.0561, C₁₉H₁₇ClNO₄S requires 390.0561.

(2E,4E)-Ethyl 5-(Furan-2-yl)-3-((4-nitrophenyl)thio)penta-2,4-dienoate

(4k). General procedure D was followed with the following modiﬁca-

tion. The reaction was placed in a microwave at 90 °C for 20 min to

yield product 4k as a pale yellow oil (19.0 mg, 0.06 mmol, 79%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate,

7:1); R_f0.60 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹3097, 2981 (C−H),

(2E,4E)-Ethyl 5-(Benzo[d][1,3]dioxol-5-yl)-3-((4-nitrophenyl)thio)-

penta-2,4-dienoate (4g). General procedure D was followed with the

following modiﬁcation. The reaction was placed in a microwave at 90 °C for

20 min to yield product 4g as a yellow solid (11.6 mg, 0.03 mmol, 47%):

1713

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

1702 (CO), 1614 (CC, diene conj), 1596 (CC, diene conj),

1514 (NO₂), 1573, 1541, 1475 (Ar C−C), 1336 (NO₂), 1174 (C−O−

C); ¹H NMR (300 MHz, CDCl₃) δ 8.21 (d, 1H, J = 16.1 Hz), 8.16 (d,

2H, J = 9.0 Hz), 7.49 (d, 2H, J = 9.0 Hz), 7.45 (d, 1H, J = 1.7 Hz), 7.11

(d, 1H, J = 16.1 Hz), 6.48 (d, 1H, J = 3.4 Hz), 6.42 (dd, 1H, J = 3.4, 1.7

Hz), 6.00 (s, 1H), 4.23 (q, 2H, J = 7.1 Hz), 1.30 (t, 3H, J = 7.1 Hz); ¹³C

NMR (75.5 MHz, CDCl₃) δ 164.8 (C), 152.0 (C), 148.5 (C), 146.6

(C), 144.4 (CH), 143.3 (C), 130.2 (CH), 125.9 (CH), 124.4 (CH),

122.1 (CH), 121.6 (CH), 113.3 (CH), 112.3 (CH), 60.6 (CH₂), 14.3

(CH₃); found (FTMS + pAPCI) [M + H]⁺346.0747, C₁₇H₁₆NO₅S

requires 346.0744. E,E stereochemistry was conﬁrmed by NOESY (δ

7.11 and 6.00):

J = 7.1 Hz), 1.03 (s, 9H); ¹³C NMR (75.5 MHz, CDCl₃) δ 164.8 (C),

153.1 (CH), 151.2 (C), 146.9 (C), 142.6 (C), 131.7 (CH), 124.2 (CH),

120.3 (CH), 118.8 (CH), 60.4 (CH₂), 34.1 (C), 29.0 (CH₃), 14.3 (CH₃);

found (FTMS + pAPCI) [M + H]⁺336.1262, C₁₇H₂₂NO₄S requires

336.1264. E,E stereochemistry conﬁrmed by NOESY (δ 8.42 and 5.78):

(2E,4E)-Ethyl 3-((4-Nitrophenyl)thio)-7-phenylhepta-2,4-dien-6-

ynoate (4o). General procedure D was followed with the following

modiﬁcation. The reaction was placed in a microwave at 90 °C for 20 min

to yield product 4o as a yellow oil (22.9 mg, 0.06 mmol, 85%) with E:Z =

4:1: puriﬁed by column chromatography (eluent hexane/ethyl acetate,

10:1); R_f0.65 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹3063 (C−H), 2981

(C−H), 2981 (CC), 1706 (CO), 1598 (CC, diene conj), 1517

(NO₂), 1577, 1561, 1476, 1442 (Ar C−C), 1338 (NO₂), 1186 (C−O−

C); ¹H NMR (300 MHz, CDCl₃) δ 8.19 (d, 2H, J = 9.0 Hz, major), 8.16

(d, 2H′, J = 9.0 Hz, minor), 8.13 (dd, 1H + 1H′, J = 15.7, 0.9 Hz), 7.54

(d, 2H′, J = 9.0 Hz, minor), 7.48 (d, 2H, J = 9.0 Hz, major), 7.42−7.45

(m, 2H + 2H′), 7.31−7.36 (m, 3H + 3H′), 6.64 (dd, 1H + 1H′, J = 15.7

Hz, 0.6 Hz), 6.00 (app t, 1H, J = 0.8 Hz, major), 5.92 (app t, 1H, J = 1.0

Hz, minor), 4.23 (q, 2H, J = 7.1 Hz, major), 4.16 (q, 2H′, J = 7.1 Hz,

minor), 1.30 (t, 3H, J = 7.1 Hz, major), 1.25 (t, 3H′, J = 7.1 Hz, minor);

¹³C NMR (75.5 MHz, CDCl₃) δ 164.3 (C, major + minor), 149.3 (C,

minor), 147.6 (C, major), 147.2 (C, minor), 146.8 (C, major), 142.5 (C,

major), 141.7 (C, minor), 134.9 (CH, major), 133.1 (CH, minor), 132.4

(CH, minor), 131.9 (CH, major), 131.4 (CH, minor), 130.5 (CH,

major), 129.0 (CH, major + minor), 128.5 (CH, minor), 128.4 (CH,

major), 124.5 (CH, major), 124.2 (CH, minor), 123.0 (CH, major),

124.1 (C, minor), 122.6 (C, major), 121.3 (CH, minor), 119.4 (CH,

major), 155.7 (CH, minor), 100.9 (C, minor), 97.8 (C, major), 88.2 (C,

major), 87.0 (C, minor), 60.8 (CH₂, major), 60.7 (CH₂, minor), 14.22

(CH₃, major), 14.17 (CH₃, minor); found (FTMS + pAPCI) [M + H]⁺

380.0951, C₂₁H₁₈NO₄S requires 380.0951. E,E stereochemistry for the

major isomer was conﬁrmed by NOESY (δ 7.48 and 6.00):

(2E,4E)-Ethyl 3-((4-Nitrophenyl)thio)-5-(thiophene-2-yl)penta-

2,4-dienoate (4l). General procedure D was followed with the

following modiﬁcation. The reaction was placed in a microwave at 90 °C

for 20 min to yield product 4l as a yellow oil (21.6 mg, 0.06 mmol, 84%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate, 10:1);

R_f0.60 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹3099, 2980 (C−H), 1698

(CO), 1596 (CC, diene conj), 1513 (NO₂), 1562, 1475, 1423 (Ar

C−C), 1335 (NO₂), 1174 (C−O−C); ¹H NMR (300 MHz, CDCl₃) δ

8.17 (d, 1H, J = 15.5 Hz), 8.16 (d, 2H, J = 9.0 Hz), 7.50 (d, 2H, J = 9.0

Hz), 7.46 (d, 1H, J = 15.5 Hz), 7.32 (dt, 1H, J = 5.0, 0.8 Hz), 7.12 (dt,

1H, J = 3.6, 0.8 Hz), 7.00 (dd, 1H, J = 5.0, 3.6 Hz), 5.97 (s, 1H), 4.22 (q,

2H, J = 7.1 Hz), 1.31 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃)

δ 164.8 (C), 148.7 (C), 146.7 (C), 143.1 (C), 141.3 (C), 131.9 (CH),

130.5 (CH), 129.6 (CH), 128.1 (CH), 127.8 (CH), 124.4 (CH), 122.8

(CH), 121.6 (CH), 60.6 (CH₂), 14.3 (CH₃); found (FTMS + pAPCI)

[M + H]⁺362.0515, C₁₇H₁₆NO₄S₂requires 362.0515. E,E stereo-

chemistry was conﬁrmed by NOESY (δ 7.50 and 5.97):

(2E,4E)-Ethyl 3-((4-Nitrophenyl)thio)deca-2,4-dienoate (4m).

General procedure D was followed with the following modiﬁcation.

The reaction was placed in a microwave at 90 °C for 60 min to yield

product 4m as a yellow oil (6.9 mg, 0.02 mmol, 42%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 80:1 to 50:1); R_f

0.53 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹2929 (C−H), 1736 (CO),

1597 (CC, diene), 1576 (Ar C−C), 1518 (NO₂), 1340 (NO₂), 1185

(2E,4E,6E)-Ethyl 3-((4-Nitrophenyl)thio)-7-phenylhepta-2,4,6-tri-

enoate (4p). General procedure D was followed with the following

modiﬁcation. The reaction was placed in a microwave at 90 °C for

20 min to yield product 4p as a yellow solid (10.2 mg, 0.03 mmol, 93%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate, 25:1

to 10:1); R_f0.66 (5:1 hexane/ethyl acetate); mp 91−94 °C; ν_max/cm⁻¹

2981 (C−H), 1702 (CO), 1592 (CC, triene conj), 1515 (NO₂),

1575, 1552, 1476 (Ar C−C), 1338 (NO₂), 1176 (C−O−C); ¹H NMR

(300 MHz, CDCl₃) δ 8.18 (d, 2H, J = 9.0 Hz), 7.89 (d, 1H, J = 14.9

Hz), 7.50 (d, 2H, J = 9.0 Hz), 7.24−7.44 (m, 5H), 7.45 (dd, 1H, J =

14.9, 10.7 Hz), 6.98 (dd, 1H, J = 16.4, 10.7 Hz), 6.73 (d, 1H, J = 16.4

Hz), 5.92 (s, 1H), 4.20 (q, 2H, J = 7.1 Hz), 1.30 (t, 3H, J = 7.1 Hz);

¹³C NMR (75.5 MHz, CDCl₃) δ 164.8 (C), 149.3 (C), 146.8 (C),

1

(C−O−C); H NMR (300 MHz, CDCl₃) δ 8.17 (d, 2H, J = 8.9 Hz),

7.45−7.54 (m, 3H), 6.54 (dt, 1H, J = 14.3, 7.0 Hz), 5.79 (s, 1H), 4.17 (q,

2H, J = 7.1 Hz), 2.20 (dq, 2H, J = 7.2, 1.1 Hz), 1.15−1.44 (m, 9H), 0.85

(t, 3H, J = 7.1 Hz); ¹³C NMR (100.6 MHz, CDCl₃), δ 164.7 (C), 150.4

(C), 146.9 (C), 143.4 (CH), 142.8 (C), 131.4 (CH), 124.3 (CH), 124.2

(CH), 118.9 (CH), 60.4 (CH₂), 33.0 (CH₂), 31.3 (CH₂), 28.3 (CH₂),

22.4 (CH₂), 14.3 (CH₃), 13.9 (CH₃); found (FTMS + pAPCI) [M +

H]⁺350.1424, C₁₈H₂₄NO₄S requires 350.1421.

(2E,4E)-Ethyl 6,6-Dimethyl-3-((4-nitrophenyl)thio)hepta-2,4-dien-

oate (4n). General procedure D was followed with the following

modiﬁcation. The reaction was placed in a microwave at 70 °C for 60 min

to yield product 4n as a pale yellow oil (19.2 mg, 0.05 mmol, 80%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate, 10:1);

R_f0.78 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹2960, 2886 (C−H), 1705

(CO), 1628 (CC, diene conj), 1597 (CC, diene conj), 1518

(NO₂), 1567, 1476 (Ar C−C), 1337 (NO₂), 1175 (C−O−C); ¹H NMR

(300 MHz, CDCl₃) δ 8.17 (d, 2H, J = 8.9 Hz), 8.42−8.52 (m, 3H), 6.52

(d, 1H, J = 15.8 Hz), 5.78 (s, 1H), 4.17 (q, 2H, J = 7.1 Hz), 1.27 (t, 3H,

143.1 (C), 139.6 (CH), 138.4 (CH), 136.4 (C), 130.7 (CH), 128.8

(CH), 128.7 (CH), 128.0 (CH), 127.1 (CH), 127.0 (CH), 124.4

(CH), 120.9 (CH), 60.6 (CH₂), 14.3 (CH₃); found (FTMS + pAPCI)

[M + H]⁺382.1108, C₂₁H₂₀NO₄S requires 382.1108. E,E,E stereo-

chemistry was conﬁrmed by NOESY (δ 7.50 and 5.92):

1714

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

7.04 (dd, 1H, J = 15.5, 0.8 Hz), 6.89 (d, 1H, J = 15.5 Hz), 6.80−6.85

(m, 2H + 2H′), 6.50 (t, 1H′, J = 7.5 Hz), 6.36 (t, 1H, J = 7.7 Hz), 3.80

(s, 3H), 3.79 (s, 3H′), 2.40−5.51 (m, 2H + 2H′), 1.58 (sext, 2H, J = 7.4

Hz), 1.47 (sext, 2H′, J = 7.4 Hz), 1.07 (t, 3H, J = 7.4 Hz), 0.93 (t, 3H′,

J = 7.4 Hz); ¹³C NMR (100.6 MHz, CDCl₃) δ 159.8 (C, major), 159.5

(C, minor), 148.4 (C, major), 147.2 (C, minor), 145.5 (CH, major),

145.3 (CH, minor), 145.0 (C, major + minor), 133.2 (CH, major),

130.6 (CH, minor), 129.44 (C, major + minor), 129.37 (C, minor),

129.3 (C, major), 128.2 (CH, minor), 127.9 (CH, major), 125.9 (CH,

minor), 125.8 (CH, major), 124.4 (CH, minor), 124.2 (CH, major),

119.9 (CH, major + minor), 114.2 (CH, major), 114.1 (CH, minor),

55.33 (CH₃, major), 55.31 (CH₃, minor), 32.7 (CH₂, minor), 31.6

(CH₂, major), 22.5 (CH₂, major), 22.4 (CH₂, minor), 13.89 (CH₃,

major), 13.87 (CH₃, minor); found (FTMS + pAPCI) [M + H]⁺

356.1316, C₂₀H₂₂NO₃S requires 356.1315.

Ethyl (E)-3-((4-Nitrophenyl)thio)-5,5-diphenylpenta-2,4-dienoate

(4q). General procedure D was followed to yield product 4q as a

yellow oil (29.3 mg, 0.07 mmol, 100%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 20:1 to 10:1); R_f0.30

(10:1 hexane/ethyl acetate); ν_max/cm⁻¹3056, 2980 (C−H), 1703

(CO), 1596 (CC, diene conj), 1516 (NO₂), 1493, 1476, 1443

(Ar C−C), 1339 (NO₂), 1183 (C−O−C); ¹H NMR (300 MHz,

CDCl₃) δ 8.13 (d, 2H, J = 8.9 Hz), 7.27−7.41 (m, 8H), 7.20−7.23 (m,

2H), 7.19 (d, 1H, J = 1.7 Hz), 7.13−7.17 (m, 2H), 5.68 (d, 1H, J = 1.7

Hz), 4.14 (q, 2H, J = 7.1 Hz), 1.23 (t, 3H, J = 7.1 Hz); ¹³C NMR

(100.6 MHz, CDCl₃) δ 164.6 (C), 153.7 (C), 148.5 (C), 147.4 (C),

141.5 (C), 141.0 (C), 139.2 (C), 133.5 (CH), 130.4 (CH), 128.55

(CH), 128.51 (CH), 128.3 (CH), 128.2 (CH), 127.9 (CH), 124.1

(CH), 123.2 (CH), 118.4 (CH), 60.3 (CH₂), 14.3 (CH₃); found

(FTMS + pAPCI) [M + H]⁺432.1262, C₂₅H₂₂NO₄S requires 432.1264.

(E)-(4-Nitrophenyl)(4-phenylbuta-1,3-dien-2-yl)sulfane (4r). Gen-

eral procedure D was followed with the following modiﬁcation. The

reaction was placed in a microwave at 90 °C for 60 min to yield

product 4r as the major product and the formal S_N2 product (6r) as a

side product in a 5:1 ratio (14.3 mg, 0.05 mmol, 72%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 10:1); 4r and

6r inseparable by chromatography, with only the major 4r being

characterized; R_f0.71 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹3026

(C−H), 1594 (CC, diene conj), 1509 (NO₂), 1576, 1476, 1448 (Ar

C−C), 1335 (NO₂); ¹H NMR (300 MHz, CDCl₃) δ 8.10 (d, 2H, J =

9.1 Hz), 7.25−7.43 (m, 7H), 6.96 (d, 1H, J = 15.6 Hz), 6.89 (d, 1H,

J = 15.6 Hz), 6.00 (s, 1H), 5.85 (s, 1H); ¹³C NMR (75.5 MHz,

CDCl₃) δ 146.2 (C), 137.5 (C), 135.9 (C), 134.2 (CH), 128.7 (CH),

128.8 (CH), 127.9 (CH₂), 127.8 (C), 127.1 (CH), 126.9 (CH), 126.6

(CH), 124.0 (CH); found (FTMS + pAPCI) [M + H]⁺284.0737,

C₁₆H₁₄NO₂S requires 284.0740.

(E)-(4-(4-Chlorophenyl)buta-1,3-dien-2-yl)(4-nitrophenyl)sulfane

(4s). General procedure D was followed with the following modiﬁca-

tion. The reaction was placed in a microwave at 90 °C for 60 min to

yield product 4s (20.3 mg, 0.06 mmol, 91%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 10:1); note that the

product is very unstable and decomposes at room temperature in <1 h;

R_f0.59 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹3096, 2921 (C−H),

1594 (CC, diene conj), 1511 (NO₂), 1576, 1489, 1476, 1404 (Ar

C−C), 1336 (NO₂); ¹H NMR (400 MHz, CDCl₃) δ 8.10 (d, 2H, J =

9.1 Hz), 7.37 (d, 2H, J = 9.1 Hz), 7.28 (m, 4H), 6.91 (d, 1H, J = 16.0

Hz), 6.85 (d, 1H, J = 16.0 Hz), 6.01 (s, 1H), 5.86 (s, 1H); ¹³C NMR

(100 MHz, CDCl₃) δ 145.9 (C), 137.4 (C), 134.5 (C), 134.2 (C),

132.5 (CH), 129.1 (C), 132.5 (CH), 128.9 (CH), 128.2 (CH₂), 128.1

(CH), 127.2 (CH), 124.0 (CH); found (FTMS + pAPCI) [M + H]⁺

318.0344, C₁₆H₁₃NO₂SCl requires 318.0350.

((1E,3E)-1-(4-Bromophenyl)hepta-1,3-dien-3-yl)(4-nitrophenyl)-

sulfane (4u). In a sealed tube were placed InCl₃(1.0 mg, 5 mol %)

and 4-nitrothiophenol (10.9 mg, 0.07 mmol, 1.0 equiv), which were

then dissolved in CDCl₃(0.35 mL). A solution of allenol 3u (22.8 mg,

0.105 mmol, 1.5 equiv) in CDCl₃(0.15 mL) was added to the sealed

tube and washed in with CDCl₃(0.20 mL). The sealed tube was then

placed in a silicon oil bath at 90 °C and allowed to stir for 16 h (the

microwave does not heat continuously beyond 60 min, so for extended

reaction times, conventional heating was used) to yield product 4u as a

yellow oil (21.9 mg, 0.05 mmol, 77%) with a 2:1 mixture of EE/EZ

isomers: puriﬁed by column chromatography (hexane/ethyl acetate,

50:1 to 25:1); R_f0.62 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹2958,

2928, 2873 (C−H), 1576 (CC, diene conj), 1509 (NO₂), 1485,

1

1399 (Ar C−C), 1335 (NO₂); H NMR (400 MHz, CDCl₃) δ 8.07

(d, 2H′, J = 9.1 Hz, minor), 8.06 (d, 2H, J = 9.1 Hz, major), 7.42 (d,

2H, J = 8.4 Hz), 7.40 (d, 2H′, J = 8.4 Hz), 7.28 (d, 2H, J = 9.1 Hz),

7.27 (d, 2H′, J = 9.1 Hz), 7.23 (d, 2H, J = 8.4 Hz), 7.21 (d, 2H′, J = 8.4

Hz), 7.16 (dd, 1H, J = 15.5, 0.9 Hz), 6.91 (d, 1H′, J = 15.5 Hz), 6.88

(d, 1H, J = 15.5 Hz), 6.78 (d, 1H′, J = 15.5 Hz), 6.58 (t, 1H′, J = 7.5

Hz), 6.45 (t, 1H, J = 7.7 Hz), 2.41−2.51 (m, 2H + 2H′), 1.54−1.64

(m, 2H), 1.48 (sext, 2H′, J = 7.4 Hz), 1.03 (t, 3H, J = 7.3 Hz), 0.93 (t,

3H′, J = 7.4 Hz); ¹³C NMR (100.6 MHz, CDCl₃) δ 147.9 (C, major),

147.5 (CH, major), 147.4 (CH, minor), 146.7 (C, minor), 145.1 (C,

major + minor), 137.8 (CH, minor), 135.55 (C, minor), 135.51 (C,

major) 133.4 (CH, major), 131.81 (CH, major), 131.76 (CH, minor),

129.8 (CH, minor), 129.4 (CH, major), 128.5 (C, minor), 128.3 (CH,

major), 128.1 (CH, minor), 127.6 (C, major), 125.88 (CH, minor),

125.85 (CH, major), 124.1 (CH, minor), 124.0 (CH, major), 122.1

(C, major), 121.7 (C, minor), 32.8 (CH₂, minor), 31.5 (CH₂, major),

22.4 (CH₂, major), 22.3 (CH₂, minor), 13.9 (2 × CH₃); found (FTMS +

pAPCI) [M + H]⁺404.0308, C₁₉H₁₉NO₂SBr requires 404.0314.

(E)-(1,1-Diphenylhepta-1,3-dien-3-yl)(4-nitrophenyl)sulfane (4v).

General procedure D was followed with the following modiﬁcation.

The reaction was placed in a microwave at 90 °C for 60 min to yield

product 4v as a yellow oil with E:Z = 1:1 (14.9 mg, 0.04 mmol, 59%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate,

80:1 to 70:1 to 25:1); R_f0.51 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹

3056, 2958, 2928, 2870 (C−H), 1593 (CC, diene conj), 1508

((1E,3E)-1-(4-Methoxyphenyl)hepta-1,3-dien-3-yl)(4-nitrophenyl)-

sulfane (4t). In a sealed tube were placed InCl₃(1.0 mg, 5 mol %) and

4-nitrothiophenol (10.9 mg, 0.07 mmol, 1.0 equiv), which were then

dissolved in CDCl₃(0.35 mL). A solution of allenol 3t (22.8 mg,

0.105 mmol, 1.5 equiv) in CDCl₃(0.15 mL) was added to the sealed

tube and washed in with CDCl₃(0.20 mL). The sealed tube was then

placed in a silicon oil bath at 90 °C and allowed to stir for 16 h (the

microwave does not heat continuously beyond 60 min, so for extended

reaction times, conventional heating was used) to yield product 4t as a

yellow oil (21.8 mg, 0.06 mmol, 88%) with a 2:1 mixture of EE/EZ

isomers: puriﬁed by column chromatography (hexane/ethyl acetate,

20:1); note that, under standard microwave conditions (90 °C, 60 min),

the yield was 69%; R_f0.51 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹2958,

2930, 2870, 2835 (C−H), 1604 (CC, diene conj), 1576 (CC,

diene conj), 1508 (NO₂), 1476, 1462, 1420 (Ar C−C), 1333 (NO₂),

1246 (C−O−C); ¹H NMR (400 MHz, CDCl₃) δ 8.09 (d, 2H′, J = 8.9

Hz, minor), 8.06 (d, 2H, J = 9.1 Hz, major), 7.27−7.36 (m, 4H + 4H′),

1

(NO₂), 1575, 1476, 1443 (Ar C−C), 1333 (NO₂); H NMR (400

MHz, CDCl₃) δ 8.04−8.11 (m, 2H + 2H′), 7.13−7.36 (m, 10H +

10H′), 7.03−7.11 (m, 1H + 1H′), 7.02−7.05 (m, 1H + 1H′), 7.60

(app q, 1H′, J = 1.3 Hz), 6.53 (app q, 1H, J = 1.1 Hz), 6.16 (td, 1H,

J = 7.4, 1.1 Hz), 6.11 (td, 1H′, J = 7.5, 1.4 Hz), 2.24−2.18 (m, 2H),

2.20−2.14 (m, 2H′), 1.40 (sext, 2H′, J = 7.5 Hz), 1.26 (sext, 2H, J =

7.4 Hz), 0.94 (t, 3H, J = 7.4 Hz), 0.78 (t, 3H′, J = 7.5 Hz); ¹³C NMR

(100.6 MHz, CDCl₃) δ 147.6 (C), 146.8 (C), 146.3 (C), 145.3 (C),

145.2 (C), 143.7 (C), 142.4 (C), 142.3 (C), 139.78 (C), 139.77 (C),

130.0 (CH), 129.97 (CH), 128.4 (CH), 128.19 (2 × CH), 128.16

(CH), 128.08 (CH), 128.05 (CH), 127.92 (CH), 127.88 (CH),

127.78 (CH), 127.56 (CH), 127.52 (CH), 127.5 (CH), 127.30 (2 ×

C), 127.28 (CH), 127.1 (CH), 124.3 (CH), 123.77 (CH), 123.67

(CH), 122.9 (CH), 32.7 (CH₂), 32.5 (CH₂), 22.0 (CH₂), 21.97

(CH₂), 13.93 (CH₃), 13.70 (CH₃); found (FTMS + pAPCI) [M +

H]⁺402.1518, C₂₅H₂₄NO₂S requires 402.1522.

1715

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((4-(triﬂuoromethyl)-

phenyl)thio)penta-2,4-dienoate (4ba). General procedure D was

followed to yield product 4ba as a yellow solid (23.9 mg, 0.05 mmol,

74%): puriﬁed by column chromatography (eluent hexane/ethyl acetate,

5:1); R_f0.36 (5:1 hexane/ethyl acetate); mp 77−78 °C; ν_max/cm⁻¹2936

(C−H), 1699 (CO), 1599 (CC, diene conj), 1580 (CC, diene

conj), 1557, 1511, 1464 (Ar C−C), 1321 (C−F), 1160 (C−O−C); ¹H

NMR (300 MHz, CDCl₃) δ 8.23 (dd, 1H, J = 14.9, 0.4 Hz), 7.56−7.64

(m, 4H), 7.33 (d, 1H, J = 14.9 Hz), 7.06−7.12 (m, 2H), 6.84 (d, 1H, J =

8.2 Hz), 5.60 (app s, 1H), 4.16 (q, 2H, J = 7.1 Hz), 3.93 (s, 3H), 3.90 (s,

3H), 1.28 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃) δ 165.2

(C), 152.7 (C), 150.4 (C), 149.2 (C), 137.6 (CH), 135.0 (C), 133.1

(CH), 130.6 (C, q, J = 32.8 Hz), 129.0 (C), 127.6 (C, q, J = 272.1 Hz),

126.4 (CH, q, J = 3.7 Hz), 121.8 (CH), 121.7 (CH), 116.5 (CH), 111.1

(CH), 109.7 (CH), 60.2 (CH₂), 55.96 (CH₃), 55.93 (CH₃), 14.3

(CH₃); found (FTMS + pNSI) [M + H]⁺439.1177, C₂₂H₂₂O₄SF₃

requires 439.1185. E,E stereochemistry was conﬁrmed by NOESY (δ

7.56−7.64 and 5.60):

7.56 (m, 2H), 7.40−7.46 (m, 3H), 7.34 (d, 1H, J = 16.0 Hz), 7.10−

7.16 (m, 2H), 6.85 (d, 1H, J = 1.7 Hz), 5.31 (app s, 1H), 4.11 (q, 2H,

J = 7.1 Hz), 3.93 (s, 3H), 3.91 (s, 3H), 1.23 (t, 3H, J = 7.1 Hz); ¹³C

NMR (75.5 MHz, CDCl₃), δ 165.5 (C), 155.7 (C), 150.1 (C), 149.1

(C), 136.1 (CH), 135.1 (CH), 129.8 (CH), 129.7 (C), 129.4 (CH),

129.3 (C), 122.1 (CH), 121.6 (CH), 112.8 (CH), 111.1 (CH), 109.7

(CH), 59.9 (CH₂), 55.95 (CH₃), 55.94 (CH₃), 14.3 (CH₃); found

(FTMS + pNSI) [M + H]⁺371.1310, C₂₁H₂₃O₄S requires 371.1312.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-(p-tolylthio)penta-2,4-

dienoate (4bf). General procedure D was followed to yield product

4bf as a yellow solid (20.1 mg, 0.05 mmol, 72%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 5:1); R_f0.31 (5:1

hexane/ethyl acetate); mp 109−112 °C; ν_max/cm⁻¹2934 (C−H),

1697 (CO), 1615 (CC, diene conj), 1597 (CC, diene conj),

1

1581, 1556, 1511 (Ar C−C), 1176 (C−O−C); H NMR (300 MHz,

CDCl₃), δ 8.23 (dd, 1H, J = 16.1, 0.7 Hz), 7.41 (m, 3H), 7.23 (m,

2H), 7.12 (m, 2H), 6.85 (d, 1H, J = 8.3 Hz), 5.25 (app s, 1H), 4.13 (q,

2H, J = 7.1 Hz), 3.93 (s, 3H), 3.91 (s, 3H), 2.40 (s, 3H), 1.24 (t, 3H,

J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃), δ 165.5 (C), 156.5 (C),

150.1 (C), 149.1 (C), 139.9 (C), 135.8 (CH), 135.4 (CH), 130.6

(CH), 129.3 (C), 126.3 (C), 122.2 (CH), 121.5 (CH), 111.9 (CH),

111.1 (CH), 109.7 (CH), 59.8 (CH₂), 55.95 (CH₃), 55.94 (CH₃),

21.4 (CH₃), 14.4 (CH₃); found (FTMS + pNSI) [M + H]⁺385.1470,

C₂₂H₂₄O₄S requires 385.1468.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-(m-tolylthio)penta-2,4-

dienoate (4bg). General procedure D was followed to yield product

4bg as a yellow solid (14.7 mg, 0.04 mmol, 54%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 5:1); R_f0.28 (5:1

hexane/ethyl acetate); mp 69−70 °C; ν_max/cm⁻¹2932 (C−H), 1697

(CO), 1615 (CC, diene conj), 1580, 1555, 1511 (Ar C−C), 1159

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((4-ﬂuorophenyl)thio)-

penta-2,4-dienoate (4bb). General procedure D was followed to

yield product 4bb as a yellow solid (17.6 mg, 0.05 mmol, 65%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate,

5:1); R_f0.29 (5:1 hexane/ethyl acetate); mp 113−115 °C; ν_max/cm⁻¹

2935 (C−H), 1697 (CO), 1598 (CC, diene conj), 1555, 1511

(Ar C−C), 1489 (C−F), 1177 (C−O−C); ¹H NMR (300 MHz,

CDCl₃) δ 8.22 (dd, 1H, J = 16.1, 0.8 Hz), 7.50−7.55 (m, 2H), 7.34 (d,

1H, J = 16.1 Hz), 7.08−7.17 (m, 4H), 6.86 (d, 1H, J = 8.3 Hz), 5.21 (app s,

1H), 4.12 (q, 2H, J = 7.1 Hz), 3.94 (s, 3H), 3.91 (s, 3H), 1.24 (t, 3H, J =

7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃), δ 165.3 (C), 162.0 (C, d, J 251

Hz), 155.9 (C), 150.2 (C), 149.2 (C), 137.6 (CH, d, J = 8.5 Hz), 136.1

(CH), 129.2 (C), 125.3 (C, d, J = 3.5 Hz), 121.9 (CH), 121.3 (CH), 117.3

(CH, d, J = 22.0 Hz), 112.3 (CH), 111.1 (CH), 109.7 (CH), 59.9 (CH₂),

55.95 (CH₃), 55.94 (CH₃), 14.3 (CH₃); found (FTMS + pAPCI)

[M + H]⁺389.1209, C₂₁H₂₂FO₄S requires 389.1217.

1

(C−O−C); H NMR (300 MHz, CDCl₃), δ 8.23 (dd, 1H, J = 16.1,

0.8 Hz), 7.29−7.39 (m, 4H), 7.19−7.25 (m, 1H), 7.07−7.16 (m, 2H),

6.85 (d, 1H, J = 8.2 Hz), 5.31 (app s, 1H), 4.12 (q, 2H, J = 7.1 Hz),

3.94 (s, 3H), 3.91 (s, 3H), 2.38 (s, 3H), 1.24 (t, 3H, J = 7.1 Hz); ¹³C

NMR (75.5 MHz, CDCl₃), δ 165.5 (C), 156.0 (C), 150.1 (C), 149.2

(C), 139.7 (C), 136.0 (CH), 135.7 (CH), 132.2 (CH), 130.3 (CH),

129.8 (C), 129.6 (CH), 129.3 (C), 122.2 (CH), 121.6 (CH), 112.6

(CH), 111.1 (CH), 109.7 (CH), 59.9 (CH₂), 55.9 (2 × CH₃), 21.3

(CH₃), 14.4 (CH₃); found (FTMS + pNSI) [M + H]⁺385.1470,

C₂₂H₂₄O₄S requires 385.1468.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-(o-tolylthio)penta-2,4-

dienoate (4bh). General procedure D was followed to yield product

4bh as a yellow solid (20.4 mg, 0.05 mmol, 75%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 5:1); R_f0.36 (5:1

hexane/ethyl acetate); mp 78−82 °C; ν_max/cm⁻¹2934 (C−H), 1697

(CO), 1615 (CC, diene conj), 1597 (CC, diene conj), 1581, 1556,

1511 (Ar C−C), 1160 (C−O−C); ¹H NMR (300 MHz, CDCl₃), δ 8.26

(dd, 1H, J = 16.1, 0.8 Hz), 7.53 (d, 1H, J = 7.2 Hz), 7.34−7.41 (m, 3H),

7.25−7.29 (m, 1H), 7.10−7.17 (m, 2H), 6.86 (d, 1H, J = 8.3 Hz), 5.05

(app s, 1H), 4.11 (q, 2H, J = 7.1 Hz), 3.94 (s, 3H), 3.91 (s, 3H), 2.44 (s,

3H), 1.23 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃), δ 165.5 (C),

155.0 (C), 150.1 (C), 149.2 (C), 143.0 (C), 136.8 (CH), 135.8 (CH),

131.2 (CH), 130.3 (CH), 129.3 (C), 128.9 (C), 127.3 (CH), 122.2 (CH),

121.5 (CH), 111.1 (CH), 110.9 (CH), 109.7 (CH), 59.8 (CH₂), 56.0

(CH₃), 20.5 (CH₃), 14.4 (CH₃); found (FTMS + pNSI) [M + H]⁺

385.1470, C₂₂H₂₄O₄S requires 385.1468.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((4-hydroxyphenyl)-

thio)penta-2,4-dienoate (4bc). General procedure D was followed

with the following modiﬁcation. The reaction was placed in a micro-

wave at 90 °C for 60 min to yield product 4bc as a yellow oil (4.4 mg,

0.01 mmol, 29%): puriﬁed by column chromatography (eluent

hexane/ethyl acetate, 5:1 to 3:1); note that the product is unstable

and begins to decompose on the column; R_f0.14 (3:1 hexane/ethyl

acetate); ν_max/cm⁻¹3412 (O−H), 2935 (C−H), 1665 (CO), 1581

1

(CC, diene conj), 1556, 1512 (Ar C−C), 1167 (C−O−C); H

NMR (300 MHz, CDCl₃), δ 8.21 (d, 1H, J = 16.1 Hz), 7.39−7.41 (m,

3H), 7.06−7.16 (m, 2H), 6.91 (d, 2H, J = 8.6 Hz), 6.85 (d, 1H, J = 8.2

Hz), 5.17 (s, 1H), 4.12 (q, 2H, J = 7.1 Hz), 3.93 (s, 3H), 3.91 (s, 3H),

1.24 (t, 3H, J = 7.1 Hz); ¹³C NMR (100.6 MHz, CDCl₃) δ 165.7 (C),

157.4 (C), 157.3 (C), 156.1 (C), 150.1 (C), 149.2 (C), 137.7 (CH),

135.6 (CH), 132.9 (CH), 129.3 (C), 121.6 (CH), 117.0 (CH), 116.1

(CH), 111.2 (CH), 109.7 (CH), 59.9 (CH₂), 55.97 (CH₃), 55.94

(CH₃), 14.4 (CH₃); found (FTMS + pNSI) [M + H]⁺387.1261,

C₂₁H₂₃O₅S requires 387.1261.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((4-methoxyphenyl)-

thio)penta-2,4-dienoate (4bi). General procedure D was followed

to yield product 4bi as a yellow solid (14.5 mg, 0.04 mmol, 52%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate,

5:1); R_f0.20 (5:1 hexane/ethyl acetate); mp 127−130 °C; ν_max/cm⁻¹

2935 (C−H), 1695 (CO), 1615 (CC, diene conj), 1590, 1556,

1

1511 (Ar C−C), 1174 (C−O−C); H NMR (300 MHz, CDCl₃), δ

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-(phenylthio)penta-2,4-

dienoate (4be). General procedure D was followed to yield product

4be as a yellow solid (19 mg, 0.05 mmol, 73%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 5:1); R_f0.25 (5:1

hexane/ethyl acetate); mp 102−103 °C; ν_max/cm⁻¹3058 (C−H_Ar)

2934 (C−H alkyl), 1695 (CO), 1615 (CC, diene conj), 1597

(CC, diene conj), 1580, 1556, 1511 (Ar C−C), 1175 (C−O−C);

¹H NMR (300 MHz, CDCl₃), δ 8.25 (dd, 1H, J = 16.0, 0.9 Hz), 7.49−

8.22 (dd, 1H, J = 16.2, 0.9 Hz), 7.46 (d, 2H, J = 8.9 Hz), 7.36 (d, 1H,

J = 16.2 Hz), 7.15−7.10 (m, 2H), 6.97 (d, 2H, J = 8.9 Hz), 6.85 (d,

1H, J = 9.1 Hz), 5.17 (app s, 1H), 4.11 (q, 2H, J = 7.1 Hz), 3.94 (s,

3H), 3.91 (s, 3H), 3.86 (s, 3H), 1.24 (t, 3H, J = 7.1 Hz); ¹³C NMR

(75.5 MHz, CDCl₃), δ 165.6 (C), 161.0 (C), 157.3 (C), 150.2 (C),

149.1 (C), 137.4 (CH), 135.5 (CH), 129.3 (C), 122.1 (CH), 121.4

(CH), 120.0 (C), 115.5 (CH), 111.3 (CH), 111.1 (CH), 109.8 (CH),

1716

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

59.9 (CH₂), 56.1 (2 × CH₃), 55.3 (CH₃), 14.3 (CH₃); found

(FTMS + pNSI) [M + H]⁺401.1417, C₂₂H₂₅O₅S requires 401.1417.

(2E,4E)-Ethyl 3-(Benzylthio)-5-((3,4-dimethoxy)phenyl)penta-2,4-

dienoate (4bj). General procedure D was followed to yield product

4bj as a yellow solid (13.1 mg, 0.03 mmol, 49%): puriﬁed by column

chromatography (eluent hexane/ethyl acetate, 5:1); R_f0.29 (5:1

hexane/ethyl acetate); mp 99−102 °C; ν_max/cm⁻¹2934 (C−H), 1697

(CO), 1616 (CC, diene conj), 1597 (CC, diene conj), 1581,

1553, 1511 (Ar C−C), 1177 (C−O−C); ¹H NMR (300 MHz,

CDCl₃), δ 8.19 (dd, 1H, J = 16.2, 0.9 Hz), 7.28−7.41 (m, 5H), 7.21

(d, 1H, J = 16.2 Hz), 7.05−7.10 (m, 2H), 6.83 (d, 1H, J = 8.3 Hz),

5.69 (app s, 1H), 4.19 (q, 2H, J = 7.1 Hz), 4.09 (s, 2H), 3.92 (s, 3H),

3.90 (s, 3H), 1.31 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃),

δ 165.2 (C), 155.1 (C), 150.1 (C), 149.1 (C), 135.9 (C), 135.2 (CH),

129.3 (C), 129.1 (CH), 128.8 (CH), 127.7 (CH), 122.3 (CH), 121.5

(CH), 111.1 (CH), 110.4 (CH), 109.7 (CH), 59.9 (CH₂), 55.94

(CH₃), 55.91 (CH₃), 36.8 (CH₂), 14.4 (CH₃); found (FTMS + pNSI)

[M + H]⁺385.1469, C₂₂H₂₅O₄S requires 385.1468.

(CH), 111.4 (CH), 111.1 (CH), 109.7 (CH), 59.9 (CH₂), 55.94

(CH₃), 55.91 (CH₃), 44.0 (CH), 32.7 (CH₂), 26.0 (CH₂) 25.9 (CH₂),

14.5 (CH₃); found (FTMS + pAPCI) [M + H]⁺377.1774, C₂₁H₂₉O₄S

requires 377.1781.

Ethyl 5-(Benzoylthio)-5-(2,4-dimethoxyphenyl)penta-2,3-dien-

oate (6bn). General procedure D was followed to yield product 6bn

as a yellow oil and as a mixture of diastereomers in a 1:2 ratio (18 mg,

0.05 mmol, 66%): puriﬁed by column chromatography (eluent

hexane/ethyl acetate, 5:1); R_f0.19 (5:1 hexane/ethyl acetate);

ν_max/cm⁻¹3061 (C−H), 2979 (C−H), 1963 (CC, allene), 1712

(CO), 1661 (CO), 1591, 1580, 1513, (Ar C−C), 1215 (C−O−

C); ¹H NMR (CDCl₃, 300 MHz) δ 7.84−7.90 (m, 2H + 2H′), 7.45−

7.53 (m, 1H + 1H′), 7.33−7.41 (m, 2H + 2H′), 6.86−6.90 (m, 2H +

2H′), 6.72−6.79 (m, 1H + 1H′), 5.99−6.07 (m, 1H + 1H′), 5.68 (dd,

1H′, J = 5.1, 3.0 Hz, minor), 5.62 (dd, 1H, J = 6.0, 3.1 Hz, major),

5.43−5.49 (m, 1H + 1H′), 4.03−4.13 (m, 2H + 2H′), 3.84 (s, 3H′,

minor), 3.81 (s, 3H, major), 3.78 (s, 3H + 3H′), 1.14−1.23 (m, 3H +

3H′); ¹³C NMR (CDCl₃, 75.5 MHz) δ 213.0 (C, major), 212.6 (C,

minor), 190.3 (C, major), 190.1 (C, minor), 165.3 (C, minor), 165.2

(C, major), 149.1 (C, minor), 148.9 (C, major), 148.8 (C, major +

minor), 136.5 (C, major + minor), 133.7 (CH, major + minor), 131.1

(C, minor), 130.7 (C, major), 128.7 (CH, major + minor), 127.3 (CH,

major + minor), 120.5 (CH, minor), 120.4 (CH, major), 111.5 (CH,

minor), 111.3 (CH, major), 111.1 (CH, minor), 110.9 (CH, major),

98.1 (CH, major + minor), 91.7 (CH, minor), 91.4 (CH, major), 61.0

(CH₂, major + minor), 56.0 (CH₃, minor), 55.9 (CH₃, minor), 55.89

(CH₃, major), 55.87 (CH₃, major), 45.8 (CH, major), 45.2 (CH,

minor), 14.2 (CH₃, major + minor); found (FTMS + pNSI) [M + H]⁺

399.1255, C₂₂H₂₃O₅S requires 399.1261.

Ethyl 5-(Acetylthio)-5-(3,4-dimethoxyphenyl)penta-2,3-dienoate

(6bo). General procedure D was followed to yield product 6bo as a

yellow oil and as a mixture of diastereomers in a 1:0.6 ratio (10.5 mg,

0.03 mmol, 52%): puriﬁed by column chromatography (eluent

hexane/ethyl acetate, 5:1); R_f0.23 (5:1 hexane/ethyl acetate);

ν_max/cm⁻¹3061 (C−H), 2980 (C−H), 1963 (CC, allene), 1692

(CO), 1661 (CO), 1590, 1513, (Ar C−C), 1215 (C−O−C); ¹H

NMR (300 MHz, CDCl₃) δ 6.87−7.00 (m, 2H + 2H′), 6.75−6.83 (m,

1H + 1H′), 5.98 (m, 1H + 1H′), 5.75 (dd, 1H′, J = 6.1, 3.1 Hz,

minor), 5.66 (dd, 1H, J = 6.1, 3.1 Hz, major), 5.27−5.34 (m, 1H +

1H′), 4.13−4.24 (m, 2H + 2H′), 3.89 (s, 3H′, minor), 3.86 (s, 6H +

3H′), 2.33 (s, 3H, major), 2.32 (s, 3H′, minor), 1.23−1.33 (m, 3H +

3H′); ¹³C NMR (75.5 MHz, CDCl₃) δ 212.9 (C, major), 212.4 (C,

minor), 194.1 (C, major), 193.8 (C, minor), 165.3 (C, minor), 165.2 (C,

major), 149.0 (C, minor), 148.9 (C, major), 148.77 (C, minor), 148.76

(C, major), 131.2 (C, minor), 130.7 (C, major), 120.3 (CH, minor),

120.2 (CH, major), 111.3 (CH, minor), 111.2 (CH, major), 111.0 (CH,

minor), 110.9 (CH, major), 98.02 (CH, major), 97.86 (CH, minor), 91.6

(CH, minor), 91.3 (CH, major), 61.0 (CH₂, major + minor), 56.0 (CH₃,

minor), 55.9 (CH₃, minor), 55.88 (CH₃, major), 55.85 (CH₃, major),

45.7 (CH, major), 45.1 (CH, minor), 30.33 (CH₃, major), 30.28 (CH₃,

minor), 14.2 (CH₃, major + minor); found (FTMS + pNSI) [M + NH₄]⁺

354.1369, C₁₇H₂₄NO₅S requires 354.1370.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((furan-2-ylmethyl)-

thio)penta-2,4-dienoate (4bk). General procedure D was followed

to yield product 4bk as a yellow oil (13.5 mg, 0.04 mmol, 52%):

puriﬁed by column chromatography (eluent hexane/ethyl acetate,

5:1); R_f0.27 (5:1 hexane/ethyl acetate); ν_max/cm⁻¹2935 (C−H),

1697 (CO), 1581 (CC, diene conj), 1555, 1511 (Ar C−C), 1177

1

(C−O−C); H NMR (300 MHz, CDCl₃), δ 8.18 (1H, dd, J = 16.2,

0.7 Hz, CHCHCS), 7.38 (dd, 1H, J = 1.8, 0.8 Hz), 7.21 (d, 1H, J =

16.2 Hz), 7.04−7.12 (m, 2H), 6.84 (d, 1H, J = 8.3 Hz), 6.27−6.35 (m,

2H), 5.73 (app s, 1H), 4.20 (q, 2H, J = 7.1 Hz), 4.11 (s, 2H), 3.92 (s,

3H), 3.90 (s, 3H), 1.31 (t, 3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz,

CDCl₃), δ 165.2 (C), 154.0 (C), 150.1 (C), 149.1 (C), 149.0 (C),

142.6 (CH), 136.3 (CH), 129.2 (C), 122.3 (CH), 121.5 (CH), 111.3

(CH), 111.1 (CH), 110.7 (CH), 109.7 (CH), 108.6 (CH), 60.1

(CH₂), 55.94 (CH₃), 55.91 (CH₃), 29.2 (CH₂), 14.4 (CH₃); found

(FTMS + pAPCI) [M + H]⁺375.1285, C₂₀H₂₃O₅S requires 375.1261.

(2E,4E)-Ethyl 5-(3,4-Dimethoxyphenyl)-3-((3-ethoxy-3-

oxopropyl)thio)penta-2,4-dienoate (4bl). General procedure D was

followed to yield product 4al as a yellow oil (11.2 mg, 0.03 mmol,

40%): puriﬁed by column chromatography (eluent ether); R_f0.18 (1:1

hexane/ethyl acetate); ν_max/cm⁻¹2934 br (O−H), 1700 (CO),

1616 (CC, diene conj), 1581 (CC, diene conj), 1553, 1511 (Ar

1

C−C), 1178 (C−O−C); H NMR (300 MHz, CDCl₃), δ 8.19 (dd,

1H, J = 16.2, 0.7 Hz), 7.20 (d, 1H, J = 16.2 Hz), 7.04−7.13 (m, 2H),

6.84 (d, 1H, J = 8.3 Hz), 5.65 (app s, 1H), 4.20 (q, 2H, J = 7.1 Hz), 3.92 (s,

3H), 3.90 (s, 3H), 3.14 (t, 2H, J = 7.1 Hz), 2.79 (t, 2H, J = 7.1 Hz), 1.32 (t,

3H, J = 7.1 Hz); ¹³C NMR (75.5 MHz, CDCl₃), δ 176.1 (C), 165.2 (C),

153.6 (C), 150.2 (C), 149.1 (C), 136.4 (CH), 129.2 (C), 122.3 (CH),

121.6 (CH), 111.1 (CH), 110.8 (CH), 109.7 (CH), 60.0 (CH₂), 55.95

(CH₃), 55.92 (CH₃), 32.7 (CH₂), 26.2 (CH₂), 14.4 (CH₃); found

(FTMS + pNSI) [M + H]⁺365.1057, C₁₈H₂₁O₆S requires 365.1064.

E,E stereochemistry was conﬁrmed by NOESY (δ 5.65 and 3.14):

ASSOCIATED CONTENT

* Supporting Information

■

S

General experimental information, NMR spectra, optimization

studies, and X-ray data for compound 4a (CIF). This material

is available free of charge via the Internet at http://pubs.acs.org.

(2E,4E)-Ethyl 3-(Cyclohexylthio)-5-(3,4-dimethoxyphenyl)penta-

2,4-dienoate (4bm). General procedure D was followed to yield

product 4bm as a yellow oil (12 mg, 0.03 mmol, 45%): puriﬁed by

column chromatography (eluent hexane/ethyl acetate, 7:1); R_f0.4 (5:1

hexane/ethyl acetate); ν_max/cm⁻¹2929 (C−H), 1797 (CO), 1616

(CC, diene conj), 1597 (CC, diene conj), 1580, 1550, 1511 (Ar

AUTHOR INFORMATION

Corresponding Author

*E-mail: A.Lee@hw.ac.uk. Phone: +44 (0)131-4518030.

■

1

C−C), 1178 (C−O−C); H NMR (300 MHz, CDCl₃), δ 8.19 (dd,

Notes

1H, J = 16.1, 0.8 Hz), 7.25 (d, 1H, J = 16.1 Hz), 7.05−7.13 (m, 2H),

6.84 (d, 1H, J = 8.3 Hz), 5.71 (app s, 1H), 4.19 (q, 2H, J = 7.1 Hz),

3.92 (s, 3H), 3.90 (s, 3H), 3.14−3.25 (m, 1H), 2.02−2.14 (m, 2H),

1.76−1.86 (m, 2H), 1.60−1.70 (m, 1H), 1.37−1.54 (m, 5H), 1.26−

1.36 (m, 3H); ¹³C NMR (75.5 MHz, CDCl₃), δ 165.5 (C), 154.0 (C),

150.0 (C), 149.1 (C), 136.1 (CH), 129.5 (C), 123.1 (CH), 121.4

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

We thank the Engineering and Physical Sciences Research Council

(EPSRC) (Grants EP/K00736X/1 for G.B. and DTA for P.C.Y.)

■

1717

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

The Journal of Organic Chemistry

Article

(9) Bandini, M.; Tragni, M. Org. Biomol. Chem. 2009, 7, 1501.

and Heriot-Watt University (James Watt Scholarship, S.W.) for

funding. We thank Dr. Dave Ellis for NMR experiments. Mass

spectrometry data were acquired at the EPSRC UK National Mass

Spectrometry Facility at Swansea University.

(10) Gold-catalyzed intermolecular hydrothiolation and hydroxythio-

lation of allenes, however, are known. For example, see: (a) Chan, A.

O. Y.; Tsai, J. L. L.; Lo, V. K. Y.; Li, G. L.; Wong, M. K.; Che, C. M.

Chem. Commun. 2013, 49, 1428. (b) Menggenbateer; Narsireddy, M.;

Ferrara, G.; Nishina, N.; Jin, T.; Yamamoto, Y. Tetrahedron Lett. 2010,

51, 4627.

(11) For selected reviews on general allene chemistry, see: (a) Modern

Allene Chemistry; Wiley-VCH: Weinheim, Germany, 2004. (b) Ma, S.

Chem. Rev. 2005, 105, 2829.

REFERENCES

■

(1) For selected reviews on gold catalysis, see: (a) Bandini, M. Chem.

Soc. Rev. 2011, 40, 1358. (b) Bongers, N.; Krause, N. Angew. Chem.,

Int. Ed. 2008, 47, 2178. (c) Boorman, T. C.; Larrosa, I. Chem. Soc. Rev.

(12) (a) Hashmi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M.

2011, 40, 1910. (d) Furstner, A.; Davies, P. W. Angew. Chem., Int. Ed.

̈

Angew. Chem., Int. Ed. 2000, 39, 2285. (b) Hoffmann-Roder, A.;

̈

2007, 46, 3410. (e) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev.

2008, 108, 3351. (f) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395.

(g) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180. (h) Hashmi, A. S. K.;

Krause, N. Org. Lett. 2001, 3, 2537. (c) Mundal, D. A.; Lutz, K. E.;

Thomson, R. J. J. Am. Chem. Soc. 2012, 134, 5782. (d) Sun, T.;

Deutsch, C.; Krause, N. Org. Biomol. Chem. 2012, 10, 5965.

(13) Sabbasani, V. R.; Mamidipalli, P.; Lu, H.; Xia, Y.; Lee, D. Org.

Lett. 2013, 15, 1552.

Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896. (i) Jimen

́

ez-

Nunez, E.; Echavarren, A. M. Chem. Commun. 2007, 333. (j) Jimen

́

̃

Nunez, E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326. (k) Li, Z.

́

̃

(14) (a) Mudd, R. J.; Young, P. C.; Jordan-Hore, J. A.; Rosair, G. M.;

Lee, A.-L. J. Org. Chem. 2012, 77, 7633. (b) Young, P. C.; Green, S. L.

J.; Rosair, G. M.; Lee, A.-L. Dalton Trans. 2013, 42, 9645.

(15) For other examples using thiols as nucleophiles with gold

catalysis, see refs 7 and 10. Also see: (a) Ando, K. J. Org. Chem. 2010,

75, 8516. (b) Arcadi, A.; Bianchi, G.; Di Giuseppe, S.; Marinelli, F.

Green Chem. 2003, 5, 64. (c) Biswas, S.; Samec, J. S. M. Chem.

Commun. 2012, 48, 6586. (d) Biswas, S.; Watile, R. A.; Samec, J. S.

Chemistry 2014, 20, 2159. (e) Brouwer, C.; Rahatrian, R.; He, C.

Synlett 2007, 1785. (f) Corma, A.; Gonzalez-Arellano, C.; Iglesias, M.;

Sanchez, F. Appl. Catal., A 2010, 375, 49. (g) Morita, N.; Krause, N.

Angew. Chem., Int. Ed. 2006, 45, 1897.

(16) For examples of other low-valent sulfur compounds (thioethers)

employed as nucleophiles in gold catalysis, see: (a) Davies, P. W.;

Albrecht, S. J. C. Chem. Commun. 2008, 238. (b) Davies, P. W.;

Albrecht, S. J. C. Synlett 2012, 23, 70. (c) Nakamura, I.; Sato, T.;

Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 4473. (d) Peng, L.;

Zhang, X.; Zhang, S.; Wang, J. J. Org. Chem. 2007, 72, 1192.

(17) (a) Babu, G.; Perumal, P. T. Aldrichimica Acta 2000, 33, 16.

(b) Yadav, J. S.; Antony, A.; George, J.; Subba Reddy, B. V. Eur. J. Org.

Chem. 2010, 2010, 591. (c) Loh, T.-P.; Chua, G.-L. Chem. Commun.

2006, 2739. (d) Podlech, J.; Maier, T. C. Synthesis 2003, 2003, 0633.

(e) Singh, M. S.; Raghuvanshi, K. Tetrahedron 2012, 68, 8683.

(18) Kobayashi, S. Eur. J. Org. Chem. 1999, 15.

G.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239. (l) Marion, N.;

Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776. (m) Muzart, J.

Tetrahedron 2008, 64, 5815. (n) Rudolph, M.; Hashmi, A. S. K. Chem.

Soc. Rev. 2012, 41, 2448. (o) Sengupta, S.; Shi, X. ChemCatChem 2010,

2, 609. (p) Shapiro, N. D.; Toste, F. D. Synlett 2010, 675. (q) Shen, H.

C. Tetrahedron 2008, 64, 3885. (r) Shen, H. C. Tetrahedron 2008, 64,

7847.

́

(2) (a) Corma, A.; Leyva-Perez, A.; Sabater, M. J. Chem. Rev. 2011,

111, 1657. (b) Hashmi, A. S. K.; Buehrle, M. Aldrichimica Acta 2010,

43, 27.

(3) For reviews, see: (a) Biannic, B.; Aponick, A. Eur. J. Org. Chem.

2011, 6605. (b) Bandini, M. Angew. Chem., Int. Ed. 2011, 50, 994.

(4) For selected examples, see: (a) Aponick, A.; Biannic, B. Org. Lett.

2011, 13, 1330. (b) Aponick, A.; Biannic, B.; Jong, M. R. Chem.

Commun. 2010, 46, 6849. (c) Aponick, A.; Li, C. Y.; Biannic, B. Org.

Lett. 2008, 10, 669. (d) Bandini, M.; Monari, M.; Romaniello, A.;

Tragni, M. Chem.Eur. J. 2010, 16, 14272. (e) Biannic, B.;

Ghebreghiorgis, T.; Aponick, A. Beilstein J. Org. Chem. 2011, 7, 802.

(f) Cera, G.; Chiarucci, M.; Mazzanti, A.; Mancinelli, M.; Bandini, M.

Org. Lett. 2012, 14, 1350. (g) Chiarucci, M.; Locritani, M.; Cera, G.;

Bandini, M. Beilstein J. Org. Chem. 2011, 7, 1198. (h) Ghebreghiorgis,

T.; Biannic, B.; Kirk, B. H.; Ess, D. H.; Aponick, A. J. Am. Chem. Soc.

2012, 134, 16307. (i) Kothandaraman, P.; Foo, S. J.; Chan, P. W. H. J.

Org. Chem. 2009, 74, 5947. (j) Mukherjee, P.; Widenhoefer, R. A. Org.

Lett. 2010, 12, 1184. (k) Mukherjee, P.; Widenhoefer, R. A. Org. Lett.

2011, 13, 1334. (l) Mukherjee, P.; Widenhoefer, R. A. Angew. Chem.,

Int. Ed. 2012, 51, 1405. (m) Unsworth, W. P.; Stevens, K.; Lamont, S.

G.; Robertson, J. Chem. Commun. 2011, 47, 7659. (n) Mukherjee, P.;

Widenhoefer, R. A. Chem.Eur. J. 2013, 19, 3437.

(19) Ma, J.; Peng, L. L.; Zhang, X.; Zhang, Z.; Campbell, M.; Wang, J.

B. Chem.Asian J. 2010, 5, 2214.

(20) The allenic acetate version of 3a gives a poorer 43% yield of 4a

under InCl₃catalysis, so there is no beneﬁt in turning the alcohol into

a better leaving group (OAc).

(21) The reaction also works with R = electron-rich aryls, but the

diene products were too unstable to isolate.

(5) For selected examples, see: (a) Kanbayashi, N.; Onitsuka, K. J.

Am. Chem. Soc. 2010, 132, 1206. (b) Lam, F. L.; Au-Yeung, T. T.-L.;

Kwong, F. Y.; Zhou, Z.; Wong, K. Y.; Chan, A. S. C. Angew. Chem., Int.

Ed. 2008, 47, 1280. (c) Liu, Z.; Du, H. Org. Lett. 2010, 12, 3054.

(d) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258. (e) Lyothier, I.;

Defieber, C.; Carreira, E. M. Angew. Chem., Int. Ed. 2006, 45, 6204.

(f) Onitsuka, K.; Okuda, H.; Sasai, H. Angew. Chem., Int. Ed. 2008, 47,

1454. (g) Roggen, M.; Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50,

5568. (h) Roggen, M.; Carreira, E. M. Angew. Chem., Int. Ed. 2012, 51,

8652. (i) Ueno, S.; Hartwig, J. F. Angew. Chem., Int. Ed. 2008, 47, 1928.

(6) (a) Young, P. C.; Schopf, N. A.; Lee, A.-L. Chem. Commun. 2013,

49, 4262. (b) Wright, J. R.; Young, P. C.; Lucas, N. T.; Lee, A.-L.;

Crowley, J. D. Organometallics 2013, 32, 7065. (c) Coutant, E.; Young,

P. C.; Barker, G.; Lee, A.-L. Beilstein J. Org. Chem. 2013, 9, 1797.

(7) Herkert, L.; Green, S. L. J.; Barker, G.; Johnson, D. G.; Young, P.

C.; Macgregor, S. A.; Lee, A.-L. Chem.Eur. J. 2014, 20, 11540.

(22) For In(III) vs Au(I) studies in hydroarylations, see: (a) Kumar,

A.; Li, Z. H.; Sharma, S. K.; Parmar, V. S.; Van der Eycken, E. V. Chem.

Commun. 2013, 49, 6803. See also: (b) Alcaide, B.; Almendros, P.;

Martínez del Campo, T. Chem.Eur. J. 2008, 14, 7756.

(23) Microwave with sealed tube and external surface sensor.

(24) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127.

(25) (a) Zhuo, L. G.; Zhang, J. J.; Yu, Z. X. J. Org. Chem. 2012, 77,

8527. (b) Zhuo, L. G.; Zhang, J. J.; Yu, Z. X. J. Org. Chem. 2014, 79,

3809.

(26) Lin, M.; Hao, L.; Liu, X.-T.; Chen, Q.-Z.; Wu, F.; Yan, P.; Xu, S.-

X.; Chen, X.-L.; Wen, J.-J.; Zhan, Z.-P. Synlett 2011, 665.

+

(27) Recent computational studies indicate InCl₂as the active

catalyst (see ref 25), although previous reports have also suggested

InCl₃; see: Huang, G. P.; Cheng, B.; Xu, L.; Li, Y. H.; Xia, Y. Z.

Chem.Eur. J. 2012, 18, 5401.

(8) (a) Backvall, J.-E.; Ericsson, A. J. Org. Chem. 1994, 59, 5850.

̈

(28) Alternatively, 6 could be formed via an allylic cation

intermediate.

(b) Heintzelman, G. R.; Meigh, I. R.; Mahajan, Y. R.; Weinreb, S. M.

Diels-Alder Reactions of Imino Dienophiles. Organic Reactions; John

Wiley & Sons, Inc.: Hoboken, NJ, 2005. (c) Proteau, P. J.; Hopkins, P.

B. J. Org. Chem. 1985, 50, 141. (d) Chou, S. S. P.; Chen, K. W. Synth.

Commun. 2004, 34, 4573. (e) Baeckvall, J. E.; Juntunen, S. K. J. Am.

Chem. Soc. 1987, 109, 6396.

(29) De, S.; Day, C.; Walker, M. E. Tetrahedron 2007, 63, 10939.

(30) Kuang, J.; Xie, X.; Ma, S. Synthesis 2013, 45, 592.

(31) Kuang, J.; Luo, H.; Ma, S. Adv. Synth. Catal. 2012, 354, 933.

1718

DOI: 10.1021/jo502648w

J. Org. Chem. 2015, 80, 1703−1718

Article Doi

Dehydrative thiolation of allenols: Indium vs gold catalysis

DOI: 10.1021/jo502648w

Source and publish data:

Authors:

Article abstract of DOI:10.1021/jo502648w

Full text of DOI:10.1021/jo502648w

Products guided by the article

R&D Labs maybe for 1370531-14-8

Relevant to this article

Hot Product