Hantzsch Ester-Mediated Photochemical Transformations in the Ketone Series: Remote C(sp3)-H Arylation and Cyclopentene Synthesis through Strain Release

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Hantzsch Ester-Mediated Photochemical Transformations in the

Ketone Series: Remote C(sp³)−H Arylation and Cyclopentene

Synthesis through Strain Release

Jan Paternoga, Jonas Kuhlborn, Nils Ole Rossdam, and Till Opatz*

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ABSTRACT: A metal-free Hantzsch ester-mediated synthesis of

cyclopentenylketones as well as γ-hetarylketones starting from

ketocyclopropanes under eco-friendly conditions was developed.

The versatility of the developed conditions is shown by reacting

ketocyclopropanes in both a formal [3 + 2] cycloaddition with

terminal alkynes (further investigated using theoretical calculations)

and a radical C−C-coupling with cyanopyridines. The newly

developed methodologies were later on utilized as a downstream

reaction for photogenerated cyclopropanes combining UV and

visible light photochemistry. Following this procedure, a UV-driven

Norrish−Yang-type reaction induces the ring strain of the

intermediates, which serves as activation energy for the subsequent

ring transformation.

Our laboratory has recently contributed to the ﬁeld of ring

strain-releasing chemistry by developing two-step sequences

that employ photogenerated 2-acylazirines in the synthesis of

imidazoles⁷and (fused) pyrroles.^8,9Based on the remarkable

work on the Norrish−Yang reactions by Wessig, it appeared

attractive to use photogenerated cyclopropanes as the simplest

strained carbocycle intermediates in similar sequences. In

terms of subsequent reactions of the ketocyclopropanes,

several reports on both metal-¹⁰and photoredox-catalyzed¹¹

strain-releasing reactions were reported that were able to point

out the synthetic potential for remote ring opening of such

strained substrates by activation of the carbonyl group. Based

on the reported lack of diastereoselectivity for the investigated

ketocyclopropanes by Wessig,⁵we aimed at subjecting the

photogenerated cyclopropanes to photoredox conditions to

achieve a stereoconvergent synthesis via radical intermediates.

In terms of single electron transfer (SET)-induced formal [3 +

2] reactions of substrates of this type, ring opening has

successfully been triggered using a tandem catalytic system

consisting of [Ru(bpy)₃]²⁺as a photoredox catalyst and the

Lewis acid Gd(OTf)₃to lower the redox potential of the

carbonyl group.^11a,bAlternatively, a chiral rhodium-based

INTRODUCTION

■

The utilization of ring strain as the driving force is a versatile

tool in organic synthesis as complex structures can be

synthesized from simple precursors ideally under very mild

conditions. The incorporation of strained substrates ideally

permits traceless transformations, where no low-energy co-

products (e.g., metal halides, phosphine oxides, or borate salts)

need to be formed simultaneously to eﬀect the formation of

new C−C or C−heteroatom bonds.¹The inherent ring strain

energy of small-ring systems, dominantly consisting of angular

(Baeyer) strain and torsional (Pitzer) strain, makes them the

ideal substrates for such reactions.^1,2Eco-friendly trans-

formations can be achieved when the ring strain is induced

in a previous step by a photochemical valence isomerization or

cycloaddition. In terms of green chemistry, light absorption in

these cases provides the activation energy for both the

synthesis of the strained intermediate and the downstream

reaction in a two-step sequence. In the context of the

photochemical generation of small-ring systems, the Nor-

rish−Yang cyclization is an attractive methodology and can be

used to generate diﬀerent kinds of highly strained inter-

mediates.³While the conventional Norrish−Yang reaction

leads to the formation of hydroxycyclobutanes,⁴Wessig

reported the formation of cyclopropylketones 2 by installing

a leaving group in the α-position of the acyclic ketone substrate

(Scheme 1).⁵As such cyclopropylketones contain a carbonyl

group, the activation of which can trigger ring opening, they

can serve as starting materials for various kinds of strain-

releasing reactions.^1,6

Received: October 30, 2020

Published: January 29, 2021

https://dx.doi.org/10.1021/acs.joc.0c02591

J. Org. Chem. 2021, 86, 3232−3248

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ring opening. Since terminal alkenes have already been

extensively studied as reaction partners,^11a−cwe focused on

the use of terminal alkynes and phenylacetylene was chosen as

the model substrate. The reaction conditions were sub-

sequently optimized with respect to solvent, concentration,

as well as equivalents of Hantzsch ester (HE) and amine

additive (Table 1). The best results were obtained using

Scheme 1. Previous Work Regarding the Photochemical

Synthesis and Related Ring-Opening Reactions of

Ketocyclopropanes

a

Table 1. Optimization Studies

b

#

solvent

amine (equiv)

alkyne eq. HE equiv yield (%)

1

2

3

4

5

6

7

8

MeCN

MTBE

PhMe

DMSO

MeOH

PhMe

DABCO (2.0)

TEA (2.0)

Me-Im (2.0)

DIPEA (2.0)

DIPEA (1.1)

5.00

2.00

1.05

0.80

1.05

21

34

42

17

8

35

39

49

50

37

62

40

9

10

11

12

13

14

15

16

c

10.0

88 (84 )

10.0

48

0

DIPEA (1.1)

d

1.05

0

a

Standard conditions: 0.1 mmol scale, 0.05 M, 5 cm distance to blue

b

LED, Me-Im = 1-Methylimidazole. Yields determined using

phenanthrene or 1,4-bistrimethylsilylbenzene as internal standard.

c

d

Isolated yield. Performed in the absence of light.

photocatalyst that combines both of these functions in a single

molecule can be used when the cyclopropane substrate

contains an N-mesitylimidazole coordination anchor (Scheme

1).^11c

nonpolar solvents such as methyl tert-butyl ether (MTBE) and

toluene, in which the HE is poorly soluble and therefore only a

low concentration of dihydropyridine is present (entries 1−5).

The comparison of diﬀerent amine additives revealed little

inﬂuence on the yield (entries 6−8). Nevertheless, the

incorporation of diisopropylethylamine (DIPEA) showed the

best results among the tested amines. Considering the results

of the control reaction without additive which only led to a

reduction in yield (entry 14) and the relatively high oxidation

potential of methylimidazole (entry 7), the amine presumably

only acts as a proton shuttle (vide infra). The yield was

furthermore found to strongly depend on the concentration of

the acetylene (entries 12−13). When the amount of acetylene

was lowered, high-performance liquid chromatography/elec-

trospray ionization mass spectrometry (HPLC/ESI-MS)

reaction control qualitatively showed a higher percentage of

ring-opened dimerization and hydrogenation products. Con-

trol reactions showed the reaction to selectively occur via the

excited HE as both the reaction without the dihydropyridine

and without light showed no conversion of the cyclopropane

starting material (entries 15−16).

Although these methodologies oﬀer an elegant solution to

overcome the highly negative reduction potential of the

carbonyl groups of ketones 2, we sought to identify reaction

conditions and a readily available and sustainable photo-

catalytic system to exploit the “green” aspects of such

sequences. Encouraged by recent reports on the use of the

strongly reducing photoexcited Hantzsch ester in SET

reductions of aldehyde and ketone substrates,¹²it was

attempted to ﬁrst develop a metal-free methodology without

additional Lewis acid activation of the carbonyl group or the

use of an aiding anchor group starting from conventionally

synthesized cyclopropanes. The newly developed methodology

should be subsequently applied to cyclopropanes generated by

the Norrish−Yang reaction with the spin-center shift described

by Wessig.⁵

RESULTS AND DISCUSSION

■

The initial task of the present study was the identiﬁcation of

suitable reaction conditions for the Hantzsch ester-mediated

formal [3 + 2] cycloaddition of cyclopropylketones 2.

To investigate the robustness of the developed method-

ology, several terminal alkynes (cyclopentenes 4a−e) and

cyclopropanes (cylopentenes 4i−n) were subjected to the

optimized reaction procedure.

The conditions were optimized on model compound 2a, as

it is easily accessible through the Norrish−Yang cyclization and

furnishes a benzyl-stabilized radical intermediate after initial

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As shown in Table 2, terminal alkynes containing radical

stabilizing aryl, alkenyl, and alkoxycarbonyl substituents

furnished the corresponding cyclopentenes in high yields

(71−89%) with a moderate diastereomeric ratio in the range of

2:1 to 3:1. In all of the investigated examples, the 1,4-cis

conﬁguration was found to be favored over the 1,4-trans

conﬁguration (determined using NOESY correlations on the

diastereomeric mixtures). Both internal and terminal alkynes

without stabilizing substituents (cyclopentenes 4f−g) were

found to give no [3 + 2] adducts, and only dimerized and

hydrogenated products of the ring-opened cyclopropane were

detected by HPLC/ESI-MS. The decoration of both the R¹

and R²aryl substituents in the cyclopropane with halogen,

cyano, or methoxy substituents (cyclopentenes 4i−m) as well

as the incorporation of a gem-dimethyl group in the position of

R²(cyclopentene 4n) were tolerated well. Nevertheless, the

higher reduction potential of the carbonyl accompanied with

the increased electron density of the conjugated aromatic

system in the synthesis of methoxy derivative 4i resulted in

longer reaction times and lower yield. Additionally, no product

formation was observed when a cyclopropane with a mono-

methylated R²group (cyclopentene 4h) was incorporated in

the cyclization. The incorporation of a nitro-substituted arene

as R²(cyclopentene 4m) gave the amino-substituted cyclo-

propane ﬁrst (as judged by HPLC/ESI-MS; see Figures S4 and

S5 in the Supporting Information (SI)), which could be further

reacted to the corresponding cyclopentene by increasing the

amount of HE to 2.5 equiv. Although recent examples already

showed the potential of the Hantzsch ester in deoxygenation

reactions of nitroaromatics,¹³to the best of our knowledge, no

photoreduction with the HE of an aromatic nitro group to the

aniline has been described so far. For reasons of puriﬁcation,

the aniline was quantitatively transformed into the acetanilide

derivative 4m, which was obtained in 57% over two steps.

After a brief optimization of the Norrish−Yang reaction with

spin-center shift toward higher yields and eco-friendliness for

the investigated substrates (see Table S1 in the SI), a two-step

telescoped methodology for the synthesis of cyclopentenes 4

starting from α-mesyloxyketones 1 was developed and

investigated (cyclopentenes 4o−s). Initially, a one-pot

procedure was envisioned by adding the reactants of the

formal [3 + 2] cycloaddition to the reaction mixture after the

photoisomerization. However, as the precipitated imidazolium

methanesulfonate salt was found to interfere with the

downstream reaction, the salt was removed by simple ﬁltration

before performing the ring enlargement. As shown in Table 2,

electronic variation of the aromatic R¹moiety by introducing

halogen, triﬂuoromethyl, or methyl groups was tolerated well

and gave the corresponding cyclopentenes 4a+o−q in

moderate yields (48−57%) over two steps. Although HPLC/

ESI-MS predictably showed diastereomeric mixtures for the

photogenerated cyclopropane intermediates, the ﬁnal products

were formed with the same diastereoselectivity when starting

from the pure trans-conﬁgurated cyclopropanes 2.

Table 2. Substrate Scope of the Metal-Free Formal [3 + 2]

Cycloaddition

To elucidate the symmetrizing eﬀect of the radical

intermediate 7 (vide infra), the diphenyl-substituted cyclo-

pentene 4a was both synthesized starting from α-mesylox-

yketone 1a and from pure 1,2-trans-conﬁgurated cyclopropane

2a (Scheme 2). The photoisomerization of α-mesyloxyketone

1a was previously found to give the cyclopropane 2a in a

diastereomeric ratio of 1.6:1 (Table S1 in the SI). The two-

step protocol gave the cyclopentene 4a in a similar

diastereomeric ratio of 2.5 to 1 as the single-step reaction,

conﬁrming the symmetrizing eﬀect of radical intermediate 7

(Scheme 3). Consequently, the formal cycloaddition was

found to occur via a stereoselective mechanism, where the

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yield due to a higher tendency of the ring-opened radical 7

toward H-atom transfer (HAT) from HE. Such hydrogenation

products were only found in traces for the other substrates.

Subsequently, the mechanism of the developed reaction was

investigated. Since the Norrish−Yang reaction with spin-center

shift has already been intensively studied,⁵we focused on the

photoredox-mediated downstream reaction using the Hantzsch

ester as a photoreductant. Initially, the ring opening of the

cyclopropane was investigated by radical trapping experiments.

The addition of 2,2,6,6-tetramethylpiperidine-1-oxyl

(TEMPO) to the reaction mixture of the formal [3 + 2]

cycloaddition under standard conditions both inhibited the

cyclization and gave the TEMPO adduct of ring-opened radical

7, which could be veriﬁed with high-resolution mass

spectrometry (HR-MS) and HPLC by comparing it with an

authentic sample synthesized diﬀerently (see the SI for

procedure and chromatograms).¹⁴Additionally, we were not

able to observe any product formation by directly exciting the

cyclopropane 2a with UV-B irradiation, suggesting no energy

transfer pathway to be present. Subsequently, we investigated

the existence of an electron donor−acceptor (EDA) complex

between the HE and the other reaction partners by UV/Vis

titration experiments. Such experiments revealed characteristic

charge transfer absorption bands in other HE-related

reactions.^12c,13,15Although we are unable to unambiguously

rule out the presence of an EDA complex at present, no such

CT bands could be found in our experiments (Figure 1, top;

for detailed UV spectra with all reaction partners, see the SI).

The light on/oﬀ experiment showed no product formation in

the dark phases. During these studies, the aromatized Hantzsch

pyridine HP was found to be formed in substoichiometric

amounts with ratios of around three molecules of cyclopentene

4a per molecule of pyridine (Figure 1, middle). The

optimization studies also showed full conversion of the

cyclopropane 2a with substoichiometric amounts of HE

(Table 1, entry 10), indicating the dihydropyridine to act as

a catalyst to some extent. However, these reaction conditions

were discarded due to lower yields and prolonged reaction

times (see Table S2 in the SI). The SET-oxidized Hantzsch

ester is rather known as an H-atom donor in HAT processes

than for its reductive regeneration, which would be required in

the redox-neutral reaction sequence. Moreover, no oxidizing

agent was present in the reaction mixture so that the ketyl

radical 9 is likely to be transformed into cyclopentene 4

through an HAT pathway involving the radical 9 as an H-atom

donor. Possible HAT acceptors are the terminal acetylene 3 or

the [HE-H] radical (vide infra). As the group of Yoon has

challenged the signiﬁcance of light on/oﬀ experiments in the

investigation of radical chain mechanisms, an HAT to

cyclopropane 2 cannot be excluded.¹⁶Evidence for HAT

processes involving the acetylene used in excess were found

during the puriﬁcation of cyclopentene 4c, where the

nonvolatile 4-(tert-butyl)phenylacetylene could be reisolated

to ﬁnd a consumption of around 3.5 equiv based on the

cyclopropane starting material. Accordingly, the cyclopentene

formation is likely to proceed via the following mechanism

(Scheme 3).

Scheme 2. Comparison between Single-Ring Expansion

Reaction and Strain Induce/Strain Release Sequence with

respect to Yield and Diastereomeric Ratio of the Cyclization

Product and Intermediate

Scheme 3. Proposed Mechanism for the Hantzsch Ester-

Mediated Synthesis of Cyclopentenes 4

stereoinformation of the cyclopropane 2 is obviously not

transferred to cyclopentene 4 and the outcome of the reaction

in terms of diastereoselctivity is solely based on the kinetics of

the cyclization itself (see Figure 2). The 2-thienyl derivative 4r

as a model substrate for ﬁve-membered heteroaromatics as

substituent R¹only gave trace amounts of the respective

product. Based on HPLC/ESI-MS, the limitation for this

substrate likely results from an ineﬀective photoisomerization

rather than from a problem in the formal [3 + 2] cycloaddition.

Other radical stabilizing groups such as a nitrile group as R²

(4s) were also tolerated but gave the cyclopentene in lower

The ring-opened key intermediate 7 is generated by SET

from the excited Hantzsch ester (E_1/2,calc.(HE^•+/HE*) = −2.28

V vs SCE)^12cto the carbonyl of cyclopropane 2 (E_1/2,MeCN(2a/

2a^•−) = −2.01 V vs SCE) followed by proton transfer and ring

opening. The assumption was further conﬁrmed by Stern−

Volmer studies showing the cyclopropane to quench the

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Figure 2. Elucidation of the preferred formation of the 1,4-cis isomers

on model cyclopentene 4a during the 5-exo-trig cyclization based on

the energy diﬀerence of the crucial transition states by density

functional theory (DFT) calculations.

We opted for the use of the M06-2X functional^18a

(unrestricted formalism due to the open-shell system) in

combination with the D3BJ dispersion correction,^18f,gwhich

was found to be the best hybrid functional for computing

reaction energies by Grimme and Goerigk.¹⁹The unrestricted

formalism was chosen rather than a restricted open-shell

formalism since it has a lower computational cost and proved

to be reasonably accurate for various applications.²⁰The

calculated results nicely matched the experimental observations

in our case as well. The energies of the radicals 8a with a

geometrical preorientation leading to the two possible

diastereomers were found to be identical. The energy of the

transition states (TS_8a/9a), on the other hand, matches well

with the observed d.r. values. Assuming the cyclization to be

kinetically controlled, the energy diﬀerence of 0.55 kcal/mol

favoring the transition state of the 1,4-cis over the 1,4-trans

diastereomer translates into a calculated d.r. value of 2.5:1 at

298 K,²¹which matches exactly the experimental value (see

Scheme 2). Further evidence for a kinetic control in the

cyclization was found experimentally. An attempt of a

subsequent thermodynamically driven equilibration of the

diastereomeric mixture of cyclopentene 4a toward higher d.r.

values by activation of the carbonyl with Al₂O₃only led to an

ablation of the diastereoselectivity (see Figure S20 in the SI),

indicating only little diﬀerence between the energies of the two

diastereomers of cyclization product 4a.

Next, the reactivity of the ring-opened radical 7 towards

other reaction partners was investigated. Our lab has positive

experience with reductively generated persistent radical anions

of cyanopyridines in photoredox-mediated reactions.²²Addi-

tionally, the Chu Lab demonstrated the Hantzsch ester to be

able to reductively generate such radical anions via excited-

state SET reduction.¹⁵As a test case and based on the

relatively long lifetime of these radical anions, it was attempted

to incorporate them in a radical−radical recombination with

the HE-generated ring-opened radical 7. In this reaction, the

photoexcited HE serves as a single electron donor for the

generation of both the cyanopyridine radical anion and the

radical 7. Gratifyingly, the C−C-coupling product 6a between

model cyclopropane 2a and 4-cyanopyridine 5 was already

formed in the ﬁrst attempt. After conducting optimization

experiments (Table S3 in the SI), the developed methodology

was applied to a series of cyanopyridines (6a−c), cyclo-

propanes (6d−f), and α-mesyloxyketones (6a+g−h) to

Figure 1. UV/Vis titration experiment (top), light on/oﬀ experiment

(middle), and ﬂuorescence quenching studies of Hantzsch ester (5 ×

10⁻⁴M in degassed CHCl₃) by 4-cyanopyridine 5 (green),

cyclopropane 2a (blue), phenylacetylene (orange) and DIPEA

(black) (bottom).

ﬂuorescence of the HE with the highest rate within the

reaction components (Figure 1, bottom). The order and

mechanism of the proton and the electron transfer were not

investigated and might either involve sequential steps or a

concerted mechanism, which was proposed for other HE-

mediated reactions generating ketyl radicals.^12d,f,17In this

regard, the amine additive might act as a proton shuttle for the

poorly soluble Hantzsch ester. Radical addition into the triple

bond of the alkyne regioselectively leads to the more stabilized

radical 8 that undergoes 5-exo-trig cyclization forming ketyl

radical 9. The already discussed HAT ﬁnally yields cyclo-

pentene 4.

To gain insight into the origin of the preference for the 1,4-

cis diastereomers during the 5-exo-trig cyclization, DFT

calculations on the uM06-2X-D3/6-31+G(d,p)/SMD-

(toluene) level of theory¹⁸on the related transition states

leading to the two possible diastereomers in the synthesis of

model cyclopentene 4a were performed (Figure 2).

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demonstrate the scope of the procedure (Scheme 4). The

reaction of 4-cyanopyridine and model cyclopropane 2a gave

Once again, the incorporation of an electron-rich substituent in

the aromatic R¹resulted in longer reaction times and lower

yields. The developed methodology could also be transformed

into a telescoped procedure starting from α-mesyloxyketones

1, formally leading to a dual-wavelength double photochemical

remote reductive hetarylation of these substrates. Comparable

to the results of the formal [3 + 2] cycloaddition sequence, the

pyridinylated products 6a+g−h were obtained in moderate

yield over two steps (38−52%).

Scheme 4. Substrate Scope of the Metal-Free

Functionalization of Cyclopropanes with Cyanopyridines

Based on the previous results, the mechanism of the

pyridinylation of the cyclopropane is assumed to be

straightforward (Scheme 5). Both the ring-opened radical 7

Scheme 5. Proposed Mechanism for the Synthesis of γ-

Pyridinylated Ketones 6

and the radical anion of the cyanopyridine 5 (E_1/2(5/5^•−) =

−1.87 V vs SCE)²³are reductively generated by the excited

HE. This assumption was further conﬁrmed as cyclopropane

2a and 4-cyaonpyridine 5 were found to quench the

ﬂuorescence of HE in a similar magnitude (Figure 1, bottom).

Radical−radical coupling as a consequence of the higher

concentration of the long-lived cyanopyridine radical anion 10

(persistent radical eﬀect)²⁴followed by elimination of cyanide

subsequently give the γ-pyridinylated ketone 6. While the

generation of the ring-opened radical 7 was veriﬁed in the

radical trapping experiments, the ability of the HE to generate

the persistent radical anions of 4-cyanopyridine was demon-

strated in the literature.¹⁵

the 4-pyridinylated product in 70% yield. The 2-pyridinylated

analogue 6b was isolated in a moderate yield of 48%.

Preliminary work showed the radical anion of 2-cyanopyridines

not only to have signiﬁcant electron density in the ipso-position

but also in the 5-position, frequently resulting in lower

yields.^22aWhen the 5-position is blocked, for example, in 1-

cyanoisoquinoline as a benzo-annulated 2-cyanopyridine

analogue, the yield of the corresponding product 6c increased

to 59%.

A variation of the cyclopropane precursor again demon-

strated the tolerance of methoxy-, halogen-, and cyano-

substituted aromatics as R¹and R²furnishing the γ-

pyridinylated ketones 6d−f in moderate yields (49−68%).

CONCLUSIONS

■

In summary, a metal-free photochemical synthesis of

ketocyclopentenes and γ-hetarylated ketones was developed

starting from conventionally synthesized ketocyclopropanes.

Furthermore, the methodology could be implemented into a

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were puriﬁed by automatic ﬂash column chromatography (eluent:

cyclohexane/ethyl acetate) to aﬀord the ketones 12.

facile metal-free two-step double photochemical synthesis of

such products combining a strain-inducing UV-driven step for

the generation of a strained cyclopropane intermediate with

the downstream visible light photoredox-catalyzed strain-

releasing reactions. To emphasize the sustainability aspects of

the sequences, the use of benign solvents as well as the readily

available Hantzsch ester as a photoreductant was implemented

for the two reactions.

1,4-Diphenylbutan-1-one (12a). Following the general procedure

using benzonitrile (3.06 mL, 30.0 mmol, 0.98 mL, 1.00 equiv) after

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

95:5 → 80:20) aﬀorded the title compound (6.10 g, 27.2 mmol, 91%)

as a colorless solid. R_f= 0.51 (4:1 cyclohexane/ethyl acetate). Mp:

54−55 °C (cyclohexane/ethyl acetate), lit.²⁷mp: 54−57 °C. IR/cm⁻¹

(ATR): 3061, 2936, 3026, 1684, 1597, 1496, 1407, 1226, 744, 691.

¹H NMR (300 MHz, CDCl₃) δ 7.95−7.90 (m, 2H), 7.58−7.52 (m,

1H), 7.48−7.41 (m, 2H), 7.36−7.24 (m, 2H), 7.24−7.17 (m, 3H),

2.99 (t, J = 7.5 Hz, 1H), 2.73 (t, J = 7.5 Hz, 1H), 2.15−2.03 (m, 2H).

¹³C{H} NMR (75 MHz, CDCl₃) δ 200.1, 141.7, 137.0, 132.9, 128.6,

128.5, 128.4, 128.0, 125.9, 37.7, 35.2, 25.7. MS (ESI): m/z = 225.1

[M + H]⁺. The spectroscopic data are in accordance with the

literature.²⁷

1-(4-Triﬂuoromethylphenyl)-4-phenylbutan-1-one (12b). Follow-

ing the general procedure using 4-triﬂuoromethylbenzonitrile (20.0

mmol, 2.68 mL, 1.00 equiv) after column chromatography (SiO₂,

eluent: cyclohexane/ethyl acetate, 95:5 → 80:20) aﬀorded the title

compound (3.09 g, 10.60 mmol, 53%) as a colorless solid. R_f= 0.41

(4:1 cyclohexane/ethyl acetate). Mp: 69−71 °C (cyclohexane/ethyl

acetate), lit.²⁸mp: 74−75 °C. IR/cm⁻¹(ATR): 2942, 1686, 1410,

1328, 1161, 1115, 1069, 827, 748, 703. ¹H NMR (300 MHz, CDCl₃)

δ 8.04−7.98 (m, 2H), 7.75−7.68 (m, 2H), 7.35−7.27 (m, 2H), 7.25−

7.18 (m, 3H), 3.00 (t, J = 7.4 Hz, 2H), 2.74 (t, J = 7.4 Hz, 2H), 2.19−

2.03 (m, 2H). ¹³C{H} NMR (75 MHz, CDCl₃) δ 199.0, 141.4, 139.6,

134.3 (q, J = 32.7 Hz), 128.51, 128.47, 128.3, 126.1, 125.7 (q, J = 3.8

Hz), 123.6 (q, J = 272.7 Hz), 37.9, 35.0, 25.4. MS (ESI): m/z = 293.1

[M + H]⁺. The spectroscopic data are in accordance with the

literature.²⁸

1-(3-Chlorophenyl)-4-phenylbutan-1-one (12c). Following the

general procedure using 3-chlorobenzonitrile (20.0 mmol, 2.41 mL,

1.00 equiv) after column chromatography (SiO₂, eluent: cyclohexane/

ethyl acetate, 95:5 → 80:20) aﬀorded the title compound (3.65 g,

14.1 mmol, 71%) as a yellow oil. R_f= 0.47 (4:1 cyclohexane/ethyl

acetate). IR/cm⁻¹(ATR): 3026, 1688, 1571, 1241, 1222, 1196, 786,

752, 700, 680. ¹H NMR, COSY (300 MHz, CDCl₃) δ 7.88 (t, J = 1.6

Hz, 1H, H-2′), 7.78 (dt, J = 7.8, 1.6 Hz, 1H, H-6′), 7.55−7.49 (m,

1H, H-4′), 7.39 (t, J = 7.8 Hz, 1H, H-5′), 7.34−7.27 (m, 2H, H-3″ +

H-5″), 7.24−7.16 (m, 3H, H-2″ + H-4″ + H-6″), 2.95 (t, J = 7.5 Hz,

2H, H-2), 2.72 (t, J = 7.5 Hz, 2H, H-4), 2.08 (p, J = 7.5 Hz, 2H, H-3).

¹³C{H} NMR, HSQC, HMBC (75 MHz, CDCl₃) δ 198.8 (C-1),

141.5 (C-1″), 138.5 (C-1′), 134.9 (C-3′), 132.9 (C-4′), 129.9 (C-5′),

128.5 (C-3″ + C-5″), 128.5 (C-2″ + C-6″), 128.2 (C-2′), 126.1 (C-

6′), 126.0 (C-4″), 37.7 (C-2), 35.1 (C-4), 25.5 (C-3). MS (ESI): m/z

= 259.1 [M + H]⁺. HRMS (APCI-ToF) m/z: [M + H]⁺calcd for

C₁₆H₁₆ClO 259.0884, found 259.0883.

1-(3-Methylphenyl)-4-phenylbutan-1-one (12d). Following the

general procedure using 3-methylbenzonitrile (20.0 mmol, 2.40 mL,

1.00 equiv) after column chromatography (SiO₂, eluent: cyclohexane/

ethyl acetate, 97:3 → 85:15) aﬀorded the title compound (4.38 g,

18.4 mmol, 66%) as a colorless solid. R_f= 0.60 (4:1 cyclohexane/ethyl

acetate). Mp: 39−40 °C (cyclohexane/ethyl acetate). IR/cm⁻¹

(ATR): 2924, 1683, 1604, 1454, 1270, 745, 699. ¹H NMR (400

MHz, CDCl₃) δ 7.75−7.69 (m, 2H), 7.38−7.32 (m, 2H), 7.32−7.27

(m, 2H), 7.24−7.17 (m, 3H), 2.97 (t, J = 7.5 Hz, 2H), 2.73 (t, J = 7.5

Hz, 2H), 2.40 (s, 3H), 2.09 (p, J = 7.5 Hz, 2H). ¹³C{H} NMR (101

MHz, CDCl₃) δ 200.4, 141.7, 138.3, 137.0, 133.7, 128.6, 128.5,

128.42, 128.39, 125.9, 125.3, 37.7, 35.2, 25.8, 21.4. MS (ESI): m/z =

239.1 [M + H]⁺. The spectroscopic data are in accordance with the

literature.²⁹

EXPERIMENTAL SECTION

■

Materials and Methods. Acetonitrile (MeCN), dichloromethane

(DCM), 1,2-dichloroethane (DCE), and cyclohexane were distilled

from calcium hydride under a nitrogen atmosphere. Solvents were

degassed using freeze−pump−thaw cycles or by bubbling argon

through the liquid in an ultrasonic bath. Deuterochloroform was

stored over basic alumina (Brockmann activity I). All reagents were

purchased from commercial suppliers and used without further

puriﬁcation. Water- or oxygen-sensitive reactions were performed

under an atmosphere of nitrogen in oven-dried glassware using

standard Schlenk techniques. Photochemical reactions using UV light

were performed in quartz tubes using a photochemical reactor

equipped with a circular array of 16 UV lamps (Ushio G8T5E (7.2 W,

λ_max= 306 nm)), a magnetic stirrer, and a cooling fan. Visible light

photochemical reactions were performed using blue LEDs (Kessil

A150W Deep Ocean Blue, 34 W, λ_max≈ 460 nm) that were placed

next to the reaction mixture in a 10 mL Schlenk tube (distance, 5 cm).

For more information and the emission spectra of the lamps, see the

Supporting Information. Thin-layer chromatography was carried out

on silica gel 60 F₂₅₄plates and visualized using UV light. Preparative

normal-phase chromatography was carried out on silica gel (35−70

μm) using manual ﬂash chromatography or an automatic ﬂash

puriﬁcation system. Preparative reversed-phase chromatography was

performed on an HPLC system with a C₁₈PFP or H-Tec column

(pore size: 5 μm, length: 15 cm, diameter: 30 mm) or on an

automatic ﬂash puriﬁcation system with C₁₈-modiﬁed silica gel

columns and using mixtures of acetonitrile and water as eluent.

Melting points were determined in open capillary tubes and are not

corrected. NMR spectra were recorded on a 300, 400, or 600 MHz

1

instrument at 23 °C using standard pulse sequences. The H and

¹³C{H} chemical shifts (δ) were referenced to the residual solvent

signal as an internal standard (CDCl₃: δ = 7.26 and 77.16 ppm).²⁵

The ¹⁹F NMR were referenced to an external standard (¹⁹F: α,α,α-

triﬂuorotoluene in CDCl₃, δ = −63.9 ppm). Structural assignments

were made with additional information from gCOSY, gHSQC,

gNOESY, and gHMBC experiments. FT-IR spectra (given in cm⁻¹)

were recorded using a diamond ATR unit. HPLC/ESI-MS spectra

were recorded using an HPLC system with a UV diode array detector

coupled with an LC/MSD ion trap. Mixtures of water (with 0.1%

formic acid) and acetonitrile were used as an eluent at a total ﬂow rate

of 1.0 mL/min. High-resolution masses (APCI-MS and ESI-MS) were

recorded using a Q-ToF instrument with dual source and suitable

external calibrant.

Ketone Synthesis. Ketones 12 were synthesized using an

optimized method of Van Aerschot and co-workers:²⁶To a solution

of 1-bromo-3-phenylpropane (1.40 equiv) and magnesium (1.40

equiv) in dry THF (c = 0.60 mmol/mL) was added a catalytic amount

of iodine, and the suspension was reﬂuxed for 0.5 h. The reaction

mixture was cooled to room temperature, and the corresponding

nitrile (1.00 equiv) in THF (c = 2.00 mmol/mL) was added dropwise.

The solution was stirred at 70 °C until thin-layer chromatography

(TLC) or HPLC/ESI-MS showed full consumption of the starting

material (2−16 h). The reaction mixture was cooled to room

temperature, and saturated ammonium chloride solution (50 mL) was

slowly added to quench the excess of Grignard reagent. The phases

were separated, and the aqueous phase was further extracted with

ethyl acetate (3 × 50 mL). The organic phase was dried over

NaHCO₃, and the solvent was removed in vacuo. The crude products

1-(2-Thienyl)-4-phenylbutan-1-one (12e). Following the general

procedure using 2-cyanothiophene (20.0 mmol, 1.86 mL, 1.00 equiv)

after column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 95:5 → 80:20) aﬀorded the title compound (1.69 g, 7.30

mmol, 37%) as a yellow oil. R_f= 0.38 (4:1 cyclohexane/ethyl acetate).

1

IR/cm⁻¹(ATR): 2937, 1660, 1416, 1236, 857, 725, 700. H NMR,

COSY (300 MHz, CDCl₃) δ 7.65 (dd, J = 3.8, 1.1 Hz, 1H, H-3′), 7.62

(dd, J = 5.0, 1.1 Hz, 1H, H-5′), 7.33−7.26 (m, 2H, H-3″ + H-5″),

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7.24−7.16 (m, 3H, H-2″ + H-4″ + H-6″), 7.11 (dd, J = 5.0, 3.8 Hz,

1H, H-4′), 2.92 (t, J = 7.5 Hz, 2H, H-2), 2.72 (t, J = 7.5 Hz, 2H, H-

4), 2.16−2.03 (m, 2H, H-3). ¹³C{H} NMR, HSQC, HMBC (75

MHz, CDCl₃) δ 193.1 (C-1), 144.4 (C-2′), 141.5 (C-1″), 133.4 (C-

5′), 131.7 (C-3′), 128.5 (C-2″ + C-6″), 128.4 (C-3″ + C-5″), 128.0

(C-4′), 126.0 (C-4″), 38.5 (C-2), 35.2 (C-4), 26.1 (C-3). MS (ESI):

m/z = 231.0 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for

C₁₄H₁₅OS 231.0838, found 231.0838.

4′), 130.3 (C-5′), 128.9 (C-3″ + C-5″), 128.8 (C-2″ + C-6″), 128.5

(C-2′), 126.8 (C-4″), 126.4 (C-6″), 79.6 (C-2), 39.5 (SO₂CH₃), 33.9

(C-3), 31.1 (C-4). MS (ESI): m/z = 375.0 [M + Na]⁺. HRMS (ESI-

ToF) m/z: [M + H]⁺calcd for C₁₇H₁₈ClO₄S 353.0609, found

353.0606.

1-(3-Methylphenyl)-2-mesyloxy-4-phenylbutan-1-one (1d). Fol-

lowing the general procedure using 1-(3-methylphenyl)-4-phenyl-

butan-1-one (3.00 mmol, 0.71 g, 1.00 equiv) after 16 h at 70 °C,

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

95:5 → 60:40) aﬀorded the title compound (789 mg, 2.38 mmol,

79%) as a colorless oil. R_f= 0.22 (4:1 cyclohexane/ethyl acetate). IR/

4-Cyano-1-phenylbutan-1-one (12f). The title compound was

synthesized using a procedure of the Streuﬀ group.³⁰The

spectroscopic data are in accordance with the literature.³⁰

1

cm⁻¹(ATR): 2937, 1696, 1348, 1260, 1170, 937, 846, 681, 525. H

α-Mesyloxyketone synthesis. The α-mesyloxyketones 1 were

synthesized applying a modiﬁed method of Wessig:⁵To a solution of

the corresponding ketone 12 (1.00 equiv) in MeCN (c = 0.40 M) was

added [hydroxy(mesyloxy)iodo]benzene (1.20 equiv), and the

solution was stirred at 70 °C until TLC or HPLC/ESI-MS showed

full consumption of the starting material (16−40 h). The excess of

hypervalent iodine reagent was quenched with saturated sodium

thiosulfate solution (20 mL), and the mixture was extracted with ethyl

acetate (3 × 50 mL). The combined organic extracts were dried over

Na₂SO₄, and the solvent was removed in vacuo. The residue was

puriﬁed by automatic ﬂash column chromatography (eluent: cyclo-

hexane/ethyl acetate) to aﬀord the α-mesyloxyketones 1.

NMR, COSY (300 MHz, CDCl₃) δ 7.55−7.49 (m, 1H, H-6′), 7.46−

7.43 (m, 1H, H-2′), 7.42−7.36 (m, 1H, H-4′), 7.36−7.28 (m, 3H, H-

5′ + H-2″ + H-6″), 7.27−7.20 (m, 3H, H-3″-5″), 5.94−5.85 (m, 1H,

H-2), 3.17 (s, 3H, SO₂CH₃), 2.97−2.77 (m, 2H, H-3), 2.39−2.32 (m,

3H, C-3′-CH₃), 2.28−2.14 (m, 2H, H-4). ¹³C{H} NMR, HSQC,

HMBC (75 MHz, CDCl₃) δ 195.3 (C-1), 139.8 (C-1″), 139.0 (C-3′),

135.1 (C-4′), 133.8 (C-1′), 129.1−128.9 (6C, C-2′ + C-5′ + C-2″-3″

+ C-5″-6″), 126.7 (C-4″), 125.7 (C-6″), 80.1 (C-2), 39.6 (SO₂CH₃),

34.3 (C-4), 31.2 (C-3), 21.4 (C-3′-CH₃). MS (ESI): m/z = 333.1 [M

+ H]⁺. HRMS (ESI-ToF) m/z: [M + Na]⁺calcd for C₁₈H₂₀O₄SNa

355.0974, found 355.0971.

1,4-Diphenyl-2-mesyloxybutan-1-one (1a). Following the general

procedure using 1,4-diphenylbutan-1-one (2.24 g, 10.0 mmol, 1.00

equiv) after 16 h, column chromatography (SiO₂, eluent: cyclo-

hexane/ethyl acetate, 95:5 → 60:40) aﬀorded the title compound

(2.23 g, 7.00 mmol, 70%) as a slightly yellow solid. R_f= 0.21 (4:1

cyclohexane/ethyl acetate). Mp: 40−42 °C (cyclohexane/ethyl

acetate), lit.⁵mp: 52−57 °C. IR/cm⁻¹(ATR): 3028, 2938, 1699,

1597, 1450, 1352, 1173, 883, 697, 525. ¹H NMR (300 MHz, CDCl₃)

δ 7.75−7.67 (m, 2H), 7.65−7.55 (m, 1H), 7.48−7.38 (m, 2H), 7.39−

7.29 (m, 2H), 7.31−7.17 (m, 3H), 5.92−5.85 (m, 1H), 3.17 (s, 3H),

2.97−2.77 (m, 2H), 2.28−2.15 (m, 2H). ¹³C{H} NMR (75 MHz,

CDCl₃) δ 195.2, 139.7, 134.3, 133.9, 129.1, 128.9, 128.6, 126.8, 80.2,

39.6, 34.3, 31.3. MS (ESI): m/z = 341.1 [M + Na]⁺. The

spectroscopic data are in accordance with the literature.⁵

1-(2-Thienyl)-2-mesyloxy-4-phenylbutan-1-one (1e). Following

the general procedure using 4-phenyl-1-(2-thienyl)-butan-1-one

(3.00 mmol, 0.69 g, 1.00 equiv) after 18 h at 70 °C, column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 95:5 →

70:30) aﬀorded the title compound (640 mg, 2.00 mmol, 66%) as a

yellow solid. R_f= 0.15 (4:1 cyclohexane/ethyl acetate). Mp: 68−70

°C (cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3028, 1673, 1413,

1

1353, 1251, 1173, 969, 922, 854, 731, 525. H NMR, COSY (300

MHz, CDCl₃) δ 7.72 (dd, J = 5.0, 1.1 Hz, 1H, H-5′), 7.48 (dd, J = 3.9,

1.1 Hz, 1H, H-3′), 7.37−7.30 (m, 2H, H-3″ + H-5″), 7.28−7.20 (m,

3H, H-2″ + H-4″ + H-6″), 7.11 (dd, J = 5.0, 3.9 Hz, 1H, H-4′), 5.66−

5.60 (m, 1H, H-2), 3.14 (s, 3H, SO₂CH₃), 3.00−2.76 (m, 2H, H-4),

2.35−2.23 (m, 2H, H-3). ¹³C{H} NMR, HSQC, HMBC (75 MHz,

CDCl₃) δ 187.8 (C-1), 140.0 (C-2′), 139.6 (C-1″), 135.5 (C-5′),

133.2 (C-3′), 128.8 (C-3″ + C-5″), 128.7 (C-2″ + C-6″), 128.6 (C-

4′), 126.6 (C-4″), 80.3 (C-2), 39.4 (SO₂CH₃), 34.8 (C-4), 31.1 (C-

3). MS (ESI): m/z = 325.1 [M + H]⁺. HRMS (ESI-ToF) m/z: [M +

Na]⁺calcd for C₁₅H₁₆O₄S₂Na 347.0382, found 347.0382.

4-Cyano-2-mesyloxy-1-phenylbutan-1-one (1f). Following the

general procedure using 4-cyano-1-phenylbutan-1-one (4.00 mmol,

0.69 g, 1.00 equiv) after 18 h at 70 °C, column chromatography

(SiO₂, eluent: cyclohexane/ethyl acetate, 92:8 → 50:50) aﬀorded the

title compound (850 mg, 3.20 mmol, 80%) as a colorless solid. R_f=

0.17 (2:1 cyclohexane/ethyl acetate). Mp: 57−58 °C (cyclohexane/

ethyl acetate), lit.⁵mp: 60−62 °C. IR/cm⁻¹(ATR): 2940, 1699,

1354, 1174, 1056, 1001, 930, 698, 524. ¹H NMR (400 MHz, CDCl₃)

δ 7.99−7.89 (m, 2H), 7.72−7.62 (m, 1H), 7.59−7.48 (m, 2H), 6.11−

6.00 (m, 1H), 3.18 (s, 3H), 2.71−2.52 (m, 2H), 2.43−2.34 (m, 1H),

2.27−2.17 (m, 1H). ¹³C{H} NMR (101 MHz, CDCl₃) δ 193.5,

134.8, 133.3, 129.3, 128.6, 118.0, 77.9, 39.4, 28.3, 13.4. MS (ESI): m/

z = 268.0 [M + H]⁺. The spectroscopic data are in accordance with

the literature.⁵

Cyclopropane synthesis. The corresponding cyclopropanes

were synthesized using an optimized procedure of Yoon and co-

workers.^11bThe α,β-unsaturated ketones were commercially available

or previously synthesized in our group using standard conditions.³¹

To a mixture of trimethylsulfoxonium iodide (1.20 equiv) and NaH

(60% in mineral oil, 1.20 equiv), dimethyl sulfoxide (DMSO) (c =

0.60 M) was added dropwise. After the hydrogen evolution ended, the

corresponding chalcone (1.00 equiv) was added (portion-wise in case

of solids, or dropwise in case of liquids as solution in DMSO (c = 2.00

M)). The mixture was stirred at room temperature until TLC or

HPLC/ESI-MS showed full consumption of the starting material. The

reaction was carefully quenched with water (50 mL) and extracted

with Et₂O (3 × 50 mL). The combined organic extracts were dried

over Na₂SO₄, and the solvent was removed in vacuo. The crude

1-(4-Triﬂuoromethylphenyl)-2-mesyloxy-4-phenylbutan-1-one

(1b). Following the general procedure using 4-phenyl-1-(4-triﬂuor-

methylphenyl)-butan-1-one (5.00 mmol, 1.46 g, 1.00 equiv) after 16 h

at 70 °C, column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 95:5 → 70:30) aﬀorded the title compound (1.45 g, 3.70

mmol, 75%) as a colorless solid. R_f= 0.13 (4:1 cyclohexane/ethyl

acetate). Mp: 108−110 °C. IR/cm⁻¹(ATR): 1706, 1323, 1168, 1128,

1

1067, 932, 820, 701, 524. H NMR, COSY (300 MHz, CDCl₃) δ

7.80−7.76 (m, 2H, H-2′ + H-6′), 7.70−7.66 (m, 2H, H-3′ + H-5′),

7.38−7.32 (m, 2H, H-3′ + H-5″), 7.30−7.25 (m, 1H, H-4″), 7.24−

7.20 (m, 2H, H-2″ + H-6″), 5.87−5.80 (m, 1H, H-2), 3.18 (s, 3H,

SO₂CH₃), 2.97−2.78 (m, 2H, H-4), 2.25−2.15 (m, 2H, H-3). ¹³C{H}

NMR, HSQC, HMBC (75 MHz, CDCl₃) δ 194.4 (C-1), 139.31 (C-

1″), 136.5 (C-1′), 135.3 (q, ²J_CF= 33.0 Hz, C-4′), 128.9 + 128.2 (C-

2′ + C-6′ + C-3″ + C-5″), 128.8 (C-2″ + C-6″), 126.8 (C-4″), 126.0

3

1

(q, J_CF= 3.7 Hz, C-3′ + C-5′), 123.30 (q, J_CF= 273.0 Hz, C-4′-

CF₃), 79.6 (C-2), 39.4 (SO₂CH₃), 33.8 (C-3), 31.1 (C-4). ¹⁹F NMR

(376 MHz, CDCl₃) δ −63.34 (s, CF₃). MS (ESI): m/z = 409.1 [M +

Na]⁺. HRMS (ESI-ToF) m/z: [M + Na]⁺calcd for C₁₈H₁₇F₃O₄SNa

409.0692, found 409.0692.

1-(3-Chlorophenyl)-2-mesyloxy-4-phenylbutan-1-one (1c). Fol-

lowing the general procedure using 4-phenyl-1-(3-chlorophenyl)-

butan-1-one (5.00 mmol, 1.29 g, 1.00 equiv) after 18 h at 70 °C,

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

95:5 → 70:30) aﬀorded the title compound (1.38 g, 3.90 mmol, 78%)

as a colorless solid. R_f= 0.25 (4:1 cyclohexane/ethyl acetate). Mp:

107−108 °C. IR/cm⁻¹(ATR): 3065, 1703, 1351, 1240, 1172, 938,

753, 701, 525. ¹H NMR, COSY (300 MHz, CDCl₃) δ 7.67 (t, J = 1.9

Hz, 1H, H-2′), 7.58−7.51 (m, 2H, H-4′ + H-6′), 7.39−7.28 (m, 4H,

H-5′ + H-3″-5″), 7.28−7.19 (m, 2H, H-2″ + H-6″), 5.79 (t, J = 6.2

Hz, 1H, H-2), 3.17 (s, 3H, SO₂CH₃), 2.97−2.76 (m, 2H, H-4), 2.25−

2.15 (m, 2H, H-3). ¹³C{H} NMR, COSY, HSQC (75 MHz, CDCl₃)

δ 194.0 (C-1), 139.3 (C-1″), 135.4 + 135.2 (C-1′ + C-3′), 134.1 (C-

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product was puriﬁed by automatic ﬂash column chromatography

(eluent: cyclohexane/ethyl acetate) to aﬀord cyclopropanes 2.

Phenyl-[phenylcyclopropyl]methanone (2a). Following the gen-

eral procedure using (2E)-1,3-diphenyl-2-propen-1-one (36.0 mmol,

7.50 g, 1.00 equiv) after stirring at room temperature for 16 h, ﬂash

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

98:2 → 80:20) aﬀorded the title compound (5.78 g, 26.0 mmol, 72%)

as a colorless solid. R_f= 0.30 (50:1 cyclohexane/ethyl acetate). Mp:

44−46 °C (cyclohexane/ethyl acetate), lit.⁵mp: 45−47 °C. IR/cm⁻¹

(ATR): 1667, 1449, 1398, 1343, 1223, 987, 925, 697. ¹H NMR (600

MHz, CDCl₃) δ 8.02−7.99 (m, 2H), 7.57 (m, 1H), 7.49−7.45 (m,

2H), 7.35−7.30 (m, 2H), 7.26−7.22 (m, 1H), 7.20−7.18 (m, 2H),

2.92 (m, 1H), 2.71 (m, 1H), 1.94 (m, 1H), 1.57 (m, 1H). ¹³C{H}

NMR (151 MHz, CDCl₃) δ 198.6, 140.5, 137.7, 133.0, 128.6, 128.1,

126.6, 126.2, 30.1, 29.4, 19.3. MS (ESI): m/z = 223.1 [M + H]⁺. The

spectroscopic data are in accordance with the literature.⁵

(4-Methoxyphenyl)-[2-phenylcyclopropyl]methanone (2b). Fol-

lowing the general procedure using (2E)-3-phenyl-1-(4-

methoxyphenyl)prop-2-en-1-one (10.0 mmol, 2.38 g, 1.00 equiv)

after stirring for 18 h at room temperature, ﬂash column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 97:3 →

75:25) aﬀorded the title compound (2.07 g, 8.20 mmol, 82%) as a

colorless solid. R_f= 0.47 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹

(ATR): 3006, 1656, 1599, 1260, 1228, 1168, 1027, 986, 742, 697. ¹H

NMR (400 MHz, CDCl₃) δ 8.03−7.96 (m, 2H), 7.33−7.28 (m, 2H),

7.25−7.20 (m, 1H), 7.20−7.16 (m, 2H), 6.97−6.91 (m, 2H), 3.87 (s,

3H), 2.90−2.82 (m, 1H), 2.71−2.63 (m, 1H), 1.94−1.84 (m, 1H),

1.55−1.48 (m, 1H). ¹³C{H} NMR (101 MHz, CDCl₃) δ 196.9,

163.4, 140.7, 130.7, 130.4, 128.5, 126.5, 126.2, 113.7, 55.5, 29.5, 28.9,

18.9. MS (ESI): m/z = 253.1 [M + H]⁺. The spectroscopic data are in

accordance with the literature.³²

cyanophenyl)prop-2-en-1-one (3.50 mmol, 820 mg, 1.00 equiv)

after stirring at room temperature for 18 h, ﬂash column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 97:3 →

90:10) aﬀorded the title compound (685 mg, 2.80 mmol, 79%) as a

colorless solid. R_f= 0.25 (4:1 cyclohexane/ethyl acetate). Mp: 85−86

°C (cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3058, 2227, 1667,

1

1608, 1450, 1396, 1340, 1224, 988, 821, 713, 559. H NMR (400

MHz, CDCl₃) δ 8.01−7.96 (m, 2H), 7.62−7.56 (m, 3H), 7.51−7.45

(m, 2H), 7.30−7.23 (m, 2H), 2.97−2.92 (m, 1H), 2.77−2.70 (m,

1H), 2.01−1.93 (m, 1H), 1.61−1.55 (m, 1H). ¹³C{H} NMR (101

MHz, CDCl₃) δ = 197.8, 146.4, 137.5, 133.4, 132.5, 128.8, 128.3,

127.0, 110.4, 29.7, 29.3, 19.9. MS (ESI): m/z = 248.1 [M + H]⁺. The

spectroscopic data are in accordance with the literature.³⁴

(4-Chlorophenyl)-[2-(3-nitrophenyl)cyclopropyl]methanone (2f).

Following the general procedure using (2E)-3-(4-chlorophenyl)-1-(3-

nitrophenyl)prop-2-en-1-one (3.5 mmol, 1.01 g, 1.00 equiv) after

stirring for 20 h at room temperature, ﬂash column chromatography

(SiO₂, eluent: cyclohexane/ethyl acetate, 97:3 → 90:10) aﬀorded the

title compound (0.75 g, 2.48 mmol, 71%) as a yellow solid. R_f= 0.28

(4:1 cyclohexane/ethyl acetate). Mp: 102−103 °C (cyclohexane/

ethyl acetate). IR/cm⁻¹(ATR): 1668, 1572, 1407, 1349, 1221, 1092,

1

1004, 734, 680. H NMR, COSY (300 MHz, CDCl₃) δ 8.12−8.05

(m, 1H, H-4‴), 7.98 (t, J = 2.0 Hz, 1H, H-2‴), 7.96−7.91 (m, 2H, H-

2′ + H-6′), 7.56−7.52 (m, 1H, H-6‴), 7.49 (d, J = 7.9 Hz, 1H, H-5‴),

7.47−7.43 (m, 2H, H-3′ + H-6′), 2.94−2.88 (m, 1H, H-1″), 2.85−

2.78 (m, 1H, H-2″), 2.02−1.92 (m, 1H, H-3″_a), 1.68−1.59 (m, 1H,

H-3″_b). ¹³C{H} NMR, HSQC, HMBC (101 MHz, CDCl₃) δ 196.5

(CO), 148.6 (C-3‴), 142.6 (C-1‴), 139.8 (C-4′), 135.6 (C-1′), 133.0

(C-6‴), 129.6 (C-2′ + C-6′), 129.5 (C-5‴), 129.0 (C-3′ + C-5′),

121.7 (C-4‴), 120.5 (C-2‴), 29.2 (C-1″), 28.7 (C-2″), 19.7 (C-3″).

MS (ESI): m/z = 302.1 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺

calcd for C₁₆H₁₃ClNO₃302.0579, found 302.0587.

(4-Fluorophenyl)-[2-(4-methoxyphenyl)cyclopropyl]methanone

(2c). Following the general procedure using (2E)-3-(4-methoxyphen-

yl)-1-(4-ﬂuorophenyl)prop-2-en-1-one (8.20 mmol, 2.10 g, 1.00

equiv) after stirring at room temperature for 16 h, ﬂash column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 96:4 →

80:20) aﬀorded the title compound (1.87 g, 6.90 mmol, 84%) as a

colorless solid. R_f= 0.36 (4:1 cyclohexane/ethyl acetate). Mp: 74−75

°C (cyclohexane/ethyl acetate), lit.³³mp: 74−75 °C. IR/cm⁻¹

(2,2-Dimethylcyclopropyl)(phenyl)methanone (2g). Following

the general procedure using 3,3-dimethyl-1-phenylprop-2-en-1-one

(10.0 mmol, 1.60 g, 1.00 equiv) after stirring at room temperature for

18 h, ﬂash column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 98:2 → 90:10) aﬀorded the title compound (1.46 g, 8.40

mmol, 84%) as a yellow oil. R_f= 0.45 (4:1 cyclohexane/ethyl acetate).

1

IR/cm⁻¹(ATR): 2959, 1711, 1604, 1290, 1245, 766, 753, 530. H

1

(ATR): 1666, 1598, 1516, 1250, 1223, 1156, 1033, 834, 596. H

NMR (400 MHz, CDCl₃) δ 7.97−7.92 (m, 2H), 7.58−7.51 (m, 1H),

7.50−7.43 (m, 2H), 2.51−2.45 (m, 1H), 1.55−1.50 (m, 1H), 1.36 (s,

3H), 1.09 (s, 3H), 0.98−0.93 (m, 1H). ¹³C{H} NMR (101 MHz,

CDCl₃) δ 198.6, 139.1, 132.4, 128.5, 128.0, 32.9, 27.1, 27.0, 22.0,

18.5. MS (ESI): m/z = 175.1 [M + H]⁺. The spectroscopic data are in

accordance with the literature.³⁴

NMR (400 MHz, CDCl₃) δ 8.05−7.98 (m, 2H), 7.16−7.08 (m, 4H),

6.88−6.83 (m, 2H), 3.80 (s, 3H), 2.80−2.74 (m, 1H), 2.69−2.62 (m,

1H), 1.92−1.86 (m, 1H), 1.55−1.49 (m, 1H). ¹⁹F NMR (282 MHz,

CDCl₃) δ −(105.93−107.61) (m). ¹³C{H} NMR (101 MHz, CDCl₃)

δ 197.0, 165.7 (d, J = 254.4 Hz), 158.5, 134.2 (d, J = 3.2 Hz), 132.3,

130.7 (d, J = 9.3 Hz), 127.4, 115.6 (d, J = 21.8 Hz), 114.0, 55.3, 29.7,

29.1, 19.0. MS (ESI): m/z = 271.1 [M + H]⁺. The spectroscopic data

are in accordance with the literature.³³

Cyclopentene Synthesis. Method A. In an oven-dried Schlenk

tube (10 mL) under nitrogen atmosphere, cyclopropanes 2 (0.40

mmol, 1.00 equiv) and Hantzsch ester (0.42 mmol, 106 mg, 1.05

equiv) were suspended in dry toluene (8.00 mL, c = 0.05 M). DIPEA

(0.44 mmol, 75.0 μL, 1.10 equiv) and the corresponding alkyne (4.00

mmol, 10.0 equiv) were added, and the mixture was degassed and

then placed in front of a blue LED (see the materials section) at a

distance of 5 cm. The vessel was irradiated until TLC or HPLC/ESI-

MS indicated full consumption of the starting material (58−144 h).

The solvent was removed in vacuo, and the residue was puriﬁed by

ﬂash chromatography to aﬀord the cyclopentenes 4. The d.r. was

calculated by comparison of the ¹H NMR signals (H-3 of the

cyclopentenes) of the corresponding diastereomers. The relative

conﬁguration was determined using NOESY contacts (see the SI).

Some of the products were further puriﬁed using preparative HPLC

with mixtures of water and acetonitrile as eluent.

Method B. In an oven-dried quartz tube under nitrogen

atmosphere, α-mesyloxyketones 1 (0.40 mmol, 1.00 equiv) and 1-

methylimidazole (0.80 mmol, 64.0 μL, 2.00 equiv) were dissolved in

dry toluene (40.0 mL, c = 0.01 M). The reaction tube was degassed

and placed in a Rayonet photoreactor. The vessel was irradiated (λ_max

= 300 nm, 16 × 8 W) at room temperature until TLC or HPLC/ESI-

MS indicated full consumption of the starting material (0.5−2.0 h).

The precipitated imidazolium methanesulfonate was ﬁltered, washed

with toluene, and the solvent was removed in vacuo. The residue was

(4-Fluorophenyl)-[2-(2-chlorophenyl)cyclopropyl]methanone

(2d). Following the general procedure using (2E)-3-(2-chlorophenyl)-

1-(4-ﬂuorophenyl)prop-2-en-1-one (7.50 mmol, 1.95 g, 1.00 equiv)

after stirring at room temperature for 18 h, ﬂash column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 97:3 →

80:20) aﬀorded the title compound (1.96 g, 7.20 mmol, 95%) as a

colorless oil. R_f= 0.52 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹

1

(ATR): 2925, 1669, 1599, 1509, 1224, 1156, 1031, 754. H NMR,

COSY (300 MHz, CDCl₃) δ 8.10−8.02 (m, 2H, H-2′ + H-6′), 7.41−

7.35 (m, 1H, H-3‴), 7.28−7.09 (m, 5H, H-3′ + H-5′ + H-4‴-6‴),

2.98−2.85 (m, 1H, H-2″), 2.79−2.67 (m, 1H, H-1″), 1.96−1.87 (m,

1H, H-3″a), 1.68−1.53 (m, 1H, H-3″b). ¹⁹F NMR (282 MHz,

CDCl₃) δ −106.78 (tt, J = 8.6, 5.4 Hz). ¹³C{H} NMR, HSQC,

1

HMBC (101 MHz, CDCl₃) δ 197.2 (CO), 165.85 (d, J_CF= 254.4

4

Hz), 137.9 (C-1‴), 136.0 (C-2‴), 134.2 (d, J_CF= 3.0 Hz, C-1′),

3

130.9 (d, J_CF= 9.3 Hz, C-2′ + C-6′), 129.6 (C-3‴), 128.2 (C-4‴),

127.6 (C-6‴), 127.0 (C-5‴), 115.8 (d, ²J_CF= 21.9 Hz, C-3′ + C-5′),

28.3 (C-2″), 27.5 (C-1″), 17.7 (C-3″). MS (ESI): m/z = 275.1 [M +

H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for C₁₆H₁₃ClFO

275.0634, found 275.0636.

(Phenyl)-[2-(4-cyanophenyl)cyclopropyl]methanone (2e). Fol-

lowing the general procedure using (2E)-3-phenyl-1-(4-

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dissolved in dry toluene (8.00 mL, c = 0.05 M) and transferred to a 10

mL Schlenk tube charged with Hantzsch ester (0.42 mmol, 106 mg,

1.05 equiv). DIPEA (0.44 mmol, 75.0 μL, 1.10 equiv) and

phenylacetylene (4.00 mmol, 439 μL, 10.0 equiv) were added, the

mixture was degassed, and afterward placed in front of a blue LED

(see the materials section) with a distance of 5 cm. The vessel was

irradiated until TLC or HPLC/ESI-MS indicated full consumption of

the starting material (48−89 h). The solvent was removed in vacuo,

and the residue was puriﬁed by ﬂash chromatography to aﬀord the

CDCl₃) δ 8.09−8.06 (m, 0.6H, H-2‴ + H-6‴, minor), 8.06−8.03 (m,

2.0H, H-2‴ + H-6‴, major), 7.63−7.59 (m, 0.3H, H-4‴, minor),

7.59−7.56 (m, 1.0H, H-4‴, major), 7.52 (d, J = 7.8 Hz, 0.8H, H-3‴ +

H-5‴, minor), 7.48 (t, J = 7.8 Hz, 2.0H, H-3‴ + H-5‴, major), 7.35−

7.23 (m, 8.8H, H-2′ + H-6′ + H-2″-3″ + H-5″-6″, major; H-2′ + H-6′

+ H-2″-6″, minor), 7.22−7.18 (m, 1.0H, H-4″, major), 6.81 (d, J =

7.1 Hz, 0.6H, H-3′ + H-5′, minor), 6.80−6.78 (m, 2.0H, H-3′ + H-5′,

major), 6.41−6.40 (m, 0.3H, H-3, minor), 6.29−6.26 (m, 1.0H, H-3,

major), 5.13−5.09 (m, 0.3H, H-1, minor), 5.08−5.03 (m, 1.0H, H-1,

major), 4.25−4.21 (m, 0.3H, H-4, minor), 4.21−4.17 (m, 1.0H, H-4,

major), 3.77 (s, 1.0H, OCH₃, minor), 3.76 (s, 3.0H, OCH₃, major),

3.19−3.05 (m, 1.0H, H-5a, major), 2.68−2.59 (m, 0.3H, H-5a,

minor), 2.48−2.38 (m, 0.4H, H-5b), 2.06−1.94 (m, 1.1H, H-5b,

major). ¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 201.4

(CO, major), 200.8 (CO, minor), 159.1 (C-4′, minor), 158.9 (C-4′,

major), 145.3 (C-1″, minor), 145.2 (C-1″, major), 142.2 (C-2,

major), 142.0 (C-2, minor), 136.6 (C-1‴, major), 136.3 (C-1‴,

minor), 133.3 (C-4‴, minor), 133.2 (C-4‴, major), 131.3 (C-3,

minor), 131.1 (C-3, major), 128.8 (C-3‴ + C-5‴, minor), 128.73 (C-

3‴ + C-5‴, major), 128.70 (C-2‴ + C-6‴, minor), 128.68 (C-2‴ + C-

6‴, major), 128.64 (C-3″ + C-5″, minor), 128.57 (C-3″ + C-5″,

major), 128.2 (C-1′, major), 127.8 (C-1′, minor), 127.7 (C-2″ + C-

6″, major), 127.4 (C-2″ + C-6″, minor), 127.3 (C-2′ + C-6′, major),

127.2 (C-2′ +C-6′, minor), 126.6 (C-4″, minor), 126.5 (C-4″, major),

113.92 (C-3′ + C-5′, minor), 113.88 (C-3′ + C-5′, major), 55.29

(OCH₃, minor), 55.26 (OCH₃, major), 53.7 (C-1, major), 53.6 (C-1,

minor), 51.4 (C-4, major), 50.8 (C-4, minor), 40.4 (C-5, minor), 39.7

(C-5, major). MS (ESI): m/z = 355.1 [M + Na]⁺. HRMS (ESI-ToF)

m/z: [M + H]⁺calcd for C₂₅H₂₃O₂355.1693, found 355.1694.

(2-(4-tert-Butylphenyl)-4-phenylcyclopent-2-en-1-yl)(phenyl)-

methanone (4c). Following general procedure A, a mixture of phenyl-

[phenylcyclopropyl]methanone (0.40 mmol, 88.8 mg, 1.00 equiv) and

4-(tert-butyl)phenylacetylene (4.00 mmol, 722 μL, 10.0 equiv) was

irradiated for 58 h with a blue LED. After column chromatography

(SiO₂, eluent: cyclohexane/ethyl acetate, 98:2 → 75:25), the title

compound (126 mg, 0.36 mmol, 89%, 2.7:1 d.r.) was obtained as a

colorless solid. Additionally, 457 mg (2.89 mmol, 72%) acetylene

were reisolated. R_f= 0.47 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹

(ATR): 3027, 2962, 1682, 1492, 1448, 1269, 1209, 1006, 830, 701.

¹H NMR, COSY, TOCSY, NOESY (600 MHz, CDCl₃) δ 8.09−8.07

(m, 0.8H, H-2‴ + H-6‴, minor), 8.07−8.04 (m, 2.0H, H-2‴ + H-6‴,

major), 7.63−7.60 (m, 0.4H, H-4‴, minor), 7.60−7.57 (m, 1.1H, H-

4‴, major), 7.53−7.51 (m, 0.8H, H-3‴ + H-5‴, minor), 7.49 (t, ³J_HH

= 7.7 Hz, 2.1H, H-3″ + H-5″, major), 7.34−7.27 (m, 10.4H, H-2′-3′

+ H-5′-6′ + H-2″-3″ + H-5″-6″, major + minor), 7.25−7.22 (m, 0.7H,

H-4″, minor), 7.22−7.18 (m, 1.1H, H-4″, major), 6.51 (dd, J = 2.2,

1.1 Hz, 0.4H, H-3, minor), 6.37 (t, J = 2.1 Hz, 1.1H, H-3, major),

5.16−5.11 (m, 0.5H, H-1, minor), 5.10−5.05 (m, 1.1H, H-1, major),

4.26−4.21 (m, 0.5H, H-4, minor), 4.21−4.17 (m, 1.1H, H-4, major),

3.16−3.08 (m, 1.2H, H-5a, major), 2.66−2.60 (m, 0.5H, H-5a,

minor), 2.46−2.39 (m, 0.5H, H-5b, minor), 2.03−1.96 (m, 1.2H, H-

5b, major), 1.28 (s, 3.2H, C(CH₃)₃, minor), 1.27 (s, 9.0H, C(CH₃)₃,

major). ¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 201.4

(CO, major), 200.8 (CO, minor), 150.5 (C-4′, minor), 150.3 (C-4′,

major), 145.2 (C-1″, minor), 145.1 (C-1″, major), 142.5 (C-2,

major), 142.3 (C-2, minor), 136.6 (C-1‴, major), 136.3 (C-1‴,

minor), 133.3 (C-4‴, minor), 133.1 (C-4‴, major), 132.5 (C-3,

minor), 132.4 (C-1′, major), 132.2 (C-3, major), 132.1 (C-1′, minor),

128.8 (C-3‴ + C-5‴, minor), 128.71 (C-3‴ + C-5‴, major), 128.69

(minor), 128.67 (C-2‴ + C-6‴, major), 128.63 (minor), 128.55 (C-

3″ + C-5″,major), 127.8 (major, C-2″ + C-6″), 127.4 (C-2″ + C-6″,

minor), 126.6 (C-4″, minor), 126.5 (C-4″, major), 125.7 + 125.4 (C-

2′-3′ + C-5′-6′, major), 125.6 + 125.5 (C-2′-3′ + C-5′-6′, minor),

53.38 (C-1, major), 53.4 (C-1, minor), 51.4 (C-4, major), 50.8 (C-4,

minor), 40.4 (C-5, minor), 39.6 (C-5, major), 34.53 (C(CH₃)₃,

minor), 34.50 (C(CH₃)₃, major), 31.2 (C(CH₃)₃). MS (ESI): m/z =

381.2 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for

C₂₈H₂₉O 381.2213, found 381.2219.

1

cyclopentenes 4. The d.r. was calculated by integration of the H

NMR signals (H-3 of the cyclopentenes) of the diastereomers in the

crude mixture. The relative conﬁguration was determined using

NOESY correlations (see the SI). Some of the products were further

puriﬁed using preparative HPLC with mixtures of water and

acetonitrile as an eluent.

(2,4-Diphenylcyclopent-2-en-1-yl)(phenyl)methanone (4a). Fol-

lowing general procedure A, a mixture of phenyl-[phenylcyclopropyl]-

methanone (0.40 mmol, 88.8 mg, 1.00 equiv) and phenylacetylene

(4.00 mmol, 439 μL, 10.0 equiv) was irradiated for 86 h with a blue

LED. After column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 98:2 → 75:25), the title compound (108 mg, 0.34 mmol,

84%, 2.5:1 d.r.) was obtained as a colorless solid.

Following general procedure B, 1,4-diphenyl-2-mesyloxybutan-1-

one (0.40 mmol, 127 mg, 1.00 equiv) was irradiated for 1 h using UV-

B irradiation and 72 h using a blue LED. After column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 96:4 →

70:30), the title compound (67.4 mg, 0.21 mmol, 52%, 2.5:1 d.r.) was

obtained as a colorless solid. In an up-scaled batch reaction, 1,4-

diphenyl-2-mesyloxybutan-1-one (2.00 mmol, 636 mg, 1.00 equiv)

was irradiated for 1.5 h using UV-B irradiation and 96 h using two

blue LED. After column chromatography (SiO₂, eluent: cyclohexane/

ethyl acetate, 96:4 → 70:30), the title compound (285 mg, 0.88

mmol, 44%, 2.5:1 d.r.) was obtained as a colorless solid.

R_f= 0.35 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3058,

1

3026, 1681, 1597, 1493, 1447, 1210, 697. H NMR, COSY, NOESY

(400 MHz, CDCl₃) δ 8.10−8.07 (m, 0.8H, H-2‴ + H-6‴, minor),

8.06−8.04 (m, 2.0H, H-2‴ + H-6‴, major), 7.63−7.60 (m, 0.4H, H-

4‴, minor), 7.60−7.57 (m, 1.0H, H-4‴, major), 7.54−7.50 (m, 1.0H,

H-3‴ + H-5‴, minor), 7.50−7.46 (t, 2.0H, H-3‴ + H-5‴, major),

7.40−7.17 (m, 13.0H, H-2′-6′ + H-2″-6″, major + minor), 6.56−6.53

(m, 0.4H, H-3, minor), 6.40 (t, J = 2.1 Hz, 1.0H, H-3, major), 5.17−

5.13 (m, 0.4H, H-1, minor), 5.13−5.08 (m, 1.0H, H-1, major), 4.27−

4.23 (m, 0.4H, H-4, minor), 4.23−4.19 (m, 1.0H, H-4, major), 3.16−

3.10 (m, 1.0H, H-5a, major), 2.67−2.62 (m, 0.4H, H-5a, minor),

2.48−2.42 (m, 0.4H, H-5b, minor), 2.05−2.00 (m, 1.0H, H-5b,

major). ¹³C{H} NMR, HSQC, HMBC (101 MHz, CDCl₃) δ 201.2

(CO, major), 200.6 (CO, minor), 145.0 (C-1″, minor), 144.9 (C-1″,

major), 142.8 (C-2, major), 142.6 (C-2, minor), 136.5 (C-1‴, major),

136.3 (C-1‴, minor), 135.4 (C-1′, major), 135.0 (C-1′, minor),

133.33 + 133.31 (C-3 + C-4‴, minor), 133.2 (C-4‴, major), 133.1

(C-3, major), 128.8 (C-3‴ + C-5‴, minor), 128.72 (C-3‴ + C-5‴,

major), 128.70 (C-2‴ + C-6‴, minor), 128.66 (C-2‴ + C-6‴, major;,

C-3″ + C-5″, minor), 128.6 (C-3″ + C-5″, major), 128.52 (C-3′ + C-

5′, minor), 128.46 (C-3′ + C-5′, major), 127.7 (C-2″ + C-6″, major),

127.6 (C-4′, minor), 127.4 (C-4′, major; C-2″ + C-6″, minor), 126.6

(C-4″, minor), 126.5 (C-4″, major), 126.02 (C-2′ + C-6′, major),

125.96 (C-2′ + C-6′, minor), 53.5 (C-1, major), 53.4 (C-1, minor),

51.4 (C-4, major), 50.8 (C-4, minor), 40.4 (C-5, minor), 39.7 (C-5,

major). MS (ESI): m/z = 347.3 [M + Na]⁺. HRMS (APCI-ToF) m/

z: [M + H]⁺calcd for C₂₄H₂₁O 325.1587, found 325.1583.

(2-(4-Methoxyphenyl)-4-phenylcyclopent-2-en-1-yl)(phenyl)-

methanone (4b). Following general procedure A, a mixture of

phenyl-[phenylcyclopropyl]methanone (0.40 mmol, 88.8 mg, 1.00

equiv) and 4-methoxyphenylacetylene (4.00 mmol, 519 μL, 10.0

equiv) was irradiated for 96 h with a blue LED. After column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 98:2 →

75:25), the title compound (100 mg, 0.28 mmol, 71%, 2.8:1 d.r.) was

obtained as a colorless solid. R_f= 0.35 (4:1 cyclohexane/ethyl

acetate). IR/cm⁻¹(ATR): 3025, 1671, 1509, 1493, 1315, 1261, 1214,

1169, 1028, 842, 699. ¹H NMR, COSY, TOCSY, NOESY (600 MHz,

(2-(Cyclohex-1-en-1-yl)-4-phenylcyclopent-2-en-1-yl)(phenyl)-

methanone (4d). Following general procedure A, a mixture of

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phenyl-[phenylcyclopropyl]methanone (0.40 mmol, 88.8 mg, 1.00

equiv) and 1-ethynylcyclohexene (4.00 mmol, 470 μL, 10.0 equiv)

was irradiated for 82 h with a blue LED. After column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 98:2 →

75:25), the title compound (105 mg, 0.32 mmol, 80%, 2.2:1 d.r.) was

obtained as a colorless oil. R_f= 0.42 (4:1 cyclohexane/ethyl acetate).

IR/cm⁻¹(ATR): 2929, 1682, 1597, 1493, 1447, 1338, 1209, 759, 701.

¹H NMR, COSY, TOCSY, NOESY (400 MHz, CDCl₃) δ 8.09−7.98

H]⁺. HRMS (ESI-ToF) m/z: [M + Na]⁺calcd for C₂₁H₂₀O₃Na

343.1304, found 343.1307.

(2,4-Diphenylcyclopent-2-en-1-yl)(4-methoxyphenyl)methanone

(4i). Following general procedure A, a mixture of 4-methoxyphenyl-

[phenylcyclopropyl]methanone (0.40 mmol, 101 mg, 1.00 equiv) and

phenylacetylene (4.00 mmol, 439 μL, 10.0 equiv) was irradiated for

144 h with two blue LED. After column chromatography (SiO₂,

eluent: cyclohexane/ethyl acetate, 98:2 → 75:25), the title compound

(84.0 mg, 0.24 mmol, 59%, 2.6:1 d.r.) was obtained as a colorless

solid. R_f= 0.33 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR):

2934, 1672, 1598, 1509, 1262, 1215, 1170, 1028, 843, 699. ¹H NMR,

COSY, TOCSY, NOESY (600 MHz, CDCl₃) δ 8.11−8.09 (m, 0.8H,

H-2‴ + H-6‴, minor), 8.09−8.06 (m, 2.0H, H-2‴ + H-6‴, major),

7.42−7.20 (m, 14.7H, H-2′-6′ + H-2″-6″, major + minor), 7.03−7.00

(m, 0.8H, H-3‴ + H-5‴, minor), 7.00−6.97 (m, 2.0H, H-3‴ + H-5‴,

major), 6.57−6.56 (m, 0.4H, H-3, minor), 6.42−6.40 (m, 1.0H, H-3,

major), 5.16−5.12 (m, 0.4H, H-1, minor), 5.11−5.06 (m, 1.0H, H-1,

major), 4.30−4.26 (m, 0.4H, H-4, minor), 4.24−4.20 (m, 1.0H, H-4,

major), 3.92 (s, 1.2H, OCH₃, minor), 3.90 (s, 3.0H, OCH₃, major),

3.18−3.07 (m, 1.0H, H-5a, major), 2.69−2.62 (m, 0.4H, H-5a,

minor), 2.51−2.41 (m, 0.4H, H-5b, minor), 2.04 (dt, J = 13.7, 7.1 Hz,

1.0H, H-5b, major). ¹³C{H} NMR, HSQC, HMBC (151 MHz,

CDCl₃) δ 199.8 (CO, major), 199.3 (CO, minor), 163.7 (C-4‴,

minor), 163.6 (C-4‴, major), 145.2 (C-1″, minor), 145.0 (C-1″,

major), 143.1 (C-2, major), 142.8 (C-2, minor), 135.6 (C-1′, major),

135.2 (C-1′, minor), 133.2 (C-3, minor), 133.0 (C-3, major), 131.03

(C-2‴ + C-6‴, minor), 130.98 (C-2‴ + C-6‴, major), 129.6 (C-1‴,

major), 129.3 (C-1‴, minor), 128.7 (C-3″ + C-5″, minor), 128.6 (C-

3″ + C-5″, major), 128.52 (C-3′ + C-5′, minor), 128.46 (C-3′ + C-5′,

major), 127.8 (C-2″ + C-6″, major), 127.5 (C-4′, minor), 127.43 (C-

2″ + C-6″, minor), 127.37 (C-4′, major), 126.6 (C-4″, minor), 126.5

(C-4″, major), 126.03 (C-2′ + C-6′, major), 125.98 (C-2′ + C-6′,

minor), 114.0 (C-3‴ + C-5‴, minor), 113.9 (C-3‴ + C-5‴, major),

55.57 (OCH₃, minor), 55.54 (OCH₃, major), 53.2 (C-1, major), 53.1

(C-1, minor), 51.4 (C-4, major), 50.9 (C-4, minor), 40.6 (C-5,

minor), 39.9 (C-5, major). MS (ESI): m/z = 377.1 [M + Na]⁺.

HRMS (ESI-ToF) m/z: [M + H]⁺calcd for C₂₅H₂₃O₂355.1693,

found 355.1693.

(m, 2.8H, H-2‴ + H-6‴, major + minor), 7.62−7.53 (m, 1.5H, H-4‴,

major + minor), 7.52−7.44 (m, 3.1H, H-3‴ + H-5‴, major + minor),

7.35−7.24 (m, 6.5H, H-2′-3′ + H-5′-6′, major; H-2′ + H-.6′, minor),

7.24−7.15 (m, 2.5H, H-4″, major; H-3″-5″, minor), 6.02 (s, 0.5H, H-

3, minor), 5.94−5.92 (m, 1.0H, H-3, major), 5.46−5.39 (m, 1.5H, H-

2′, major + minor), 4.90−4.85 (m, 0.5H, H-1, minor), 4.82−4.76 (m,

1.0H, H-1, major), 4.16−4.11 (m, 0.5H, H-4, minor), 4.11−4.05 (m,

1.0H, H-4, major), 3.02−2.92 (m, 1.1H, H-5a, major), 2.52−2.44 (m,

0.6H, H-5a, minor), 2.42−2.28 (m, 3.1H, H-3′, major + minor),

2.26−2.21 (m, 0.6H, H-5b, minor), 2.06−1.97 (m, 3.4H, H-6′, major

+ minor), 1.91−1.83 (m, 1.1H, H-5b, major), 1.76−1.41 (m, 6.8H,

H-4′-5′, major + minor). ¹³C{H} NMR, HSQC, HMBC (101 MHz,

CDCl₃) δ 201.8 (CO, major), 201.0 (CO, minor), 145.4 (C-1″, major

+ minor), 144.72 (C-2, minor), 144.67 (C-2, major), 136.8 (C-1‴,

major), 136.5 (C-1‴, minor), 133.1 (C-4‴, minor), 132.9 (C-4‴,

major), 132.5 (C-1′, minor), 132.2 (C-1′, major), 131.0 (C-3, minor),

130.5 (C-3, major), 128.7 (C-3‴ + C-5‴, minor), 128.6 (C-3‴ + C-

5‴, major), 128.54 (C-3″ + C-5″, minor), 128.52 (C-2‴ + C-6‴,

major + minor), 128.4 (C-3″ + C-5″, major), 127.7 (C-2″ + C-6″,

major), 127.4 (C-2″ + C-6″, minor), 126.40 (C-2′, minor), 126.37

(C-2′, major), 126.3 (C-4″, major), 126.2 (C-4″, minor), 52.7 (C-1,

major), 52.4 (C-1, minor), 51.3 (C-4, major), 50.5 (C-4, minor), 40.2

(C-5, minor), 39.1 (C-5, major), 26.4 (C-6′, major), 26.2 (C-6′,

minor), 25.8 (C-3′, minor), 25.7 (C-3′, major), 22.59 (C-5′, major),

22.56 (C-5′, minor), 22.2 (C-4′, major + minor). MS (ESI): m/z =

329.2 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺Calcd. for

C₂₄H₂₅O 329.1900, found 329.1905.

(2-Ethoxycarbonyl-4-phenylcyclopent-2-en-1-yl)(phenyl)-

methanone (4e). Following general procedure A, a mixture of

phenyl-[phenylcyclopropyl]methanone (0.40 mmol, 88.8 mg, 1.00

equiv) and ethyl propiolate (4.00 mmol, 405 μL, 10.0 equiv) was

irradiated for 58 h with a blue LED. After column chromatography

(SiO₂, eluent: cyclohexane/ethyl acetate, 98:2 → 75:25), the title

compound (113 mg, 0.35 mmol, 88%, 2.7:1 d.r.) was obtained as a

colorless oil. R_f= 0.30 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹

(2-Phenyl-4-(4-methoxyphenyl)cyclopent-2-en-1-yl)(4-

ﬂuorophenyl)methanone (4j). Following general procedure A, a

mixture of 4-ﬂuorophenyl-[(4-methoxyphenyl)cyclopropyl]-

methanone (0.40 mmol, 108 mg, 1.00 equiv) and phenylacetylene

(4.00 mmol, 439 μL, 10.0 equiv) was irradiated for 64 h with a blue

LED. After column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 99:1 → 80:20), the title compound (115 mg, 0.32 mmol,

78%, 2.9:1 d.r.) was obtained as a colorless solid. R_f= 0.41 (4:1

cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 2921, 2851, 1682, 1511,

1245, 1208, 1034, 831, 759, 695. ¹H NMR, COSY, TOCSY, NOESY

(600 MHz, CDCl₃) δ 8.13−8.09 (m, 0.6H, H-2‴ + H-6‴, minor),

8.09−8.06 (m, 2.0H, H-2‴ + H-6‴, major), 7.37−7.35 (m, 0.8H, H-

2′ + H-6′, minor), 7.35−7.33 (m, 2.0H, H-2′ + H-6′, major), 7.30−

7.26 (m, 2.5H, H-3′ + H-5′, minor + major), 7.25 (d, J = 8.5 Hz,

2.2H, H-2″ + H-6″, major), 7.23−7.20 (m, 1.2H, H-4″, major), 7.20−

7.17 (m, 1.5H, H-2‴ + H-6″ + H-3‴ + H-5‴, minor), 7.15 (t, J = 8.5

Hz, 2.2H, H-3‴ + H-5‴), 6.88 (d, J = 8.5 Hz, 0.8H, H-3″ + H-5″,

minor), 6.86 (d, J = 8.5 Hz, 2.0H, H-3″ + H-5″, major), 6.53−6.51

(m, 0.3H, H-3, minor), 6.39−6.37 (m, 1.0H, H-3, major), 5.11−5.08

(m, 0.4H, H-1, minor), 5.06−5.00 (m, 1.0H, major), 4.23−4.19 (m,

0.4H, H-4, minor), 4.19−4.14 (m, 1.0H, H-4, major), 3.81 (s, 1.1H,

OCH₃, minor), 3.79 (s, 3.0H, OCH₃, major), 3.13−3.06 (m, 1.0H, H-

5a, major), 2.63−2.57 (m, 0.4H, H-5a, minor), 2.43−2.37 (m, 0.4H,

H-5b, minor), 2.00−1.93 (m, 1.0H, H-5b, major). ¹⁹F NMR (282

MHz, CDCl₃) δ−106.04 (tt, J = 8.2, 5.3 Hz, minor),−106.21 (tt, J =

1

(ATR): 2980, 1713, 1681, 1448, 1257, 1214, 1100, 1024, 701. H

NMR, COSY, TOCSY, NOESY (600 MHz, CDCl₃) δ = 8.08−8.02

(m, 2.9H, H-2″ H-6″, major + minor), 7.62−7.57 (m, 1.5H, H-4″,

major + minor), 7.53−7.47 (m, 2.9H, H-3″ + H-5″, major + minor),

7.38−7.35 (m, 0.7H, H-3′ + H-5′, minor), 7.35−7.31 (m, 2.3H, H-3′

+ H-5′, major), 7.30−7.27 (m, 2.9H, H-2′ + H-6′, major + minor),

7.26−7.21 (m, 1.8H, H-4′, major + minor), 7.09−7.06 (m, 0.3H, H-3,

minor), 6.99−6.95 (m, 1.0H, H-3, major), 5.05−4.99 (m, 0.4H, H-1,

minor), 4.94−4.88 (m, 1.1H, H-1, major), 4.31−4.26 (m, 0.4H, H-4,

minor), 4.25−4.13 (m, 4.1H, H-4, major; OCH₂CH₃, major +

minor), 3.07−3.00 (m, 1.2H, H-5a, major), 2.62−2.57 (m, 0.4H, H-

5a, minor), 2.44−2.37 (m, 0.4H, H-5b, minor), 2.01−1.95 (m, 1.2H,

H-5b, major), 1.24 (t, J = 7.2 Hz, 0.9H, OCH₂CH₃, minor), 1.21 (t, J

= 7.2 Hz, 3.2H, OCH₂CH₃, major). ¹³C{H} NMR, HSQC, HMBC

(151 MHz, CDCl₃) δ 201.0 (CO, major), 200.7 (CO, minor), 164.39

(CO₂Et, major), 164.35 (CO₂Et, minor), 148.4 (C-3, minor), 147.5

(C-3, major), 143.2 (C-1′, minor), 143.0 (C-1′, major), 137.0 (C-2,

major), 136.8 (C-2, minor), 136.5 (C-1″, major), 136.3 (C-1″,

minor), 133.3 (C-4″, minor), 133.2 (C-4″, major), 128.84 + 128.76 +

128.69 (C-2″-3″ + C-5″-6″ + C-3′ + C-5′, minor), 128.74 + 128.65 +

128.63 (C-2″-3″ + C-5″-6″ + C-3′ + C-5′, major), 127.7 (C-2′ + C-

6′, major), 127.34 (C-2′ + C-6′, minor), 127.0 (C-4′, minor), 126.9

(C-4′, major), 60.7 (CO₂CH₂CH₃, minor), 60.6 (CO₂CH₂CH₃,

major), 51.6 + 51.5 (C-1 + C-4, major; C-1, minor), 51.2 (C-4,

minor), 39.4 (C-5, minor), 39.1 (C-5, major), 14.14 (CO₂CH₂CH₃,

minor), 14.11 (CO₂CH₂CH₃, major). MS (ESI): m/z = 321.0 [M +

8.2, 5.3 Hz, major). ¹³C{H} NMR, HSQC, HMBC (151 MHz,

1

CDCl₃) δ 199.8 (CO, major), 199.3 (CO, minor), 165.95 (d, J_CF

=

1

255.1 Hz, C-4‴, minor), 165.87 (d, J_CF= 255.1 Hz, C-4‴, major),

158.5 (OCH₃, minor), 158.4 (OCH₃, major), 142.4 (C-2, major),

142.2 (C-2, minor), 137.1 (C-1″, major), 137.0 (C-1″, minor), 135.5

(C-1′, major), 135.1 (C-1′, minor), 133.9 (C-3, minor), 133.6 (C-3,

major), 133.0 (d, ⁴J_CF= 2.9 Hz, C-1‴, major), 132.8 (d, ⁴J_CF= 2.9 Hz,

3242

https://dx.doi.org/10.1021/acs.joc.0c02591

J. Org. Chem. 2021, 86, 3232−3248

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

C-1‴, minor), 131.43 (d, ³J_CF= 9.2 Hz, C-3‴ + C-5‴, minor), 131.39

(d, ³J_CF= 9.2 Hz, C-3‴ + C-5‴, major), 128.8 (C-2″ + C-6″, major),

128.64 (C-3′ + C-5′, minor), 128.59 (C-3′ + C-5′, major), 128.4 (C-

major), 5.21−5.18 (m, 0.5H, H-1, minor), 5.17−5.13 (m, 1.0H, H-1,

major), 4.34−4.30 (m, 0.5H, H-4, minor), 4.30−4.25 (m, 1.1H, H-4,

major), 3.23−3.15 (m, 1.1H, H-5a, major), 2.71−2.66 (m, 0.5H, H-

5a, minor), 2.45−2.37 (m, 0.5H, H-5b, minor), 2.02−1.95 (m, 1.1H,

H-5b, major). ¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ

201.1 (CO, major), 200.2 (CO, minor), 150.60 (C-1″, minor), 150.56

(C-1″, major), 144.2 (C-2, major), 144.1 (C-2, minor), 136.3 (C-1‴,

major), 136.1 (C-1‴, minor), 134.8 (C-1′, major), 134.6 (C-1′,

minor), 133.54 (C-4‴, minor), 133.49 (C-4‴, major), 132.6 (C-3″ +

C-5″, minor), 132.5 (C-3″ + C-5″, major), 131.5 (C-3, minor), 131.2

(C-3, major), 128.91 (C-3‴ + C-5‴, minor), 128.87 (C-3‴ + C-5‴,

major), 128.70 (C-2‴ + C-6‴, minor), 128.67 (C-2″ + C-6″, major),

128.64 (C-2‴ + C-6‴, major; C-3′ + C-5′, minor), 128.58 (C-3′ + C-

5′, major), 128.2 (C-2″ + C-6″, minor), 128.0 (C-4′, minor), 127.8

(C-4′, major), 126.1 (C-2′ + C-6′, major), 126.0 (C-2′ + C-6′,

minor), 119.1 (CN, major), 119.0 (CN, minor), 110.5 (C-4″, minor),

110.3 (C-4″, major), 53.2 (C-1, minor), 53.0 (C-1, major), 51.3 (C-4,

major), 50.8 (C-4, minor), 40.1 (C-5, minor), 38.9 (C-5, major). MS

(ESI): m/z = 372.1 [M + Na]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺

calcd for C₂₅H₂₀NO 350.1540, found 350.1543.

2″ + C-6″, minor), 127.7 (C-4′, minor), 127.5 (C-4′, major), 126.1

2

(C-2′ + C-6′, major), 126.0 (C-2′ + C-6′, minor), 116.00 (d, J_CF

=

21.8 Hz, C-3‴ + C-5‴, minor), 115.92 (d, ²J_CF= 21.8 Hz, C-3‴ + C-

5‴, major), 114.13 (C-3″ + C-5″, minor), 114.05 (C-3″ + C-5″,

major), 55.42 (OCH₃, minor), 55.39 (OCH₃, major), 53.53 (C-1,

major), 53.46 (C-1, minor), 50.7 (C-4, major), 50.1 (C-4, minor),

40.6 (C-5, minor), 39.8 (C-5, major). MS (ESI): m/z = 395.1 [M +

Na]⁺. HRMS (ESI-ToF) m/z: [M + K]⁺calcd for C₂₅H₂₁FO₂K

411.1163, found 411.1161.

(2-Phenyl-4-(2-chlorophenyl)cyclopent-2-en-1-yl)(4-

ﬂuorophenyl)methanone (4k). Following general procedure A, a

mixture of 4-ﬂuorophenyl-[(2-chlorophenyl)cyclopropyl]methanone

(0.40 mmol, 110 mg, 1.00 equiv) and phenylacetylene (4.00 mmol,

439 μL, 10.0 equiv) was irradiated for 64 h with a blue LED. After

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

99:1 → 80:20), the title compound (119 mg, 0.32 mmol, 79%, 2.0:1

d.r.) was obtained as a colorless solid. R_f= 0.46 (4:1 cyclohexane/

ethyl acetate). IR/cm⁻¹(ATR): 3060, 1682, 1597, 1505, 1229, 1208,

N-Acetyl-(2-phenyl-4-(3-aminophenyl)cyclopent-2-en-1-yl)(4-

chlorophenyl)methanone (4m). Following a modiﬁed general

procedure A, a mixture of 4-chlorophenyl-[(3-nitrophenyl)-

cyclopropyl]methanone (0.40 mmol, 121 mg, 1.00 equiv), Hantzsch

ester (1.00 mmol, 253 mg, 2.50 equiv) and phenylacetylene (4.00

mmol, 439 μL, 10.0 equiv) was irradiated for 120 h with a blue LED

(see the materials section). Reversed-phase column chromatography

(SiO₂-C₁₈, eluent: water/acetonitrile, 99:1 → 80:20) gave the crude

amine (88 mg), which was dissolved in MeCN (5 mL) and reacted

with NEt₃(0.29 mmol, 40.0 μL, 1.20 equiv) and Ac₂O (0.29 mmol,

27.0 μL, 1.20 equiv) for 1 h at room temperature. Ethyl acetate (25

mL) and water (25 mL) were added, the phases were separated, and

the aqueous phase was extracted with ethyl acetate (3 ×25 mL). The

combined organic extracts were dried over Na₂SO₄, and the solvent

was removed under reduced pressure. Preparative HPLC (C₁₈PFP,

eluent: water/acetonitrile, 45:55, t_R= 13.6 min) yielded the title

compound (94 mg, 0.23 mmol, 57%, 2.1:1 d.r.) as a colorless solid. R_f

= 0.13 (2:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3308, 2935,

1672, 1589, 1552, 1488, 1210, 1092, 760, 731, 696. ¹H NMR, COSY,

TOCSY, NOESY (600 MHz, CDCl₃) δ 8.00−7.98 (m, 0.8H, H-2‴ +

H-6‴, minor), 7.98−7.95 (m, 2.0H, H-2‴ + H-6‴, major), 7.58−7.54

(m, 1.0H, H-4″, major), 7.49−7.47 (m, 0.7H, H-3‴ + H-5‴, minor),

7.47−7.44 (m, 2.0H, H-3‴ + H-5‴, major), 7.43−7.40 (m, 0.4H, H-

4″, minor), 7.35−7.33 (m, 1.4H, H-2″ + H-2′ + H-6′, minor), 7.33−

7.30 (m, 2.0H, H-2′ + H-6′, major), 7.30−7.23 (m, 5.4H, H-3′ + H-5′

+ H-2″ + H-5″, major; H-3′ + H-5′ + H-5″, minor), 7.24−7.18 (m,

2.0H, H-4′, minor + major), 7.03 (dt, J = 7.6, 1.3 Hz, 1.0H, H-6″,

major), 6.99 (d, J = 7.6 Hz, 0.4H, H-6″, minor), 6.50−6.48 (m, 0.4H,

H-3, minor), 6.39−6.36 (m, 1.0H, H-3, major), 5.09−5.05 (m, 0.4H,

H-1, minor), 5.04−5.00 (m, 1.0H, H-1, major), 4.24−4.15 (m, 1.4H,

H-4, minor + major), 3.14−3.07 (m, 1.0H, H-5a, major), 2.62−2.56

(m, 0.4H, H-5a, minor), 2.44−2.38 (m, 0.4H, H-5b, minor), 2.16 (s,

3.9H, COCH₃, minor + major), 1.97−1.91 (m, 1.0H, H-5b, major).

¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 200.4 (CO,

major), 199.6 (CO, minor), 168.31 (COCH₃, major), 168.29

(COCH₃, minor), 145.9 (C-1″, minor), 145.8 (C-1″, major),

142.72 (C-2, major), 142.65 (C-2, minor), 139.8 (C-4‴, minor +

major), 138.20 (C-3″, major), 138.16 (C-3″, minor), 135.0 (C-1′,

major), 134.8 (C-1′, minor), 134.6 (C-1‴, major), 134.5 (C-1‴,

minor), 133.0 (C-3, minor), 132.8 (C-3, major), 130.08 (C-2‴ + C-

6‴, minor), 130.06 (C-2‴ + C-6‴, major), 129.33 (C-5″, minor),

129.28 (C-5″, major), 129.12 (C-3‴ + C-5‴, minor), 129.10 (C-3‴ +

C-5‴, major), 128.6 (C-3′ + C-5′, minor + major), 127.7 (C-4′,

minor), 127.6 (C-4′, major), 125.96 (C-2′ + C-6′, major), 125.93 (C-

2′ + C-6′, minor), 123.7 (C-6″, major), 123.4 (C-6″, minor), 118.70

(C-2″, major), 118.68 (C-2″, minor), 118.3 (C-4″, minor), 118.2 (C-

4″, major), 53.4 (C-1, minor + major), 51.2 (C-4, major), 50.7 (C-4,

minor), 40.0 (C-5, minor), 39.3 (C-5, major), 24.68 (COCH₃,

major), 24.66 (COCH₃, minor). MS (ESI): m/z = 416.1 [M + H]⁺.

1

1156, 1046, 848, 753, 693. H NMR, COSY, TOCSY, NOESY (600

MHz, CDCl₃): δ 8.10−8.07 (m, 1.0H, H-2‴ + H-6‴, minor), 8.06−

8.02 (m, 2.0H, H-2‴ + H-6‴,major), 7.48−7.45 (m, 1.0H, H-6″,

major), 7.39−7.35 (m, 3.6H, H-2′ + H-6′, major; H-3′ + H-6′ + H-

3″, minor), 7.34−7.32 (m, 1.0H, H-3″, major), 7.31−7.27 (m, 3.5H,

H-3′ + H-5′, major; H-2′ + H-6′ + H-6″, minor), 7.25−7.21 (m,

2.8H, H-4′ + H-5″, major + minor), 7.20−7.17 (m, 1.3H, H-4″ + H-

3‴ + H-5‴, minor), 7.16−7.12 (m, 3.3H, H-4″ + H-3‴ + H-5‴,

major), 6.52−6.50 (m, 0.5H, H-3, minor), 6.43−6.40 (m, 1.0H, H-3,

major), 5.10−5.07 (m, 0.5H, H-1, minor), 5.07−5.02 (m, 1.0H, H-1,

major), 4.72−4.69 (m, 0.5H, H-4, minor), 4.69−4.65 (m, 1.1H, H-5,

major), 3.28−3.19 (m, 1.0H, H-5a, major), 2.79−2.72 (m, 0.5H, H-

5a, minor), 2.36−2.30 (m, 0.5H, H-5b, minor), 1.90−1.83 (m, 1.0H,

H-5b, major). ¹⁹F NMR (282 MHz, CDCl₃): δ−105.95 (tt, J = 8.3,

5.3 Hz, minor),−106.07 (tt, J = 8.3, 5.3 Hz, major). ¹³C{H} NMR,

HSQC, HMBC (151 MHz, CDCl₃) δ 199.3 (CO, major), 199.0 (CO,

1

minor), 165.9 (d, J_CF= 255 Hz, C-4‴, minor), 165.8 (d, J_CF= 255

Hz, C-4‴, major), 143.7 (C-2, major), 143.4 (C-2, minor), 142.4 (C-

1″, minor), 142.2 (C-1″, major), 135.2 (C-1′, major), 134.9 (C-1′,

4

minor), 133.7 (C-2″, minor), 133.3 (C-2″, major), 132.7 (d, J_CF

=

4

3.0 Hz, C-1‴, major), 132.6 (d, J_CF= 3.0 Hz, C-1‴, minor), 131.8

(C-3, minor), 131.4 (d, ⁴J_CF= 8.8 Hz, C-2‴ + C-6‴, minor), 131.3 (d,

⁴J_CF= 8.7 Hz, C-2‴ + C-6‴, major), 129.6 (C-3″, minor), 129.2 (C-

3″, major), 129.0 (C-6″, major), 128.6 (C-3′ + C-5′, minor), 128.5

(C-3′ + C-5′, major), 128.0 (C-6″, minor), 127.9 (C-4″, minor),

127.8 (C-4″, major), 127.7 (C-4′, minor), 127.6 (C-4′, major), 127.2

(C-5′, major), 127.1 (C-5′, minor), 126.0 (C-2′ + C-6′, major), 125.9

2

(C-2′ + C-6′, minor), 115.92 (d, J_CF= 21.9 Hz, C-3‴ + C-5‴,

2

minor), 115.86 (d, J_CF= 21.9 Hz, C-3‴ + C-5‴, major), 53.2 (C-1,

major), 53.1 (C-1, minor), 47.43 (C-4, minor), 47.35 (C-4, major),

38.4 (C-5, minor), 37.9 (C-5, major). MS (ESI): m/z = 377.1 [M +

H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for C₂₄H₁₉ClFO

377.1103, found 377.1104.

(2-Phenyl-4-(4-cyanophenyl)cyclopent-2-en-1-yl)(phenyl)-

methanone (4l). Following general procedure A, a mixture of phenyl-

[(4-cyanophenyl)cyclopropyl]methanone (0.40 mmol, 98.8 mg, 1.00

equiv) and phenylacetylene (4.00 mmol, 439 μL, 10.0 equiv) was

irradiated for 96 h with a blue LED. After column chromatography

(SiO₂, eluent: cyclohexane/ethyl acetate, 98:2 → 75:25), the title

compound (117 mg, 0.34 mmol, 84%, 2.0:1 d.r.) was obtained as a

colorless solid. R_f= 0.28 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹

(ATR): 2930, 2227, 1682, 1607, 1496, 1448, 1211, 1003, 843, 693.

¹H NMR, COSY, TOCSY, NOESY (600 MHz, CDCl₃) δ 8.10−8.07

(m, 1.0H, H-2‴ + H-6‴, minor), 8.07−8.04 (m, 2.1H, H-2‴ + H-6‴,

major), 7.66−7.59 (m, 4.8H, H-3″ + H-5″ + H-4‴, major + minor),

7.57−7.50 (m, 3.2H, H-3‴ + H-5‴, major + minor), 7.49−7.44 (m,

2.1H, H-2″ + H-6″, major), 7.41−7.35 (m, 4.2H, H-2′ + H-6′, major

+ minor; H-2″ + H-6″, minor), 7.33−7.22 (m, 5.3H, H-3′-5′, major +

minor), 6.52−6.47 (m, 0.5H, H-3, minor), 6.39−6.35 (m, 1.0H, H-3,

3243

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J. Org. Chem. 2021, 86, 3232−3248

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

HRMS (ESI-ToF) m/z: [M + Na]⁺calcd for C₂₆H₂₂ClNO₂Na

438.1231, found 438.1233.

2‴, major), 7.90−7.88 (m, 0.3H, H-6‴, minor), 7.87−7.84 (m, 1.0H,

H-3‴, major), 7.53−7.51 (m, 0.3H, H-4‴, minor), 7.51−7.47 (m,

1.0H, H-4‴, major), 7.41−7.38 (m, 0.3H, H-5‴, minor), 7.38−7.35

(m, 1.0H, H-5‴, major), 7.31−7.14 (m, 13.2H, H-2′-6′ + H-2″-6″,

minor + major), 6.50−6.48 (m, 0.3H, H-3, minor), 6.36−6.33 (m,

1.0H, H-3, major), 5.05−5.01 (m, 0.3H, H-1, minor), 5.00−4.95 (m,

1.0H, H-1, major), 4.20−4.14 (m, 1.2H, H-4, minor + major), 3.12−

3.03 (m, 1.0H, H-5a, major), 2.61−2.54 (m, 0.3H, H-5a, minor),

2.43−2.36 (m, 0.3H, H-5b, minor), 1.98−1.91 (m, 1.0H, H-5b,

major). ¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 199.9

(CO, major), 199.4 (CO, minor), 144.70 (C-1″, minor) 144.66 (C-

1″, major), 142.5 (C-2, major), 142.2 (C-2, minor), 137.9 (C-1‴,

major), 137.8 (C-1‴, minor), 135.2 (C-1′, major), 135.1 (C-1′,

minor), 135.0 (C-3‴, major), 134.8 (C-3‴, minor), 133.5 (C-3,

minor), 133.19 (C-4‴, minor), 133.18 (C-3, major), 133.1 (C-4‴,

major), 130.1 (C-5‴, minor), 130.0 (C-5‴, major), 128.72 (C-2‴,

minor + major), 128.65 (C-3″ + C-5″, minor), 128.6 (C-3″ + C-5″,

major), 128.53 (C-3′ + C-5′, minor), 128.48 (C-3′ + C-5′, major),

127.64 (C-2″ + C-6″, major), 127.63 (C-4′, minor), 127.5 (C-4′,

major), 127.3 (C-2″ + C-6″, minor), 126.68 (C-6‴, minor), 126.67

(C-4″, major; C-6‴, minor), 126.6 (C-4″, major), 125.94 (C-2′ + C-

6′, major), 125.88 (C-2′ + C-6′, minor), 53.7 (C-1, major), 53.5 (C-1,

minor), 51.3 (C-4, major), 50.8 (C-4, minor), 40.1 (C-5, minor), 39.5

(C-5, major). MS (ESI): m/z = 359.1 [M + H]⁺. HRMS (ESI-ToF)

m/z: [M + H]⁺calcd for C₂₄H₂₀ClO 359.1200, found 359.1197.

(2,4-Diphenyl-cyclopent-2-en-1-yl)(3-methylphenyl)methanone

(4q). Following general procedure B, 1-(3-methylphenyl)-2-mesyloxy-

4-phenylbutan-1-one (0.40 mmol, 133 mg, 1.00 equiv) was irradiated

for 1 h using UV-B irradiation and 89 h using a blue LED. After

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

98:2 → 70:30), the title compound (75.8 mg, 0.22 mmol, 56%, 2.0:1

d.r.) was obtained as a colorless solid. R_f= 0.48 (4:1 cyclohexane/

ethyl acetate). IR/cm⁻¹(ATR): 3058, 1680, 1601, 1494, 1447, 1244,

1160, 699. ¹H NMR, COSY, TOCSY, NOESY (600 MHz, CDCl₃) δ

7.89−7.86 (m, 1.0H, H-2‴ + H-6‴, minor), 7.86−7.83 (m, 2.0H, H-

2‴ + H-6‴, major), 7.44−7.28 (m, 11.6H, H-2′ + H-6′ + H-2″-3″ +

H-5″-6″ + H-4‴-5‴, major; H-2′-3′ + H-5′-6′ + H-3″ + H-5″ + H-

4‴-5‴, minor), 7.27−7.22 (m, 3.8H, H-3′ + H-5′, major; H-4′ + H-2″

+ H-6″, minor), 7.23−7.18 (m, 2.3H, H-4′ + H-4″, major; H-4″,

minor), 6.55−6.53 (m, 0.5H, H-3, minor), 6.40−6.38 (m, 1.0H, H-3,

major), 5.16−5.12 (m, 0.5H, H-1, minor), 5.11−5.06 (m, 1.0H, H-1,

major), 4.25−4.22 (m, 0.5H, H-4, minor), 4.22−4.18 (m, 1.0H, H-4,

major), 3.16−3.08 (m, 1.0H, H-5a, major), 2.66−2.60 (m, 0.5H, H-

5a, minor), 2.47−2.42 (m, 0.5H, H-5b, major), 2.44 (s, 1.4H, C-3‴-

CH₃, minor), 2.42 (s, 2.9H, C-3‴-CH₃, major), 2.03−1.97 (m, 1.0H,

H-5b, minor). ¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ

201.4 (CO, major), 200.8 (CO, minor), 145.04 (C-1″, minor), 144.95

(C-1″, major), 142.9 (C-2, major), 142.7 (C-2, minor), 138.6 (C-3‴,

minor), 138.5 (C-3‴, major), 136.5 (C-1‴, major), 136.3 (C-1‴,

minor), 135.4 (C-1′, major), 135.0 (C-1′, minor), 134.1 (C-4‴,

minor), 134.0 (C-4‴, major), 133.3 (C-3, minor), 133.0 (C-3, major),

129.21 (C-2‴, minor), 129.18 (C-2‴, major), 128.64 (C-3″ + C-5″ +

C-5‴, minor), 128.57 (C-3″ + C-5″ + C-5‴, major), 128.49 (C-3′ +

C-5′, minor), 128.4 (C-3′ + C-5′, major), 127.7 (C-2″ + C-6″,

major), 127.5 (C-4″, minor), 127.40 (C-2″+ C-6″, minor), 127.36

(C-4″, major), 126.6 (C-4′, minor), 126.5 (C-4′, major), 126.02 (C-

2′ + C-6′, major), 125.96 (C-2′ + C-6′, minor), 125.89 (C-6‴,

minor), 125.86 (C-6‴, major), 53.5 (C-1, major), 53.4 (C-1, minor),

51.4 (C-4, major), 50.8 (C-4, minor), 40.5 (C-5, minor), 39.7 (C-5,

major), 21.45 (C-3‴-CH₃, minor), 21.42 (C-3‴-CH₃, major). MS

(ESI): m/z = 361.1 [M + Na]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺

calcd for C₂₅H₂₃O 339.1744, found 339.1748.

(2-Phenyl-4,4-dimethylcyclopent-2-en-1-yl)(phenyl)methanone

(4n). Following general procedure A, a mixture of (2,2-

dimethylcyclopropyl)(phenyl)methanone (0.40 mmol, 69.6 mg, 1.00

equiv) and phenylacetylene (4.00 mmol, 439 μL, 10.0 equiv) was

irradiated for 120 h with a blue LED. After column chromatography

(SiO₂, eluent: cyclohexane/ethyl acetate, 99:1 → 80:20), the title

compound (89.0 mg, 0.32 mmol, 81%) was obtained as a colorless oil.

R_f= 0.53 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 2953,

2863, 1682, 1445, 1237, 1206, 1012, 751, 706, 691. ¹H NMR, COSY,

TOCSY, NOESY (600 MHz, CDCl₃) δ 8.07−8.03 (m, 2H, H-2″ +

H-6″), 7.61−7.57 (m, 1H, H-4″), 7.53−7.48 (m, 2H, H-3″ + H-5″),

7.30−7.27 (m, 2H, H-2′ + H-6′), 7.25−7.21 (m, 2H, H-3′ + H-5′),

7.19−7.15 (m, 1H, H-4′), 6.26−6.24 (m, 1H, H-3), 5.06−5.01 (m,

1H, H-1), 2.41 (dd, J = 13.0, 10.2 Hz, 1H, H-5a), 1.96 (dd, J = 13.0,

5.4 Hz, 1H, H-5b), 1.22 + 1.19 (2 × s, 2 × 3H, 2 × CH₃). ¹³C{H}

NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 201.5 (CO), 140.1 (C-

3), 138.3 (C-2), 136.5 (C-1″), 135.6 (C-1′), 133.1 (C-4″), 128.7 (C-

2″-3″ + C-5″-6″), 128.4 (C-3′ + C-5′), 127.1 (C-4′), 125.8 (C-2′ +

C-6′), 53.4 (C-1), 45.7 (C-4), 44.7 (C-5), 29.4 + 28.9 (2 × CH₃). MS

(ESI): m/z = 277.1 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺

calcd for C₂₀H₂₁O 277.1587, found 277.1587.

(2,4-Diphenyl-cyclopent-2-en-1-yl)(4-triﬂuormethylphenyl)-

methanone (4o). Following general procedure B, 1-(4-triﬂuorome-

thylphenyl)-2-mesyloxy-4-phenylbutan-1-one (0.40 mmol, 154 mg,

1.00 equiv) was irradiated for 1 h using UV-B irradiation and 48 h

using a blue LED. After column chromatography (SiO₂, eluent:

cyclohexane/ethyl acetate, 98:2 → 70:30) and preparative HPLC

(C₁₈PFP, eluent: water/acetonitrile, 35:65), the title compound (89.4

mg, 0.23 mmol, 57%, 2.2:1 d.r.) was obtained as a colorless solid. R_f=

0.41 (4:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 1686, 1494,

1409, 1321, 1168, 1128, 1066, 699. ¹H NMR, COSY, TOCSY,

NOESY (600 MHz, CDCl₃) δ 8.16 (d, J = 8.1 Hz, 0.9H, H-2‴ + H-

6‴, minor), 8.13 (d, J = 8.1 Hz, 2.0H, H-2‴ + H-6‴, major), 7.77 (d, J

= 8.1 Hz, 1.0H, H-3‴ + H-5‴, minor), 7.74 (d, J = 8.1 Hz, 2.0H, H-

3‴ +H-5‴, major), 7.38−7.18 (m, 13.9H, H-2′-6′ + H-2″-6″, major +

minor), 6.55−6.53 (m, 0.4H, H-3, minor), 6.42−6.40 (m, 1.0H, H-3,

major), 5.15−5.11 (m, 0.4H, H-1, minor), 5.09−5.05 (m, 1.0H, H-1,

major), 4.29−4.19 (m, 1.3H, H-4, major + minor), 3.17−3.10 (m,

1.0H, H-5a, major), 2.66−2.60 (m, 0.4H, H-5a, minor), 2.49−2.43

(m, 0.4H, H-5b, minor), 2.04−1.97 (m, 1.0H, H-5b, major). ¹⁹F

NMR (282 MHz, CDCl₃): δ −64.28 (s, CF₃, minor),−64.29 (s, CF₃,

major).¹³C{H} NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 200.3

(CO, major), 199.8 (CO, minor), 144.7 (C-1″, minor), 144.6 (C-1″,

major), 142.5 (C-2, major), 142.2 (C-2, minor), 139.2 (C-1‴, major),

139.0 (C-1‴, minor), 135.2 (C-1′, major), 134.8 (C-1′, minor), 134.4

(q, ²J_CF= 32.7 Hz, C-4‴, major + minor), 133.6 (C-3, minor), 133.3

(C-3, major), 129.00 (C-3‴ + C-5‴, minor), 128.97 (C-3‴ + C-5‴,

major), 128.73 (C-2′ + C-6′, minor), 128.67 (C-2′ + C-6′, major),

128.62 (C-3′ + C-5′, minor), 128.57 (C-3′ + C-5′, major), 127.8 (C-

4′, minor), 127.7 (C-2″ + C-6″, major), 127.6 (C-4′, major), 127.4

(C-2″ + C-6″, minor), 126.8 (C-4″, minor), 126.7 (C-4″, major),

126.0 (C-3″ + C-5″, major), 125.9 (C-3″ + C-5″, minor), 125.88 (q,

⁴J_CF= 3.7 Hz, C-2‴ + C-6‴, minor), 125.8 (q, ⁴J_CF= 3.7 Hz, C-2‴ +

C-6‴, major), 123.6 (C q, ¹J_CF= 272.9 Hz, CF₃, major + minor), 54.0

(C-1, major), 53.8 (C-1, minor), 51.4 (C-4, major), 50.8 (C-4,

minor), 40.0 (C-5, minor), 39.4 (C-5, major). MS (ESI): m/z = 393.1

[M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for C₂₅H₂₀F₃O

393.1461, found 393.1454.

(2,4-Diphenyl-cyclopent-2-en-1-yl)(3-chlorophenyl)methanone

(4p). Following general procedure B, 1-(4-chlorophenyl)-2-mesyloxy-

4-phenylbutan-1-one (0.40 mmol, 141 mg, 1.00 equiv) was irradiated

for 1 h using UV-B irradiation and 48 h using a blue LED. After

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

98:2 → 70:30), the title compound (68.8 mg, 0.19 mmol, 48%, 2.9:1

d.r.) was obtained as a colorless solid. R_f= 0.48 (4:1 cyclohexane/

ethyl acetate), IR/cm⁻¹(ATR): 3026, 1686, 1571, 1493, 1204, 759,

(2-Phenyl-4-cyanocyclopent-2-en-1-yl)(phenyl)methanone (4s).

Following general procedure B, 4-cyano-2-mesyloxy-1-phenylbutan-

1-one (0.40 mmol, 107 mg, 1.00 equiv) was irradiated for 1.5 h using

UV-B irradiation and 24 h using a blue LED. After column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 98:2 →

70:30) and preparative HPLC (H-Tec, eluent: water/acetonitrile,

45:55), the two diastereomers could be isolated as colorless oils

(combined 35 mg, 0.13 mmol, 32%, 2.0:1 d.r.).

1

735, 699. H NMR, COSY, TOCSY, NOESY (600 MHz, CDCl₃) δ

7.97 (t, J = 1.9 Hz, 0.3H, H-2‴, minor), 7.96 (t, J = 1.9 Hz, 1.0H, H-

3244

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J. Org. Chem. 2021, 86, 3232−3248

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

(1,4-cis)(2-Phenyl-4-cyanocyclopent-2-en-1-yl)(phenyl)-

methanone (cis-4s). The (1,4-cis) diastereomer (23 mg, 0.09 mmol,

22%) was isolated as a colorless oil. R_f= 0.31 (2:1 cyclohexane/ethyl

acetate). IR/cm⁻¹(ATR): 3059, 2238, 1681, 1596, 1447, 1329, 1212,

1002, 761, 693. ¹H NMR, COSY, TOCSY, NOESY (400 MHz,

CDCl₃) δ 8.04−7.99 (m, 2H, H-2″ + H-6″), 7.65−7.60 (m, 1H, H-

4″), 7.54−7.48 (m, 2H, H-3″ + H-5″), 7.33−7.21 (m, 5H, H-2′-6′),

6.25−6.22 (m, 1H, H-3), 5.08−5.01 (m, 1H, H-1), 3.94−3.87 (m,

1H, H-4), 3.02−2.92 (m, 1H, H-5a), 2.53−2.41 (m, 1H, H-5b).

¹³C{H} NMR, HSQC, HMBC (101 MHz, CDCl₃) δ 198.8 (C-1),

147.1 (C-2), 135.9 (C-1‴), 133.73 (C-1′), 133.67 (C-4‴), 128.9 (C-

3‴ + C-5‴), 128.7 (C-2′ + C-6′ + C-2‴ + C-6‴), 128.6 (C-4′), 126.3

(C-3′ + C-5′), 122.8 (C-3), 119.9 (CN), 52.7 (C-1), 34.1 + 34.0 (C-4

+ C-5). HRMS (ESI-ToF) m/z: [M + Na]⁺calcd for C₁₉H₁₅NONa

296.1046, found 296.1051.

Following general procedure B, 1,4-diphenyl-2-mesyloxybutan-1-

one (0.30 mmol, 95.4 mg, 1.00 equiv) was irradiated for 1 h with UV-

B and after mixing with 4-cyanopyridine (0.39 mmol, 40.6 mg, 1.30

equiv) for 48 h with a blue LED at room temperature. After column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 90:10 →

0:100), the title compound (42.0 mg, 0.14 mmol, 46%) was obtained

as a colorless oil.

R_f= 0.33 (2:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3027,

1

1682, 1596, 1449, 1413, 1181, 992, 752, 701. H NMR, COSY (300

MHz, CDCl₃) δ 8.53 (s, 2H, H-2‴ + H-6‴), 7.92−7.84 (m, 2H, H-2′

+ H-6′), 7.60−7.53 (m, 1H, H-4′), 7.49−7.40 (m, 2H, H-3′ + H-5′),

7.38−7.31 (m, 2H, H-3″ + H-5″), 7.29−7.20 (m, 5H, H-2″ + H-4″ +

H-6″ + H-3‴ + H-5‴), 4.04 (t, J = 7.9 Hz, 1H, H-4), 3.00−2.91 (m,

2H, H-2), 2.61−2.45 (m, 2H, H-3). ¹³C{H} NMR, HSQC, HMBC

(75 MHz, CDCl₃) δ 199.5 (C-1), 153.5 (C-1‴), 150.1 (C-2‴ + C-

6‴), 142.5 (C-1″), 136.9 (C-1′), 133.3 (C-4′), 129.0 (C-3″ + C-5″),

128.7 (C-3′ + C-5′), 128.1 (C-2′ + C-6′ + C-2″ + C-6″), 127.1 (C-

4″), 123.3 (C-3‴ + C-5‴), 49.9 (C-4), 36.5 (C-2), 29.1 (C-3). MS

(ESI): m/z = 302.2 [M + H]⁺. The spectroscopic data are in

accordance with the literature.³⁵

(1,4-trans)(2-Phenyl-4-cyanocyclopent-2-en-1-yl)(phenyl)-

methanone (trans-4s). The (1,4-trans) isomer (12 mg, 0.04 mmol,

10%) was isolated as a colorless oil. R_f= 0.49 (2:1 cyclohexane/ethyl

acetate). IR/cm⁻¹(ATR): 3059, 2238, 1681, 1595, 1447, 1212, 989,

946, 691. ¹H NMR, COSY, NOESY (400 MHz, CDCl₃) δ 8.05−7.98

(m, 2H, H-2″ + H-6″), 7.68−7.61 (m, 1H, H-4″), 7.57−7.49 (m, 2H,

H-3″ + H-5″), 7.31−7.23 (m, 5H, H-2′-6′), 6.34−6.27 (m, 1H, H-3),

5.20−5.06 (m, 1H, H-1), 4.00−3.90 (m, 1H, H-4), 2.85−2.73 (m,

1H, H-5a), 2.65−2.52 (m, 1H, H-5b). ¹³C{H} NMR, HSQC, HMBC

(101 MHz, CDCl₃) δ 199.3 (CO), 146.5 (C-2), 135.7 (C-1″), 133.9

(C-4″), 133.5 (C-1′), 129.0 (C-3″ + C-5″), 128.7 + 128.6 (C-2′ + C-

4′ + C-6′ + C-2″ + C-6″), 126.2 (C-3′ + C-5′), 123.6 (C-3), 120.6

(CN), 52.0 (C-1), 34.8 (C-5), 34.3 (C-4). HRMS (ESI-ToF) m/z:

[M + Na]⁺calcd for C₁₉H₁₅NONa 296.1046, found 296.1051.

Synthesis of γ-Pyridinylated Ketones. Method A. An oven-

dried Schlenk tube (10 mL) was charged with the corresponding

cyclopropane 2 (0.30 mmol, 1.00 equiv), cyanopyridine 5 (0.39

mmol, 1.30 equiv), and Hantzsch ester (0.69 mmol, 175 mg, 2.30

equiv) under nitrogen atmosphere. The mixture was suspended in dry

MTBE (10.0 mL, c = 0.03 M). The mixture was degassed and then

placed in front of a blue LED (see the materials section) at a distance

of 5 cm. The vessel was irradiated until TLC or HPLC/ESI-MS

indicated full consumption of the starting material (24−72 h). The

solvent was removed in vacuo, and the residue was puriﬁed by ﬂash

chromatography to aﬀord the γ-pyridinylated ketones 6. Some of the

products were puriﬁed using preparative HPLC with mixtures of

water and acetonitrile as an eluent.

Method B. In an oven-dried quartz tube under nitrogen

atmosphere, the α-mesyloxyketones 1 (0.30 mmol, 1.00 equiv) and

1-methylimidazole (0.60 mmol, 47.8 μL, 2.00 equiv) were dissolved in

dry toluene (30.0 mL, c = 0.01 M). The reaction tube was degassed

and placed into a Rayonet photoreactor. The vessel was irradiated

(λ_max= 300 nm, 16 × 8 W) until TLC or HPLC/ESI-MS indicated

full consumption of the starting material (1.0 h). The precipitated

methanesulfonate salt was ﬁltered, washed with toluene, and the

solvent was removed in vacuo. The residue was dissolved in dry

MTBE (10.0 mL, c = 0.03 M) and transferred to a 10 mL Schlenk

tube charged with cyanopyridine (0.39 mmol, 1.30 equiv) and

Hantzsch ester (0.42 mmol, 1.05 equiv) under nitrogen atmosphere.

The suspension was degassed and placed in front of a blue LED at a

distance of 5 cm. The vessel was irradiated until TLC or HPLC/ESI-

MS indicated full consumption of the starting material (24−48 h).

The solvent was removed in vacuo, and the residue was puriﬁed by

ﬂash column chromatography to aﬀord the corresponding γ-

pyridinylated ketones 6. Some of the products were further puriﬁed

using preparative HPLC with mixtures of water and acetonitrile as an

eluent.

1,4-Diphenyl-4-(pyridine-2-yl)butan-1-one (6b). Following gen-

eral procedure A, (phenyl)-[2-phenylcyclopropyl]methanone (0.30

mmol, 66.6 mg, 1.00 equiv) and 2-cyanopyridine (0.39 mmol, 37.6

μL, 1.30 equiv) were irradiated for 48 h at room temperature. After

column chromatography (SiO₂, eluent: cyclohexane/ethyl acetate,

90:10 → 0:100) and preparative HPLC (C₁₈PFP, eluent: water/

acetonitrile, 50/50, t_R= 11.8 min), the title compound (43.0 mg, 0.14

mmol, 48%) was obtained as a colorless oil. R_f= 0.49 (2:1

cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3060, 2931, 1682, 1589,

1

1449, 1433, 749, 701, 523. H NMR, COSY, NOESY (600 MHz,

CDCl₃) δ 8.60−8.56 (m, 1H, H-6‴), 7.91−7.83 (m, 2H, H-2′ + H-

6′), 7.62−7.56 (m, 1H, H-4‴), 7.54−7.51 (m, 1H, H-4′), 7.44−7.39

(m, 2H, H-3′ + H-5′), 7.38−7.35 (m, 2H, H-2″ + H-6″), 7.32−7.28

(m, 2H, H-3″ + H-5″), 7.23−7.19 (m, 2H, H-4″ + H-3‴), 7.15−7.10

(m, 1H, H-5‴), 4.22 (t, J = 7.9 Hz, 1H, H-4), 2.98−2.93 (m, 2H, H-

2), 2.73−2.65 (m, 1H, H-3a), 2.58−2.49 (m, 1H, H-3b). ¹³C{H}

NMR, HSQC, HMBC (151 MHz, CDCl₃) δ 200.0 (C-1), 163.1 (C-

2‴), 149.0 (C-6‴), 143.0 (C-1″), 136.8 (C-1′ + C-4‴), 133.0 (C-4′),

128.7 (C-3″ + C-5″), 128.5 (C-3′ + C-5′), 128.1 (C-2′ + C-6′ + C-2″

+ C-6″), 126.7 (C-4″), 123.0 (C-3‴), 121.6 (C-5‴), 52.6 (C-4), 36.8

(C-2), 29.4 (C-3). MS (ESI): m/z = 302.1 [M + H]⁺. HRMS (ESI-

ToF) m/z: [M+H]⁺calcd for C₂₁H₂₀NO 302.1547, found 302.1540.

1,4-Diphenyl-4-(isoquinolin-1-yl)butan-1-one (6c). Following

general procedure A, (phenyl)-[2-phenylcyclopropyl]methanone

(0.30 mmol, 66.6 mg, 1.00 equiv) and 1-cyaonisoquinoline (0.39

mmol, 60.1 mg, 1.30 equiv) were irradiated for 48 h at room

temperature. After column chromatography (SiO₂, eluent: cyclo-

hexane/ethyl acetate, 90:10 → 50:50), the title compound (62.0 mg,

0.18 mmol, 59%) was obtained as a colorless oil. R_f= 0.54 (2:1

cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 2930, 1681, 1598, 1561,

1

1493, 1232, 825, 746, 701. H NMR, COSY (400 MHz, CDCl₃) δ

8.59 (d, J = 5.7 Hz, 1H, H-8‴), 8.22 (d, J = 8.5 Hz, 1H, H-3‴), 7.92−

7.86 (m, 2H, H-2′ + H-6′), 7.81−7.76 (m, 1H, H-6‴), 7.63 7.58 (m,

1H, H-4‴), 7.56 (d, J = 5.7 Hz, 1H, H-7‴), 7.53−7.47 (m, 2H, H-4′ +

H-4‴), 7.45−7.34 (m, 4H, H-3′ + H-5′ + H-2″ + H-6″), 7.29−7.20

(m, 2H, H-3″ + H-5″), 7.18−7.12 (m, 1H, H-4″), 5.12−5.03 (m, 1H,

H-4), 3.13−3.04 (m, 1H, H-2a), 3.01−2.96 (m, 1H, H-2b), 2.95−

2.89 (m, 1H, H-3a), 2.71−2.56 (m, 1H, H-3b). ¹³C{H} NMR,

HSQC, HMBC (101 MHz, CDCl₃) δ 200.5 (C-1), 161.4 (C-2‴),

143.6 (C-1), 141.5 (C-8‴), 136.9 (C-1′), 136.6 (C-6a‴), 132.9 (C-

4′), 129.8 (C-5‴), 128.6 + 128.5 (C-3′ + C-5′), 128.1 (C-2′ + C-6′ +

C-2″ + C-6″), 127.4 (C-6‴), 127.3 (C-2a‴), 126.5 (C-4″), 125.2 (C-

3‴), 119.8 (C-7‴), 47.7 (C-4), 36.9 (C-2), 30.4 (C-3). MS (ESI): m/

z = 352.1 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for

C₂₅H₂₂NO 352.1696, found 352.1704.

1,4-Diphenyl-4-(pyridine-4-yl)butan-1-one (6a). Following gen-

eral procedure A, phenyl-[phenylcyclopropyl]methanone (0.30 mmol,

66.6 mg, 1.00 equiv) and 4-cyanopyridine (0.39 mmol, 40.6 mg, 1.30

equiv) were irradiated for 48 h at room temperature. After column

chromatography (SiO₂, eluent: cyclohexane/ethyl acetate, 90:10 →

0:100), the title compound (63 mg, 0.21 mmol, 70%) was obtained as

a colorless oil.

1-(4-Methoxyphenyl)-4-phenyl-4-(pyridin-4-yl)butan-1-one (6d).

Following general procedure A, (4-methoxyphenyl)-[2-

phenylcyclopropyl]methanone (0.30 mmol, 75.6 mg, 1.00 equiv)

and 4-cyanopyridine (0.39 mmol, 40.6 mg, 1.30 equiv) were

irradiated for 48 h at room temperature. After column chromatog-

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raphy (SiO₂, eluent: cyclohexane/ethyl acetate, 90:10 → 0:100), the

title compound (49.0 mg, 0.15 mmol, 49%) was obtained as a

colorless oil. R_f= 0.23 (1:1 cyclohexane/ethyl acetate). IR/cm⁻¹

cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3026, 1686, 1595, 1414,

1224, 1202, 995, 768, 744, 701, 558. H NMR, COSY (400 MHz,

1

CDCl₃) δ 8.52 (s, 2H, H-2‴ + H-6‴), 7.82 (t, J = 1.9 Hz, 1H, H-2′),

7.71 (dt, J = 7.9, 1.4 Hz, 1H, H-6′), 7.51 (ddd, J = 7.9, 1.9, 1.4 Hz,

1H, H-4′), 7.40−7.35 (m, 1H, H-5′), 7.35−7.30 (m, 2H, H-3″ + H-

5″), 7.25−7.19 (m, 5H, H-2″ + H-4″ + H-6″ + H-3‴ + H-5‴), 4.01

(t, J = 7.9 Hz, 1H, H-4), 2.94−2.86 (m, 2H, H-2), 2.57−2.44 (m, 2H,

H-3). ¹³C{H} NMR, HSQC, HMBC (101 MHz, CDCl₃) δ 198.1 (C-

1), 153.6 (C-4‴), 149.8 (C-2‴ + C-6‴), 142.1 (C-1″), 138.3 (C-1′),

135.0 (C-3′), 133.1 (C-4′), 130.0 (C-5′), 129.0 (C-3″ + C-5″), 128.1

(C-2′), 128.0 (C-2″ + C-6″), 127.1 (C-4″), 126.0 (C-6′), 123.2 (C-

3‴ + C-5‴), 49.7 (C-4), 36.5 (C-2), 28.8 (C-3). MS (ESI): m/z =

336.1 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for

C₂₁H₁₉ClNO 336.1150, found 336.1153.

1

(ATR): 1673, 1598, 1415, 1257, 1171, 1029, 984, 702. H NMR,

COSY (300 MHz, CDCl₃) δ 8.54−8.47 (m, 2H, H-2‴ + H-6‴),

7.87−7.77 (m, 2H, H-2′ + H-6′), 7.35−7.28 (m, 2H, H-3″ + H-5″),

7.25−7.19 (m, 5H, H-2″ + H-4″ + H-6″ + H-3‴ + H-5‴), 6.91−6.86

(m, 2H, H-3′ + H-5′), 4.07−3.97 (m, 1H, H-4), 3.84 (s, 3H, OCH₃),

2.93−2.83 (m, 2H, H-2), 2.55−2.43 (m, 2H, H-3). ¹³C{H} NMR,

HSQC, HMBC (75 MHz, CDCl₃) δ 198.1 (C-1), 163.6 (C-4′), 154.1

(C-4‴), 149.6 (C-2‴ + C-6‴), 142.4 (C-1″), 130.3 (C-2′ + C-6′),

129.9 (C-1′), 129.0 (C-3″ + C-5″), 128.1 (C-2″ + C-6″), 127.1 (C-

4″), 123.4 (C-3‴ + C-5‴), 113.8 (C-3′ + C-5′), 55.6 (OCH₃), 49.9

(C-4), 36.1 (C-2), 29.2 (C-3). MS (ESI): m/z = 332.1 [M + H]⁺.

HRMS (ESI) m/z: [M + H]⁺calcd for C₂₂H₂₂NO₂332.1645, found

332.1650.

1-(3-Methylphenyl)-4-phenyl-4-(pyridin-4-yl)butan-1-one (6h).

Following general procedure B, 1-(3-methylphenyl)-2-mesyloxy-4-

phenylbutan-1-one (0.30 mmol, 99.6 mg, 1.00 equiv) was irradiated

for 1 h with UV-B and after mixing with 4-cyanopyridine (0.39 mmol,

40.6 mg, 1.30 equiv) for 48 h with a blue LED at room temperature.

After column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 90:10 → 0:100) and preparative HPLC (C₁₈PFP, eluent:

water/acetonitrile, 90:10 → 10:90, t_R= 15.3 min), the title compound

(49 mg, 0.16 mmol, 52%) was obtained as a colorless oil. R_f= 0.14

(2:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 3026, 1681, 1595,

1-(4-Fluorophenyl)-4-(4-methoxyphenyl)-4-(pyridin-4-yl)butan-

1-one (6e). Following general procedure A, (4-ﬂuorophenyl)-[2-(4-

methoxyphenyl)cyclopropyl]methanone (0.30 mmol, 81.1 mg, 1.00

equiv) and 4-cyanopyridine (0.39 mmol, 40.6 mg, 1.30 equiv) were

irradiated for 48 h at room temperature. After column chromatog-

raphy (SiO₂, eluent: cyclohexane/ethyl acetate, 90:10 → 0:100), the

title compound (67.0 mg, 0.19 mmol, 64%) was obtained as a

colorless oil. R_f= 0.35 (1:1 cyclohexane/ethyl acetate). IR/cm⁻¹

1

(ATR): 2935, 1682, 1596, 1509, 1247, 1229, 1156, 809, 560. H

1414, 1257, 1178, 993, 770, 701, 558. H NMR, COSY (300 MHz,

NMR, COSY (300 MHz, CDCl₃) δ 8.50 (s, 2H, H-2‴ + H-6‴),

7.92−7.81 (m, 2H, H-2′ + H-6′), 7.21−7.16 (m, 2H, H-3‴ + H-5‴),

7.16−7.12 (m, 2H, H-2″ + H-6″), 7.12−7.05 (m, 2H, H-3′ + H-5′),

6.90−6.81 (m, 2H, H-3″ + H-5″), 3.95 (t, J = 7.9 Hz, 1H, H-4), 3.78

(s, 3H, OCH₃), 2.89 (t, J = 7.3 Hz, 2H, H-2), 2.56−2.35 (m, 2H, H-

3). ¹⁹F NMR (282 MHz, CDCl₃): δ −105.10 (tt, J = 8.5, 5.3 Hz).

¹³C{H} NMR, HSQC, HMBC (75 MHz, CDCl₃) δ 197.8 (C-1),

165.74 (d, ¹J_CF= 255.0 Hz, C-4′), 158.5 (C-4″), 153.9 (C-4″), 149.8

(C-2‴ + C-6‴), 134.2 (C-1″), 133.18 (d, ⁴J_CF= 3.0 Hz, C-1′), 130.6

(d, ³J_CF= 9.4 Hz, C-2′ + C-6′), 128.9 (C-2″ + C-6″), 123.1 (C-3″ +

C-5″), 115.68 (d, ²J_CF= 21.8 Hz, C-3′ + C-5′), 114.2 (C-3″ + C-5″),

55.3 (OCH₃), 48.9 (C-4), 36.3 (C-2), 29.1 (C-3). MS (ESI): m/z =

350.1 [M + Na]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for

C₂₂H₂₁FNO₂350.1551, found 350.1558.

1-Phenyl-4-(4-cyanophenyl)-4-(pyridin-4-yl)butan-1-one (6f).

Following general procedure A, (phenyl)-[2-(4-cyanophenyl)-

cyclopropyl]methanone (0.30 mmol, 74.1 mg, 1.00 equiv) and 4-

cyanopyridine (0.39 mmol, 40.6 mg, 1.30 equiv) were irradiated for

48 h at room temperature. After column chromatography (SiO₂,

eluent: cyclohexane/ethyl acetate, 90:10 → 0:100), the title

compound (67.2 mg, 0.20 mmol, 68%) was obtained as a yellow

oil. R_f= 0.21 (1:1 cyclohexane/ethyl acetate). IR/cm⁻¹(ATR): 2927,

2228, 1721, 1683, 1596, 1448, 1253, 747, 691, 598. ¹H NMR, COSY

(300 MHz, CDCl₃) δ 8.60−8.48 (m, 2H, H-2‴ + H-6‴), 7.88−7.80

(m, 2H, H-2′ + H-6′), 7.64−7.58 (m, 2H, H-3″ + H-5″), 7.58−7.52

(m, 1H, H-4′), 7.46−7.39 (m, 2H, H-3′ + H-5′), 7.38−7.33 (m, 2H,

H-2″ + H-6″), 7.22−7.15 (m, 2H, H-3‴ + H-6‴), 4.12 (t, J = 7.9 Hz,

1H, H-4), 2.96−2.88 (m, 2H, H-2), 2.57−2.45 (m, 2H, H-3). ¹³C{H}

NMR, HSQC, HMBC (75 MHz, CDCl₃) δ 198.8 (C-1), 152.1 (C-

4‴), 149.9 (C-2‴ + C-6‴), 147.9 (C-1″), 136.5 (C-1′), 133.4 (C-4′),

132.7 (C-3″ + C-5″), 128.8 (C-2″ + C-6″), 128.7 (C-3′ + C-5′),

127.9 (C-2′ + C-6′), 123.3 (C-3‴ + C-5‴), 118.5 (CN), 111.1 (C-

4″), 49.6 (C-4), 35.9 (C-2), 28.5 (C-3). MS (ESI): m/z = 327.1 [M +

H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺calcd for C₂₂H₁₉N₂O

327.1492, found 327.1498.

CDCl₃) δ = 8.53 (s, 2H, H-2‴ + H-6‴), 7.70−7.63 (m, 2H, H-2′ +

H-6′), 7.41−7.31 (m, 4H, H-4′-5′, H-3″ + H-5″), 7.30−7.20 (m, 5H,

H-2″ + H-4″ + H-6″ + H-3‴ + H-5‴), 4.04 (t, J = 7.9 Hz, 1H, H-4),

2.98−2.90 (m, 2H, H-2), 2.57−2.46 (m, 2H, H-3), 2.40 (s, 3H, C-3′-

CH₃). ¹³C{H} NMR, HSQC, HMBC (75 MHz, CDCl₃) δ 199.7 (C-

1), 153.6 (C-4‴), 149.9 (C-2‴ + C-6‴), 142.4 (C-1″), 138.4 (C-3′),

136.8 (C-1′), 133.9 (C-2′), 128.9 (C-3″ + C-5″), 128.5 (C-4′ + C-

6′), 128.0 (C-2″ + C-6″), 127.0 (C-4″), 125.2 (C-5′), 123.3 (C-3‴ +

C-5‴), 49.8 (C-4), 36.5 (C-2), 29.1 (C-3), 21.4 (C-3′-CH₃). MS

(ESI): m/z = 316.1 [M + H]⁺. HRMS (ESI-ToF) m/z: [M + H]⁺

calcd for C₂₂H₂₂NO 316.1696, found 316.1702.

ASSOCIATED CONTENT

* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.0c02591.

■

sı

Detailed information on light sources and irradiation

setup, further information regarding the synthesis of

amino-substituted cyclopentene 4m, reoptimization of

the Norrish−Yang as well as optimization of formal [3 +

2] and radical−radical coupling reaction, additional

information and procedures of the mechanistic studies,

1

computational data, and copies of the H, ¹³C{H}, and

relevant HSQC, HMBC, and NOESY spectra (PDF)

XYZ-coordinates of all calculated structures used for the

computation of the energy proﬁle of the ring-closing

mechanism (ZIP)

AUTHOR INFORMATION

Corresponding Author

■

Till Opatz − Department of Chemistry, Johannes Gutenberg

University, 55128 Mainz, Germany; orcid.org/0000-

0002-3266-4050; Email: opatz@uni-mainz.de

1-(3-Chlorophenyl)-4-phenyl-4-(pyridin-4-yl)butan-1-one (6g).

Following general procedure B, 1-(3-chlorophenyl)-2-mesyloxy-4-

phenylbutan-1-one (0.30 mmol, 106 mg, 1.00 equiv) was irradiated

for 1 h with UV-B and after mixing with 4-cyanopyridine (0.39 mmol,

40.6 mg, 1.30 equiv) for 48 h with a blue LED at room temperature.

After column chromatography (SiO₂, eluent: cyclohexane/ethyl

acetate, 90:10 → 0:100) and preparative HPLC (C₁₈PFP, eluent:

water/acetonitrile, 45/55, t_R= 18.0 min), the title compound (38 mg,

0.11 mmol, 38%) was obtained as a colorless oil. A further puriﬁcation

using other HPLC columns was not successful. R_f= 0.33 (1:1

Authors

Jan Paternoga − Department of Chemistry, Johannes

Gutenberg University, 55128 Mainz, Germany

̈

Jonas Kuhlborn − Department of Chemistry, Johannes

Gutenberg University, 55128 Mainz, Germany

Nils Ole Rossdam − Department of Chemistry, Johannes

Gutenberg University, 55128 Mainz, Germany

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Ohashi, M.; Ogoshi, S. Synthesis and Reactivity of Six-Membered

Oxa-Nickelacycles: A Ring-Opening Reaction of Cyclopropyl

Ketones. Chem. − Eur. J. 2009, 15, 10083−10091. (d) Tamaki, T.;

Ohashi, M.; Ogoshi, S. [3+ 2] Cycloaddition Reaction of Cyclopropyl

Ketones with Alkynes Catalyzed by Nickel/Dimethylaluminum

Chloride. Angew. Chem. 2011, 123, 12273−12276. (e) Hao, W.;

Harenberg, J. H.; Wu, X.; MacMillan, S. N.; Lin, S. Diastereo-and

enantioselective formal [3+ 2] cycloaddition of cyclopropyl ketones

and alkenes via Ti-catalyzed radical redox relay. J. Am. Chem. Soc.

2018, 140, 3514−3517.

(11) For examples of photoredox-catalyzed formal [3 + 2]

cycloadditions of ketocyclopropanes, see: (a) Amador, A. G.;

Sherbrook, E. M.; Lu, Z.; Yoon, T. P. A general protocol for radical

anion [3+ 2] cycloaddition enabled by Tandem lewis acid photoredox

catalysis. Synthesis 2018, 50, 539. (b) Amador, A. G.; Sherbrook, E.

M.; Yoon, T. P. Enantioselective photocatalytic [3+ 2] cycloadditions

of aryl cyclopropyl ketones. J. Am. Chem. Soc. 2016, 138, 4722−4725.

(c) Huang, X.; Lin, J.; Shen, T.; Harms, K.; Marchini, M.; Ceroni, P.;

Meggers, E. Asymmetric [3+ 2] Photocycloadditions of Cyclo-

propanes with Alkenes or Alkynes through Visible-Light Excitation of

Catalyst-Bound Substrates. Angew. Chem., Int. Ed. 2018, 57, 5454−

5458. (d) Feng, L.; Yan, H.; Yang, C.; Chen, D.; Xia, W. Visible-light

induced direct synthesis of polysubstituted furans from cyclopropyl

ketones. J. Org. Chem. 2016, 81, 7008−7022. (e) Luis-Barrera, J.;

Laina-Martín, V.; Rigotti, T.; Peccati, F.; Solans-Monfort, X.; Sodupe,

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.0c02591

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

Financial support of the DFG (grant Op90/12-1) is gratefully

acknowledged. The authors thank Dr. Benjamin Lipp for

helpful discussions regarding the photoredox part of this study

as well as Dr. Natalie Netz and Dr. Lisa Marie Kammer for

providing some of the chalcone starting materials. The authors

also thank Dr. Johannes C. Liermann (Mainz) for NMR

spectroscopy and Dr. Christopher Kampf (Mainz) for mass

spectrometry. Parts of this research were conducted using the

supercomputer Mogon and/or advisory services oﬀered by

Johannes Gutenberg-University Mainz (hpc.uni-mainz.de),

which is a member of the AHRP (Alliance for High

Performance Computing in Rhineland Palatinate, www.ahrp.

info) and the Gauss Alliance e.V. The authors gratefully

acknowledge the computing time granted on the super-

computer Mogon at Johannes Gutenberg-University Mainz

(hpc.uni-mainz.de).

́

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Article Doi

Hantzsch Ester-Mediated Photochemical Transformations in the Ketone Series: Remote C(sp3)-H Arylation and Cyclopentene Synthesis through Strain Release

DOI: 10.1021/acs.joc.0c02591

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