Download PDF
Synthesis 2022; 54(20): 4576-4582
DOI: 10.1055/a-1874-4935
paper

Aryl Ketone Mediated Light-Driven Naphthylation of C(sp3)–H Bonds Attached to either Oxygen or Nitrogen Substituents

Masaya Azami
,
Toshihiro Murafuji
,
Shin Kamijo∗

This research was partially supported by the Japan Society for the Promotion of Science (JSPS, KAKENHI Grant Number JP22K05096).
› Further Information
 
 PDF Download Permissions and Reprints All articles of this category


Abstract

A light-driven naphthylation was achieved at C(sp3)–H bonds attached to either oxygen or nitrogen substituents using sulfonylnaphthalenes as a naphthalene precursor in the presence of 4-benzoylpyridine at ambient temperature. The present transformation is proposed to proceed through the generation of a carbon radical species via chemoselective cleavage of the heteroatom-substituted C(sp3)–H bond by photoexcited 4-benzoylpyridine, the addition of the derived carbon radical to the electron-deficient sulfonylnaphthalene, and then rearomatization by releasing sulfinyl radical.


#

Key words

C–H functionalization - naphthylation - photoreaction - aryl ketones - ethers - amides

The synthetic methodologies targeting the functionalization of non-acidic C(sp3)–H bonds offer a simple and efficient way for the preparation of organic materials, which permits direct use of organic compounds as a reaction substrate without any pre-activations.[1] For this reason, such reactions are largely applicable for late-stage functionalization of organic molecules so that the development of C(sp3)–H functionalization has attracted much attention in recent years. At the same time, the continuous research toward the new development of C(sp3)–H functionalizations is valuable because those transformations could provide an alternative synthetic way to complement the scope and limitations of well-known synthetic methods. We have recently reported on the single-step substitutive introduction of heteroaromatic units, such as pyrimidine[2] and benzazole rings,[3] at the non-acidic ethereal C(sp3)–H bond under photoirradiation conditions utilizing an aryl ketone as a mediator.[4] Based on the success of these C–H heteroarylations, we turned our attention to introducing a naphthalene unit as a component to increase the structural complexity of organic molecules.

To achieve an alkylation of naphthalenes, the nucleophilic substitution between alkyl halides and metalated naphthalenes should be one of the conventional and representative choices,[5] although the incompatibility of electrophilic functionalities including carbonyl groups with nucleophilic metalated naphthalenes can be an inherent drawback of this method. The Friedel–Crafts reaction can be another standard and traditional option for alkylation of aromatic rings including naphthalenes.[6] In the case of the preparation of alkylated naphthalenes using the Friedel–Crafts strategy, in addition to the requirement of quite harsh reaction conditions, such as high temperature and strongly acidic media, a regioselectivity issue could arise in some cases. The coupling strategy, mostly the Suzuki–Miyaura­ coupling reaction, overcame the functional group incompatibility problems to some extent and successfully provided alkylated naphthalenes from alkylboron reagents and mesyloxylated/halogenated naphthalenes.[7] [8] Recent advancements brought a radical strategy for synthesizing alkylated naphthalenes; especially the Shirakawa group has been intensively working on the methodology development based on radical chemistry utilizing tert-butoxy radical as an initial C–H bond cleaving agent generated from t BuOO t Bu and t BuON=NO t Bu under thermal conditions.[9] Despite a variety of reaction conditions that have been recently found for generating a carbon radical species, the applicability for the alkylation of naphthalenes has not been well investigated and only scattered examples are reported; moreover, the installable unit is limited to simple naphthalene in most cases.[10] We assumed that aryl ketone mediated light-driven naphthylation of C(sp3)–H bonds should expand the scope of applicable starting substances so that we investigated the requirements, mainly focusing on the naphthalene precursor, for the synthesis of alkylated naphthalenes using a radical strategy.

To begin with our research, we planned the direct naphthylation of an ethereal C(sp3)–H bond, as shown in Scheme [1]. The homolytic cleavage of non-acidic ethereal C–H bonds could be attained by utilizing an aryl ketone, such as 4-benzoylpyridine (4-BzPy),[3] [11] under photoirradiation conditions. Owing to the electrophilic nature of the photoexcited ketone, the electron-rich ethereal C–H bond of starting substance 1 should be chemoselectively cleaved to give the carbon radical A and the ketyl-type radical B.[4] We, at this point, surmised that subjecting the derived carbon radical A to sulfonylnaphthalene 2 [12] would provide the alkylated naphthalene 3 by way of the radical intermediate C. The formation of the radical C seems to be feasible because it is a thermodynamically stabilized benzyl radical. Subsequent liberation of the sulfinyl radical from C affords the final product 3. Regeneration of 4-BzPy could be possible if the smooth formation of methanesulfinic acid is attained by the reaction between released methanesulfinyl radical and the ketyl-type radical B.[13]

Zoom Image
Scheme 1 A proposed reaction mechanism for naphthylation of an ethereal C(sp3)–H bond

We first examined the light-driven C–H naphthylation using 1-(methylsulfonyl)naphthalene (2a) and tetrahydrofuran (THF, 1a) as starting substances in the presence of 4-BzPy (Table [1], entry 1). The corresponding alkylated naphthalene 3aa was obtained as expected although its yield remained extremely low (8%). We thus re-designed the naphthalene precursor 2 based on two assumptions (see Scheme [1]): one is that the additional attachment of a substituent capable of stabilizing the generating benzyl radical intermediate C should improve the yield of the desired naphthalene product 3, and the other is that lowering the electron density of the naphthalene core in 2 should facilitate the addition of electron-rich carbon radical A derived from THF (1a) to 2. Accordingly, we prepared some sulfonylnaphthalenes 2b–i having an electron-withdrawing functionality. After several examinations, we found that the introduction of an acetyl group (2b) gave rise to the expected product 3ab in 60% yield (entry 2). The installed carbonyl functionality could stabilize benzyl radical C by extending the π-conjugated system and could lower the electron density of the naphthalene core of 2 by its electron-withdrawing ability. Other sulfonylnaphthalenes bearing a carbonyl functionality, including ester (2c), amide (2d), and carboxylic acid (2e), were all converted into the respective products 3ac, 3ad, and 3ae in 38–62% yield (entries 3–5). Even with the naphthalene precursors containing the protic amide or carboxylic acid functionality, the C–H naphthylation took place without any difficulties. Its applicability to acidic substances is one of the characteristic features of the present protocol. The attachment of other representative electron-withdrawing functionalities, such as cyano (2f) and sulfonyl (2g) groups, furnished the corresponding alkylated naphthalenes 3af and 3ag in 41% and 36% yield, respectively (entries 6 and 7). When 1,4-disulfonylated naphthalene 2g was employed as the precursor, exclusive formation of the monoalkylated product 3ag was observed and no dialkylated product was obtained. This result strongly suggested that the introduction of an electron-donating functionality to the naphthalene precursor inhibits the present C–H naphthylation.[14] The reactions using alkynylated and phenylated sulfonylnaphthalenes 2h and 2i also proceeded to some extent, affording respective products 3ah (27%, entry 8) and 3ai (14%, entry 9).

Table 1 Naphthylation of THF (1a) with Sulfonylnaphthalenes 2 Having Various Electron-Withdrawing Functionalitiesa

Entry

EWG

2

3

Yield (%)b

1

H

2a

3aa

 8c

2d

COMe

2b

3ab

60

3

CO2Me

2c

3ac

38

4

CONH2

2d

3ad

47

5

CO2H

2e

3ae

62

6

CN

2f

3af

41

7

SO2Me

2g

3ag

36

8

C≡CPh

2h

3ah

27

9

Ph

2i

3ai

14

a Reaction conditions: 2 (0.2 mmol, 1 equiv), 4-BzPy (0.2 mmol, 1 equiv), THF (1a, 4 mL), photoirradiation (365 nm LED light), argon atmosphere, rt, 19 h.

b Isolated yield.

c The starting 2a was recovered in 57% yield.

d The reaction was completed in 6 h.

Before investigating the reactivity of other C(sp3)–H bonds, more detailed optimization of the reaction conditions was carried out employing THF (1a) and 1-acetyl-4-(methylsulfonyl)naphthalene (2b) as a standard set of starting substances (Table [2]). As listed in entries 1–3, 4-BzPy exhibited superior reactivity for the ethereal C–H bond cleavage compared to benzophenone (Ph2CO), 2-benzoylpyridine (2-BzPy), and 3-benzoylpyridine (3-BzPy).[15] Among the solvents screened, benzene gave the highest yield of the expected product 3ab (entry 4). Nevertheless, it is worthy to mention that the present transformation could be conducted in a variety of both aprotic and protic solvents, including CH2Cl2, acetone, EtOAc, and t BuOH (entries 5–8). The amount of THF (1a) to that of the naphthalene precursor 2b could be decreased without substantial loss of the product yield (125 equivalents of THF in entry 9, and 22.5 equivalents of THF in entry 10), although a longer reaction time was required when the smaller amount of THF was applied (72 h, entry 10). Further investigations revealed that the addition of K2CO3 resulted in a marked acceleration of the transformation (24 h, entry 11).[16] [17] Lastly, we successfully carried out the reaction in the presence of 0.5 equivalents of 4-BzPy with the addition of 1 equivalent of K2CO3 and obtained essentially the same yield of alkylated naphthalene 3ab in 36 hours (58%, entry 12). The reaction could be promoted with 0.2 equivalents of 4-BzPy although the reaction time was prolonged to 96 hours (entry 13). Elongation of the reaction time was observed as the amount of 4-BzPy was reduced, thus 0.5 equivalents of 4-BzPy was employed in the following examinations.

Having established the optimal conditions for the C–H naphthylation, the reactions of a variety of oxygen- and nitrogen-containing starting substances 1 with sulfonylated acetylnaphthalene 2b were examined, as shown in Scheme [2]. The reactions using tetrahydropyran (1b) and oxepane (1c) led to the corresponding products 3bb (39%) and 3cb (58%), respectively, in the same manner as observed in the case of THF (1a) to 3ab (58%; Table [2], entry 12). Consequently, five- to seven-membered cyclic ethers bearing the naphthalene substituent at the α-carbon to the oxygen atom could be prepared directly from the starting cyclic ethers. When the reaction was carried out using 2-methyltetrahydrofuran (1d), the naphthalene unit was regioselectively installed at the sterically less hindered methylene carbon, and the corresponding alkylated naphthalene 3db was formed in 38% yield with a diastereomeric ratio of 68:32.[18] The naphthylation of 1,3-dioxolane (1e) took place at the C–H bond adjacent to the two oxygen atoms to give the corresponding product 3eb in 24% yield, thus the reactivity of 1,3-dioxolane (1e) appears to be low compared to THF (1a). Acyclic diethyl ether (1f) and tert-butyl methyl ether (1g) could also serve as starting substances, providing the respective products 3fb (65%) and 3gb (13%). Again, in the case of tert-butyl methyl ether (1g), the naphthalene unit was selectively introduced at the C–H bond of the methyl carbon adjacent to the oxygen substituent. This selective naphthylation of a methyl group is of note because the generation of primary alkyl radicals is generally challenging due to their instability. The reaction employing 2-pyrrolidone (1h), a nitrogen-containing cyclic compound, produced the expected product 3hb in 43% yield, which has the naphthalene substituent at the α-carbon to the nitrogen atom. Accordingly, the present protocol allows the chemoselective installation of the naphthalene unit into a non-acidic C(sp3)–H bond geminal to either oxygen or nitrogen substituents in a single step.

Table 2 Detailed Optimization of Conditions for the Reaction of THF (1a) with Sulfonylated Acetylnaphthalene 2b a

Entry

Solvent

THF (1a) (equiv)

Ketone (equiv)

Yield of 3ab (%)b

 1c,d

THF

250

Ph2CO (1)

41

 2c,e

THF

250

2-BzPy (1)

45

 3c,e

THF

250

3-BzPy (1)

29

 4f

C6H6

 10

4-BzPy (1)

42

 5f

CH2Cl2

 10

4-BzPy (1)

30

 6f

acetone

 10

4-BzPy (1)

30

 7f

EtOAc

 10

4-BzPy (1)

37

 8f

t BuOH

 10

4-BzPy (1)

31

 9g

THF/C6H6 (1:1)

125

4-BzPy (1)

59h

10i

THF/C6H6 (1:10)

 22.5

4-BzPy (1)

56

11j

THF/C6H6 (1:10)

 22.5

4-BzPy (1)

55

12k

THF/C6H6 (1:10)

 22.5

4-BzPy (0.5)

60h

13l

THF/C6H6 (1:10)

 22.5

4-BzPy (0.2)

54

a Reaction conditions unless otherwise noted: 2b (0.2 mmol, 1 equiv), ketone (0.2 mmol, 1 equiv), photoirradiation (365 nm LED light), argon atmosphere, rt.

b Yield was determined by 1H NMR analysis of the crude mixture.

c THF (1a) was used as a solvent (4 mL).

d The reaction was completed in 6 h.

e The reaction was completed in 24 h.

f The reaction was conducted using THF (1a; 0.16 mL, 10 equiv) in the solvent (4 mL) for 48 h. Recovery of 2b was observed.

g The reaction was conducted in THF/C6H6 (2 mL:2 mL) for 6 h.

h Isolated yield.

i The reaction was conducted in THF/C6H6 (0.36 mL:3.6 mL) for 72 h.

j The reaction was conducted in THF/C6H6 (0.36 mL:3.6 mL) for 24 h with addition of K2CO3 (0.2 mmol, 1 equiv).

k The reaction was conducted in THF/C6H6 (0.36 mL:3.6 mL) for 36 h with addition of K2CO3 (0.2 mmol, 1 equiv) and 4-BzPy (0.1 mmol, 0.5 equiv).

l The reaction was conducted in THF/C6H6 (0.36 mL:3.6 mL) for 96 h with addition of K2CO3 (0.2 mmol, 1 equiv) and 4-BzPy (0.04 mmol, 0.2 equiv).

Zoom Image
Scheme 2 Naphthylation of oxygen- and nitrogen-containing substances 1 with sulfonylated acetylnaphthalene 2b. Reagents and conditions: 1 (22.5 equiv), 2b (0.2 mmol, 1 equiv), 4-BzPy (0.1 mmol, 0.5 equiv), K2CO3 (0.2 mmol, 1 equiv), benzene (4 mL), photoirradiation (365 nm LED light), argon atmosphere, rt, 48 h.

Having succeeded in the light-driven naphthylation at C(sp3)–H bonds attached to either oxygen or nitrogen substituents of various starting substances, we examined the reaction between THF (1a) and sulfonylnaphthalene 2b in the presence of TEMPO to obtain mechanistic information on the present transformation (Scheme [3]). After photoirradiation of the reaction mixture for 2 hours, a significant amount of the recovered naphthalene precursor 2b was observed together with the formation of the TEMPO adduct 4 and a trace amount of the naphthalene product 3ab. The formation of the TEMPO adduct 4 clearly indicates the generation of the carbon radical A derived from THF (1a) during the reaction course. When the irradiation time was prolonged to 36 hours (standard reaction conditions as shown in Table [2], entry 12), the naphthalene precursor 2b was completely consumed and both the alkylated naphthalene 3ab and the TEMPO adduct 4 [19] were obtained. When the photoirradiation was kept for 36 hours, even after the consumption of TEMPO, the formation of the naphthalene product 3ab was observed along with the TEMPO adduct 4. Accordingly, alkylated naphthalene 3ab would presumably be produced through the intervention of carbon radical A as well.[20]

Zoom Image
Scheme 3 Naphthylation of THF (1a) in the presence of TEMPO

In conclusion, we have achieved the light-driven naphthylation of non-acidic C(sp3)–H bonds of ethers and amide in a single step under mild conditions at ambient temperature. The reaction is proposed to proceed through a radical mechanism, where the heteroatom-substituted C(sp3)–H bonds are homolytically cleaved solely by photoexcited 4-benzoylpyridine, and the naphthalene unit is delivered from sulfonylnaphthalenes. We also pointed out that the design of the naphthalene precursor, containing electron-withdrawing carbonyl functionalities, is the key to improving the reaction efficiency and the product yield. The newly developed radical naphthylation allows rapid transformation of simple organic materials containing oxygen and nitrogen atoms, and thus the present protocol should serve as a convenient and powerful tool for synthesizing alkylated naphthalene derivatives.

All reactions sensitive to air or moisture were carried out under an argon atmosphere with anhydrous conditions unless otherwise noted. Analytical TLC was performed on E. Merck silica gel 60 F254 precoated plates. Column chromatography was performed with silica gel (Fuji Silysia) or a prepacked column using a Biotage Isolera system. The 1H and 13C NMR spectra were recorded on a Bruker Avance III-400 spectrometer. Chemical shifts are reported in δ (ppm) relative to residual solvent signals [1H NMR: CHCl3 (7.26); 13C NMR: CDCl3 (77.0)]. Signal patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad peak. IR spectra were recorded on a JASCO FT/IR-4100 spectrometer. HRMS were recorded on a Thermo Fisher Scientific Orbitrap Exploris 4800/240/120 instrument. Melting points were measured on a Cornes MPA100 micro melting point apparatus. UV irradiation was carried out by using a Keyence UV-400 LED illuminator with UV-50-A (2.2 W) or UV-50-H (2.6 W) and CCS LV-24UV365-4WPCLTL (3.0 W) lamp at 365 nm.


#

1-Acetyl-4-(tetrahydrofuran-2-yl)naphthalene (3ab; Table [2], Entry 12);[10d] Typical Procedure for the Aryl Ketone Mediated Light-Driven Naphthylation of C(sp3)–H Bonds Attached to either Oxygen or Nitrogen Substituents

[CAS Reg. No. 2271147-03-4]

1-Acetyl-4-(methylsulfonyl)naphthalene (2b; 49.7 mg, 0.2 mmol), 4-benzoylpyridine (4-BzPy; 18.3 mg, 0.1 mmol, 0.5 equiv), and K2CO3 (27.6 mg, 0.2 mmol, 1 equiv) in THF/benzene (1:10, 4 mL, 0.05 M) were added to a Pyrex test tube under an argon atmosphere. The test tube was placed at ca. 5 cm distance from an LED lamp (365 nm) and was irradiated at room temperature for 36 h. The mixture was extracted with EtOAc, washed with water and brine, dried over MgSO4, and evaporated. The residue was purified by flash column chromatography (silica gel; hexane/EtOAc, 10:1 to 1:1) to provide the product 3ab.

Yield: 60% (28.6 mg); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 1.81–1.91 (m, 1 H), 1.94–2.14 (m, 2 H), 2.56–2.67 (m, 1 H) 2.74 (s, 3 H), 4.05 (ddd, J = 8.5, 7.2, 7.2 Hz, 1 H), 4.25 (ddd, J = 8.5, 8.5, 5.5 Hz, 1 H), 5.66 (dd, J = 7.2, 7.2 Hz, 1 H), 7.52–7.63 (m, 2 H), 7.69 (dd, J = 7.8, 0.8 Hz, 1 H), 7.92 (d, J = 7.8 Hz, 1 H), 7.96–8.00 (m, 1 H), 8.76–8.82 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 30.0, 34.0, 68.9, 77.7, 120.2, 123.4, 126.3, 126.8, 127.4, 128.5, 130.4, 130.7, 134.7, 144.9, 201.9.


#

1-(Tetrahydrofuran-2-yl)naphthalene (3aa)[21]

[CAS Reg. No. 136581-10-7]

Yield: 8% (3.2 mg); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 1.86–1.97 (m, 1 H), 1.97–2.14 (m, 2 H), 2.51–2.62 (m, 1 H), 4.04 (ddd, J = 8.0, 7.1, 7.1 Hz, 1 H), 4.24 (ddd, J = 8.0, 8.0, 5.6 Hz, 1 H), 5.65 (dd, J = 7.0, 7.0 Hz, 1 H), 7.43–7.54 (m, 3 H), 7.64 (br d, J = 7.4 Hz, 1 H), 7.75 (d, J = 8.2 Hz, 1 H), 7.84–7.89 (m, 1 H), 7.95–8.00 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 33.7, 68.7, 77.9, 121.8, 123.4, 125.4, 125.5, 125.7, 127.4, 128.8, 130.3, 133.7, 139.3.


#

1-(Methoxycarbonyl)-4-(tetrahydrofuran-2-yl)naphthalene (3ac)

Yield: 38% (14.9 mg); colorless oil.

IR (ATR): 1716, 1517, 1199, 1127, 1077, 1038 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.80–1.92 (m, 1 H), 1.93–2.15 (m, 2 H), 2.56–2.67 (m, 1 H), 4.00 (s, 3 H), 4.05 (ddd, J = 7.8, 7.8, 7.8 Hz, 1 H), 4.25 (ddd, J = 7.8, 7.8, 5.5 Hz, 1 H), 5.68 (dd, J = 7.2, 7.2 Hz, 1 H), 7.52–7.74 (m, 2 H), 7.69 (br d, J = 7.9 Hz, 1 H), 7.99 (br d, J = 8.2 Hz, 1 H), 8.16 (d, J = 7.9 Hz, 1 H), 8.95 (br d, J = 8.2 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 34.0, 52.0, 68.9, 77.7, 120.4, 123.5, 126.0, 126.3, 126.6, 127.1, 129.9, 130.5, 131.5, 145.1, 168.1.

HRMS (ESI): m/z [M + H]+ calcd for C16H17O3: 257.1173; found: 257.1172.


#

1-Carbamoyl-4-(tetrahydrofuran-2-yl)naphthalene (3ad)

Yield: 47% (22.5 mg); brown solid; mp 125.2–126.3 °C.

IR (ATR): 3397, 3176, 1641, 1588, 1515, 1075, 768 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.80–1.91 (m, 1 H), 1.93–2.14 (m, 2 H), 2.54–2.66 (m, 1 H), 4.04 (ddd, J = 8.5, 7.2, 7.2 Hz, 1 H), 4.24 (ddd, J = 8.5, 8.5, 5.6 Hz, 1 H), 5.66 (dd, J = 7.0, 7.0 Hz, 1 H), 5.96 (br s, 2 H), 7.53–7.61 (m, 2 H), 7.65 (d, J = 7.5 Hz, 1 H), 7.69 (d, J = 7.5 Hz, 1 H), 7.96–8.01 (m, 1 H), 8.44–8.50 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 34.0, 68.9, 77.7, 120.5, 123.6, 125.1, 126.3, 126.4, 126.7, 129.6, 130.3, 132.5, 132.8, 168.1.

HRMS (ESI): m/z [M + H]+ calcd for C15H16O2N: 242.1176; found: 242.1175.


#

1-Carboxy-4-(tetrahydrofuran-2-yl)naphthalene (3ae)

Yield: 62% (30.0 mg); yellow solid; mp 131.4–133.1 °C.

IR (ATR): 3064 (br), 1685, 1587, 1514, 1428, 1279, 1253, 1074, 903 cm–1.

1H NMR (400 MHz, CDCl3): δ (CO2H was not detected) = 1.83–1.95 (m, 1 H), 1.95–2.15 (m, 2 H), 2.58–2.70 (m, 1 H), 4.07 (ddd, J = 6.5, 6.5, 6.5 Hz, 1 H), 4.27 (ddd, J = 6.5, 6.5, 6.5 Hz, 1 H), 5.71 (dd, J = 6.2, 6.2 Hz, 1 H), 7.58 (t, J = 7.5 Hz, 1 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.75 (d, J = 7.5 Hz, 1 H), 8.01 (d, J = 7.5 Hz, 1 H), 8.37 (d, 7.5 Hz, 1 H), 9.13 (d, 7.5 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.0, 34.1, 68.9, 77.7, 120.5, 123.6, 126.1, 126.6, 127.4, 128.2, 130.6, 131.5, 131.8, 146.4, 175.4.

HRMS (ESI): m/z [M – H]– calcd for C15H13O3: 241.0870; found: 241.0868.


#

1-Cyano-4-(tetrahydrofuran-2-yl)naphthalene (3af)

Yield: 41% (17.9 mg); yellow oil.

IR (ATR): 2222, 1068, 844, 765 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.79–1.90 (m, 1 H), 1.94–2.23 (m, 2 H), 2.57–2.68 (m, 1 H), 4.05 (ddd, J = 8.5, 7.1, 7.1 Hz, 1 H), 4.24 (ddd, J = 8.5, 8.5, 5.5 Hz, 1 H), 5.66 (dd, J = 7.1, 7.1 Hz, 1 H), 7.60–7.75 (m, 3 H), 7.91 (d, J = 7.8 Hz, 1 H), 8.02 (br d, J = 8.2 Hz, 1 H), 8.26–8.31 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.0, 34.1, 69.0, 77.4, 109.3, 118.1, 121.0, 124.0, 126.1, 127.4, 128.0, 129.9, 132.5, 132.6, 146.0.

HRMS (ESI): m/z [M + H]+ calcd for C15H14ON: 224.1070; found: 224.1069.


#

1-(Methylsulfonyl)-4-(tetrahydrofuran-2-yl)naphthalene (3ag)

Yield: 36% (20.0 mg); yellow oil.

IR (ATR): 1514, 1371, 1306, 1141, 853, 772 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.81–1.92 (m, 1 H), 1.95–2.17 (m, 2 H), 2.58–2.70 (m, 1 H), 3.21 (s, 3 H), 4.06 (ddd, J = 8.0, 7.4, 7.4 Hz, 1 H), 4.26 (ddd, J = 8.0, 8.0, 5.7 Hz, 1 H), 5.68 (dd, J = 7.5, 7.5 Hz, 1 H), 7.63–7.68 (m, 1 H), 7.68–7.75 (m, 1 H), 7.80 (dd, J = 8.0, 1.0 Hz, 1 H), 8.08 (br d, J = 8.0 Hz, 1 H), 8.33 (d, J = 8.0 Hz, 1 H), 8.77–8.83 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 34.1, 44.3, 69.0, 77.5, 120.5, 124.5, 124.7, 126.8, 128.1, 128.9, 129.6, 131.0, 134.5, 147.4.

HRMS (ESI): m/z [M + H]+ calcd for C15H17O3S: 277.0893; found: 277.0892.


#

1-(Phenylethynyl)-4-(tetrahydrofuran-2-yl)naphthalene (3ah)

Yield: 27% (20.4 mg); yellow oil.

IR (ATR): 1073, 846, 757, 691 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.85–1.96 (m, 1 H), 1.97–2.15 (m, 2 H), 2.53–2.65 (m, 1 H), 4.05 (ddd, J =8.5, 7.5, 7.5 Hz, 1 H), 4.25 (ddd, J =8.5, 8.5, 5.8 Hz, 1 H), 5.66 (dd, J = 7.2, 7.2 Hz, 1 H), 7.35–7.44 (m, 3 H), 7.53–7.70 (m, 5 H), 7.77 (d, J = 7.7 Hz, 1 H), 8.00 (dd, J = 7.7, 1.5 Hz, 1 H), 8.49–8.55 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 33.9, 68.8, 77.8, 87.8, 94.1, 120.1, 121.3, 123.5, 123.6, 126.2, 126.3, 127.1, 128.3, 128.4, 129.6, 130.1, 131.6, 133.4, 140.5.

HRMS (ESI): m/z [M + H]+ calcd for C22H19O: 299.1431; found: 299.1427.


#

1-Phenyl-4-(tetrahydrofuran-2-yl)naphthalene (3ai)

Yield: 14% (7.7 mg); colorless oil.

IR (ATR): 1589, 1492, 1444, 1073, 768, 703 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.93–2.17 (m, 3 H), 2.55–2.68 (m, 1 H), 4.06 (ddd, J = 8.5, 7.2, 7.2 Hz, 1 H), 4.27 (ddd, J = 8.5, 8.5, 7.2 Hz, 1 H), 5.70 (dd, J = 7.0, 7.0 Hz, 1 H), 7.39–7.58 (m, 8 H), 7.70 (dd, J = 7.3, 0.7 Hz, 1 H), 7.94 (br d, J = 8.4 Hz, 1 H), 8.04 (d, J = 8.8 Hz, 1 H).

13C NMR (100 MHz, CDCl3): δ = 26.0, 33.8, 68.8, 77.9, 121.4, 123.6, 125.4, 125.6, 126.6, 126.9, 127.1, 128.2, 130.2, 130.6, 131.9, 138.8, 139.6, 141.0.

HRMS (ESI): m/z [M + H]+ calcd for C20H19O: 275.1431; found: 275.1429.


#

1-Acetyl-4-(tetrahydro-2H-pyran-2-yl)naphthalene (3bb)[10d]

[CAS Reg. No. 2271146-95-1]

Yield: 39% (19.8 mg); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 1.59–1.90 (m, 4 H), 1.96–2.12 (m, 2 H), 2.74 (s, 3 H), 3.73–3.83 (m, 1 H), 4.22–4.31 (m, 1 H), 5.08 (dd, J = 11.7, 1.6 Hz, 1 H), 7.52–7.63 (m, 2 H), 7.70 (d, J = 7.9 Hz, 1 H), 7.93 (d, J = 7.6 Hz, 1 H), 8.04–8.09 (m, 1 H), 8.73–8.78 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 24.2, 26.0, 30.0, 33.6, 69.4, 76.9, 121.4, 123.3, 126.3, 126.7, 127.3, 128.4, 130.3, 130.6, 135.0, 144.2, 202.0.


#

1-Acetyl-4-(oxepan-2-yl)naphthalene (3cb)

Yield: 58% (33.6 mg); yellow oil.

IR (ATR): 1680, 840, 764 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.58–2.04 (m, 7 H), 2.17–2.26 (m, 1 H), 2.73 (s, 3 H), 3.82 (ddd, J = 12.6, 8.4, 4.1 Hz, 1 H), 4.12 (ddd, J = 12.6, 5.3, 5.3 Hz, 1 H), 5.31 (dd, J = 8.2, 4.0 Hz, 1 H), 7.51–7.62 (m, 2 H), 7.73 (d, J = 7.6 Hz, 1 H), 7.93 (d, J = 7.6 Hz, 1 H), 7.97–8.02 (m, 1 H), 8.75–8.81 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 25.9, 26.8, 30.0, 30.9, 37.5, 69.6, 77.9, 121.4, 123.4, 126.2, 126.8, 127.2, 128.4, 130.3, 130.4, 134.6, 145.4, 201.9.

HRMS (ESI): m/z [M + H]+ calcd for C18H21O2: 269.1535; found: 269.1537.


#

1-Acetyl-4-(5-methyltetrahydrofuran-2-yl)naphthalene (3db)

Yield: 38% (19.2 mg); 68:32 inseparable mixture of two diastereomers; colorless oil.

1H NMR (400 MHz, CDCl3): δ (diastereomeric ratio was calculated to be 68:32 by 1H NMR) = 1.41 (d, J = 6.3 Hz, 2.04/3 H), 1.48 (d, J = 6.3 Hz, 0.96/3 H), 1.68–1.94 (m, 2 H), 2.09–2.20 (m, 1 H), 2.55–2.67 (m, 0.32/1 H), 2.74 (s, 3 H), 2.77–2.79 (m, 0.68/1 H), 4.24–4.33 (m, 0.32/1 H), 4.44–4.55 (m, 0.68/1 H), 5.66 (dd, J = 7.2, 7.2 Hz, 0.32/1 H), 5.82 (dd, J = 7.6. 7.6 Hz, 0.68/1 H), 7.50–7.66 (m, 2 H), 7.71 (dd, J = 7.6, 0.8 Hz, 0.68/1 H), 7.80 (dd, J = 7.7, 0.8 Hz, 0.32/1 H), 7.91–8.00 (m, 2 H), 8.76–8.82 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ (detectable signals) = 20.9, 21.4, 29.7, 30.0, 33.1, 33.8, 34.4, 34.8, 76.1, 76.3, 119.9, 120.6, 123.4, 123.5, 126.2, 126.3, 126.8, 127.4, 128.5, 128.6, 130.4, 130.5, 130.6, 131.0, 134.6, 145.1, 145.4, 201.9.

HRMS (ESI): m/z [M + H]+ calcd for C17H19O2: 255.1380; found: 255.1380.


#

1-Acetyl-4-(1,3-dioxolan-2-yl)naphthalene (3eb)

Yield: 24% (11.4 mg); yellow oil.

IR (ATR): 1681, 1117, 910, 850, 774 cm–1.

1H NMR (400 MHz, CDCl3): δ = 2.74 (s, 3 H), 4.14–4.22 (m, 4 H), 6.50 (s, 1 H), 7.54–7.65 (m, 2 H), 7.80 (d, J = 7.8 Hz, 1 H), 7.89 (d, J = 7.8 Hz, 1 H), 8.23–8.30 (m, 1 H), 8.65–8.71 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 30.2, 65.4, 101.5, 121.8, 124.3, 126.4, 126.8, 127.3, 127.6, 130.4, 131.5, 137.0, 137.7, 202.0.

HRMS (ESI): m/z [M + H]+ calcd for C15H15O3: 243.1016; found: 243.1014.


#

1-Acetyl-4-(1-ethoxyethyl)naphthalene (3fb)

Yield: 65% (31.5 mg); yellow oil.

IR (ATR): 1677, 1107, 845, 764 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.25 (t, J = 7.2 Hz, 3 H), 1.60 (d, J = 6.8 Hz, 3 H), 2.75 (s, 3 H), 3.39–3.51 (m, 2 H), 5.20 (q, J = 6.4 Hz, 1 H), 7.52–7.63 (m, 2 H), 7.65 (d, J = 7.8 Hz, 1 H), 7.94 (d, J = 7.8 Hz, 1 H), 8.15–8.21 (m, 1 H), 8.74–8.80 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 15.5, 23.6, 30.0, 64.4, 75.1, 121.5, 123.2, 126.3, 126.8, 127.4, 128.3, 130.5, 131.2, 135.1, 145.2, 201.9.

HRMS (ESI): m/z [M + H]+ calcd for C16H19O2: 243.1380; found: 243.1378.


#

1-Acetyl-4-(tert-butoxymethyl)naphthalene (3gb)

Yield: 13% (6.3 mg); yellow oil.

IR (ATR): 1681, 1113, 837, 771 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.38 (s, 9 H), 2.73 (s, 3 H), 4.94 (s, 2 H), 7.53–7.64 (m, 2 H), 7.66 (d, J = 7.4 Hz, 1 H), 7.91 (d, J = 7.4 Hz, 1 H), 8.02–8.08 (m, 1 H), 8.76–8.79 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 27.7, 30.0, 61.9, 74.0, 123.5, 126.4, 126.6, 127.5, 128.4, 129.0, 130.2, 131.6, 135.1, 140.6, 201.9.

HRMS (ESI): m/z [M + H]+ calcd for C17H21O2: 257.1537; found: 257.1536.


#

5-(4-Acetylnaphthalen-1-yl)pyrrolidin-2-one (3hb)

Yield: 43% (21.8 mg); yellow solid; mp 112.4–113.9 °C.

IR (ATR): 3345, 3171, 1685, 1672, 1516, 841, 768 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.98–2.10 (m, 1 H), 2.45 (t, J = 8.3 Hz, 2 H), 2.74 (s, 3 H), 2.80–2.94 (m, 1 H), 5.56 (dd, J = 8.7, 4.9 Hz, 1 H), 6.53 (br s, 1 H), 7.56 (d, J = 7.8 Hz, 1 H), 7.57–7.68 (m, 2 H), 7.90 (d, J = 7.8 Hz, 1 H), 7.94–8.00 (m, 1 H), 8.74–8.80 (m, 1 H).

13C NMR (100 MHz, CDCl3): δ = 29.5, 29.8, 30.0, 54.5, 119.7, 122.5, 126.9, 127.1, 127.8, 128.0, 130.4, 130.6, 135.6, 143.1, 178.9, 201.7.

HRMS (ESI): m/z [M + H]+ calcd for C16H16O2N: 254.1176; found: 254.1176.


#
#

Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1874-4935.
  • Supporting Information

Corresponding Author

Shin Kamijo
Graduate School of Sciences and Technology for Innovation, Yamaguchi University
Yamaguchi 753-8512
Japan   

Publication History

Received: 11 May 2022

Accepted after revision: 13 June 2022

Accepted Manuscript online:
13 June 2022

Article published online:
02 August 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


   Permissions and Reprints All articles of this category
Zoom Image
Scheme 1 A proposed reaction mechanism for naphthylation of an ethereal C(sp3)–H bond
Zoom Image
Scheme 2 Naphthylation of oxygen- and nitrogen-containing substances 1 with sulfonylated acetylnaphthalene 2b. Reagents and conditions: 1 (22.5 equiv), 2b (0.2 mmol, 1 equiv), 4-BzPy (0.1 mmol, 0.5 equiv), K2CO3 (0.2 mmol, 1 equiv), benzene (4 mL), photoirradiation (365 nm LED light), argon atmosphere, rt, 48 h.
Zoom Image
Scheme 3 Naphthylation of THF (1a) in the presence of TEMPO