n-Bu4NBr Catalyzed Brook Rearrangement/Alkylation Reaction

Man-Yi Han Hong Pan Ziyun Yao Qi Li

Citation:  Han Man-Yi, Pan Hong, Yao Ziyun, Li Qi. n-Bu4NBr Catalyzed Brook Rearrangement/Alkylation Reaction[J]. Chinese Journal of Organic Chemistry, 2020, 40(12): 4274-4283. doi: 10.6023/cjoc202005093 shu

四丁基溴化铵催化的布鲁克重排/烷基化反应

    通讯作者: 韩满意, hanmy10@126.com
  • 基金项目:

    国家自然科学基金(No.21602073)、安徽省自然科学基金(No.1708085QB39)和安徽省青年皖江学者资助项目

    安徽省自然科学基金 1708085QB39

    国家自然科学基金 21602073

摘要: 以四丁基溴化铵作为相转移催化剂,开发了α-硅醇化合物的一种新型布鲁克重排/烷基化反应.多种结构类型的α-硅醇化合物都适用于该反应,高产率(产率高达71%)地合成了具有季碳中心的反应产物.此外,通过酯基官能团的吸电子作用可以稳定布鲁克重排之后生成的碳负离子,而竞争性的布鲁克重排/质子化反应被抑制.

English

  • Since the pioneering work of Brook, [1] the base-cata- lyzed Brook rearrangement has attracted considerable attention both in its mechanism and application. Due to the synthetic utility, the α-silyloxy carbanions generated from α-silyl oxyanions could be trapped by some electron trapping agents.[2] For examples, aldehyde, [3] ketone, [4] imine[5] and unsaturated compuonds[6] were used as the electron trapping agents in these Brook rearrangement/trapping sequence. In most cases, the carbon-metal bonds were formed after Brook rearrangement processes and the carbon-carbon bonds were formed with trapping agents. In these transformations, the nucleophilic additions of acylsilanes were generally required to generate the carbon-metal bonds under dry conditions.[2e] In contrast, it is very difficult to carry out this kind of reaction in a wet environment because of the protonation of the α-silyloxy carbanions occur faster than the carbon-carbon bonds formation, and the Brook rearrangement/trapping sequence will not proceed. To tackle these problems, a new reaction model is required in wet conditions.

    Bimolecular nucleophilic substitution (SN2) reactions are ubiquitous in organic synthesis and many factors have effects on the efficiency of the reaction.[7] For example, electronegativity of the central carbon atom in the nucleophile and leaving group; the steric demand of nucleophile and leaving-group ability. Considering the challenge of SN2 reactions, the development of the Brook rearrangement/alkylation sequence of tertiary α-silyl alcohol will provide a novel solution. Thus far, only a few reactions have been reported. For instance, Kuwajim and co-workers[8] reported the BuLi-induced Brook rearrangement/alkylation reaction of 1-(trimethylsily1)allylic alcohols, generating the silyl enol ethers through lithium homoenolates. Due to a serious side reaction, unsatisfactory results were often observed with less reactive alkyl chlorides or bromides (Scheme 1, a). In 2018, Harutyunyan and co-workers[9] reported the LiOtBu catalyzed Brook rearrangement/trapping of carbon electrophiles. Several electrophiles, including acyl chlorides, aldehydes, alkyl halides and Michael acceptors were examined as the trapping agents, only methyl iodide and allyl bromide led to the Brook rearrangement/alkylation reaction products (Scheme 1, b). Moreover, Harutyunyan et al.[10] developed the elegant examples of Brook rearrangement of tertiary α-silyl alcohols with acyl chlorides as the trapping electrophiles, respectively (Scheme 1, b and c). Given the stability of carbanions generated after the Brook rearrangement, we wonder whether the carbanions could be stabilized by electron-withdrawing group and it was trapped by high reactive alkyl halides to generate the new carbon-carbon bond under the mild conditions. Herein, we disclose a new phase transfer catalyzed Brook rearrangement/alkylation reaction of tertiary α-silyl alcohols, generating the corresponding products with a quaternary carbon center in moderate yields.[11] To the best of our knowledge, this new Brook rearrangement/alkylation reaction of tertiary α-silyl alcohols has not been reported until now (Scheme 1, d).

    Scheme 1

    Scheme 1.  Brook rearrangement/trapping sequence of tertiary α-silyl alcohols

    Tertiary α-silyl alcohol 1a with an ester moiety was selected as the Brook rearrangement precursor[12] and the highly reactive carbon electrophiles of allyl bromide and benzyl bromide were initially examined in this Brook rearrangement/alkylation sequence. As shown in Scheme 2, the desired Brook rearrangement/alkylation reaction product 3 was not obtained when the reaction was catalyzed by n-Bu4NBr in toluene, and the competing Brook rearrangement/protonation product of 4a was obtained at room temperature.[13] To our delight, the reaction proceeded when the more reactive 2-bromoacetophenone was selected as the carbon electrophile, producing the messy products under phase transfer catalyst (PTC) conditions. Next, tert-butyl bromoacetate with less reactive ester group was tested. Unfortunately, only the competing Brook rearrangement/protonation product of 4a was obtained. Considering the steric hinderence of large size of tertiary butyl moieties, the small size of ethyl bromoacetate and methyl bromoacetate were applied in the reaction. Fortunately, the desired Brook rearrangement/alkylation reaction products 3a and 3b were obtained albeit in low yields. In this transformation, the competing protonation product of 4a was achieved in high yields and how to depress this pathway was the next key factor in the Brook rearrangement/alkylation reaction.

    Scheme 2

    Scheme 2.  Brook rearrangement/SN2 sequence with trapping of carbon electrophiles

    To depress the competing protonation product, the model reaction of tertiary α-silyl alcohol 1a and ethyl bromoacetate 2a was selected to optimize the reaction conditions (Table 1). Based on our preliminary results (Scheme 2 and Table 1, Entry 1), different bases were initially screened when the reaction was performed in toluene at room temperature by using 10 mol% of n-Bu4NBr as catalyst (Table 1, Entries 2~7). Compared to the weak bases, including K2CO3, Na2CO3, LiOH, the competing reaction product 4a was depressed when the strong bases, such as NaOH, KOH and CsOH, were applied to the reaction. To our delight, the yield of 3a was increased to 57% in 1 h when KOH was employed as the base. Encouraged by this result, the catalytic activity of catalyst was further investigated (Table 1, Entries 8~15). However, no improvement were observed. Subsequently, solvent screening revealed that the ideal solvent was toluene (Table 1, Entries 16~20). To further improve the reaction yield and minimize the competing side reaction, the reaction temperature was finally examined (Table 1, Entries 21~24). Surprisingly, the yield of 3a was improved to 71% and the competing product 4a was lowered to 25% when the reaction was run at -40 ℃ (Table 1, Entry 23). However, a further decrease in the amount of KOH led to a decrease in yield of 3a (Table 1, Entry 25). The control experiment showed that protonation product 4a was obtained in the absence of n-Bu4NBr (Table 1, Entry 26) and no reaction was observed without KOH (Table 1, Entry 27). The decreased yield was observed when the loading of the catalyst was further optimized (Table 1, Entries 28~29). To our surprise, the reaction was extremely sluggish and only product 4a was obtained when the reaction was performed in a mixture of solvents (toluene and H2O) (Table 1, Entry 30).

    Table 1

    Table 1.  Optimization of reaction conditionsa
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    Entry Catalyst Base Solvent Time/h Yieldb/% of 3a Yieldb/% of 4a
    1 n-Bu4NBr Cs2CO3 Toluene 16 24 58
    2 n-Bu4NBr K2CO3 Toluene 16 Trace 56
    3 n-Bu4NBr Na2CO3 Toluene 16 0 Trace
    4 n-Bu4NBr LiOH Toluene 24 0 88
    5 n-Bu4NBr NaOH Toluene 2 46 42
    6 n-Bu4NBr KOH Toluene 1 57 35
    7 n-Bu4NBr CsOH Toluene 0.1 55 28
    8 n-Bu4NCl KOH Toluene 1 53 23
    9 n-Bu4NI KOH Toluene 1 36 47
    10 n-Bu4NHSO4 KOH Toluene 1 50 35
    11 n-Bu4NOH KOH Toluene 1 36 50
    12 n-Bu4NClO4 KOH Toluene 1 38 53
    13 n-Bu4NBF4 KOH Toluene 1 57 31
    14 Et4NBr KOH Toluene 1 11 58
    15 n-Pr4NBr KOH Toluene 1 14 52
    16 n-Bu4NBr KOH Mesitylene 1 35 46
    17 n-Bu4NBr KOH CH2Cl2 1.5 52 22
    18 n-Bu4NBr KOH EtOAc 1 54 35
    19 n-Bu4NBr KOH CH3CN 1 26 44
    20 n-Bu4NBr KOH EtOH 1 0 88
    21c n-Bu4NBr KOH Toluene 5 39 56
    22d n-Bu4NBr KOH Toluene 6 54 31
    23e n-Bu4NBr KOH Toluene 19 71 25
    24f n-Bu4NBr KOH Toluene 24 Trace Trace
    25e, g n-Bu4NBr KOH Toluene 19 62 31
    26e KOH Toluene 19 0 97
    27e n-Bu4NBr Toluene 19 0 0
    28e, h n-Bu4NBr KOH Toluene 26 36 44
    29e, i n-Bu4NBr KOH Toluene 22 61 33
    30e n-Bu4NBr KOH Toluene/H2O 36 0 25
    aReaction conditions: a mixture of tertiary α-silyl alcohol 1a (0.1 mmol), ethyl bromoacetate 2a (0.3 mmol), catalyst (0.01 mmol) and base (0.3 mmol) in 1 mL of solvent was stirred for the indicated time. bIsolated yield. cReaction at 0 ℃. dReaction at -20 ℃. e Reaction at -40 ℃. fReaction at -60 ℃. g0.2 mmol of KOH was used. h5 mo%l of n-Bu4NBr was used. i20 mol% of n-Bu4NBr was used.

    With the optimized reaction conditions in hand, the substrate scope for the Brook rearrangement/alkylation reaction was then investigated. In general, the reaction has good compatibility when different substrates, including electron-withdrawing and the electron-donating group, were applied to the reaction. As shown in Table 2, we firstly examined the substrate with the methyl substituent at the ortho- or para-position of the benzene ring on the tertiary α-silyl alcohol 1. The reaction worked well to give the desired products 3c (51% yield) and 3d (50% yield) in good yields. The halogen-substituted (F, Cl and Br) substrates were also examined under optimized conditions, providing the corresponding products (3e~3k) in moderate yields. The reaction proceeded well when the tertiary α-silyl alcohol with electron-withdrawing or electron-donating groups were applied to the reaction, generating the desired products (3l~3n) in moderate yields. Moreover, other tertiary α-silyl alcohols 1 containing naphthyl, cyclic or different chain length substituents provided the desired products (3o~3s) in moderate yields.

    Table 2

    Table 2.  Scope of tertiary α-silyl alcohols with alkene moietiesabrrhzimage:6:erhhz
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    aReaction conditions: a mixture of tertiary α-silyl alcohol 1a (0.1 mmol), ethyl bromoacetate 2 (0.3 mmol), n-Bu4NBr (0.01 mmol) and KOH (0.3 mmol) in 1 mL of solvent was stirred for the indicated time.

    To further explore the scope of the reaction, tertiary α-silyl alcohols with ketone moieties 5 as the substrates were examined (Table 3). Compared to the ethyl bromoacetate, a slightly lower yield of 6b was observed when methyl bromoacetate was used as a carbon electrophile. While a methyl substituent on the benzene ring of tertiary α-silyl alcohols 5 was used as the substrate, the desired product 6c was obtaiend in moderate yield. Morover, the halogen-substrates of tertiary α-silyl alcohols 5 (F, Cl and Br) were also examined, providing the corresponding products (6d~6g) in moderate yield. The reactions also proceed well with various moderate yields. Interestingly, the more bulky naphthyl substituent on 5 was also successfully employed to give the corresponding product 6h in moderate yield.

    Table 3

    Table 3.  Scope of tertiary α-silyl alcohols with ketone moietiesa
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    aReaction conditions: a mixture of tertiary α-silyl alcohol 5 (0.1 mmol), ethyl bromoacetate 2 (0.3 mmol), n-Bu4NBr (0.01 mmol) and KOH (0.3 mmol) in 1 mL of solvent was stirred for the indicated time.

    To further explore the asymmetric version of Brook rearrangement/alkylation reaction, [11] some chiral PTC catalysts were investigated (Scheme 3). Surprisingly, no desired product 3a was obtained when chiral catalysts ~ were used in toluene at -40 ℃. In contrast, only Brook rearrangement/protonation product 4a was obtained with 0% ee. These results suggested that the structure of PTC catalyst has an important influence on the Brook rearrangement/alkylation reaction products. Compared to the n-Bu4NBr, the chiral catalysts with bulky steric hiderence were benefit for the competing Brook rearrangement/protonation product 4a.

    Scheme 3

    Scheme 3.  Attempts for chiral PTC-catalyzed Brook rearrangement/alkylation reaction

    Next, a control experiment was conducted under standard conditions. As shown in Scheme 4, Brook rearrangement/protonation product 4a was employed as the strating material under the PTC conditions and no reaction was observed (Scheme 4a). The control experiment showed that the carbanion generated after the Brook rearrangement could be stabilized by the electron-withdrawing group of ester with the assistance of n-Bu4NBr. As shown in Scheme 4b, the reaction mechanism was proposed via PTC pathway. First, the tertiary α-silyl alcohol 1a was deprotonated by the KOH and the carbanion generated after the Brook rearrangement of . In this step, the enolate coulld be direcly trapped by ethyl bromoacetate 2a to generate the product 3a.

    Scheme 4

    Scheme 4.  Control experiment and proposed reaction mechanism

    In summary, a novel Brook rearrangement/alkylation reaction sequence of tertiary α-silyl alcohols was developed, generating the products with a quaternary carbon center in high yields (up to 71%). In this reaction, the carbanions intermediate could be stabilized by the electron- withdrawing group of ester with the assistance of n-Bu4NBr. Further studies on the new reaction of Brook rearrangement/trapping sequence are currently underway in our laboratory.

    All 1H NMR and 13C NMR spectra were recorded on a Bruker 400 MHz NMR spectrometer. Tetramethylsilane (TMS, δ 0.00) or CHCl3 (δ 7.26) served as an internal standard for 1H NMR while CDCl3 was used as an internal standard (δ 77.0) for 13C NMR. HRMS data were obtained on a Bruker Apex Ⅱ mass instrument (ESI) or an Agilent Technologies 6540 UHD Accurate-Mass Q-TOF LC/MS (ESI). Chemicals and analytical grade solvents were purchased from commercial suppliers and used without further purification unless otherwise stated. Flash column chromatography was performed on silica gels (200~300 mesh).

    A mixture of tertiary α-silyl alcohol 1 or 5 (0.1 mmol), ethyl bromoacetate 2 (33.3 μL, 0.3 mmol), n-Bu4NBr (3.2 mg, 0.01 mmol) in 1 mL of toluene was stirred at -40 ℃, then KOH (16.8 mg, 0.3 mmol) was added. After stirring for the indicated time, the residue was purified via flash chromatography to give the desired product.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-phenylallyl)succinate (3a): 71% yield, pale oil. 1H NMR (400 MHz, CDCl3) δ: 7.35~7.20 (m, 10H), 5.28 (d, J=1.6 Hz, 1H), 5.16 (s, 1H), 4.88 (d, J=12.0 Hz, 1H), 4.33 (d, J=12.0 Hz, 1H), 4.05~3.92 (m, 2H), 3.08 (dd, J=13.6, 19.2 Hz, 2H), 2.87 (d, J=15.6 Hz, 1H), 2.62 (d, J=15.6 Hz, 1H), 1.14 (t, J=7.2 Hz, 3H), 0.82 (s, 9H), 0.18 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.6, 169.9, 143.2, 141.5, 135.4, 128.4, 128.3, 128.2, 128.1, 127.4, 126.6, 118.9, 78.2, 66.7, 60.4, 45.7, 44.5, 25.9, 18.6, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C28H38O5SiNa (M+Na)+ 505.2386, found 505.2386.

    1-Benzyl-4-methyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-phenylallyl)succinate (3b): 62% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.35~7.28 (m, 7H), 7.25~7.20 (m, 3H), 5.29 (d, J=1.6 Hz, 1H), 5.17 (s, 1H), 4.88 (d, J=12.0 Hz, 1H), 4.32 (d, J=12.0 Hz, 1H), 3.50 (s, 3H), 3.08 (dd, J=13.6, 22.0 Hz, 2H), 2.87 (d, J=15.6 Hz, 1H), 2.62 (d, J=15.6 Hz, 1H), 0.81 (s, 9H), 0.18 (s, 3H), 0.04 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 170.3, 143.1, 141.4, 135.3, 128.5, 128.3, 128.2, 128.2, 127.4, 126.6, 119.0, 78.2, 66.7, 51.4, 45.8, 44.3, 25.8, 18.6, -2.5, -3.0; HRMS (ESI) calcd for C27H37O5Si (M+H)+ 469.2410, found 469.2404.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(p-tolyl)allyl)succinate (3c): 51% yield, pale oil. 1H NMR (400 MHz, CDCl3) δ: 7.36~7.31 (m, 3H), 7.22~7.16 (m, 4H), 7.08~7.06 (m, 2H), 5.25 (d, J=1.2 Hz, 1H), 5.11 (s, 1H), 4.89 (d, J=12.0 Hz, 1H), 4.35 (d, J=12.0 Hz, 1H), 4.06~3.92 (m, 2H), 3.04 (dd, J=13.6, 19.6 Hz, 2H), 2.88 (d, J=15.6 Hz, 1H), 2.60 (d, J=15.2 Hz, 1H), 2.32 (s, 3H), 1.14 (t, J=7.2 Hz, 3H), 0.82 (s, 9H), 0.19 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.8, 163.4, 161.0, 142.2, 137.5, 135.2, 128.4, 128.4, 128.3, 128.2, 118.9, 115.1, 114.9, 78.2, 66.9, 60.5, 45.8, 44.5, 25.8, 18.6, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C29H40O5SiNa (M+Na)+ 519.2543, found 519.2540.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(o-tolyl)allyl)succinate (3d): 50% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.38~7.28 (m, 3H), 7.24~7.19 (m, 2H), 7.16~7.06 (m, 4H), 5.32 (t, J=1.2 Hz, 1H), 5.04 (d, J=2.0 Hz, 1H), 4.87 (d, J=12.4 Hz, 1H), 4.48 (d, J=12.4 Hz, 1H), 4.03~3.91 (m, 2H), 3.01 (dd, J=13.6, 30.0 Hz, 2H), 2.82 (d, J=15.2 Hz, 1H), 2.62 (d, J=15.2 Hz, 1H), 2.27 (s, 3H), 1.14 (t, J=7.2 Hz, 3H), 0.83 (s, 9H), 0.18 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.7, 143.7, 142.1, 135.3, 134.9, 130.3, 129.0, 128.5, 128.3, 128.2, 127.0, 125.5, 120.8, 78.1, 66.9, 60.4, 47.2, 44.2, 25.9, 20.2, 18.6, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C29H41O5Si (M+H)+ 497.2723, found 497.2723.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(2-fluorophenyl)allyl)succinate (3e): 61% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.38~7.30 (m, 3H), 7.24~7.14 (m, 4H), 7.06~7.02 (m, 1H), 6.98~6.93 (m, 1H), 5.31 (s, 1H), 5.24 (d, J=1.2 Hz, 1H), 4.90 (d, J=12.4 Hz, 1H), 4.43 (d, J=12.0 Hz, 1H), 4.05~3.90 (m, 2H), 3.17 (d, J=13.6 Hz, 1H), 3.04 (d, J=13.6 Hz, 1H), 2.84 (d, J=15.6 Hz, 1H), 2.63 (d, J=15.2 Hz, 1H), 1.15 (t, J=7.2 Hz, 3H), 0.81 (s, 9H), 0.17 (s, 3H), 0.04 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.8, 159.7 (d, J=246.0 Hz), 139.1, 135.3, 130.6 (d, J=4.0 Hz), 129.7 (d, J=13.0 Hz), 128.9 (d, J=8.0 Hz), 128.4, 128.2, 124.0 (d, J=3.0 Hz), 122.4, 115.7 (d, J=2.0 Hz), 78.2, 66.8, 60.4, 46.5 (d, J=4.0 Hz), 44.5, 25.8, 18.6, 14.0, -2.6, -3.0; HRMS (ESI) calcd for C28H38FO5Si (M+H)+ 501.2473, found 501.2465.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(4-fluorophenyl)allyl)succinate (3f): 58% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.36~7.31 (m, 3H), 7.25~7.22 (m, 4H), 6.96~6.91 (m, 2H), 5.23 (d, J=1.2 Hz, 1H), 5.14 (s, 1H), 4.92 (d, J=12.4 Hz, 1H), 4.46 (d, J=12.4 Hz, 1H), 4.07~3.94 (m, 2H), 3.05 (dd, J=14.0, 22.8 Hz, 2H), 2.85 (d, J=15.2 Hz, 1H), 2.62 (d, J=15.6 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.81 (s, 9H), 0.16 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.8, 162.2 (d, J=245.0 Hz), 142.2, 137.5 (d, J=3.0 Hz), 135.2, 128.4, 128.4, 128.3, 128.2, 118.9, 115.0 (d, J=22.0 Hz), 78.2, 77.2, 66.9, 60.5, 45.8, 44.5, 25.8, 18.6, 14.0, 2.5, 3.0; HRMS (ESI) calcd for C28H38FO5Si (M+H)+ 501.2473, found 501.2467.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(3-fluorophenyl)allyl)succinate (3g): 47% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.37~7.30 (m, 3H), 7.25~7.20 (m, 3H), 7.07 (d, J=7.6 Hz, 1H), 7.00~6.91 (m, 2H), 5.31 (d, J=1.2 Hz, 1H), 5.19 (s, 1H), 4.94 (d, J=12.4 Hz, 1H), 4.49 (d, J=12.4 Hz, 1H), 4.50~3.94 (m, 2H), 3.06 (dd, J=14.0, 20.4 Hz, 2H), 2.84 (d, J=15.6 Hz, 1H), 2.63 (d, J=15.6 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.80 (s, 9H), 0.15 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.8, 162.7 (d, J=244.0 Hz), 143.8, 142.2, 135.2, 129.6 (d, J=8.0 Hz), 128.5, 128.4, 128.3, 122.3 (d, J=3.0 Hz), 119.8, 114.2 (d, J=21.0 Hz), 113.6 (d, J=22.0 Hz), 78.2, 77.2, 66.9, 60.5, 45.4, 44.4, 31.4, 30.2, 25.8, 18.6, 14.0, -2.6, -3.0; HRMS (ESI) calcd for C28H38FO5Si (M+H)+ 501.2473, found 501.2470.

    1-Benzyl-4-ethyl-2-(2-(4-bromophenyl)allyl)-2-((tert-butyldimethylsilyl)oxy)succinate (3h): 63% yield, white solid, m.p. 49.5~51.0 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.37~7.33 (m, 5H), 7.23~7.21 (m, 2H), 7.14~7.12 (m, 2H), 5.26 (d, J=1.6 Hz, 1H), 5.17 (s, 1H), 4.92 (d, J=12.4 Hz, 1H), 4.44 (d, J=12.0 Hz, 1H), 4.07~3.94 (m, 2H), 3.05 (dd, J=13.6, 22.0 Hz, 2H), 2.84 (d, J=15.6 Hz, 1H), 2.62 (d, J=15.6 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.81 (s, 9H), 0.16 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.8, 142.2, 140.4, 135.2, 131.3, 128.4, 128.4, 128.3, 121.3, 119.5, 78.2, 66.9, 60.5, 45.5, 44.5, 25.8, 18.6, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C28H38BrO5Si (M+H)+ 561.1672, found 561.1668.

    1-Benzyl-4-ethyl-2-(2-(3-bromophenyl)allyl)-2-((tert-butyldimethylsilyl)oxy)succinate (3i): 61% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.429~7.425 (m, 1H), 7.38~7.32 (m, 4H), 7.26~7.21 (m, 3H), 7.16~7.12 (m, 1H), 5.28 (d, J=1.2 Hz, 1H), 5.19 (s, 1H), 4.94 (d, J=12.0 Hz, 1H), 4.51 (d, J=12.0 Hz, 1H), 4.07~3.94 (m, 2H), 3.06 (dd, J=14.0, 21.2 Hz, 2H), 2.84 (d, J=15.6 Hz, 1H), 2.64 (d, J=15.6 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.79 (s, 9H), 0.14 (s, 3H), 0.04 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.7, 143.8, 142.1, 135.1, 130.3, 129.7, 129.6, 128.6, 128.5, 128.3, 125.3, 122.4, 120.0, 78.2, 67.0, 60.5, 45.3, 44.4, 25.8, 18.6, 14.0, -2.6, -3.0; HRMS (ESI) C28H38BrO5Si (M+H)+ 561.1672, found 561.1669.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(4-chlorophenyl)allyl)succinate (3j): 66% yield, white solid, m.p. 39.8~40.9 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.36~7.32 (m, 3H), 7.23~7.18 (m, 6H), 5.26 (d, J=1.6 Hz, 1H), 5.17 (s, 1H), 4.92 (d, J=12.4 Hz, 1H), 4.45 (d, J=12.0 Hz, 1H), 4.03~3.94 (m, 2H), 3.05 (dd, J=13.6, 22.0 Hz, 2H), 2.84 (d, J=15.6 Hz, 1H), 2.62 (d, J=15.2 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.81 (s, 9H), 0.16 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.8, 163.4, 161.0, 142.2, 137.5, 135.2, 128.4, 128.4, 128.3, 128.2, 118.9, 115.1, 114.9, 78.1, 77.2, 66.9, 66.5, 45.8, 44.5, 25.8, 18.6, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C28H38ClO5Si (M+H)+ 517.2177, found 517.2176.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(2-chlorophenyl)allyl)succinate (3k): 60% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.37~7.29 (m, 3H), 7.28~7.21 (m, 3H), 7.20~7.15 (m, 3H), 5.29 (d, J=1.2 Hz, 1H), 5.19 (s, 1H), 4.94 (d, J=12.4 Hz, 1H), 4.50 (d, J=12.0 Hz, 1H), 4.07~3.94 (m, 2H), 3.06 (dd, J=14.0, 22.0 Hz, 2H), 2.84 (d, J=15.2 Hz, 1H), 2.64 (d, J=15.6 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.80 (s, 9H), 0.15 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.7, 143.5, 142.1, 135.1, 134.1, 129.4, 128.5, 128.4, 128.3, 127.4, 126.7, 124.8, 120.0, 78.1, 77.2, 66.9, 60.5, 45.3, 44.4, 25.8, 18.5, 14.0, -2.6, -3.1; HRMS (ESI) calcd for C28H38ClO5Si (M+H)+ 517.2177, found 517.2174.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(3-methoxyphenyl)allyl)succinate (3l): 61% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.35~7.28 (m, 3H), 7.23~7.17 (m, 3H), 6.88 (d, J=7.6 Hz, 1H), 6.82~6.78 (m, 2H), 5.30 (d, J=1.2 Hz, 1H), 5.16 (s, 1H), 4.91 (d, J=12.0 Hz, 1H), 4.36 (d, J=12.0 Hz, 1H), 4.02~3.91 (m, 2H), 3.73 (s, 3H), 3.05 (dd, J=14.0, 15.6 Hz, 2H), 2.88 (d, J=15.6 Hz, 1H), 2.61 (d, J=15.2 Hz, 1H), 1.15 (t, J=7.2 Hz, 3H), 0.82 (s, 9H), 0.19 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.7, 169.9, 159.4, 143.1, 142.9, 135.3, 129.2, 128.4, 128.3, 128.1, 119.1, 119.0, 113.0, 112.2, 78.1, 77.3, 66.8, 60.4, 55.1, 45.8, 44.4, 25.9, 18.6, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C29H41O6Si (M+H)+ 513.2672, found 513.2670.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(4-(trifluoromethyl)phenyl)allyl)succinate (3m): 51% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.50 (d, J=8.4 Hz, 2H), 7.36~7.32 (m, 5H), 7.21~7.19 (m, 2H), 5.33 (d, J=1.2 Hz, 1H), 5.25 (s, 1H), 4.91 (d, J=12.0 Hz, 1H), 4.42 (d, J=12.0 Hz, 1H), 4.07~3.94 (m, 2H), 3.11 (dd, J=14.0, 19.6 Hz, 2H), 2.84 (d, J=15.6 Hz, 1H), 2.66 (d, J=15.6 Hz, 1H), 1.16 (t, J=7.2 Hz, 3H), 0.79 (s, 9H), 0.14 (s, 3H), 0.04 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.4, 168.7, 144.2, 141.3, 134.1, 128.5, 128.2, 127.5, 127.4, 127.3, 126.8, 126.7, 125.9, 124.5, 124.19, 124.15, 124.12, 124.08, 121.8, 119.8, 77.2, 76.2, 65.9, 59.5, 44.2, 43.4, 24.8, 17.5, 13.0, -3.6, -4.1; HRMS (ESI) calcd for C29H38F3O5Si (M+H)+ 551.2441, found 551.2434.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(4-cyanophenyl)allyl)succinate (3n): 26% yield; colorless oil; 1H NMR (600 MHz, CDCl3) δ: 7.519~7.505 (m, 2H), 7.373~7.337 (m, 5H), 7.232~7.217 (m, 2H), 5.350 (d, J=0.3 Hz, 1H), 5.276 (s, 1H), 4.938 (d, J=12.0 Hz, 1H), 4.566 (d, J=12.6 Hz, 1H), 4.061~3.966 (m, 2H), 3.113 (dd, J=14.4, 19.8 Hz, 2H), 2.808 (d, J=15.0 Hz, 1H), 2.655 (d, J=15.6 Hz, 1H), 1.170 (t, J=7.2 Hz, 3H), 0.773 (s, 9H), 0.101 (s, 3H), 0.031 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.35, 169.60, 146.24, 142.14, 134.96, 131.99, 128.51, 128.44, 128.39, 127.26, 121.52, 118.77, 110.89, 78.23, 67.02, 60.59, 44.82, 44.36, 25.77, 18.53, 14.00, -2.65, -3.06; HRMS (ESI) calcd for C29H38NO5Si (M+H)+ 508.2519, found 508.2515.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(naphthalen-2-yl)allyl)succinate (3o): 49% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 8.00 (d, J=8.0 Hz, 1H), 7.83~7.81 (m, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.48~7.36 (m, 3H), 7.30~7.20 (m, 4H), 6.92 (d, J=6.4 Hz, 2H), 5.54 (d, J=1.6 Hz, 1H), 5.29 (d, J=2.0 Hz, 1H), 4.77 (d, J=12.0 Hz, 1H), 4.31 (d, J=12.0 Hz, 1H), 3.98~3.85 (m, 2H), 3.24 (dd, J=13.6, 39.2 Hz, 2H), 2.80 (d, J=15.2 Hz, 1H), 2.61 (d, J=15.2 Hz, 1H), 1.10 (t, J=7.2 Hz, 3H), 0.85 (s, 9H), 0.22 (s, 3H), 0.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 169.7, 142.4, 140.5, 135.0, 133.8, 131.0, 128.4, 128.1, 127.5, 125.7, 125.6, 125.1, 122.1, 78.2, 77.2, 66.9, 60.4, 43.0, 44.5, 25.9, 18.6, 13.9, -2.5, -3.0; HRMS (ESI) calcd for C32H41O5Si (M+H)+ 533.2718, found 533.2720.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-((3, 4-dihydronaphthalen-1-yl)methyl)succinate (3p): 66% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.28~7.27 (m, 3H), 7.20~7.15 (m, 2H), 7.13~7.07 (m, 4H), 5.91 (t, J=4.8 Hz, 1H), 4.93 (d, J=12.0 Hz, 1H), 4.22 (d, J=12.4 Hz, 1H), 4.09~3.97 (m, 2H), 3.13~3.05 (m, 2H), 2.83 (d, J=14.0 Hz, 1H), 2.66 (d, J=15.2 Hz, 1H), 2.62~2.45 (m, 2H), 2.16~2.11 (m, 2H), 1.17 (t, J=7.2 Hz, 3H), 0.84 (s, 9H), 0.22 (s, 3H), 0.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 173.1, 170.2, 136.4, 135.3, 134.9, 131.6, 130.4, 128.4, 128.2, 128.1, 127.7, 126.6, 126.3, 122.5, 78.3, 77.2, 66.8, 66.4, 44.6, 42.9, 28.2, 25.9, 23.2, 18.6, 14.1, -2.5, -2.9; HRMS (ESI) calcd for C30H41O5Si (M+H)+ 531.2543, found 531.2539.

    1-Benzyl-4-ethyl-2-((1H-inden-3-yl)methyl)-2-((tert-butyldimethylsilyl)oxy)succinate (3q): 54% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.42 (d, J=7.2 Hz, 1H), 7.31~7.22 (m, 5H), 7.20~7.16 (m, 1H), 7.04~7.02 (m, 2H), 6.29 (s, 1H), 5.03 (d, J=12.0 Hz, 1H), 4.76 (d, J=12.4 Hz, 1H), 4.12~3.99 (m, 2H), 3.25 (s, 2H), 3.12 (s, 2H), 3.07 (d, J=15.2 Hz, 1H), 2.78 (d, J=15.6 Hz, 1H), 1.19 (t, J=7.2 Hz, 3H), 0.84 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 173.2, 170.0, 145.5, 143.8, 138.3, 135.1, 132.7, 128.4, 128.3, 128.2, 126.0, 124.6, 123.7, 119.0, 78.4, 77.2, 67.2, 60.5, 44.5, 38.1, 38.0, 25.9, 18.6, 14.1, -2.7, -2.9; HRMS (ESI) calcd for C29H39O5Si (M+H)+ 495.2567, found 495.2560.

    1-Benzyl-4-ethyl-(Z)-2-((tert-butyldimethylsilyl)oxy)-2-(2-phenylpent-2-en-1-yl)succinate (3r): 66% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.36~7.31 (m, 3H), 7.24~7.17 (m, 7H), 5.60 (t, J=7.3 Hz, 1H), 4.88 (d, J=12.4 Hz, 1H), 4.34 (d, J=12.4 Hz, 1H), 4.01~3.89 (m, 2H), 3.17 (d, J=13.6 Hz, 1H), 3.00 (d, J=14.0 Hz, 1H), 2.79 (d, J=15.6 Hz, 1H), 2.44 (d, J=15.6 Hz, 1H), 2.25~2.11 (m, 2H), 1.11 (t, J=6.8 Hz, 3H), 1.02 (t, J=7.6 Hz, 3H), 0.83 (s, 9H), 0.24 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.9, 170.0, 143.5, 136.7, 135.4, 134.2, 128.4, 128.3, 128.2, 128.1, 126.8, 126.6, 100.0, 78.5, 66.8, 60.3, 44.8, 40.64, 25.9, 22.5, 18.5, 14.1, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C30H43O5Si (M+H)+ 511.2880, found 511.2876.

    1-Benzyl-4-ethyl-(Z)-2-((tert-butyldimethylsilyl)oxy)-2-(2-phenylbut-2-en-1-yl)succinate (3s): 70% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.36~7.30 (m, 3H), 7.25~7.16 (m, 7H), 5.71 (dd, J=6.8, 14.0 Hz, 1H), 4.88 (d, J=12.4 Hz, 1H), 4.36 (d, J=12.4 Hz, 1H), 4.03~3.90 (m, 2H), 3.20 (d, J=13.6 Hz, 1H), 3.00 (d, J=13.6 Hz, 1H), 2.78 (d, J=15.6 Hz, 1H), 2.45 (d, J=15.6 Hz, 1H), 1.77 (d, J=6.8 Hz, 3H), 1.12 (t, J=7.2 Hz, 3H), 0.83 (s, 9H), 0.24 (s, 3H), 0.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.9, 170.0, 143.6, 135.7, 135.4, 128.9, 128.4, 128.3, 128.2, 126.7, 126.6, 78.5, 66.8, 60.3, 44.8, 40.3, 25.9, 18.5, 15.1, 14.0, -2.5, -3.0; HRMS (ESI) calcd for C29H41O5Si (M+H)+ 497.2723, found 497.2720.

    A mixture of tertiary α-silyl alcohol 5 (0.1 mmol), ethyl bromoacetate 2 (33.3 μL, 0.3 mmol), n-Bu4NBr (3.2 mg, 0.01 mmol) in 1 mL of toluene was stirred at -40 ℃, then KOH (16.8 mg, 0.3 mmol) was added. After stirring for the indicated time, the residue was purified via flash chromatography to give the desired product.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-oxo-2-phenylethyl)succinate (6a): 41% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.93~7.91 (m, 2H), 7.58~7.54 (m, 1H), 7.47~7.43 (m, 2H), 7.31 (s, 5H), 5.15 (dd, J=12.4, 34.4 Hz, 2H), 4.11~4.02 (m, 2H), 3.79 (s, 2H), 3.02 (dd, J=14.8, 45.6 Hz, 2H), 1.20 (t, J=7.2 Hz, 3H), 0.76 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 197.1, 172.2, 169.9, 137.1, 135.3, 133.2, 128.6, 128.5, 128.4, 128.3, 128.1, 76.7, 67.4, 60.6, 46.4, 43.4, 25.6, 18.4, 14.0, -3.2, -3.3; HRMS (ESI) calcd for C27H37O6Si (M+H)+ 485.2359, found 485.2357.

    1-Benzyl-4-methyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-oxo-2-phenylethyl)succinate (6b): 30% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.93~7.91 (m, 2H), 7.58~7.54 (m, 1H), 7.47~7.4 (m, 2H), 7.35~7.29 (m, 5H), 5.16 (dd, J=12.0, 37.6 Hz, 2H), 3.78 (s, 2H), 3.60 (s, 3H), 3.02 (dd, J=14.8, 50.0 Hz, 2H), 0.75 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 197.1, 172.1, 170.4, 137.1, 135.3, 133.2, 128.6, 128.5, 128.5, 128.3, 128.1, 77.2, 76.7, 67.4, 51.6, 46.4, 43.2, 25.6, 18.4, -3.2, -3.3; HRMS (ESI) calcd for C26H35O6Si (M+H)+ 471.2203, found 471.2199.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-oxo-2-(p-tolyl)ethyl)succinate (6c): 58% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.83~7.81 (m, 2H), 7.34~7.29 (m, 4H), 7.26~7.23 (m, 3H), 5.15 (dd, J=12.4, 35.2 Hz, 2H), 4.10~4.01 (m, 2H), 3.75 (s, 2H), 3.01 (dd, J=14.4, 47.6 Hz, 2H), 2.40 (s, 3H), 1.20 (t, J=7.2 Hz, 3H), 0.77 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 196.6, 172.2, 169.9, 144.0, 135.3, 134.7, 129.2, 128.4, 128.4, 128.2, 77.2, 76.7, 67.3, 60.5, 46.4, 43.5, 25.6, 21.6, 18.4, 14.0, -3.2, -3.3; HRMS (ESI) calcd for C28H39O6Si (M+H)+ 499.2516, found 499.2515.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(4-fluorophenyl)-2-oxoethyl)succinate (6d): 62% yield, pale yellow solid, 167~168 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.97~7.93 (m, 2H), 7.36~7.30 (m, 5H), 7.13~7.09 (m, 2H), 5.17 (dd, J=12.0, 28.0 Hz, 2H), 4.10~4.00 (m, 2H), 3.77 (s, 2H), 3.01 (dd, J=14.8, 46.0 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H), 0.75 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 195.6, 172, 1, 169.9, 165.8 (d, J=253.0 Hz), 135.2, 133.6, 130.8 (d, J=9.0 Hz), 128.5, 128.3, 124.3, 123.5, 115.8, 115.3, 77.2, 76.4, 67.4, 61.0, 46.2, 43.2, 25.6, 18.3, 14.0, -3.25, -3.28; HRMS (ESI) calcd for C27H36FO6Si (M+H)+ 503.2265, found 503.2258.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(3-fluorophenyl)-2-oxoethyl)succinate (6e): 42% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.71 (d, J=8.0 Hz, 1H), 7.61~7.58 (m, 1H), 7.46~7.40 (m, 1H), 7.36~7.32 (m, 5H), 7.28~7.23 (m, 1H), 5.17 (dd, J=12.4, 26.8 Hz, 2H), 4.08~4.00 (m, 2H), 3.77 (s, 2H), 3.06 (d, J=14.8 Hz, 1H), 2.95 (d, J=14.8 Hz, 1H), 1.21 (t, J=7.2 Hz, 3H), 0.76 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 195.9, 172.0, 169.9, 163.0 (d, J=277.0 Hz), 139.2 (d, J=6.0 Hz), 135.2, 130.2 (d, J=8.0 Hz), 128.5 (d, J=3.0 Hz), 128.3, 123.9 (d, J=3.0 Hz), 120.2 (d, J=22.0 Hz), 114.8 (d, J=22.0 Hz), 76.4, 67.5, 60.6, 46.5, 43.2, 25.6, 18.4, 14.0, -3.2, -3.3; HRMS (ESI) calcd for C27H36FO6Si (M+H)+ 503.2265, found 503.2260.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(4-chlorophenyl)-2-oxoethyl)succinate (6f): 51% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.86 (d, J=8.8 Hz, 2H), 7.41 (d, J=8.4 Hz, 2H), 7.31 (s, 5H), 5.16 (dd, J=12.4, 26.4 Hz, 2H), 4.13~4.00 (m, 2H), 3.76 (s, 2H), 3.00 (dd, J=14.8, 46.0 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H), 0.75 (s, 9H), 0.10 (s, 3H), 0.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 196.0, 172.0, 169.9, 139.7, 135.2, 129.5, 128.9, 128.5, 128.3, 76.4, 67.5, 60.6, 46.3, 43.2, 25, 6, 18.3, 14.0, -3.3, -3, 4; HRMS (ESI) calcd for C27H36ClO6Si (M+H)+ 519.1970, found 519.1967.

    1-Benzyl-4-ethyl-2-(2-(4-bromophenyl)-2-oxoethyl)-2-((tert-butyldimethylsilyl)oxy)succinate (6g): 40% yield, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.78 (d, J=8.8 Hz, 2H), 7.58 (d, J=8.8 Hz, 2H), 7.32 (s, 5H), 5.15 (dd, J=12.0, 24.0 Hz, 2H), 4.12~4.00 (m, 2H), 3.75 (s, 2H), 3.00 (dd, J=14.8, 46.4 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H), 0.75 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 196.2, 172.0, 169.9, 135.8, 135.2, 131.9, 129.6, 128.5, 128.4, 128.3, 77.2, 76.4, 67.5, 60.6, 46.2, 43.2, 25.6, 18.4, 14.0, -3.2, -3.7; HRMS (ESI) calcd for C27H36BrO6Si (M+H)+ 563.1465, found 563.1459.

    1-Benzyl-4-ethyl-2-((tert-butyldimethylsilyl)oxy)-2-(2-(naphthalen-2-yl)-2-oxoethyl)succinate (6h): 45% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ: 8.37 (s, 1H), 7.92~7.88 (m, 2H), 7.82~7.79 (m, 2H), 7.53~7.46 (m, 2H), 7.24~7.19 (m, 5H), 5.09 (dd, J=12.0, 32.4 Hz, 2H), 4.05~3.96 (m, 2H), 3.84 (d, J=0.8 Hz, 2H), 3.04 (d, J=14.8 Hz, 1H), 2.93 (d, J=14.8 Hz, 1H), 1.14 (t, J=7.2 Hz, 3H), 0.69 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 196.9, 172.3, 170.0, 135.6, 135.3, 134.5, 132.5, 129.9, 129.7, 128.5, 128.5, 128.4, 128.3, 127.2, 126.8, 123.8, 100.0, 76.6, 67.4, 60.6, 46.6, 43.5, 25.6, 18.4, 14.1, -3.2, -3.2; HRMS (ESI) calcd for C31H39O6Si (M+H)+ 535.2516, found 535.2513.

    Supporting Information   1H NMR and 13C NMR spectra for compounds 3 and 6. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn/.


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  • Scheme 1  Brook rearrangement/trapping sequence of tertiary α-silyl alcohols

    Scheme 2  Brook rearrangement/SN2 sequence with trapping of carbon electrophiles

    Scheme 3  Attempts for chiral PTC-catalyzed Brook rearrangement/alkylation reaction

    Scheme 4  Control experiment and proposed reaction mechanism

    Table 1.  Optimization of reaction conditionsa

    Entry Catalyst Base Solvent Time/h Yieldb/% of 3a Yieldb/% of 4a
    1 n-Bu4NBr Cs2CO3 Toluene 16 24 58
    2 n-Bu4NBr K2CO3 Toluene 16 Trace 56
    3 n-Bu4NBr Na2CO3 Toluene 16 0 Trace
    4 n-Bu4NBr LiOH Toluene 24 0 88
    5 n-Bu4NBr NaOH Toluene 2 46 42
    6 n-Bu4NBr KOH Toluene 1 57 35
    7 n-Bu4NBr CsOH Toluene 0.1 55 28
    8 n-Bu4NCl KOH Toluene 1 53 23
    9 n-Bu4NI KOH Toluene 1 36 47
    10 n-Bu4NHSO4 KOH Toluene 1 50 35
    11 n-Bu4NOH KOH Toluene 1 36 50
    12 n-Bu4NClO4 KOH Toluene 1 38 53
    13 n-Bu4NBF4 KOH Toluene 1 57 31
    14 Et4NBr KOH Toluene 1 11 58
    15 n-Pr4NBr KOH Toluene 1 14 52
    16 n-Bu4NBr KOH Mesitylene 1 35 46
    17 n-Bu4NBr KOH CH2Cl2 1.5 52 22
    18 n-Bu4NBr KOH EtOAc 1 54 35
    19 n-Bu4NBr KOH CH3CN 1 26 44
    20 n-Bu4NBr KOH EtOH 1 0 88
    21c n-Bu4NBr KOH Toluene 5 39 56
    22d n-Bu4NBr KOH Toluene 6 54 31
    23e n-Bu4NBr KOH Toluene 19 71 25
    24f n-Bu4NBr KOH Toluene 24 Trace Trace
    25e, g n-Bu4NBr KOH Toluene 19 62 31
    26e KOH Toluene 19 0 97
    27e n-Bu4NBr Toluene 19 0 0
    28e, h n-Bu4NBr KOH Toluene 26 36 44
    29e, i n-Bu4NBr KOH Toluene 22 61 33
    30e n-Bu4NBr KOH Toluene/H2O 36 0 25
    aReaction conditions: a mixture of tertiary α-silyl alcohol 1a (0.1 mmol), ethyl bromoacetate 2a (0.3 mmol), catalyst (0.01 mmol) and base (0.3 mmol) in 1 mL of solvent was stirred for the indicated time. bIsolated yield. cReaction at 0 ℃. dReaction at -20 ℃. e Reaction at -40 ℃. fReaction at -60 ℃. g0.2 mmol of KOH was used. h5 mo%l of n-Bu4NBr was used. i20 mol% of n-Bu4NBr was used.
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    Table 2.  Scope of tertiary α-silyl alcohols with alkene moietiesabrrhzimage:6:erhhz

    aReaction conditions: a mixture of tertiary α-silyl alcohol 1a (0.1 mmol), ethyl bromoacetate 2 (0.3 mmol), n-Bu4NBr (0.01 mmol) and KOH (0.3 mmol) in 1 mL of solvent was stirred for the indicated time.
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    Table 3.  Scope of tertiary α-silyl alcohols with ketone moietiesa

    aReaction conditions: a mixture of tertiary α-silyl alcohol 5 (0.1 mmol), ethyl bromoacetate 2 (0.3 mmol), n-Bu4NBr (0.01 mmol) and KOH (0.3 mmol) in 1 mL of solvent was stirred for the indicated time.
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  • 发布日期:  2020-12-25
  • 收稿日期:  2020-05-31
  • 修回日期:  2020-07-11
  • 网络出版日期:  2020-08-05
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