Education Research Frontier December 2013, Volume 3, Issue 4, PP.

134-138

Addition of Diphenyldiselenide to Methylenecyclopropanes under Different Conditions: A Good Example for Students to Understand the Differences between Free Radical and Electrophilic Addition Reactions
Lei Yu#, Jun Wang, Tian Chen, Xu Zhang
School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, Peoples Republic of China #Email: yulei@yzu.edu.cn

Abstract
Different reaction conditions may cause different reaction paths for cleavage of the Se-Se bonds. Further reactions of (PhSe)2 with methylenecyclopropanes (MCPs) under different conditions lead to the construction of totally different organic skeletons. Example described herein is typical for students to understand the cleavages of chemical bonds as well as the differences between free radical additions and electrophilic additions.

Keywords: Free Radical Addition; Electrophilic Addition; Selenium Chemistry; Organic Chemistry

1 INTRODUCTION
Both free radical additions[1] and electrophilic additions[2] are important contents in organic reactions. The addition of HBr to terminal olefins under different conditions is a classic example for students to understand the difference of these two kinds of reactions (Fig. 1). In the electrophilic addition mode, the proton tends to be added into the terminal carbon of the olefin to give the thermodynamically more stable intermediate cation 2, which leads to the Markonikov adduct 3. In the free radical addition mode, the bromo free radical firstly adds to the terminal carbon of the olefin to give the intermediate radical 4, which will then capture a proton from another molecular of HBr to give the anti-Markonikov adduct 5. These are famous contrastive examples in textbooks.
H+ R R 1 Br R 4 Br 2 Br HBr H R 5 H BrBr R 3 Br (2) H (1)

FIG. 1 ADDITION OF HBR TO OLEFINS THROUGH DIFFERENT ROUTES

With above examples, students can learn the concept of hyper conjugation effect, which affects the stability of the reaction intermediates and determines the regio-selectivity of the reaction. Examples also imply that, in chemical reactions, different conditions always bring out different results. Recent works of our laboratory may provide another useful example for students to learn about.[3] Compared with
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the additions of HBr to olefins, the additions of diphenyldiselenide to methylenecyclopropanes (MCPs)[4] under different conditions could construct totally different organic skeletons due to different mechanisms. The two parallel reactions were carried out under quite mild conditions. Therefore, they are easy to perform and could be a typical example for undergraduate or graduate to learn about the paths of chemical bonds cleavage as well as the differences between free radical additions and electrophilic additions. Diphenyldiselenide is a beautiful yellow crystal. Long times ago, chemists had already known that under heat or visible light irridiation, homo-cleavage of Se-Se bond could occur to give the phenylselenyl free radical, which could add to unsaturated C=C bonds (Fig. 2, eq. 1).[5] During our studies on selenium chemistry, it was wondered whether hetero-cleavage of Se-Se could happen to generate a phenylselenium cation (an oxidant) and a phenylselenium anion (a reductant) simultaneously (Fig. 2, eq. 2).
heat or hv > 300 nm PhSe SePh homo-cleavage (1)

2 PhSe

? PhSe + PhSe (2) hetero-cleavage FIG. 2 TWO TYPES OF SE-SE BOND CLEAVAGE IN PHSESEPH. PhSe SePh

By using Lewis acid as the catalyst, our hypothesis was accomplished. The selenium atom has lone electron pairs, which could coordinate the empty orbit of the Lewis acid metal (e.g. Fe). Consequently, hetero-cleavage of Se-Se bond could take place to generate the phenylselenyl cation as well as the phenylselenyltrichloroion anion 6 (Fig. 3).
FeCl3 PhSe SePh hetero-cleavage PhSe+ + FeCl3SePh6

FIG. 3 LEWIS ACID CATALYZED SE-SE BOND HETERO-CLEAVAGE

Both phenylselenyl free radical and cation can add to olefins. Their additions to MCPs will firstly generate phenylselenyl cyclopropylcarbinyl radical 8 or cation 11 (Fig. 4).
SePh PhSe Ar 7 Ar 8 PhSe+ Ar 11 SePh 9 SePh Ar 12 PhSeSePh SePh Ar PhSe 6 FeCl3 PhSe 10 PhSe SePh (2) Ar 13 SePh Ar (1)

FIG. 4 REACTION OF MCPS WITH PHSESEPH THROUGH TWO DIFFERENT ROUTES

PhY Y = O, S, Se

YPh

FIG. 5 RING EXPANSION OF CYCLOPROPYLCARBINYL CATIONS

The properties of -phenylselenyl cyclopropylcarbinyl radical 8 and the corresponding cation 11 are quite different. Radical 8 only was rearranged to homoallylic free radical 9 through free radical ring opening. Further reaction of 9 with another molecular of PhSeSePh leads to 2,4-diphenylselenyl-1-butene 10 (Scheme 4, eq. 1). Early in 1980s, B. M. Trost had summarized that bearing a chalcogen atom on the -position, the cyclopropyl carbinyl cation would be easy to rearrange to the cyclobutyl cation through ring expansion (Fig. 5).[6]
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Therefore, in our report,[3] -phenylselenyl cyclopropyl carbinyl cation 11 was smoothly rearranged into the corresponding cyclobutyl cation 12, which then reacts with the phenylselenyltrichloroion anion 6 to give the product 1,1-diphenylselenylcyclobutane 13 and regenerate the catalyst FeCl3 (Fig. 4, eq. 2).

2 EXPERIMENTAL OVERVIEW
All chemicals are commercially available from the reagent companies. The substrate MCP 7a could be prepared by the Wittig reaction of p-bromobenzaldehyde with phosphine ylide. The preparation course was depicted in Fig. 6.[7, 8] 7a is a white stable crystal and can be stored in a refrigeratory for many months without decomposition.
Br Br + PPh3 xylene 140 o C Br 14 CHO 14 2.5 eq NaH THF, 60 o C, N2, 12 h Br PPh3 15 50 oC, N2,3h Br PPh3 Br-

7a

FIG. 6 PREPARATION OF MCP 7A

Free radical adduct 10a was synthesized by the reaction of MCP 7a with PhSeSePh under visible light irradiation (Fig. 7). The lamp-house could be a simple 300 W tungsten lamp, which was commercially available in most supermarkets.
Br PhSe hv > 300 nm (300 W tungsten lamp) + PhSeSePh 7a 10a toluene, N2 PhSe Br

FIG. 7 REACTION OF MCP 7A WITH PHSESEPH UNDER VISIBLE LIGHT IRRADIATION

Electrophilic adduct 13a was synthesized by anhydrous FeCl3- or TiCl4- catalyzed reaction of MCP 7a with PhSeSePh (Fig. 8). Since the catalyst FeCl3 is more stable to moisture, the optimal condition was obtained by using FeCl3 as the catalyst.
Br SePh SePh + PhSeSePh FeCl3, 20 mol% DCM, N2, r.t. Br 7a 13a

FIG. 8 FECL3 CATALYZED REACTION OF MCP 7A WITH PHSESEPH

Compounds 10a and 13a were characterized by 1H NMR spectra which were also confirmed with literature.[3, 5a, 5d] Besides, all of the reactions mentioned above were monitored by TLC (eluent: petroleum ether).

3 EXPERIMENTAL DETAILS
(1) Preparation of MCPs a. Preparation of phosphorus salt 14. [7] To a 250 mL flask, 26.2 g (100 mmol) of PPh3, 20.2 g (100 mmol) of 1,3-dibromopropane and 100 mL of xylene were added sequently. The mixtures were than magnetically stirred at 140C. The PPh3 dissolved initially and gave a
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transparent solution. Then, along with the reaction, the product 14 began to precipitate as a white crystal. After 16 h, the mixtures were cooled to room temperature. Filtration and washing with small amount of petroleum ether provides the product 14 as a white crystal in almost quantificational yield (45.7 g, 99% yield). b. Preparation of MCP 7a.[8] To a 125 mL flask, 18.6 g (40 mmol) of phosphorus salt 14 and 2.4g (100 mmol) of NaH (powder NaH, obtained by filtation of its 60% suspension in mine oil and purified by washing with anhydrous petroleum ether) were added. The air was then draw out by a vacuum pump and replaced with nitrogen. Under nitrogen atmosphere, 50 mL of anhydrous THF (treated with sodium) was injected. The mixture was stirred at 60oC under nitrogen protection. The color turned red (due to the generation of phosphine ylide). After 12 h, the temperature was controlled to 50oC and 7.4 g (40 mmol) of 4-bromo-benzaldehyde was added. The mixture was stirred at this temperature for 3 h and then cooled to room temperature. 50 mL of water was added to quench the reaction. After extraction (ether, 3 50 mL), the combined organic layer was dried by anhydrous MgSO4. The solvent was evaporated by vacuum. Column chromatogram (eluent: petroleum ether) of the residue gave 4.3 g of the compound 7a (51%). (2) Addition of PhSeSePh to MCPs through different routes a. Visible light activated free radical addition of PhSeSePh to MCP 7a.[5d] To a Schlenk tube, 63 mg (0.3 mmol) of MCP 7a and 94 mg (0.3 mmol) of PhSeSePh were added. The air was then draw out by a vacuum pump and replaced with nitrogen. Under nitrogen atmosphere, 5 mL of toluene was added. The mixtures were irradiated by a 300 W tungsten lamp for 5 h. Solvent was then evaporated by vacuum and the residue was subjected to preparative TLC (eluent: petroleum ether) to give 134 mg of the adduct 10a (86%)(Z-E 1:1 mixture). b. FeCl3 catalyzed electrophilic addition of PhSeSePh to MCP 7a.[3b] To a Schlenk tube, 62.4 mg of PhSeSePh (0.2 mmol) and 6.4 mg of anhydrous FeCl3 (20%) were added. The air was then draw out by a vacuum pump and replaced with nitrogen. Under nitrogen atmosphere, a solution of 0.24 mmol of MCP 7a in 1 mL of dichloromethane (DCM) was injected. The liquid turned to blood red (the color of FeCl3SePhanion) soon and was stirred at room temperature for 8 h. The liquid was then concentrated to less than 0.5 mL and subjected to preparative TLC (eluent: petroleum ether) to give the electrophilic adduct 85 mg of 13a (82%)

4 HAZARDS
Solvents toluene and DCM might cause cancer. PhSeSePh is toxic. Therefore, it is necessary to wear goggles and gloves in the experiment.

5 CONCLUSIONS
The addition reactions of PhSeSePh to MCPs through different routes are good examples for students to directly learn about the differences between free radical and electrophic additions as well as the differences between the homo-cleavage and hetero-cleavage of the chemical bonds. Experimental operations of both free radical additions and electrophilic additions are simple and can be conveniently conducted in university laboratories. Therefore, the combination of theoretical and experimental teaching might be possible and effective.

ACKNOWLEDGMENTS
We thanked NNSFC (21202141), Priority Academic Program Development of Jiangsu Higher Education Institutions, the opening foundation of the Key Laboratory of Environmental Materials and Engineering of Jiangsu Province (K11024, K090030) for financial support. We also thank the Analysis Center of Yangzhou University.

REFERENCES
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AUTHORS
Lei Yu. (1982- ). Ph. D. Associate Professor of Yangzhou University; P. I. Of the Organic Methodology Group, School of Chemistry & Chemical Engineering; Head of the Graduate Work Station, Jiangsu Yangnong Chemical Group Co. Ltd. Jun Wang. Master student. Research direction: Organic Synthesis; Email: 1057255484@qq.com. Tian Chen Associate Professor. Research direction: Organic Synthesis; Email: chen_t_yz@163.com. Xu Zhang. Ph. D. Research direction: Organic Synthesis; Email: zhangxu@yzu.edu.cn.

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