Cooperative Photoredox- And Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

DOI: 10.1021/acs.joc.1c01018

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Journal of Organic Chemistry p. 12577 - 12590 (2021)

Update date:2022-08-04

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Authors:

Zhang, Yulin

Tanabe, Yoshiaki

Kuriyama, Shogo

Nishibayashi, Yoshiaki

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Article abstract of DOI:10.1021/acs.joc.1c01018

Cooperative photoredox- and nickel-catalyzed alkylative cyclization reactions of iodoalkynes with 4-alkyl-1,4-dihydropyridines as alkylation reagents under visible light irradiation have been achieved to afford the corresponding alkylated cyclopentylidenes in good to high yields. Introduction of substituents at the propargylic position of iodoalkynes has led to the stereoselective formation of E-isomers. The present reaction system provides a novel synthetic method for alkylative cyclization reactions of both terminal and internal alkynes with cooperative photoredox and nickel catalysis.

Full text of DOI:10.1021/acs.joc.1c01018

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Article

Cooperative Photoredox- and Nickel-Catalyzed Alkylative

Cyclization Reactions of Alkynes with 4‑Alkyl-1,4-dihydropyridines

Yulin Zhang, Yoshiaki Tanabe, Shogo Kuriyama, and Yoshiaki Nishibayashi*

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ABSTRACT: Cooperative photoredox- and nickel-catalyzed alkylative

cyclization reactions of iodoalkynes with 4-alkyl-1,4-dihydropyridines as

alkylation reagents under visible light irradiation have been achieved to

aﬀord the corresponding alkylated cyclopentylidenes in good to high yields.

Introduction of substituents at the propargylic position of iodoalkynes has

led to the stereoselective formation of E-isomers. The present reaction

system provides a novel synthetic method for alkylative cyclization reactions

of both terminal and internal alkynes with cooperative photoredox and nickel catalysis.

Chart 1. Nickel-Catalyzed Alkylative Cyclization Reactions

of Iodoalkynes with Alkylation Reagents

INTRODUCTION

■

Recently, our group and others have demonstrated that 4-alkyl-

1,4-dihydropyridines can be used as powerful alkylation

reagents to oﬀer a variety of alkylative reactions in photo-

redox-catalyzed molecular transformations,¹⁻¹³providing an

alternative to using classical, but highly reactive, organometallic

alkylation reagents. The use of visible light excitement of a

photoredox catalyst, followed by single-electron-transfer (SET)

processes, leads to the generation of alkyl radicals from 4-alkyl-

1,4-dihydropyridines,^1,2,14enabling not only simple alkyla-

tion³⁻⁵but also alkylative reactions accompanied by other

transformations such as cross-coupling reactions in the

presence of additional catalysts.^6−13,15In fact, we have recently

succeeded in photoredox-catalyzed aromatic substitution

reactions of cyanoarenes with 4-alkyl-1,4-dihydropyridines³

and cooperative nickel- and photoredox-catalyzed cross-

coupling reactions of aryl and alkenyl halides with 4-alkyl-

1,4-dihydropyridines.^8,9

the irradiation of visible light to aﬀord the corresponding

alkylated cyclopentylidenes. In addition, introduction of

substituents at the propargylic position of 6-iodohex-1-ynes

has led to the stereoselective formation of E-isomers (Chart

1B).

In the course of our study to expand the utility of 4-alkyl-1,4-

dihydropyridines toward alkylative reactions, we next planned

to apply 4-alkyl-1,4-dihyropyridines to the alkylative cyclization

reactions of haloalkynes.^16,17Indeed, transition-metal-catalyzed

alkylative cyclization reactions have been explored intensively

to prepare the corresponding cyclic compounds valuable for

both biological and pharmaceutical utilities.¹⁸⁻²⁰As a selected

example, Knochel and co-workers reported nickel-catalyzed

alkylative cyclization reactions of 6-iodohex-1-ynes with alkyl

zinc reagents to aﬀord the corresponding alkylated cyclo-

pentylidenes, where a lower temperature was required to

suppress side reactions (Chart 1A).¹⁶Thus, we have applied 4-

alkyl-1,4-dihydropyridines to the alkylative cyclization reac-

tions of 6-iodohex-1-ynes in the presence of photoredox and

nickel dual catalysts.²¹Here, we wish to report the cooperative

photoredox- and nickel-catalyzed alkylative cyclization reac-

tions of 6-iodohex-1-ynes with 4-alkyl-1,4-dihydropyridines

employed as alkylation reagents at room temperature under

RESULTS AND DISCUSSION

■

We initially investigated the reaction of 6-iodohex-1-yne (1a)

with 4-benzyl-3,5-bis(ethoxycarbonyl)-2,6-dimethyl-1,4-dihy-

dropyridine (2a) as typical substrates for the photoredox-

and nickel-catalyzed alkylative cyclization reaction to aﬀord (2-

cyclopentylideneethyl)benzene (3aa) as the major product

(Table 1). When the reaction of 1a with 3 equiv of 2a in THF

was carried out in the presence of 2 mol % of fac-[Ir(ppy)₃]

(ppy = 2-(2-pyridyl)phenyl), 10 mol % of anhydrous NiCl₂, 15

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skeleton, improved the yield of 3aa up to 75% (Table 1,

entry 10) compared to those found for using dtbbpy (Table 1,

entry 5), 4,4′-dimethyl-2,2′-bipyridine (dMebpy) (Table 1,

entry 11), or 2,2′-bipyridine (bpy) (Table 1, entry 12). When

reactions were carried out in the absence of fac-[Ir(ppy)₃],

anhydrous NiCl₂, or visible light irradiation, 3aa was not

obtained at all (Table 1, entries 13−15), demonstrating that

both nickel and photoredox catalysts as well as visible light

irradiation are all essential to promote the catalytic reaction. In

addition, a longer reaction time (24 h) slightly improved the

yield of 3a in up to 83% yield (Table 1, entry 16).

Table 1. Photoredox- and Nickel-Catalyzed Alkylative

Cyclization of 1a with 2a

With the optimized reaction conditions in hand, reactions of

1a with various 4-alkyl-1,4-dihydropyridines (2a−2s) were

next investigated (Scheme 1A). All the 4-benzyl-1,4-

entry

ligand

additive

solvent

THF

1,4-dioxane

MeCN

DME

yield (%)

dtbbpy

Cs₂CO₃

none

Scheme 1. Photodedox- and Nickel-Catalyzed Alkylative

Cyclization Reactions

K₂CO₃

NaOAc

Cs₂CO₃

Et₂O

none

1,4-dioxane

dMeObpy

dMebpy

bpy

dMeObpy

Reactions of 1a (0.25 mmol) with 2a (0.75 mmol) were carried out

in the presence of fac-[Ir(ppy)₃] (0.005 mmol), anhydrous NiCl₂

(0.025 mmol), a ligand (0.0375 mmol), and an additive (0.375

mmol) in solvent (2.5 mL) with 12 W white LED illumination at 25

°C for 18 h. Isolated yield. Not detected by GC−MS. In the

absence of fac-[Ir(ppy)₃]. In the absence of anhydrous NiCl₂. In the

absence of visible light. 24 h instead of 18 h.

mol % of 4,4′-di-tert-butyl-2,2′-bipyridine (dtbbpy), and 1.5

equiv of Cs₂CO₃as a photoredox catalyst, a cross-coupling

catalyst, a coordination ligand for the nickel catalyst, and an

additive, respectively, at 25 °C for 18 h under visible light

illumination with a 12 W white light-emitting diode (LED),

3aa was isolated in 50% yield (Table 1, entry 1). Here,

addition of a base like Cs₂CO₃, well-known as an excellent and

mild base to trap HI to promote cross-coupling reactions,²²

was necessary to produce 3aa (Table 1, entry 2), whereas other

bases like K₂CO₃and NaOAc were found to be less eﬀective to

obtain 3aa than Cs₂CO₃(Table 1, entries 3 and 4). Solvent

selection in catalysis was also examined to ﬁnd out that use of

1,4-dioxane as a solvent instead of THF increased the yield of

3aa up to 69% yield (Table 1, entry 5), while the use of other

solvents such as acetonitrile, 1,2-dimethoxyethane (DME), and

diethyl ether gave lower yields of 3aa, respectively (Table 1,

entries 6−8). Addition of a catalytic amount of a 2,2′-

bipyridine derivative as a coordination ligand for nickel species

was also found to be necessary for the formation of 3aa, which

was not obtained in the absence of dtbbpy (Table 1, entry 9).

Further investigation on ligand selection for 2,2′-bipyridine

derivatives revealed that use of 4,4′-dimethoxyl-2,2′-bipyridine

(dMeObpy), where more electron-donating substituents were

introduced onto the 4,4′-positions of the 2,2′-bipyridine

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dihydropyridine derivatives, where either electron-donating or

electron-withdrawing substituents (MeO: 2b, Me: 2c, Ph: 2d,

Cl: 2e) were introduced at the 4-position of the benzene

moiety, were successfully used as alkylation reagents to aﬀord

the corresponding alkylated cyclopentylidenes (3aa−3ae) in

good to high yields, whereas only a trace amount of the

corresponding desired product was obtained for the

introduction of a cyano substituent at the same position

(CN: 2f) with most of 2f transformed into p-tolunitrile as the

major product. Introduction of a methyl group at the 3- or 2-

position of the benzene moiety (3-Me: 2g, 2-Me: 2h) was also

applicable to give the corresponding products (3ag and 3ah)

in good to high yields. Other 1,4-dihydropyridine derivatives

with primary alkyl groups (1-naphthylmethyl: 2i, n-nonyl: 2j)

or even with secondary alkyl groups (2-pentyl: 2ak, cyclohexyl:

2l) were also found to aﬀord the corresponding alkylated

cyclopentylidenes (3ai−3al) in good to high yields. The best

yield (97%) was obtained for the isolation of (2-

methylpentylidene)cyclopentane (3ak). On the other hand,

the use of a bulkier secondary alkyl group such as CH(Me)Ph

(2m) gave only a trace amount of the corresponding desired

product. Alkylated cyclopentylidenes with ether or amine

groups (3an and 3ao) were also obtained in high yields from

the corresponding 1,4-dihydropyridine derivatives (benzylox-

ymethyl: 2n, N,N-dibenzylaminomethyl: 2o), although in-

troduction of an ester group was not successful (CH(Me)-

CO₂Et: 2p). It must be markworthy that the formation of the

compounds with cyclopentylidene and heterocyclic units was

achieved by using 4-methyl-1,4-dihydropyridine derivatives

with heterocycle substituents (2-furyl: 2q, 2-thienyl: 2r)

introduced to the methyl group to give the corresponding

products (3q and 3r) in high yields, whereas no desired

product for the reaction of 1a with a 3-pyridyl substituent (2s),

mostly transformed into 3-methylpyridine.

In addition to 1a containing a terminal alkyne moiety,

conversion of internal iodoalkynes with methyl or phenyl

groups introduced at the alkynyl group of 6-iodohex-1-yne

(Me: 1b, Ph: 1c) were further investigated to react with 2a to

aﬀord the corresponding alkylative cyclization products (3ba,

3ca) in good yields (Scheme 1A). Thus, the present catalytic

system is applicable to the internal alkynes, which was not

achieved in the previous alkylative cyclization reactions using

alkyl zinc reagents in the presence of nickel catalysts.¹⁶

Catalytic alkylative cyclization reactions of 6-iodohex-1-ynes

containing one or two aryl or alkyl substituents introduced at

the propargylic position with 2a were further investigated

(Scheme 1A). Indeed, treatment of (6-iodohex-1-yn-3-yl)-

benzene (1d) with 2a under the optimized reaction conditions

aﬀorded 2-(2-phenylcyclopentylidene)ethyl)benzene (3da) in

62% isolated yield as a mixture of E- and Z-isomers with the

former as the major product (E/Z = 92/8). Introduction of

one alkyl group such as ethyl (1e), n-butyl (1f), n-heptyl (1g),

and cyclohexyl groups (1h) at the propargylic position in the

starting iodohexynes also gave the corresponding desired

products (3ea−3ha) in good yields with an excellent

stereoselectivity (E/Z up to 93/7). Furthermore, the use of

6-iodo-3,3-dimethylhex-1-yne (1i), a terminal alkyne with two

methyl groups introduced at the propargylic position, led to

the formation of (2-(2,2-dimethylcyclopentylidene)ethyl)-

benzene (3ia) in 77% yield almost selectively as an (E)-

isomer (E/Z > 99/1). Similarly, reaction of 1i with 2i aﬀorded

1-(2-(2,2-dimethylcyclopentylidene)ethyl)naphthalene (3ii)

almost solely as an (E)-isomer (E/Z > 99/1), whose structure

was determined by a single-crystal X-ray diﬀraction study

(Scheme 1A).²³The alkylative cyclization reaction of (7-

iodohept-2-yn-4-yl)benzene (1j), an internal alkyne with one

phenyl group introduced at the propargylic position, also

proceeded to aﬀord (2-(2-phenylcyclopentylidene)propyl)-

benzene (3ja) as a mixture of two isomers with an E-

stereoselectivity (E/Z = 89/11).

It must be noted that 3aa was not obtained in a similar

manner from the reaction of 6-bromohex-1-yne (1a-Br) or 6-

chlorohex-1-yne (1a-Cl) instead of 1a with 2a under the

typical reaction conditions, where 3aa was obtained only in 4%

yield (Scheme 1B). This result suggests that the existence of an

iodide substituent as a leaving group is necessary for the dual

catalytic system to proceed eﬃciently.²⁴

Besides the alkylative cyclization reactions of 6-iodohex-1-

ynes, the reaction of 7-iodohept-1-yne (4a) with 2a was

examined. Under the similar reaction conditions, the

corresponding six-membered alkylative cyclization product

(2-cyclohexylideneethyl)benzene (5aa) was obtained only in

5% yield (Scheme 1C). Expecting the Thorpe−Ingold eﬀect,²⁵

introduction of substituents at the homopropargylic (4b) or

propargylic position (4c) was also examined, but was in vain.

Thus, the present catalytic alkylative cyclization reaction

system is only eﬀective for constructing a ﬁve-membered ring.

In order to obtain further mechanistic information, we next

examined the reaction of 1a with 2a under the optimized

reaction conditions but in the presence of 3 equiv of (2,2,6,6-

tetramethylpiperidin-1-yl)oxyl (TEMPO) as a radical inhibitor.

In fact, formation of the desired alkylative cyclization product

3aa was perfectly inhibited. Instead, 1-(benzyloxy)-2,2,6,6-

tetramethylpiperidine (6a),²⁶the TEMPO-trapped benzyl

adduct, was obtained in 69% yield. This experimental result

demonstrates that the formation of a benzyl radical as a

reactive intermediate is involved in the main catalytic reaction

pathway (Figure 1A).^{3,4,8,10,11,19,27}

Subsequently, Stern−Volmer analyses for emission quench-

ing of fac-[Ir(ppy)₃] with 1 and 2a were performed in 1,4-

dioxane (Figure 1B). From the slopes obtained by the plot and

the excited-state lifetime of fac-[Ir(ppy)₃] (τ = 1.90 μs),²⁸the

rate constants for the reduction of 1a or 1d and the oxidation

of 2a were determined to be at k = (1.5 0.2) × 10⁷M⁻¹s⁻¹

(1a), k = (1.4 0.2) × 10⁷M⁻¹s⁻¹(1d), and k = (7.3 0.7)

× 10⁷M⁻¹s⁻¹(2a), respectively. This result indicates that

reduction of 1 or oxidation of 2a can occur via the SET

process, where the oxidation of 2a is 5 times as fast as the

reduction of 1. Additionally, the quantum yield of the typical

reaction of 1a with 2a was measured to be Φ = 0.063

0.001,²³suggesting that the rate-determining step of the

catalytic formation of 3aa proceeds not via a radical chain

process²⁹but rather via sequential redox pathways, where alkyl

radicals are mainly generated by the SET process between

alkyl-1,4-dihydropyridines and an excited-state photoredox

catalyst.^3,8,9,30,31A light on/oﬀ experiment was further

conducted for the reaction of 1a with 2a to aﬀord 3aa under

the typical catalytic reaction conditions to present that the

alkylative cyclization reaction perfectly ceased in the dark,

which indicates that a chain propagation is not the main

reaction pathway and that continuous irradiation of visible

light is necessary for the reaction (Figure 1C).

On the other hand, formation of (2-(iodomethylene)-

cyclopentyl)benzene (7d), a cyclic vinyl iodide, was observed

spectroscopically as a reactive intermediate during the reaction

of 1d with 2a to aﬀord 3da under the typical catalytic reaction

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Figure 2. Formation of cyclopentylidene iodide as a reactive

intermediate for the reactions of 1d with 2a. (A) Time proﬁle of

the reaction. (B) Reaction in the absence of 2a. (C) Reaction in the

presence of a catalytic amount of 2a but in the absence of Ni catalysts.

(D) Reaction of (E)-7d with 2a to aﬀord (E)-3da without E/Z

isomerization.

Figure 1. Mechanistic studies on the reactions of 1a with 2a. (A)

Reaction in the presence of TEMPO. (B) Determination of

quenching constants by Stern−Volmer plot for fac-[Ir(ppy)₃] with

1a, 1d, and 2a. (C) Time proﬁle of the reaction with and without

visible light irradiation.

conditions (Figure 2A). Indeed, 7d was isolated as the major

product in 57% yield with an E/Z ratio of 83/17 for the

reaction of 1d under the typical catalytic reaction conditions

but in the absence of 2a (Figure 2B) with the quantum yield

length,^10,13while almost no reaction occurred for the control

experiment of Figure 2C in the absence of fac-[Ir(ppy)₃],

conﬁrming that 2a does not work as an eﬃcient photo-

sensitizer and that the presence of fac-[Ir(ppy)₃] is necessary

for visible-light-induced cyclization reactions. Cyclization

reaction of 6-iodohex-1-ynes to aﬀord cyclopentylidenes has

been already known to be promoted by radical initiators,³²and

similar visible- or UV-light-induced cyclization reactions of 6-

iodohex-1-ynes to aﬀord cyclopentylidenes have been more

recently reported by the groups of Martin³³and Zhang,³⁴

where cyclization has been proposed to occur via the formation

of a weak charge-transfer complex between an amine and alkyl

iodide capable of forming an exciplex state under irradiation of

blue light,³³or via chain propagation pathways triggered by the

abstraction of an iodine atom from alkyl iodide.^33,34In the

present reaction conditions, 2a does not work to form an

exciplex state,³⁵thus a propagation pathway is more plausible

for the formation of 7d, although the low quantum yield at Φ =

0.067 0.003 obtained under the reaction conditions similar

found at Φ = 0.072

0.002.²³The control experiments

exhibited that the conversion of 1d into 7d did not take place

in the absence of any of fac-[Ir(ppy)₃], anhydrous NiCl₂,

dMeObpy, Cs₂CO₃, or visible light irradiation, revealing that

all these elements are required for the cyclization reaction to

aﬀord 7d, when 2a is not present. However, 7d was also

isolated as the major product in 59% yield with E/Z ratio of

83/17 without the formation of 3da for the reaction of 1d

under the typical reaction conditions in the absence of

anhydrous NiCl₂and dMeObpy but in the presence of a

catalytic amount of 2a (0.1 equiv) (Figure 2C), clearly

indicating that the cyclization reaction of 1d into 7d actually

does not require nickel catalyst, when 2a is present. It must be

noted that Melchiorre and co-workers have recently demon-

strated that 4-alkyl-1,4-dihydropyridines including 2a have an

ability to absorb visible light less than 420 nm in wave-

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to Figure 2C²³and the moderate quantum yield at Φ = 0.290

0.003 obtained under the reaction conditions similar to

Figure 2C but in the presence of 3 equiv of 2a²³have disclosed

that the propagation is inhibited by any radicals formed in situ

and that the reaction pathways of the initial cyclization

reaction are rather complicated counting the contribution of

nickel catalysis in the absence of 2a,²³which requires more

deep mechanistic studies to clarify the roles of photoredox and

nickel catalysts, and of 4-alkyl-dihydropyridines and 6-iodohex-

1-ynes in catalysis. In all cases for the formation of 7d, E/Z

selectivity (83/17) is almost the same, which is thus likely

controlled mainly by the steric hindrance of the substituent

introduced to 6-iodohex-1-yne.

Scheme 2. Plausible Reaction Pathway

In order to conﬁrm that vinyl iodide species like 7d are the

reactive intermediate of the present alkylative cyclization

reactions, the reaction of isolated (E)-7d with 2a under the

similar catalytic conditions was further examined to elucidate

that (E)-3da was obtained in 73% isolated yield as the sole

stereoisomer (Figure 2D) with the low quantum yield

observed at Φ = 0.028

0.001. This result demonstrates

that 7d may be formed as a reactive intermediate. The

photoredox- and nickel-catalyzed cross-coupling reaction of

(E)-7 with 2a proceeds to aﬀord (E)-3da without E/Z

isomerization, which matches our previous report.⁹

A plausible reaction pathway for the cooperative photo-

redox- and nickel-catalyzed alkylative cyclization reactions can

be drawn as shown in Scheme 2, consisting of two sequential

reactions, i.e., (1) cyclization reaction of 1 into 7 and (2)

alkylation of 7 into 3, both of which require the Ir photoredox

catalyst. In the initial iridium photoredox cycle, excitation of

the Ir(III) catalyst fac-[Ir(ppy)₃] ([Ir]) by the absorption of

visible light occurs to give the excited state ([Ir]*). The

subsequent SET processes between [Ir]* and other substrates

including 1 or nickel species are possible, but the fastest SET

process can occur between [Ir]* and 2 as suggested by the

Stern−Volmer analysis (Figure 1B) to aﬀord the reduced Ir(II)

species ([Ir]⁻) and a radical cationic 1,4-dihydropyridine,

which is further converted to an alkyl radical (·R¹) and an

aromatized pyridine derivative via C−C bond cleavage.^3,30

Here, [Ir]⁻is capable of abstracting iodide (I⁻) from 1 to

generate [Ir] and the hex-5-yn-1-yl radical (A), which is further

cyclized into the cyclopentylidene radical (B).^33,34B can be

engaged in the iodine atom transfer with 1 to aﬀord the radical

A and the cyclopentylidene iodide 7, where the (E)-isomer is

rather preferentially formed. On the other hand, rather low

quantum yields observed for the formation of 7 suggest that

such propagation is inhibited by alkyl and other radicals

formed in situ. It goes without saying that other reaction

pathways including the cooperative photoredox- and nickel-

catalyzed cyclization reaction pathway can also contribute to

the formation of 7,²³which are not shown in Scheme 2 for

clarity.

(Z)-7 can also participate in the nickel-catalyzed trans-

formation to aﬀord (Z)-3, although (E)-7 more preferentially

adds the nickel catalyst to aﬀord (E)-3, resulting in a slight

increase in the ratio of (E)-3 compared to that of (E)-7 (83/17

to 92/8 in the case of 7d and 3da, respectively). The

combination of two sequential reactions, i.e., (1) cyclization

reaction of 1 into 7 and (2) alkylation of 7 into 3, can cause a

long induction period for the conversion of 7d into 3da as it

appears in Figure 2A, where the generated alkyl radical ·R¹can

be quenched in several ways.

Finally, a larger scale reaction of 1d (2.5 mmol) with 2a (7.5

mmol) was performed under the optimized reaction conditions

to aﬀord the alkylative cyclization product 3da in 64% isolated

yield as a mixture of E- and Z-isomers with an E/Z ratio of 91/

9 (Scheme 3).

Subsequently to the formation of 7, alkylation of 7 with the

alkyl radical ·R¹into 3 occurs by the cooperation of

photoredox and nickel catalyst. In the nickel cycle, capture

of the alkyl radical ·R¹by an in situ-generated Ni(0) species

oxidative addition of (E)-7 occurs to give a Ni(III)

(alkenyl)(alkyl) iodide complex (E), followed by the reductive

elimination of the desired coupling product (E)-3 along with

the formation of a Ni(I) iodide complex (F). Finally, the nickel

catalytic cycles are completed by a SET process between the

reduced Ir(II) catalyst [Ir]⁻and the Ni(I) iodide complex F.

Scheme 3. Large-Scale Preparation of 3da

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to obtain (6-iodohex-1-yn-3-yl)benzene (1d) without further

puriﬁcation.

CONCLUSION

■

We have achieved the cooperative photoredox- and nickel-

catalyzed alkylative cyclization reactions of 6-iodohex-1-ynes

with 4-alkyl-1,4-dihydropyridines employed as alkylation

reagents at room temperature under the irradiation of visible

light to aﬀord the corresponding alkylated cyclopentylidenes in

good to high yields. In addition to terminal alkynes, internal

alkynes can also be converted into the desired products, which

were not achieved in the previously reported catalytic alkylative

cyclization reactions with alkyl zinc reagents as alkylation

reagents.¹⁶Introduction of substituents at the propargylic

position of 6-iodohex-1-ynes has led to the stereoselective

formation of E-isomers. We consider that the method

described herein expands the usage of 4-alkyl-1,4-dihydropyr-

idines as mild formal alkylation reagents in the combination of

photoredox and transition metal catalysts to provide novel

transformations of organic compounds under mild reaction

conditions.

In a 100 mL Schlenk ﬂask were placed 1d-Cl (2.60 g, 13.5 mmol),

NaI (10.1 g, 67.5 mmol), and acetone (40 mL) under N₂, and the

reaction mixture was stirred and reﬂuxed for 18 h by using an oil bath.

Then, acetone was removed in vacuo, and the resultant mixture was

diluted with 100 mL of n-hexane and was ﬁltered. Solvent was

removed from the collected ﬁltrate under reduced pressure, and the

residue was puriﬁed by column chromatography (SiO₂) with n-hexane

as an eluent to aﬀord (6-iodohex-1-yn-3-yl)benzene (1d) as a

colorless oil (3.64 g, 12.8 mmol, 95% yield based on the amount of

1d-Cl, 64% yield based on the amount of prop-2-yn-1-ylbenzene).

HRMS (FAB) m/z [M]⁺Calcd for C₁₂H₁₃I 284.0062; Found:

284.0059. ¹H NMR (400 MHz, CDCl₃, δ): 7.36−7.16 (m, 5H, CH of

Ph), 3.62 (td, J = 6.0, 2.3 Hz, 1H, CHC), 3.12 (t, J = 6.8 Hz, 2H,

CH₂I), 2.24 (d, J = 2.3 Hz, 1H, HC), 2.01−1.73 (m, 4H, CH₂).

¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 140.7 (ipso-C of Ph), 128.5,

127.2 (o- and m-CH of Ph), 126.9 (p-CH of Ph), 85.0 (C), 71.6

(HC), 38.7, 36.4, 30.8 (CH(CH₂)₂), 6.2 (CH₂I).

3-Ethyl-6-iodohex-1-yne (1e). A colorless oil (283 mg, 1.20 mmol,

12% yield based on the amount of pent-1-yne (680 mg, 9.98 mmol)).

HRMS (FAB) m/z [M]⁺Calcd for C₈H₁₃I 236.0062; Found:

236.0054. H NMR (400 MHz, CDCl₃, δ): 3.19 (t of pseudo d, J =

EXPERIMENTAL SECTION

■

4.8, 2.1 Hz, 2H, CH₂I), 2.31−2.22 (m, 1H, CHC), 2.10−1.97 (m,

1H, CH₂CH₂I), 2.05 (d, J = 2.4 Hz, 1H, HC), 1.96−1.84 (m, 1H,

CH₂CH₂I), 1.62−1.39 (m, 4H, CH₂CHCH₂), 0.99 (t, J = 7.6 Hz, 3H,

CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 86.8 (C), 69.8

(HC), 35.1, 32.2, 31.0, 27.9 (CH₂CH(CH₂)₂), 11.6 (CH₃), 6.7

(CH₂I).

General Information. All reactions were carried out under a dry

nitrogen atmosphere by using standard Schlenk techniques. 1a,³⁶1a-

Br,³⁷1b,³⁸1c,³⁹1i,⁴⁰2a,⁴¹2b,⁴¹2c,⁴¹2d,⁸2e,⁴¹2g,³2h,³2i,⁹2j,⁴²

2k,⁴¹2l,⁴¹2m,⁴¹2n,⁸2o,³2p,⁴²2r,⁶2s,⁴³4a,⁴⁴4c,⁴⁵and 5aa⁴⁶were

prepared according to the literature procedures. Other reagents

including starting materials for the preparation of 1a−j, 2a−s, 4a−c,

1a-Cl, fac-[Ir(ppy)₃], fac-[Ir(Fppy)₃], anhydrous NiCl₂, ligands (bpy,

dtbbpy, dMebpy, dMeObpy), bases, TEMPO, and solvents were

obtained from commercial sources. Acetonitrile, diethyl ether, n-

hexane, and THF were puriﬁed by passing through a puriﬁcation

system (Glass Contour) and were degassed before use. Other solvents

were dried by general methods and degassed before use. Flash column

chromatography was carried out on a Yamazen YFLC-AI-580 system.

Gas chromatography−mass spectroscopy (GC−MS) was performed

on a Shimadzu GCMS-QP2010 PLUS instrument. E/Z ratios were

determined by quantitative measurements of GC−MS. X-ray analysis

was performed by a Rigaku XtaLAB Synergy-S diﬀractometer.

Photoluminescence spectra were measured on a Shimadzu RF-

5300PC spectrophotometer. Melting points were measured by using a

Stanford Research Systems OptiMelt MPA100. High-resolution FAB

mass spectra were measured on a JEOL JMS-700 mass spectrometer.

¹H NMR (400 MHz) and ¹³C{¹H} NMR (100 MHz) spectra were

4-Ethynyl-1-iodooctane (1f). A colorless oil (451 mg, 1.71 mmol,

17% yield based on the amount of hept-1-yne (962 mg, 10.0 mmol)).

HRMS (FAB) m/z [M]⁺Calcd for C₁₀H₁₇I 264.0375; Found:

264.0383. H NMR (400 MHz, CDCl₃, δ): 3.20 (t of pseudo d, J =

6.9, 2.5 Hz, 2H, CH₂I), 2.38−2.28 (m, 1H, CHC), 2.14−1.98 (m,

1H, CH₂CH₂I), 2.05 (d, J = 2.2 Hz, 1H, HC), 1.97−1.84 (m, 1H,

CH₂CH₂I), 1.64−1.22 (m, 8H, (CH₂)₃CHCH₂), 0.90 (t, J = 7.2 Hz,

3H, CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 87.1 (C), 69.7

(HC), 35.5, 34.6, 31.1, 30.5, 29.3, 22.5 ((CH₂)₃CH(CH₂)₂), 14.0

(CH₃), 6.7 (CH₂I).

4-Ethynyl-1-iodoundecane (1g). A colorless oil (334 mg, 1.09

mmol, 11% yield based on the amount of 1-bromo-3-chloropropane

(1.57 g, 9.99 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₃H₂₃I

306.0845; Found: 306.0840. ¹H NMR (400 MHz, CDCl₃, δ): 3.20 (t

of pseudo d, J = 7.0, 2.4 Hz, 2H, CH₂I), 2.37−2.28 (m, 1H, CHC),

2.12−1.98 (m, 1H, CH₂CH₂I), 2.04 (d, J = 2.4 Hz, 1H, HC),

1.97−1.84 (m, 1H, CH₂CH₂I), 1.63−1.20 (m, 14H, (CH₂)₆CHCH₂),

0.87 (t, J = 6.8 Hz, 3H, CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ):

87.1 (C), 69.7 (HC), 35.6, 34.9, 31.8, 31.1, 30.6, 29.4, 29.2, 27.2,

22.6 ((CH₂)₆CH(CH₂)₂), 14.1 (CH₃), 6.7 (CH₂I).

measured in CDCl₃on a JEOL ECS-400 spectrometer with δ values

calibrated by using residual peaks of CHCl₃(¹H: 7.26) and CDCl₃

(¹³C: 77.0), respectively.

General Procedure for the Preparation of 6-Iodohex-1-yne

Derivatives (1) (Taking (6-Iodohex-1-yn-3-yl)benzene (1d) as

an Example). In a 100 mL Schlenk ﬂask were placed prop-2-yn-1-

ylbenzene (2.32 g, 20.0 mmol) and THF (25 mL) at −78 °C by using

a dry ice−methanol bath under N₂, where a hexane solution of ⁿBuLi

(32 mL, 1.57 M, ca. 50 mmol) was added dropwise. The reaction

mixture was gradually warmed to 30 °C by using an oil bath and was

further stirred for 2 h. Then the reaction mixture was cooled back to

−78 °C by using a dry ice−methanol bath, and 1-bromo-3-

chloropropane (3.15 g, 20.0 mmol) was added dropwise. The

reaction mixture was gradually warmed to 40 °C by using an oil bath

and was further stirred for 2 h. The resultant mixture was quenched

with a saturated aqueous solution of NH₄Cl (40 mL), and the

aqueous phase was extracted with Et₂O (50 mL × 3). The combined

organic layers were washed with brine (50 mL), dried over anhydrous

MgSO₄, and ﬁltered. The ﬁltrate was collected, and the solvent was

removed under reduced pressure. The residue was further puriﬁed by

column chromatography (SiO₂) with n-hexane as an eluent to aﬀord

(6-chlorohex-1-yn-3-yl)benzene (1d-Cl) as a colorless oil (2.72 g,

14.1 mmol, 71% yield based on the amount of prop-2-yn-1-

ylbenzene), which was directly used in the subsequent transformation

(6-Iodohex-1-yn-3-yl)cyclohexane (1h). A colorless oil (627 mg,

2.16 mmol, 28% yield based on the amount of 1-bromo-3-

chloropropane (1.21 g, 7.69 mmol)). HRMS (FAB) m/z [M]⁺

Calcd for C₁₂H₁₉I 290.0532; Found: 290.0528. ¹H NMR (400

MHz, CDCl₃, δ): 3.18 (t of pseudo d, J = 6.9, 1.5 Hz, 2H, CH₂I),

2.22−2.16 (m, 1H, CHC), 2.08−1.98 (m, 1H, CH of Cy), 2.03 (d,

J = 2.4 Hz, 1H, HC), 1.91−1.44, 1.36−1.04 (both m, 8H and 6H,

respectively, CH₂of CyCH(CH₂)₂). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 85.7 (C), 70.6 (HC), 40.9, 40.8, 36.7, 32.7, 31.3,

31.1, 29.0, 26.2, 26.1 (CyCH(CH₂)₂), 6.8 (CH₂I).

Preparation of (7-Iodohept-2-yn-4-yl)benzene (1j). In a 100

mL Schlenk ﬂask were placed prop-2-yn-1-ylbenzene (1.16 g, 10.0

mmol) and THF (14 mL) at −78 °C by using a dry ice−methanol

bath under N₂, where a hexane solution of ⁿBuLi (16.1 mL, 1.57 mol/

L, ca. 25 mmol) was added dropwise. The reaction mixture was

gradually warmed to 30 °C by using an oil bath and was further stirred

for 2 h. The reaction mixture was cooled back to −78 °C by using a

dry ice−methanol bath, and 1-bromo-3-chloropropane (1.57 g, 10.0

mmol) was added dropwise. The reaction mixture was gradually

warmed to 40 °C by using an oil bath and was further stirred for 2 h.

Then, the reaction mixture was cooled to 0 °C by using an ice−water

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bath, and iodomethane (1.42 g, 10.0 mmol) was added dropwise. The

reaction mixture was gradually warmed to 40 °C by using an oil bath

and was further stirred for 2 h. The resultant mixture was quenched

with a saturated solution of NH₄Cl (40 mL), and the aqueous phase

was extracted with Et₂O (30 mL × 3). The combined organic layers

were washed with brine (20 mL × 2), dried over MgSO₄, and ﬁltered.

The ﬁltrate was collected, and the solvent was removed under reduced

pressure. The residue was further puriﬁed by column chromatography

(SiO₂) with n-hexane as an eluent to aﬀord (7-chlorohept-2-yn-4-

yl)benzene (1j-Cl) as a colorless oil (924 mg, 0.447 mmol, 45% yield

based on the amount of 1-bromo-3-chloropropane), which was

directly used in the subsequent transformation to obtain (7-iodohept-

2-yn-4-yl)benzene (1j) without further puriﬁcation.

130.8, 130.7 (o- and m-CH of C₆H₄), 119.3 (CN), 109.2 (p-C of

C₆H₄), 101.0 (3-C of 1,4-dihydropyridine), 59.6 (CH₃CH₂), 42.3 (4-

CHCH₂of 1,4-dihydropyridine), 35.4 (4-CHCH₂of 1,4-dihydropyr-

idine), 18.9 (2-CCH₃of 1,4-dihydropyridine), 14.3 (CH₃CH₂).

General Procedure for the Preparation of Alkylated

Cyclopentylidenes (Taking (2-Cyclopentylideneethyl)benzene

(3aa) as an Example). In a 20 mL Schlenk ﬂask were placed 6-

iodohex-1-yne (1a) (50.1 mg. 0.241 mmol), diethyl 4-benzyl-2,6-

dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (2a) (260 mg, 0.756

mmol), fac-[Ir(ppy)₃] (3.4 mg, 0.0052 mmol), anhydrous NiCl₂(3.4

mg, 0.026 mmol), dMeObpy (8.0 mg, 0.037 mmol), and Cs₂CO₃

(122 mg, 0.375 mmol) under N₂, where 1,4-dioxane (2.5 mL) was

added at room temperature. The reaction ﬂask was placed in an As

One LTB-125 constant low temperature water bath set at 25 °C and

was illuminated from the bottom of the bath with an Aitech System

TMN100×120−22WD 12 W white LED lamp (400−750 nm) at a

distance of approximately 2 cm from the light source for 24 h. The

volatiles were removed in vacuo, and the residue was puriﬁed by

column chromatography (SiO₂) with n-hexane as an eluent to aﬀord

(2-cyclopentylideneethyl)benzene (3aa) as a colorless oil (34.5 mg,

0.200 mmol, 83% yield based on the amount of 1a). HRMS (FAB)

In a 100 mL Schlenk ﬂask were placed 1j-Cl (621 mg, 3.02 mmol),

NaI (2.25 g, 15.0 mmol), and acetone (40 mL) under N₂, and the

reaction was stirred and reﬂuxed by using an oil bath for 18 h. Then,

acetone was removed in vacuo, and the resultant mixture was diluted

with 100 mL of n-hexane and was ﬁltered. Solvent was removed from

the collected ﬁltrate under reduced pressure, and the residue was

puriﬁed by column chromatography (SiO₂) with n-hexane as an

eluent to aﬀord (7-iodohept-2-yn-4-yl)benzene (1j) as a colorless oil

(608 mg, 2.04 mmol, 68% yield based on the amount of 1j-Cl, 20%

yield based on the amount of 1-bromo-3-chloropropane). HRMS

m/z [M]⁺Calcd for C₁₃H₁₆172.1252; Found: 172.1247. H NMR

(400 MHz, CDCl₃, δ): 7.30 (t, J = 7.6 Hz, 2H, m-CH of Ph), 7.24−

7.17 (m, 3H, o- and p-CH of Ph), 5.47 (tt, J = 7.2, 2.3 Hz, 1H,

CH), 3.35 (d, J = 7.2 Hz, 2H, CH₂CH), 2.31 (pseudo q, J = 7.6

Hz, 4H, α-CH₂of cyclopentylidene), 1.73, 1.65 (both quint, J = 6.9

Hz, 2H each, β-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 144.4 (ipso-C of cyclopentylidene), 141.8 (ipso-C of Ph),

128.3, 128.3 (o- and m-CH of Ph), 125.7 (p-CH of Ph), 118.6

(CH), 35.9 (CH₂CH), 33.6, 28.8 (α-CH₂of cyclopentylidene),

26.4, 26.3 (β-CH₂of cyclopentylidene).

(FAB) m/z [M]⁺Calcd for C₁₃H₁₅I 298.0219; Found 298.0207. H

NMR (400 MHz, CDCl₃, δ): 7.38−7.30 (m, 4H, o-and m-CH of Ph),

7.24 (tt, J = 6.7, 2.1 Hz, 1H, p-CH of Ph), 3.62 (t of pseudo t, J = 8.3,

2.4 Hz, 1H, CHC), 3.20 (t, 2H, J = 6.8, CH₂I), 2.04−1.89 (m, 2H,

CH₂CH₃), 1.88 (d, J = 2.8 Hz, 3H, CH₃), 1.88−1.74 (m, 2H,

CH₂CH₂CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 142.0 (ipso-C

of Ph), 128.3, 127.2 (o- and m-CH of Ph), 126.6 (p-CH of Ph), 80.0,

78.9 (CC), 39.2, 36.7, 31.1 (CH(CH₂)₂), 6.5, 3.6 (CH₂I and

CH₃).

1-(2-Cyclopentylideneethyl)-4-methoxylbenzene (3ab). A color-

less oil (39.4 mg, 0.195 mmol, 81% yield based on the amount of 1a

(50.3 mg, 0.242 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₄H₁₈O

General Procedure for the Preparation of Diethyl 4-Alkyl-

2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Deriva-

tives (1) (Taking Diethyl 4-(Furan-2-ylmethyl)-2,6-dimethyl-

1,4-dihydropyridine-3,5-dicarboxylate (2q) as an Example). In

a 50 mL Schlenk ﬂask were placed 2-furanacetaldehyde (396 mg, 3.60

mmol), ethyl acetoacetate (938 mg, 7.20 mmol), and ethanol (20

mL) at room temperature under N₂, where an aqueous solution of 28

wt % NH₃(1.1 mL, ca. 18 mmol) was added. The reaction mixture

was stirred and reﬂuxed for 18 h by using an oil bath, then was dried

in vacuo. The residue was further puriﬁed by column chromatography

(SiO₂) with a mixture of n-hexane/ethyl acetate (7:3) as an eluent to

aﬀord diethyl 4-(furan-2-ylmethyl)-2,6-dimethyl-1,4-dihydropyridine-

3,5-dicarboxylate (2q) as a white solid (600 mg, 1.80 mmol, 50%

yield based on the amount of 2-furanacetaldehyde). mp 106.0−107.3

°C. HRMS (FAB) m/z [M]⁺Calcd for C₁₈H₂₃NO₅333.1576; Found

333.1579. ¹H NMR (400 MHz, CDCl₃, δ): 7.24 (dd, J = 1.8, 1.0 Hz,

1H, 5-CH of furyl), 6.19 (dd, J = 3.1, 1.8 Hz, 1H, 4-CH of furyl), 5.84

(d, J = 3.1 Hz, 1H, 3-CH of furyl), 5.69 (br, 1H, NH), 4.18 (t, J = 5.7

Hz, 1H, 4-CH of 1,4-dihydropyridine), 4.15−4.03 (m, 4H, CH₃CH₂),

2.59 (d, J = 5.7 Hz, 2H, CH₂of furan-2-ylmethyl), 2.22 (s, 6H, 2-

CCH₃of 1,4-dihydropyridine) 1.25 (t, J = 7.0 Hz, 6H, CH₃CH₂).

¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 167.6 (CO₂), 154.0 (2-C of

202.1358; Found: 202.1357. H NMR (400 MHz, CDCl₃, δ): 7.11,

6.84 (both dt, J = 8.8, 2.2 Hz, 2H each, C₆H₄), 5.44 (t of quint, J =

7.1, 2.1 Hz, 1H, CH), 3.79 (s, 3H, CH₃), 3.28 (d, J = 7.1 Hz, 2H,

CH₂CH), 2.33−2.25 (m, 4H, α-CH₂of cyclopentylidene), 1.71,

1.64 (both quint, J = 6.7 Hz, 2H each, β-CH₂of cyclopentylidene).

¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 157.7 (p-C of C₆H₄), 144.0

(ipso-C of cyclopentylidene), 133.9 (ipso-C of C₆H₄), 129.1 (o-C of

C₆H₄), 119.0 (CH), 113.7 (m-C of C₆H₄), 55.2 (CH₃), 35.0

(CH₂CH), 33.6, 28.8 (α-CH₂of cyclopentylidene), 26.4, 26.3 (β-

CH₂of cyclopentylidene).

1-(2-Cyclopentylideneethyl)-4-methylbenzene (3ac). A colorless

oil (36.8 mg, 0.198 mmol, 82% yield based on the amount of 1a (50.1

mg, 0.241 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₄H₁₈

186.1409; Found: 186.1400. ¹H NMR (400 MHz, CDCl₃, δ):

7.17−7.06 (m, 4H, C₆H₄), 5.46 (t of quint, J = 7.1, 1.9 Hz, 1H,

CH), 3.31 (d, J = 7.1 Hz, 2H, CH₂CH), 2.34 (s, 3H, CH₃),

2.34−2.26 (m, 4H, α-CH₂of cyclopentylidene), 1.72, 1.65 (both

quint, J = 6.8 Hz, 2H each, β-CH₂of cyclopentylidene). ¹³C{¹H}

NMR (100 MHz, CDCl₃, δ): 144.1 (ipso-C of cyclopentylidene),

138.7, 135.1 (ipso- and p-C of C₆H₄), 129.0, 128.1 (CH of C₆H₄),

118.9 (CH), 35.5 (CH₂CH), 33.6, 28.8 (α-CH₂of cyclo-

pentylidene), 26.4, 26.3 (β-CH₂of cyclopentylidene), 21.0 (CH₃).

4-(2-Cyclopentylideneethyl)-1,1′-biphenyl (3ad). A colorless oil

(46.6 mg, 0.188 mmol, 78% yield based on the amount of 1a (50.1

mg, 0.241 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₉H₂₀

furyl), 145.3 (2-C of 1,4-dihydropyridine), 140.8 (5-CH of furyl),

110.1, 106.8 (3-CH and 4-CH of furyl), 101.9 (3-C of 1,4-

dihydropyridine), 59.7 (CH₃CH₂), 34.2, 33.9 (4-CHCH₂of 1,4-

dihydropyridine), 19.3 (2-CCH₃of 1,4-dihydropyridine), 14.3

(CH₃CH₂).

248.1565; Found: 248.1561. H NMR (400 MHz, CDCl₃, δ): 7.58

Diethyl 4-(4-Cyanobenzyl)-2,6-dimethyl-1,4-dihydropyridine-

3,5-dicarboxylate (2f). A white solid (371 mg, 1.01 mmol, 25%

yield based on the amount of 4-(2-oxoethyl)benzonitrile (581 mg,

4.00 mmol)). mp 156.7−158.5 °C. HRMS (FAB) m/z [M]⁺Calcd

(dt, J = 7.8, 1.8 Hz, 2H, 2′- and 6′-CH of 1,1′-biphenyl), 7.53 (dt, J =

8.5, 1.8 Hz, 2H, 2- and 6-CH of 1,1′-biphenyl), 7.44 (tt, J = 7.8, 1.8

Hz, 2H, 3′- and 5′-CH of 1,1′-biphenyl), 7.33 (tt, J = 7.8, 1.8 Hz, 1H,

4′-CH of 1,1′-biphenyl), 7.28 (d, J = 8.5 Hz, 2H, 3- and 5-CH of 1,1′-

biphenyl), 5.50 (t of quint, J = 7.2, 2.3 Hz, 1H, CH), 3.39 (d, J =

7.2 Hz, 2H, CH₂CH), 2.34, 2.32 (both t, J = 6.7 Hz, 2H each, α-

CH₂of cyclopentylidene), 1.73, 1.66 (both quint, J = 6.7 Hz, 2H

each, β-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃,

δ): 144.6 (ipso-C of cyclopentylidene), 141.2, 140.9, 138.7 (1, 1′-, and

4-C of 1,1′-biphenyl), 128.7, 127.1, 127.0 (o- and m-CH of 1,1′-

for C₂₁H₂₄N₂O₄368.1736; Found: 368.1741. H NMR (400 MHz,

CDCl₃, δ): 7.44, 7.10 (both d, J = 8.0 Hz, 2H each, C₆H₄), 5.74 (br,

1H, NH), 4.21 (t, J = 5.4 Hz, 1H, 4-CH of 1,4-dihydropyridine),

4.12−3.98 (m, 4H, CH₃CH₂), 2.62 (d, J = 5.4 Hz, 2H, CH₂of 4-

cyanobenzyl), 2.14 (s, 6H, 2-CCH₃of 1,4-dihydropyridine) 1.21 (t, J

= 7.2 Hz, 6H, CH₃CH₂). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 167.5

(CO₂), 146.0 (ipso-C of C₆H₄), 145.4 (2-C of 1,4-dihydropyridine),

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biphenyl with two resonances overlapping at δ 128.7), 126.9 (4′-CH

of 1,1′-biphenyl), 118.5 (CH), 35.6 (CH₂CH), 33.7, 28.9 (α-

CH₂of cyclopentylidene), 26.5, 26.4 (β-CH₂of cyclopentylidene).

1-Chloro-4-(2-cyclopentylideneethyl)benzene (3ae). A colorless

oil (32.6 mg, 0.158 mmol, 65% yield based on the amount of 1a (50.1

mg, 0.241 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₃H₁₅Cl

(2-Methylpentylidene)cyclopentane (3ak). A colorless oil (35.7

mg, 0.234 mmol, 97% yield based on the amount of 1a (50.2 mg,

0.241 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₁H₂₀152.1565;

Found 152.1559. ¹H NMR (400 MHz, CDCl₃, δ): 5.00 (d of quint, J

= 9.2, 2.5 Hz, 1H, CH), 2.25−2.13 (m, 5H, CHCH₃and α-CH₂of

cyclopentylidene), 1.64, 1.58 (both quint, J = 7.0 Hz, 2H each, β-CH₂

of cyclopentylidene), 1.33−1.14 (m, 4H, (CH₂)₂), 0.90 (d, J = 6.8 Hz,

3H, CH₃), 0.86 (t, J = 7.0 Hz, 3H, CH₃). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 141.2 (ipso-C of cyclopentylidene), 126.9 (CH), 40.1

(CH₂CHCH), 34.0 (α-CH₂of cyclopentylidene), 33.5

(CHCH), 28.5 (α-CH₂of cyclopentylidene), 26.4, 26.4 (β-CH₂

of cyclopentylidene), 21.1, 20.6 (CH₃CH and CH₂CH₃), 14.3

(CH₃CH₂).

(Cyclopentylidenemethyl)cyclohexane (3al). A colorless oil (23.0

mg, 0.140 mmol, 58% yield based on the amount of 1a (50.2 mg,

0.241 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₂H₂₀164.1565;

Found 164.1564. ¹H NMR (400 MHz, CDCl₃, δ): 5.12−5.08 (m, 1H,

CH), 2.23−2.13 (m, 4H, α-CH₂of cyclopentylidene), 2.08−1.95

(m, 1H, CH of Cy), 1.74−1.52, 1.32−1.08, 1.07−0.94 (all m, 8H, 4H,

and 2H, respectively, CH₂of Cy and β-CH₂of cyclopentylidene).

¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 141.1 (ipso-C of cyclo-

pentylidene), 126.4 (CH), 38.7 (1-CH of Cy), 33.5 (α-CH₂of

cyclopentylidene), 33.2 (2- and 6-CH₂of Cy), 28.4 (α-CH₂of

cyclopentylidene), 26.4, 26.3, 26.2 (4-CH₂of Cy and β-CH₂of

cyclopentylidene), 26.2 (3- and 5-CH₂of Cy).

206.0862; Found: 206.0863. H NMR (400 MHz, CDCl₃, δ): 7.24,

7.12 (both d, J = 7.8 Hz, 2H each, C₆H₄), 5.41 (t of quint, J = 7.4, 2.4

Hz, 1H, CH), 3.30 (d, J = 7.4 Hz, 2H, CH₂CH), 2.28 (t, J = 6.7

Hz, 4H, α-CH₂of cyclopentylidene), 1.71, 1.64 (both quint, J = 6.7

Hz, 2H each, β-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 145.0 (ipso-C of cyclopentylidene), 140.2 (ipso-C of

C₆H₄), 131.3 (p-C of C₆H₄), 129.6, 128.4 (CH of C₆H₄), 118.1

(CH), 35.2 (CH₂CH), 33.6, 28.8 (α-CH₂of cyclopentylidene),

26.4, 26.3 (β-CH₂of cyclopentylidene).

1-(2-Cyclopentylideneethyl)-3-methylbenzene (3ag). A colorless

oil (31.7 mg, 0.170 mmol, 70% yield based on the amount of 1a (50.3

mg, 0.242 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₄H₁₈

186.1409; Found: 186.1411. H NMR (400 MHz, CDCl₃, δ): 7.18

(t, J = 7.6, 1H, 5-CH of C₆H₄), 7.03−6.98 (m, 3H, 1-, 4-, and 6-CH of

C₆H₄), 5.45 (t of quint, J = 7.4, 2.3 Hz, 1H, CH), 3.31 (d, J = 7.4

Hz, 2H, CH₂CH), 2.34 (s, 3H, CH₃), 2.34−2.26 (m, 4H, α-CH₂of

cyclopentylidene), 1.72, 1.64 (both quint, J = 7.0 Hz, 2H each, β-CH₂

of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 144.2

(ipso-C of cyclopentylidene), 141.7, 137.9 (1- and 3-C of C₆H₄),

129.1, 128.2, 126.4, 125.3 (CH of C₆H₄), 118.8 (CH), 35.9

(CH₂CH), 33.6, 28.8 (α-CH₂of cyclopentylidene), 26.4, 26.3 (β-

CH₂of cyclopentylidene), 21.4 (CH₃).

((2-Cyclopentylideneethoxy)methyl)benzene (3an). A colorless

oil (33.9 mg, 0.168 mmol, 70% yield based on the amount of 1a (50.1

mg, 0.241 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₄H₁₈O

1-(2-Cyclopentylideneethyl)-2-methylbenzene (3ah). A white

solid (54.1 mg, 0.186 mmol, 77% yield based on the amount of 1a

(52.2 mg, 0.242 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₄H₁₈

202.1358; Found 202.1352. H NMR (400 MHz, CDCl₃, δ): 7.39−

7.25 (m, 5H, CH of Ph), 5.52 (t of quint, J = 6.9, 2.3 Hz, 1H, CH),

4.51 (s, 2H, CH₂Ph), 4.01 (d of quint, J = 6.9, 1.1 Hz, 2H,

CH₂CH), 2.30, 2.22 (both t, J = 6.8 Hz, 2H each, α-CH₂of

cyclopentylidene), 1.68, 1.62 (both quint, J = 6.8 Hz, 2H each, β-CH₂

of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 148.6

(ipso-C of cyclopentylidene), 138.6 (ipso-C of Ph), 128.3, 127.8 (o-

and m-CH of Ph), 127.5 (p-CH of Ph), 116.4 (CH), 72.0

(OCH₂Ph), 68.1 (CH₂CH), 33.7, 28.8 (α-CH₂of cyclopentyli-

dene), 26.3, 26.0 (β-CH₂of cyclopentylidene).

186.1409; Found 186.1413. H NMR (400 MHz, CDCl₃, δ): 7.22−

7.09 (m, 4H, C₆H₄), 5.40 (t of quint, J = 7.2, 2.4 Hz, 1H, CH),

3.31 (d, J = 7.2 Hz, 2H, CH₂CH), 2.32 (s, 3H, CH₃), 2.35−2.27

(m, 4H, α-CH₂of cyclopentylidene), 1.73, 1.65 (both quint, J = 7.0

Hz, 2H each, β-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 144.2 (ipso-C of cyclopentylidene), 139.9, 136.1 (1- and

2-C of C₆H₄), 130.0, 128.6, 125.9, 125.9 (CH of C₆H₄), 117.9

(CH), 33.7, 33.6, (CH₂CH and α-CH₂of cyclopentylidene),

28.8 (α-CH₂of cyclopentylidene), 26.4, 26.4 (β-CH₂of cyclo-

pentylidene), 19.5 (CH₃).

N,N-Dibenzyl-2-cyclopentylideneethan-1-amine (3ao). A white

solid (54.1 mg, 0.186 mmol, 74% yield based on the amount of 1a

(52.2 mg, 0.251 mmol)). mp 176.8−178.0 °C (decomp.). HRMS

(FAB) m/z [M]⁺Calcd for C₂₁H₂₅N 291.1987; Found 291.1985. H

1-(2-Cyclopentylideneethyl)naphthalene (3ai). A colorless oil

(35.6 mg, 0.160 mmol, 66% yield based on the amount of 1a (50.3

mg, 0.242 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₇H₁₈

NMR (400 MHz, CDCl₃, δ): 7.70−7.66 (m, 4H, CH of Ph), 7.46−

7.40 (m, 6H, CH of Ph), 5.65 (t of quint, J = 5.8, 2.2 Hz, 1H, CH),

4.20−4.06 (m, 4H, CH₂Ph), 3.53−3.47 (m, 2H, CH₂CH), 2.39−

2.33, 1.99−1.93 (both m, 2H each, α-CH₂of cyclopentylidene),

1.69−1.59 (m, 4H, β-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100

MHz, CDCl₃, δ): 155.7 (ipso-C of cyclopentylidene), 131.2, 129.3 (o-

and m-CH of Ph) 129.8 (p-CH of Ph), 129.0 (ipso-C of Ph), 107.2

(CH), 55.9 (NCH₂Ph), 50.7 (CH₂CH), 34.3, 29.5 (α-CH₂of

cyclopentylidene), 26.0, 25.9 (β-CH₂of cyclopentylidene).

2-(2-Cyclopentylideneethyl)furan (3aq). A colorless oil (29.1 mg,

0.179 mmol, 71% yield based on the amount of 1a (52.2 mg, 0.251

mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₁H₁₄O 162.1045;

Found 162.1041. ¹H NMR (400 MHz, CDCl₃, δ): 7.31 (d, J = 1.4 Hz,

1H, 5-CH of furyl), 6.28 (dd, J = 3.2, 1.4 Hz, 1H, 4-CH of furyl), 5.98

(dd, J = 3.2, 0.9 Hz, 1H, 3-CH of furyl), 5.43 (t of quint, J = 7.2, 2.5

Hz, 1H, CH), 3.33 (dd, J = 7.2, 0.9 Hz, 2H, CH₂CH), 2.32−

2.23 (m, 4H, α-CH₂of cyclopentylidene), 1.74−1.58 (m, 4H, β-CH₂

of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 155.3,

145.8 (ipso-C of cyclopentylidene and 2-C of furyl), 140.9 (5-CH of

furyl), 114.9, 110.1, 104.5 (3- and 4-CH of furyl and CH), 33.6,

28.7, 28.5 (CH₂CH and α-CH₂of cyclopentylidene), 26.4, 26.3 (β-

CH₂of cyclopentylidene).

222.1409; Found: 222.1402. H NMR (400 MHz, CDCl₃, δ): 8.05

(d, 1H, J = 8.0 Hz, 1H, 4-CH of 1-naphthyl), 7.86 (d, J = 7.6 Hz, 1H,

8-CH of 1-naphthyl), 7.73 (d, J = 7.6 Hz, 1H, 4-CH of 1-naphthyl),

7.56−7.46, 7.45−7.34 (both m, 2H each, 2-, 3-, 6-, and 7-CH of 1-

naphthyl), 5.56 (t of quint, J = 6.5, 2.1 Hz, 1H, CH), 3.78 (d, J =

6.5 Hz, 2H, CH₂CH), 2.39, 2.30 (both br, 2H each, α-CH₂of

cyclopentylidene), 1.75, 1.65 (both quint, J = 6.7 Hz, 2H each, β-CH₂

of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 144.5

(ipso-C of cyclopentylidene), 137.8, 133.8, 132.0 (1-, 4a-, and 8a-C of

1-naphthyl), 128.6, 126.5, 125.7, 125.6, 125.5, 125.4, 124.1 (CH of 1-

naphthyl), 118.3 (CH), 33.7 (α-CH₂of cyclopentylidene), 33.3

(CH₂CH), 28.9 (α-CH₂of cyclopentylidene), 26.5, 26.4 (β-CH₂of

cyclopentylidene).

Decylidenecyclopentane (3aj). A colorless oil (27.1 mg, 0.130

mmol, 54% yield based on the amount of 1a (50.2 mg, 0.241 mmol)).

HRMS (FAB) m/z [M]⁺Calcd for C₁₅H₂₈208.2191; Found

208.2183. H NMR (400 MHz, CDCl₃, δ): 5.23 (t, J = 6.9 Hz, 1H,

CH), 2.21, 2.16 (both t, J = 7.0 Hz, 2H each, α-CH₂of

cyclopentylidene), 1.94 (q, J = 6.9 Hz, 2H, CH₂CH), 1.65, 1.58

(both quint, J = 7.0 Hz, 2H each, β-CH₂of cyclopentylidene), 1.35−

1.21 (m, 14H, (CH₂)₇), 0.88 (t, J = 6.6 Hz, 3H, CH₃). ¹³C{¹H} NMR

(100 MHz, CDCl₃, δ): 142.9 (ipso-C of cyclopentylidene), 120.4

(CH), 33.5 (α-CH₂of cyclopentylidene), 31.9, 29.7, 29.7, 29.6,

29.4, 29.4 ((CH₂)₇with two resonances overlapping at δ 29.6), 28.6

(α-CH₂of cyclopentylidene), 26.5, 26.4 (β-CH₂of cyclopentylidene),

22.7 (CH₂CH₃), 14.1 (CH₃).

2-(2-Cyclopentylideneethyl)thiophene (3ar). A colorless oil (30.8

mg, 0.173 mmol, 69% yield based on the amount of 1a (52.2 mg,

0.251 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₁H₁₄S 178.0816;

Found 178.0814. H NMR (400 MHz, CDCl₃, δ): 7.11 (dd, J = 4.9,

1.7 Hz, 1H, 5-CH of thienyl), 6.92 (dd, J = 4.9, 3.2 Hz, 1H, 4-CH of

thienyl), 6.79 (dd, J = 3.2, 1.7 Hz, 1H, 3-CH of thienyl), 5.50 (t of

https://doi.org/10.1021/acs.joc.1c01018

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

quint, J = 6.6, 2.2 Hz, 1H, CH ), 3.52 (d, J = 6.6 Hz, 2H,

CH₂CH ), 2.32−2.26 (m, 4H, α-CH₂of cyclopentylidene), 1.76−

1.59 (m, 4H, β-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 145.2, 145.0 (ipso-C of cyclopentylidene and 2-C of

thienyl), 126.7, 123.7, 123.0 (3-, 4- and 5-CH of thienyl), 118.0

(CH ), 33.6, 30.1, 28.7 (CH₂CH and α-CH₂of cyclo-

pentylidene), 26.4, 26.3 (β-CH₂of cyclopentylidene).

1H each, 3-CH₂of cyclopentylidene), 1.72−1.53 (m, 2H, 4-CH₂of

cyclopentylidene), 1.35−1.20 (m, 2H, CH₂CH₃), 0.94 (t, J = 7.4 Hz,

3H, CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 147.9 (1-C of

cyclopentylidene), 141.9 (ipso-C of Ph), 128.3, 128.3 (o- and m-CH

of Ph), 125.6 (p-CH of Ph), 118.3 (CH), 46.0 (2-CH of

cyclopentylidene), 35.7 (5-CH₂of cyclopentylidene), 32.3

(CH₂CH), 29.5 (4-CH₂of cyclopentylidene), 27.1 (CH₂CH₃),

24.1 (3-CH₂of cyclopentylidene), 12.1 (CH₃). (Z)-3ea (overlapping

(1-Cyclopentylideneethane-1,2-diyl)dibenzene (3ba). A colorless

oil (35.4 mg, 0.143 mmol, 57% yield based on the amount of 1b (71.0

mg, 0.250 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₉H₂₀

peaks indistinctive from those of (E)-3ea not listed): H NMR (400

MHz, CDCl₃, δ): 5.44 (tq, J = 8.0, 1.9 Hz, 1H, CH), 3.44 (dd, J =

15.8, 8.0 Hz, 1H, CH₂CH), 2.63 (br, 1H, 2-CH of cyclo-

pentylidene), 0.95 (t, J = 7.4 Hz, 3H, CH₃). ¹³C{¹H} NMR (100

MHz, CDCl₃, δ): 148.2 (1-C of cyclopentylidene), 128.1 (o- or m-CH

of Ph), 125.7 (p-CH of Ph), 119.1 (CH), 41.9 (2-CH of

cyclopentylidene), 35.4 (5-CH₂of cyclopentylidene), 33.4

(CH₂CH), 31.4 (4-CH₂of cyclopentylidene), 27.8 (CH₂CH₃),

24.0 (3-CH₂of cyclopentylidene), 12.3 (CH₃).

248.1565; Found 248.1561. H NMR (400 MHz, CDCl₃, δ): 7.26−

7.09 (m, 10H, CH of Ph), 3.74 (s, 2H, CH₂C), 2.47, 2.26 (both t, J

= 6.9 Hz, 2H each, α-CH₂of cyclopentylidene), 1.74, 1.62 (both

quint, J = 6.9 Hz, 2H each, β-CH₂of cyclopentylidene). ¹³C{¹H}

NMR (100 MHz, CDCl₃, δ): 143.7, 142.6, 140.3 (ipso-C of

cyclopentylidene and Ph), 129.9 (C), 128.4, 128.3, 128.1, 127.8

(o- and m-CH of Ph), 125.8, 125.6 (p-CH of Ph), 41.1 (CH₂C),

32.7, 31.2 (α-CH₂of cyclopentylidene), 27.1, 26.4 (β-CH₂of

cyclopentylidene).

(2-(2-Butylcyclopentylidene)ethyl)benzene (3fa). A colorless oil

(37.1 mg, 0.162 mmol, 65% yield based on the amount of 1f (66.0

mg, 0.250 mmol)) as a mixture of E and Z isomers (E/Z = 90/10).

HRMS (FAB) m/z [M]⁺Calcd for C₁₇H₂₄228.1878; Found

(2-Cyclopentylidenepropyl)benzene (3ca). A colorless oil (28.1

mg, 0.151 mmol, 60% yield based on the amount of 1c (55.6 mmol,

0.250 mmol)). HRMS (FAB) m/z [M]⁺Calcd for C₁₄H₁₈186.1409;

Found 186.1411. ¹H NMR (400 MHz, CDCl₃, δ): 7.33−7.25 (m, 2H,

m-CH of Ph), 7.24−7.15 (m, 3H, o- and p-CH of Ph), 3.38 (s, 2H,

CH₂C), 2.38, 2.27 (both br, 2H each, α-CH₂of cyclopentylidene),

1.72, 1.71 (both quint, J = 7.0 Hz, 2H each, β-CH₂of

cyclopentylidene), 1.59 (s, 3H, CH₃). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 140.9 (ipso-C of cyclopentylidene), 138.2 (ipso-C of Ph),

128.5, 128.2 (o- and m-CH of Ph), 125.6 (p-CH of Ph), 123.8 (C),

41.5 (CH₂C), 30.8, 30.8 (α-CH₂of cyclopentylidene), 27.1, 26.8

(β-CH₂of cyclopentylidene), 18.9 (CH₃).

228.1882. (E)-3fa: H NMR (400 MHz, CDCl₃, δ): 7.34−7.27 (m,

2H, m-CH of Ph), 7.24−7.16 (m, 3H, o- and p-CH of Ph), 5.38 (tq, J

= 7.0, 2.4 Hz, 1H, CH), 3.37 (d, J = 7.0 Hz, 2H, CH₂CH),

2.49−2.38 (m, 1H, 5-CH₂of cyclopentylidene), 2.38−2.20 (m, 2H, 2-

CH and 5-CH₂of cyclopentylidene), 1.95−1.85, 1.84−1.73 (both m,

1H each, 3-CH₂of cyclopentylidene), 1.67−1.51 (m, 2H, 4-CH₂of

cyclopentylidene), 1.42−1.16 (m, 6H, (CH₂)₃CH₃), 0.91 (t, J = 6.0

Hz, 3H, CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 148.2 (1-C of

cyclopentylidene), 141.9 (ipso-C of Ph), 128.3 (o- and m-CH of Ph),

125.6 (p-CH of Ph), 118.1 (CH), 44.3 (2-CH of cyclo-

pentylidene), 35.7 (5-CH₂of cyclopentylidene), 34.2 (1-CH₂of

ⁿBu), 32.8 (CH₂CH), 30.1 (2-CH₂of ⁿBu), 29.4 (4-CH₂of

cyclopentylidene), 24.1 (3-CH₂of cyclopentylidene), 23.0 (3-CH₂of

ⁿBu), 14.2 (CH₃). (Z)-3fa (overlapping peaks indistinctive from those

(2-(2-Phenylcyclopentylidene)ethyl)benzene (3da). A colorless

oil (38.6 mg, 0.155 mmol, 62% yield based on the amount of 1d (55.6

mmol, 0.250 mmol)) as a mixture of E and Z isomers (E/Z = 92/8).

(E)-3da: HRMS (FAB) m/z [M]⁺Calcd for C₁₉H₂₀248.1565; Found

248.1558. H NMR (400 MHz, CDCl₃, δ): 7.33−7.12 (m, 10H, CH

of (E)-3fa not listed): H NMR (400 MHz, CDCl₃, δ): 5.40 (tq, J =

of Ph), 5.13 (tq, J = 7.8, 2.5 Hz, 1H, CH ), 3.59 (pseudo t, J = 8.2

Hz, 1H, 2-CH of cyclopentylidene), 3.37 (d, J = 7.8 Hz, 2H,

CH₂CH ), 2.65−2.44 (m, 2H, 5-CH₂of cyclopentylidene), 2.22−

2.11, 2.01−1.89 (both m, 1H each, 3-CH₂of cyclopentylidene),

1.83−1.65 (m, 2H, 4-CH₂of cyclopentylidene). Relative NOE’s

observed at 2.0% for δ 3.37 and 2.55 (PhCH₂CH CCH₂) and at

1.7% for δ 5.13 and 3.59 (PhCH₂CHCCCHPh), respectively.

¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 147.9, 145.2, 141.4 (ipso-C of

cyclopentylidene and Ph), 128.4, 128.3, 128.2, 128.2 (o- and m-CH of

Ph), 125.9, 125.7 (p-CH of Ph), 121.4 (C), 51.6 (2-CH of

cyclopentylidene), 36.6 (CH₂CH), 35.8 (5-CH₂of cyclopentyli-

dene), 29.7 (4-CH₂of cyclopentylidene), 24.6 (3-CH₂of cyclo-

pentylidene). (Z)-3da: HRMS (FAB) m/z [M]⁺Calcd for C₁₉H₂₀

7.6, 1.8 Hz, 1H, CH), 3.34 (dd, J = 15.6, 7.6 Hz, 1H, CH₂CH),

2.68 (br, 1H, 2-CH of cyclopentylidene), 0.91 (t, J = 7.4 Hz, 3H,

CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 148.4 (1-C of

cyclopentylidene), 128.1 (o- or m-CH of Ph), 125.7 (p-CH of Ph),

118.9 (CH), 40.2 (2-CH of cyclopentylidene), 35.4 (5-CH₂of

cyclopentylidene), 34.8 (1-CH₂of Bu), 33.3 (CH₂CH), 31.9 (2-

CH₂of ⁿBu), 24.1 (3-CH₂of cyclopentylidene), 22.8 (3-CH₂of ⁿBu).

(2-(2-Heptylcyclopentylidene)ethyl)benzene (3ga). A colorless oil

(41.9 mg, 0.155 mmol, 65% yield based on the amount of 1g (73.1

mg, 0.239 mmol)) as a mixture of E and Z isomers (E/Z = 93/7).

HRMS (FAB) m/z [M]⁺Calcd for C₂₀H₃₀270.2348; Found

270.2338. (E)-3ga: H NMR (400 MHz, CDCl₃, δ): 7.33−7.26 (m,

2H, m-CH of Ph), 7.24−7.16 (m, 3H, o- and p-CH of Ph), 5.38 (tq, J

= 6.8, 2.0 Hz, 1H, CH), 3.37 (d, J = 6.8 Hz, 2H, CH₂CH),

2.48−2.38 (m, 1H, 5-CH₂of cyclopentylidene), 2.38−2.26 (m, 2H, 2-

CH and 5-CH₂of cyclopentylidene), 1.95−1.86, 1.84−1.73 (both m,

1H each, 3-CH₂of cyclopentylidene), 1.65−1.51 (m, 2H, 4-CH₂of

cyclopentylidene), 1.45−1.16 (m, 12H, (CH₂)₆), 0.90 (t, J = 6.6 Hz,

3H, CH₃). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 148.2 (1-C of

cyclopentylidene), 141.9 (ipso-C of Ph), 128.3 (o- and m- CH of Ph,

overlapping), 125.6 (p-CH of Ph), 118.1 (C), 44.4 (2-CH of

cyclopentylidene), 35.7 (5-CH₂of cyclopentylidene), 34.5 (1-CH₂of

n-heptyl), 32.8 (CH₂CH), 31.9 (5-CH₂of n-heptyl), 29.9 (3-CH₂

of n-heptyl), 29.4 (4-CH₂of n-heptyl and 4-CH₂of cyclopentylidene,

overlapping), 27.8 (2-CH₂of n-heptyl), 24.1 (3-CH₂of cyclo-

pentylidene), 22.7 (6-CH₂of n-heptyl), 14.1 (CH₃). (Z)-3ga

(overlapping peaks indistinctive from those of (E)-3ga not listed):

¹H NMR (400 MHz, CDCl₃, δ): 5.40 (tq, J = 7.6, 1.8 Hz, 1H,

CH), 3.34 (dd, J = 15.6, 7.6 Hz, 1H, CH₂CH), 2.68 (br, 1H, 2-

CH of cyclopentylidene), 0.91 (t, J = 7.4 Hz, 3H, CH₃). ¹³C{¹H}

NMR (100 MHz, CDCl₃, δ): 148.5 (1-C of cyclopentylidene), 128.0

(o- or m-CH of Ph), 125.5 (p-CH of Ph), 118.9 (CH), 40.2 (2-CH

of cyclopentylidene), 35.4 (5-CH₂of cyclopentylidene), 35.1 (1-CH₂

of n-heptyl), 33.4 (CH₂CH), 29.8 (3-CH₂of n-heptyl).

248.1565; Found 248.1560. H NMR (400 MHz, CDCl₃, δ): 7.33−

7.09 (m, 8H, CH of Ph), 6.94 (d, J = 7.2 Hz, 2H, o-CH of Ph), 5.60

(tq, J = 7.2, 1.9 Hz, 1H, CH), 3.86 (pseudo t, J = 7.0 Hz, 1H, 2-CH

of cyclopentylidene), 3.12, 2.98 (both dd, J = 15.5, 7.2 Hz, 1H each,

CH₂CH), 2.62−2.40 (m, 2H, 5-CH₂of cyclopentylidene), 2.33−

2.22 (m, 1H, 3-CH₂of cyclopentylidene), 1.84−1.54 (m, 3H, 3- and

4-CH₂of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ):

146.6, 146.1, 141.4 (ipso-C of cyclopentylidene and Ph), 128.4, 128.3,

128.2, 127.6 (o- and m-CH of Ph), 125.6, 125.6 (p-CH of Ph), 121.9

(C), 47.1 (2-CH of cyclopentylidene), 38.3 (CH₂CH), 35.6 (5-

CH₂of cyclopentylidene), 35.3 (4-CH₂of cyclopentylidene), 25.1 (3-

CH₂of cyclopentylidene).

(2-(2-Ethylcyclopentylidene)ethyl)benzene (3ea). A colorless oil

(37.6 mg, 0.188 mmol, 75% yield based on the amount of 1e (59.1

mmol, 0.250 mmol)) as a mixture of E and Z isomers (E/Z = 88/12).

HRMS (FAB) m/z [M]⁺Calcd for C₁₅H₂₀200.1565; Found

200.1572. (E)-3ea: H NMR (400 MHz, CDCl₃, δ): 7.32−7.28 (m,

2H, m-CH of Ph), 7.24−7.19 (m, 3H, o- and p-CH of Ph), 5.39 (tq, J

= 7.2, 2.4 Hz, 1H, CH), 3.38 (d, J = 7.2 Hz, 2H, CH₂CH),

2.49−2.39 (m, 1H, 5-CH₂of cyclopentylidene), 2.38−2.25 (m, 2H, 2-

CH and 5-CH₂of cyclopentylidene), 1.96−1.86, 1.85−1.73 (both m,

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(2-(2-Cyclohexylcyclopentylidene)ethyl)benzene (3ha). A color-

less oil (33.0 mg, 0.130 mmol, 51% yield based on the amount of 1h

(73.5 mg, 0.253 mmol)) as a mixture of E and Z isomers (E/Z = 91/

9). HRMS (FAB) m/z [M]⁺Calcd for C₁₉H₂₆254.2035; Found

HRMS (FAB) m/z [M]⁺Calcd for C₂₀H₂₂262.1722; Found

262.1723. (E)-3ja: H NMR (400 MHz, CDCl₃, δ): 7.32−7.23 (m,

4H, m-CH of Ph), 7.23−7.11 (m, 6H, o- and p-CH of Ph), 3.87 (dd, J

= 7.6, 2.4 Hz, 1H, 2-CH of cyclopentylidene), 3.44 (s, 2H,

CH₂CH), 2.58 (t, J = 6.4 Hz, 2H, 5-CH₂of cyclopentylidene),

2.24−2.14, 1.80−1.64 (both m, 1H and 3H, respectively, 3- and 4-

CH₂of cyclopentylidene), 1.33 (s, 3H, CH₃). ¹³C{¹H} NMR (100

MHz, CDCl₃, δ): 146.8, 140.7, 140.3 (ipso-C of cyclopentylidene and

Ph), 128.5, 128.3, 128.2, 127.5 (o- and m-CH of Ph), 127.4 (C),

125.7, 125.3 (p-CH of Ph), 48.3 (2-CH of cyclopentylidene), 41.8

(CH₂CH), 37.9 (5-CH₂of cyclopentylidene), 32.0 (4-CH₂of

cyclopentylidene), 24.6 (3-CH₂of cyclopentylidene), 19.2 (CH₃).

(Z)-3ja (overlapping peaks indistinctive from those of (E)-3ga not

listed): ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 128.4 (o- or m-CH of

Ph), 125.5 (p-CH of Ph), 36.7 (5-CH₂of cyclopentylidene), 31.6 (4-

CH₂of cyclopentylidene), 22.6 (3-CH₂of cyclopentylidene), 14.1

(CH₃).

254.2035. (E)-3ha: H NMR (400 MHz, CDCl₃, δ): 7.33−7.27 (m,

2H, m-CH of Ph), 7.24−7.16 (m, 3H, o- and p-CH of Ph), 5.36 (tq, J

= 7.1, 2.4 Hz, 1H, CH), 3.39 (d, J = 7.2 Hz, 2H, CH₂CH),

2.49−2.39 (m, 1H, 5-CH₂of cyclopentylidene), 2.34−2.26 (m, 1H, 2-

CH of cyclopentylidene), 2.24−2.13 (m, 1H, 5-CH₂of cyclo-

pentylidene), 1.82−1.63, 1.61−1.42, 1.31−1.02 (all m, 7H, 3H, and

4H, respectively, CH and CH₂of Cy, and 3- and 4-CH₂of

cyclopentylidene), 0.93 (qd, J = 11.9, 2.8 Hz, 1H, 3-CH of

cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 146.2 (1-

C of cyclopentylidene), 141.9 (ipso-C of Ph), 128.3 (o- and m-CH of

Ph, overlapping), 125.6 (p-CH of Ph), 118.7 (CH), 50.0 (2-CH of

cyclopentylidene), 40.3 (1-CH of Cy), 35.8 (5-CH₂of cyclo-

pentylidene), 32.4 (CH₂CH), 29.8 (3-CH₂of cyclopentylidene),

28.1 (2- and 6-CH₂of Cy, overlapping), 27.0 (4-CH₂of Cy), 26.8,

26.7 (3- and 5-CH₂of Cy), 24.5 (4-CH₂of cyclopentylidene). (Z)-

3ha (overlapping peaks indistinctive from those of (E)-3ha not

listed): ¹H NMR (400 MHz, CDCl₃, δ): 5.45 (tq, J = 7.3, 1.8 Hz, 1H,

CH), 3.46 (dd, J = 16.0, 7.3 Hz, 1H, CH₂CH), 3.33 (dd, J =

15.8, 7.3 Hz, 1H, CH₂CH), 2.69−2.55 (m, 1H, 2-CH of

cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 147.0 (1-

C of cyclopentylidene), 128.1, 128.0 (o- and m- CH of Ph), 125.5 (p-

CH of Ph), 119.8 (CH), 45.8 (2-CH of cyclopentylidene), 41.4 (1-

CH of Cy), 35.6 (5-CH₂of cyclopentylidene), 34.4 (3-CH₂of

cyclopentylidene), 31.9 (CH₂CH), 28.9, 28.0 (2- and 6-CH₂of

Cy), 26.9 (4-CH₂of Cy), 26.7, 26.6 (3- and 5-CH₂of Cy), 24.0 (4-

CH₂of cyclopentylidene).

Preparation of Dimethyl 2-(3-Iodopropyl)-2-(prop-2-yn-1-

yl)malonate (4b). In a 50 mL Schlenk ﬂask were placed a

suspension of NaH, prepared from 461 mg of NaH (60% dispersion

in mineral oil, 11.5 mmol) and 11 mL of THF at 0 °C by using an

ice−water bath under N₂, where a THF solution (10 mL) of dimethyl

propargylmalonate (1.70 g, 10.0 mmol) was added dropwise. The

reaction mixture was gradually warmed to room temperature and was

further stirred for 2 h. Then the reaction mixture was cooled back to 0

°C by using an ice−water bath, and 1-bromo-3-chloropropane (4.72

g, 30.0 mmol) was added dropwise. The reaction mixture was

gradually warmed to room temperature and then was further reﬂuxed

for 24 h by using an oil bath. The resultant mixture was quenched

with a saturated aqueous solution of NH₄Cl (20 mL), and the

aqueous phase was extracted with ethyl acetate (20 mL × 3). The

combined organic layers were washed with brine (30 mL), dried over

anhydrous MgSO₄, and ﬁltered. The ﬁltrate was collected, and the

solvent was removed under reduced pressure. The residue was further

puriﬁed by column chromatography (SiO₂) with a mixture of n-

hexane/ethyl acetate (7:3) as an eluent to aﬀord dimethyl 2-(3-

chloropropyl)-2-(prop-2-yn-1-yl)malonate (4b-Cl) as a colorless oil

(1.61 g, 6.54 mmol, 65% yield based on the amount of dimethyl

propargylmalonate), which was directly used in the subsequent

transformation to obtain 2-(3-iodopropyl)-2-(prop-2-yn-1-yl)-

malonate (4b) without further puriﬁcation.

In a 50 mL Schlenk ﬂask were placed 4b-Cl (1.61 g, 6.54 mmol),

NaI (4.88 g, 32.6 mmol), and acetone (20 mL) under N₂, and the

reaction mixture was stirred and reﬂuxed for 22 h by using an oil bath.

Then, acetone was removed in vacuo, and the resultant mixture was

diluted with 20 mL of ethyl acetate and was ﬁltered. Solvent was

removed from the collected ﬁltrate under reduced pressure, and the

residue was puriﬁed by column chromatography (SiO₂) with a

mixture of n-hexane/ethyl acetate (7:3) as an eluent to aﬀord

dimethyl 2-(3-iodopropyl)-2-(prop-2-yn-1-yl)malonate (4b) as a

white waxy oil (1.72 g, 5.09 mmol, 78% yield based on the amount

of 4b-Cl, 65% yield based on the amount of dimethyl

propargylmalonate). mp 266.5−268.1 °C (decomp.). HRMS (FAB)

m/z [M]⁺Calcd for C₁₁H₁₅IO₄338.0015; Found: 338.0019. ¹H NMR

(400 MHz, CDCl₃, δ): 3.76 (CO₂Me), 3.17 (t, J = 7.0 Hz, 2H, CH₂I),

2.83 (d, J = 2.5 Hz, 2H, CH₂C), 2.19−2.13 (m, 2H,

CH₂CH₂CH₂I), 2.03 (t, J = 2.5 Hz, 1H, HC), 1.81−1.71 (m,

2H, CH₂CH₂I). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ): 170.3 (CO₂),

78.4 (C), 71.7 (HC), 56.3 (C(CH₂)₃I), 52.9 (CH₃), 33.2

(CH₂(CH₂)₂I), 28.3 (CH₂CH₂I), 23.2 (CH₂C), 5.2 (CH₂I).

Preparation of (E)-(2-(Iodomethylene)cyclopentyl)benzene

((E)-7d). Method 1 (in the Absence of 2a). In a 20 mL Schlenk ﬂask

were placed 1d (71.2 mg. 0.251 mmol), fac-[Ir(ppy)₃] (3.4 mg,

0.0052 mmol), anhydrous NiCl₂(3.4 mg, 0.026 mmol), dMeObpy

(8.2 mg, 0.038 mmol), and Cs₂CO₃(122 mg, 0.374 mmol) under N₂,

where 1,4-dioxane (2.5 mL) was added at room temperature. The

reaction ﬂask was placed in an As One LTB-125 constant low

temperature water bath set at 25 °C and was illuminated from the

bottom of the bath with an Aitech System TMN100×120−22WD 12

W white LED lamp (400−750 nm) at a distance of approximately 2

(E)-(2-(2,2-Dimethylcyclopentylidene)ethyl)benzene ((E)-3ia). A

colorless oil (39.0 mg, 0.195 mmol, 77% yield based on the amount of

1i (59.9 mg, 0.254 mmol)). HRMS (FAB) m/z [M]⁺Calcd for

C₁₅H₂₀200.1565; Found 200.1564. ¹H NMR (400 MHz, CDCl₃, δ):

7.31−7.24 (m, 2H, m-CH of Ph), 7.21−7.15 (m, 3H, o- and p-CH of

Ph), 5.30 (tt, J = 7.2, 2.5 Hz, 1H, CH), 3.33 (d, J = 7.2 Hz, 2H,

CH₂CH), 2.42 (tdt, J = 7.1, 2.5, 1.3 Hz, 2H, 3-CH₂of

cyclopentylidene), 1.70 (quint, J = 7.1 Hz, 2H, 4-CH₂of

cyclopentylidene), 1.53 (t, J = 7.1 Hz, 2H, 5-CH₂of cyclo-

pentylidene), 1.06 (s, 6H, CH₃). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 152.9 (1-C of cyclopentylidene), 141.9 (ipso-C of Ph),

128.6 (o- and m-CH of Ph), 125.6 (p-CH of Ph), 116.7 (CH), 42.2

(3-CH₂of cyclopentylidene), 41.9 (2-C of cyclopentylidene), 35.5

(CH₂CH), 29.3 (5-CH₂of cyclopentylidene), 28.8 (CH₃), 22.3 (4-

CH₂of cyclopentylidene).

(E)-1-(2-(2,2-Dimethylcyclopentylidene)ethyl)naphthalene ((E)-

3ii). A colorless oil (38.2 mg, 0.153 mmol, 61% yield based on the

amount of 1i (59.0 mmol, 0.250 mmol)). Colorless block crystals

suitable for crystallographic study were further obtained by

recrystallization from diethyl ether at −30 °C. HRMS (FAB) m/z

[M]⁺Calcd for C₁₉H₂₂250.1722; Found 250.1724. H NMR (400

MHz, CDCl₃, δ): 8.02 (dd, J = 8.0, 1.6 Hz, 1H, 5-CH of 1-naphthyl),

7.86 (dd, J = 8.0, 1.6 Hz, 8-CH of 1-naphthyl), 7.72 (d, J = 7.5 Hz,

1H, 4-CH of 1-naphthyl), 7.51 (td, J = 8.0, 1.6 Hz, 1H, 6-CH of 1-

naphthyl), 7.48 (td, J = 8.0, 1.6 Hz, 7-CH of 1-naphthyl), 7.40 (t, J =

7.5 Hz, 1H, 3-CH of 1-naphthyl) 7.33 (d, J = 7.5 Hz, 1H, 2-CH of 1-

naphthyl), 5.38 (tt, J = 7.2, 2.6 Hz, 1H, CH), 3.75 (d, J = 6.8 Hz,

2H, CH₂CH), 2.50 (tdt, J = 7.2, 2.6, 1.3 Hz, 2H, 3-CH₂of

cyclopentylidene), 1.74 (quint, J = 7.2 Hz, 2H, 4-CH₂of

cyclopentylidene), 1.55 (t, J = 7.2 Hz, 2H, 5-CH₂of cyclo-

pentylidene), 1.07 (s, 6H, CH₃). ¹³C{¹H} NMR (100 MHz,

CDCl₃, δ): 153.0 (1-C of cyclopentylidene), 137.8, 133.8, 132.1

(1-, 4a-, and 8a-C of 1-naphthyl), 128.6, 126.5, 125.6, 125.4, 125.3,

124.1 (CH of 1-naphthyl with two resonances overlapping at δ

125.6), 116.6 (CH), 42.2 (3-CH₂of cyclopentylidene), 42.1 (2-C

of cyclopentylidene), 32.9 (CH₂CH), 29.4 (5-CH₂of cyclo-

pentylidene), 28.8 (CH₃), 22.4 (4-CH₂of cyclopentylidene).

(2-(2-Phenylcyclopentylidene)propyl)benzene (3ja). A colorless

oil (32.8 mg, 0.125 mmol, 50% yield based on the amount of 1j (75.0

mg, 0.251 mmol)) as a mixture of E and Z isomers (E/Z = 89/11).

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cm from the light source for 48 h. The volatiles were removed in

vacuo, and the residue was puriﬁed by column chromatography

(SiO₂) with n-hexane as an eluent to aﬀord ((2-(iodomethylene)-

cyclopentyl)benzene (7d) as a colorless oil (40.6 mg, 0.143 mmol,

57% yield based on the amount of 1d) as a mixture of E and Z

isomers (E/Z = 83/17). Further puriﬁcation by column chromatog-

raphy (SiO₂) with n-hexane as an eluent gave (E)-((2-

(iodomethylene)cyclopentyl)benzene) ((E)-7d) in a pure form

(35.5 mg, 0.125 mmol, 50% yield based on the amount of 1d).

Method 2 (in the Presence of a Catalytic Amount of 2a but in

the Absence of NiCl₂/dMeObpy). In a 20 mL Schlenk ﬂask were

placed 1d (71.1 mg. 0.250 mmol), 2a (8.7 mg, 0.025 mmol), fac-

[Ir(ppy)₃] (3.4 mg, 0.0052 mmol), and Cs₂CO₃(122 mg, 0.374

mmol) under N₂, where 1,4-dioxane (2.5 mL) was added at room

temperature. The reaction ﬂask was placed in an As One LTB-125

constant low temperature water bath set at 25 °C and was illuminated

from the bottom of the bath with an Aitech System TMN100×120−

22WD 12 W white LED lamp (400−750 nm) at a distance of

approximately 2 cm from the light source for 24 h. The volatiles were

removed in vacuo, and the residue was puriﬁed by column

chromatography (SiO₂) with n-hexane as an eluent to aﬀord ((2-

(iodomethylene)cyclopentyl)benzene (7d) as a colorless oil (42.0 mg,

0.148 mmol, 59% yield based on the amount of 1d) as a mixture of E

and Z isomers (E/Z = 83/17). Further puriﬁcation by column

chromatography (SiO₂) with n-hexane as an eluent gave (E)-((2-

(iodomethylene)cyclopentyl)benzene) ((E)-7d) in a pure form (33.4

mg, 0.118 mmol, 47% yield based on the amount of 1d).

ASSOCIATED CONTENT

* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.1c01018.

■

sı

Experimental procedures and characterization data for

new compounds (PDF)

Accession Codes

CCDC 2061338 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif, or by emailing

data_request@ccdc.cam.ac.uk, or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

AUTHOR INFORMATION

Corresponding Author

■

Yoshiaki Nishibayashi − Department of Applied Chemistry,

School of Engineering, The University of Tokyo, Tokyo 113-

8656, Japan; orcid.org/0000-0001-9739-9588;

Email: ynishiba@g.ecc.u-tokyo.ac.jp

Authors

Yulin Zhang − Department of Applied Chemistry, School of

Engineering, The University of Tokyo, Tokyo 113-8656,

Japan

Yoshiaki Tanabe − Department of Applied Chemistry, School

of Engineering, The University of Tokyo, Tokyo 113-8656,

Japan; orcid.org/0000-0001-5858-7834

Shogo Kuriyama − Department of Applied Chemistry, School

of Engineering, The University of Tokyo, Tokyo 113-8656,

Japan

HRMS (FAB) m/z [M]⁺Calcd for C₁₂H₁₃I 284.0062; Found:

284.0063. ¹H NMR (400 MHz, CDCl₃, δ): 7.35−7.28 (m, 2H, m-CH

of Ph), 7.27−7.16 (m, 3H, o- and p-CH of Ph), 5.57 (pseudo quint, J

= 2.4 Hz, 1H, CH), 3.57 (t, J = 7.6 Hz, 1H, 2-CH of

cyclopentylidene), 2.59−2.49, 2.48−2.36, 2.36−2.27, 2.00−1.84,

1.82−1.68 (all m, 1H, 1H, 1H, 2H, and 1H respectively, 3-, 4-, and

5-CH of cyclopentylidene). ¹³C{¹H} NMR (100 MHz, CDCl₃, δ):

159.4 (1-C of cyclopentylidene), 142.8 (ipso-C of Ph), 128.5, 128.2

(o- and m-CH of Ph), 126.5 (p-CH of Ph), 72.9 (CH), 53.6 (2-CH

of cyclopentylidene), 37.8, 37.6 (4- and 5-CH₂of cyclopentylidene),

23.8 (3-CH₂of cyclopentylidene).

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.1c01018

Preparation of (E)-3da by the Reaction of (E)-7d with 2a. In

a 20 mL Schlenk ﬂask were placed (E)-7d (71.0 mg. 0.251 mmol), 2a

(257 mg, 0.751 mmol), fac-[Ir(ppy)₃] (3.4 mg, 0.0052 mmol),

anhydrous NiCl₂(3.5 mg, 0.027 mmol), dMeObpy (8.0 mg, 0.037

mmol), and Cs₂CO₃(123 mg, 0.378 mmol) under N₂, where 1,4-

dioxane (2.5 mL) was added at room temperature. The reaction ﬂask

was placed in an As One LTB-125 constant low temperature water

bath set at 25 °C and was illuminated from the bottom of the bath

with an Aitech System TMN100×120−22WD 12 W white LED lamp

(400−750 nm) at a distance of approximately 2 cm from the light

source for 24 h. The volatiles were removed in vacuo, and the residue

was puriﬁed by column chromatography (SiO₂) with n-hexane as an

eluent to aﬀord (E)-3da as a colorless oil (45.3 mg, 0.182 mmol, 73%

yield based on the amount of (E)-7d).

Large-Scale Preparation of 3da. In a 100 mL Schlenk ﬂask were

placed 1d (710 mg. 2.50 mmol), 2a (2.57 g, 7.49 mmol), fac-

[Ir(ppy)₃] (32.0 mg, 0.0489 mmol), anhydrous NiCl₂(34.2 mg, 0.264

mmol), dMeObpy (81.0 mg, 0.375 mmol), and Cs₂CO₃(1.22 g, 3.74

mmol) under N₂, where 1,4-dioxane (25.1 mL) was added at room

temperature. The reaction ﬂask was placed in an As One LTB-125

constant low temperature water bath set at 25 °C and was illuminated

from the bottom of the bath with an Aitech System TMN100×120−

22WD 12 W white LED lamp (400−750 nm) at a distance of

approximately 2 cm from the light source for 24 h. The volatiles were

removed in vacuo, and the resultant mixture was extracted with

dichloromethane via ﬁltration. Solvent was removed from the

collected ﬁltrate under reduced pressure, and the residue was puriﬁed

by column chromatography (SiO₂) with n-hexane as an eluent to

aﬀord 3da as a colorless oil (397 mg, 1.60 mmol, 64% yield based on

the amount of 1d) as a mixture of E and Z isomers (E/Z = 91/9).

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

The present project is supported by CREST, JST (JPMJCR-

1541). We acknowledge Grants-in-Aid for Scientiﬁc Research

(Grants 20H05671, 20K05680, and 20K21203) from JSPS and

MEXT.

REFERENCES

■

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Article Doi

Cooperative Photoredox- And Nickel-Catalyzed Alkylative Cyclization Reactions of Alkynes with 4-Alkyl-1,4-dihydropyridines

DOI: 10.1021/acs.joc.1c01018

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Article abstract of DOI:10.1021/acs.joc.1c01018

Full text of DOI:10.1021/acs.joc.1c01018

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