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Synlett 2019; 30(11): 1361-1365
DOI: 10.1055/s-0037-1611841
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© Georg Thieme Verlag Stuttgart · New York

Synthesis of β-Selenylated Cyclopentanones via Photoredox-Catalyzed Selenylation/Ring-Expansion Cascades of Alkenyl Cyclobutanols

Hye Im Jung
,
Dae Young Kim  *
Department of Chemistry, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea   Email: dyoung@sch.ac.kr
› Author Affiliations

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (Grant-No. NRF-2016-R1D1A1B03933723) and Soonchunhyang University Research Fund.
Further Information

Publication History

Received: 19 April 2019

Accepted after revision: 08 May 2019

Publication Date:
29 May 2019 (online)

 
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Abstract

A photoredox strategy to access β-selenated cyclic ketone derivatives through the coupling reaction of 1-(1-arylvinyl)cyclobutanols with diselenides under blue LED irradiation and an air atmosphere was developed. This reaction employs the easily accessible and shelf-stable diselenides as a selenium radical source, and the reaction has advantages of mild reaction conditions and broad substrate scope.


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Key words

selenylation - semipinacol rearrangement - 1,2-alkyl migration - 1-(1-arylvinyl)cyclobutanols - photoredox reaction

Organoselenium compounds have attracted considerable attention in pharmaceutical and material sciences due to their biological and chemical properties.[1] It can also be used as a chemical intermediate for organic synthesis.[2] The widespread application of these compounds has led to intensive efforts to develop novel and convenient synthetic methods.[3] Deselenide, a reagent that is easily accessible and stable on the shelf, has emerged as a valuable selenium formulation for synthesizing organic selenium compounds. Various reactions of diselenides with alkene, boronic acid, aromatics, and diazonium salt have been used to supply a variety of organoselenium compounds.[4]

The radical-initiated addition reaction to alkenes provided a practical protocol for the difunctionalization of unactivated alkenes with high chemoselectivity.[5] [6] Recently, several groups reported radical additions and ring-expansion cascades via semipinacol rearrangement of alkenyl alcohols with a variety of radicals, such as acyl, alkyl, amine, aryl, azido, difluoromethyl, phenylsulfonyl, and trifluoromethyl radicals, for the synthesis of β-functionalized carbonyl compounds (Scheme [1, a]).[7]

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Scheme 1 Strategy for photoredox-catalyzed selenylation/ring-expansion sequences

Over the last decade, the visible-light-mediated photoredox catalysis has emerged as a powerful approach for organic chemists to introduce the functional group to organic compounds because of its environmentally friendly and practical properties.[8] Very recently, we have reported the electrochemical selenylation/ring-expansion sequences of alkenyl cyclobutanols (Scheme [1, b]).[7j] Although this method has been achieved by this system, a more efficient, mild, and environmentally benign approaches for the selenylation/ring-expansion sequences of alkenyl alcohols are highly desired. We envisioned transformation of alkenyl cyclobutanols to β-selenated cyclopentanones by visible-light-mediated photoredox-catalyzed selenylation/ring-expansion sequence via semipinacol rearrangement with diselenides as selenium radical precursors (Scheme [1, c]).

As part of a study for redox reaction and ring closure, we have reported internal redox reactions[9] and radical additions/ring-expansion sequences under mild conditions.[7`] [e] [f] [g] [h] [i] [j] [k] [l] [m]

Table 1 Optimization of Reaction Conditionsa

Entry

Photocatalyst

Solvent

Time (h)

Yield (%)b

 1

eosin Y

MeCN

12

37

 2

Na2eosin Y

MeCN

16

46

 3

eosin B

MeCN

16

24

 4

rhodamine B

MeCN

12

29

 5

rhodamine 6G

MeCN

16

30

 6

fac-Ir(ppy)3

MeCN

12

41

 7

F(Ir)picc

MeCN

12

45

 8

Ru(bpy)3Cl2·6H2O

MeCN

11

94

 9

Ru(bpy)3(PF6)2

MeCN

11

37

10

Ru(bpy)3Cl2·6H2O

DMSO

22

trace

11

Ru(bpy)3Cl2·6H2O

DMF

22

trace

12

Ru(bpy)3Cl2·6H2O

MeOH

21

trace

13

Ru(bpy)3Cl2·6H2O

H2O

21

20

14

Ru(bpy)3Cl2·6H2O

Acetone

21

32

15

Ru(bpy)3Cl2·6H2O

PhMe

24

24

16

Ru(bpy)3Cl2·6H2O

EA

21

22

17

Ru(bpy)3Cl2·6H2O

THF

11

37

18

Ru(bpy)3Cl2·6H2O

DCM

22

65

19

Ru(bpy)3Cl2·6H2O

DCE

21

55

20d

Ru(bpy)3Cl2·6H2O

MeCN

14

94

21e

Ru(bpy)3Cl2·6H2O

MeCN

14

78

22f

Ru(bpy)3Cl2·6H2O

MeCN

21

66

23g

Ru(bpy)3Cl2·6H2O

MeCN

21

64

24h

–

MeCN

24

 0

25i

Ru(bpy)3Cl2·6H2O

MeCN

24

 0

26j

Ru(bpy)3Cl2·6H2O

MeCN

24

25

a Reaction conditions: 1-[1-(4-methoxyphenyl)vinyl]cyclobutanol (1c, 0.1 mmol), diphenyl diselenide (2a, 0.06 mmol), photocatalyst, solvent (1 mL), blue LEDs, room temperature under air.

b Isolated yields.

c F(Ir)pic = bis(3,5-difluoro-2-(2-pyridyl)phenyl-(2-carboxypyridyl) iridium (III).

d 3 mol% photocatalyst loading.

e 1 mol% photocatalyst loading.

f White LEDs instead of blue LEDs.

g Green LEDs instead of blue LEDs.

h Without photocatalyst.

i The reaction was performed in the dark.

j The reaction was performed under N2.

Herein, we report photoredox catalytic selenylation/ring-expansion cascades via semipinacol rearrangement of alkenyl cyclobutanols. To determine optimized reaction conditions for visible-light-mediated photoredox catalytic selenylation/1,2-alkyl-migration sequences of alkenyl cyclobutanol derivatives, we choose 1-[1-(4-methoxyphenyl)vinyl] cyclobutanol (1c) and diphenyl diselenide (2a) as the model substrates. The reaction proceeded in visible-light irradiation using blue LED (5 W, λmax = 455 nm) in acetonitrile with 5 mol% of photocatalyst. The reaction was conducted with various organic and metal photocatalysts (Table [1], entries 1–9), among which a ruthenium complex, Ru(bpy)3Cl2·6H2O, afforded the optimal result (94% yield, Table [1], entry 8). An intensive screening revealed that the reaction is best conducted in acetonitrile (Table [1], entries 8 and 10–19). The reaction tolerates photocatalyst loading down to 3 mol% without a decrease in yield (Table [1], entries 20 and 21). Using white or green LEDs to replace blue LEDs led to a slight decrease in reaction yields (Table [1], entries 22 and 23). The controlled experiments showed that the reaction completely suppressed in the absence of photocatalyst or light source (Table [1], entries 24 and 25).

We turned our attention to study the substrate scope of 1-(1-arylvinyl)cyclobutanols 1 with diphenyl diselenide (2a, Scheme [2]). The reactions of cyclobutanol substrates 1a–h showed that a variety of functional groups were well tolerated, including methyl, methoxy, fluoro, and chloro; and the corresponding cyclopentanone products 3a–h were obtained with 64–94% yields (Scheme [2]). The electronic effect on the aryl of cyclobutanols 1 is important to the reactivity of this selenylation and ring-expansion sequences: cyclopentanones containing electron-donating-substituted aryl groups had higher yields than those with electron-withdrawing ones. The 2-naphthyl-substituted cyclobutanol 1i provided the corresponding product 3i in 72% yield. Notably, this radical selenylation/1,2-alkyl-migration reaction with alkyl-substituted alkenyl cyclobutanol gave 61% yield of corresponding product 3j under the optimized reaction conditions. Next, dibenzyl diselenide (2b) was also effective in the reaction, resulting in the corresponding products 3k–o were obtained in moderate to high yields (55–75%, Scheme [2]).

Zoom Image
Scheme 2 Substrate scope. Reaction conditions: allylic alcohol 1 (0.1 mmol), R2SeSeR2 2 (0.06 mmol), Ru(bpy)3Cl2·6H2O (3 μmol), MeCN (1 mL), blue LEDs, room temperature under air. Isolated yields are given.

The practical synthesis of β-selenated cyclic ketones has been achieved by the photoredox-catalyzed selenylation and ring-expansion cascades of 1-(1-arylvinyl)cyclobutanol derivatives with diselenides. Under the optimized reaction conditions, 1-[1-(p-tolyl)vinyl]cyclobutanol (1b) with diphenyl diselenide (2a) afford the desired β-selenated cyclopentanone 3b with 81% yield (Scheme [3]). It is noteworthy that this cascade can also be conducted on gram scale.

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Scheme 3 Gram-scale synthesis of 3b

To demonstrate the feasibility of this protocol, we decided to further investigate synthetic utility of β-selenated cyclopentanones 3 through Dowd–Beckwith-type ring expansion to afford ring-enlarged cyclohexanone derivatives 4.[10] The reaction of cyclopentanones 3 with Bu3SnH and azobis(isobutyronitrile) (AIBN) affords high yields of ring-enlarged cyclohexanones 4 in toluene at 100 °C for 5 hours (Scheme [4]).

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Scheme 4 Dowd–Beckwith rearrangement of 3

In order to gain insight into the reaction mechanism, some control experiments were performed. When the reaction was carried out under anhydrous nitrogen, significantly reducing yield of product was obtained (Table [1], entry 26). This result indicates that the oxygen plays an important role in the reaction. In addition, when 2,2,6,6-tetramethylpiperidin-1-yloxyl (TEMPO), as a radical inhibitor, was added into the reaction, no desired product was detected (Scheme [5]). This outcome was consistent with our hypothesis that a radical pathway can be involved in this cascade reaction. We propose the reaction mechanism as shown in Scheme [6] based on the results of the experiment and related literature.[11] A photocatalyst Ru(bpy)3Cl2·6H2O is converted into the excited state [Ru(bpy)3Cl2·6H2O]* under visible-light irradiation. Energy-transfer process then occurs to diphenyl diselenide (2a) and would generate ground-state Ru(bpy)3Cl2·6H2O and selenium radicals I. After that, selenium radical I react with 1-(1-phenylvinyl) cyclobutanol (1a) to give carbon radical III, which is oxidized to cation intermediate IV by oxygen (path a). The semipinacol rearrangement through 1,2-alkyl migration of intermediate IV affords the cyclopentanone 3a. Alternatively, radical I can also be oxidized by oxygen to selenium cation II which react with 1-(1-phenylvinyl) cyclobutanol (1a) to give corresponding cation IV (path b).

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Scheme 5 Radical-trapping experiment
Zoom Image
Scheme 6 Proposed reaction mechanism

In conclusion, we have developed a practical synthesis of β-selenated cyclopentanone derivatives 3 via photoredox-catalyzed selenylation and ring-expansion cascade of alkenyl cyclobutanol derivatives 1 with diselenides.[12] [13] This approach is environmentally friendly by using shelf-stable diselenides as selenium radical source and visible light as source of energy. This synthetic method affords a facile way to prepare β-selenated cyclopentanone derivatives.


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Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0037-1611841.
  • Supporting Information


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Zoom Image
Scheme 1 Strategy for photoredox-catalyzed selenylation/ring-expansion sequences
Zoom Image
Scheme 2 Substrate scope. Reaction conditions: allylic alcohol 1 (0.1 mmol), R2SeSeR2 2 (0.06 mmol), Ru(bpy)3Cl2·6H2O (3 μmol), MeCN (1 mL), blue LEDs, room temperature under air. Isolated yields are given.
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Scheme 3 Gram-scale synthesis of 3b
Zoom Image
Scheme 4 Dowd–Beckwith rearrangement of 3
Zoom Image
Scheme 5 Radical-trapping experiment
Zoom Image
Scheme 6 Proposed reaction mechanism