Intra/Intermolecular Direct Allylic Alkylation via Pd(II) - American ...

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Sep 9, 2008 - Song Lin,† Chun-Xiao Song,† Gui-Xin Cai,† Wen-Hua Wang,† and .... whether an electron-withdrawing or electron-donating group was.
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Intra/Intermolecular Direct Allylic Alkylation via Pd(II)-Catalyzed Allylic C-H Activation Song Lin,† Chun-Xiao Song,† Gui-Xin Cai,† Wen-Hua Wang,† and Zhang-Jie Shi*,†,‡ Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering and Green Chemistry Center, Peking UniVersity, Beijing 100871, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China Received May 9, 2008; E-mail: [email protected]

Tsuji-Trost reaction (Pd-catalyzed allylic alkylation) is an important transformation to construct C-C bonds in organic synthesis.1 Many efforts have been devoted to this methodology to improve its efficiency and selectivity, which made it more powerful and applicable.2 Generally, a functional group at the allylic position is required in Tsuji-Trost alkylation to serve as a reacting and leaving group.3 Many trials have already been made to eliminate the allylic substituents for this chemistry, but failed (Scheme 1).4 Trost and co-workers observed that allylic alkylation could proceed via C-H activation in two steps in the presence of stoichiometric Pd species, mostly because the in situ reoxidation of Pd(0) into Pd(II) is difficult.5 This challenge was also depicted by Li and co-workers, who have made a significant contribution to address this issue through a different pathway.6a Very recently, White and co-workers made significant progresses in the allylic C-O/N formation via Pd(II)-catalyzed C-H activation.7 Liu and co-workers also reported a Pd(II)-catalyzed oxidative amination of allylic C-H bond.8 During these processes, allylpalladium species 1 was proposed as the key intermediate. We envisioned that allylpalladium species 1 may also serve as an intermediate in direct allylic alkylation. To the best of our knowledge, direct alkylation of allylic C-H via Pd-catalysis is still unknown. Herein, we demonstrated the first example of the intra/intermolecular direct allylic alkylation of alkenes. Our attention was initially paid to the annulation via intramolecular allylic C-H activation. After systematically screening, we gratifyingly found that, in the presence of the prepared 1,2-bis(benzylsulfinyl)ethane palladium acetate (2) as the catalyst and benzoquinone as the oxidant, 3a was transformed into the desired product 4a in a good yield. Encouraged by this result, we further designed various substrates to construct fused, mono, and spiro rings (Table 1). Polysubstituted indane and 1,2,3,4-tetrahydronaphthalene (4a-e) with quaternary carbons were easily obtained in good efficiencies. When a prochiral substrate was used, two diastereoisomers were isolated (4c and 4d). To our delight, when the aliphatic allylic substrates (3f-k) were submitted to the similar conditions, the annulations occurred smoothly with moderate to good yields (entry 6-11). For 4f-j, high diastereoselectivities were achieved and only trans adducts were detected, which was clearly elucidated by X-ray structure of 4j (Figure 1). We also discovered that (1) without the γ-substituents of the dione, a fivemembered ring was more efficiently formed than a six-membered one (4f vs 4g); however, (2) when steric hindrance was introduced at the γ-position, results were reversed, wherein the five-membered ring was hardly constructed (4h vs 4i,j). The reason for these intriguing results may arise from the tuned configuration by introducing the steric hindrance at the γ-position (Thorpe-Ingold effect).9 In some cases, the coupling products were partially dehydrogenated to form highly conjugated compounds (4i′-k′). Unexpectedly, when we attempted † ‡

Peking University. Chinese Academy of Sciences.

10.1021/ja803452p CCC: $40.75  2008 American Chemical Society

Table 1. Intramolecular Direct Allylic Alkylation via

Palladium-Catalyzed sp3 C-H Activationa

a The reactions were carried out with 3 (0.3 mmol) in the presence of 2, BQ (1.3 equiv), toluene (2.1 mL) under a balloon pressure of O2 for 60 h unless otherwise noted, and isolated yields were reported. b With 10 mol% of 2. c With 20 mol% of 2. d With 15 mol% of 2.

Scheme 1. Traditional Tsuji–Trost Alkylation and Our Proposed Allylic C-H Alkylation

to afford the endo adduct 4l′, only 4l was isolated instead, which may be generated via allylic C-H activation followed by β-H elimination (entry 9). On the basis of these results, we started tackling a more ambitious proposal, wherein intermolecular allylic alkylation would be facilitated J. AM. CHEM. SOC. 2008, 130, 12901–12903

9

12901

COMMUNICATIONS Table 3. Intermolecular Direct Allylic Alkylation with Different Allylarenesa

Figure 1. ORTEP diagram of 4d and 4j showing the 40% probability

thermal ellipsoids for all non-hydrogen atoms. Table 2. Intermolecular Direct Allylic Alkylation with Different

Nucleophilesa

entry

R1

R2

7

yield (%)b

1 2 3 4 5 6c

Ph Ph Et Me Me Oet

Me Ph Et Me Oet Oet

7aa 7ab 7ac 7ad 7ae 7af

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