Organocatalytic Asymmetric Vinylogous Aldol Reaction of Allyl Aryl

of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China. J. Org. Chem. , 2018, 83 (3), pp 1518–1524. DOI: 10.1021/acs.jo...
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Organocatalytic Asymmetric Vinylogous Aldol Reaction of Allyl Aryl Ketones to Silyl Glyoxylates Man-Yi Han,*,† Wen-Yu Luan,† Pei-Lin Mai,† Pinhua Li,† and Lei Wang*,†,‡ †

Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P. R. China State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China

‡

S Supporting Information *

ABSTRACT: A direct organocatalytic asymmetric vinylogous aldol reaction of allyl aryl ketones to silyl glyoxylates has been developed through the bifunctional catalyst, giving the α-hydroxysilanes with excellent enantioselectivity (up to 95% ee) and in high yields (up to 96%). The success of this catalytic methodology offers an opportunity to tackle the problems in the nucleophilic addition to acylsilanes. To activate both allyl aryl ketones and acylsilanes, the utilized bifunctional catalyst was an ideal organocatalyst in this unprecedented transformation.

O

duced a Cu-catalyzed addition of a nucleophilic silicon species to aldehydes, affording secondary α-hydroxysilanes with high enantioselectivities (Scheme 1d). As an aldehyde equivalent, acylsilanes are valuable electrophiles in nucleophilic addition.1a,c However, based on our previous work,3f,5 the direct activation of unactivated acylsilanes is a great challenge, particularly by organocatalysis.6 From a synthetic point of view, some major difficulties during the asymmetric nucleophilic addition to acylsilanes arise from, for example, (1) the steric hindrance of the silicon moiety in the acylsilane, which can hinder the nucleophilic addition of the negatively charged nucleophile attacking the carbonyl group of the acylsilane, (2) the low activity of the carbonyl group of the acylsilane, which can impede the addition reaction with the nucleophile, and (3) the competing Brook rearrangement involving the tetrahedral intermediate obtained from the addition of the nucleophile to the acylsilane. To tackle these problems, a new addition model for acylsilanes is needed. Our previous work indicated that the carbonyl group in the acylsilane could be activated by coordination to a carboxylic acid via hydrogen bonding (Scheme 1e).3f In this context, we envisioned that the carbonyl group in the acylsilane may be activated by thiourea via strong hydrogen bonding. Moreover, considering the steric hindrance of the silicon moiety in the acylsilane, allyl aryl ketones could serve as suitable nucleophiles following γ-selectivity with less steric hindrance, and noncatalytic Meerwein−Ponndorf−Verley-type reduction could be avoided using nonorganometallic reagents as nucleophiles.7 In

ptically active organosilanes, which are useful intermediates in the formation of carbon−carbon bonds and rearrangement reactions,1 are ubiquitous building blocks in synthetic chemistry. Moreover, the enantioselective installation of silicon into molecules is becoming increasingly significant in medicinal chemistry, due to silicon’s low toxicity and favorable metabolic profiles.2 Accordingly, the development of efficient catalytic methods for synthesizing chiral organosilanes is highly desirable. Investigations have shown that catalytic asymmetric nucleophilic addition to acylsilanes is one of the most straightforward strategies for the preparation of optically active organosilanes, particularly for α-hydroxysilanes.3 For example, using a hydride as a nucleophile, the Ohkuma group3b reported the enantioselective Ru-catalyzed reduction of acylsilanes, providing secondary α-silylalcohols with high enantioselectivities (Scheme 1a). As an alternative method, carbon-based nucleophilic addition to acylsilanes is appealing. In this regard, organometallic reagents are suitable nucleophiles with a high nucleophilicities. For instance, the Mark group3c reported a Zncatalyzed asymmetric alkynylation of acylsilanes with an alkyne as the nucleophile in 2013, affording the addition products with high enantioselectivities (Scheme 1b). In 2015, Harutyunyan3e reported a catalytic asymmetric alkylation of acylsilanes with Grignard reagents as the nucleophiles, giving the tertiary αsilylalcohols with excellent enantioselectivities (Scheme 1c). Owning to the unique properties of acylsilanes, the catalytic methods are still limited, and the development of a general nucleophilic addition strategy of acylsilanes remains more challenging for catalytic asymmetric reactions. As a complementary nucleophilic addition, Riant and co-workers4 intro© 2017 American Chemical Society

Received: October 7, 2017 Published: December 29, 2017 1518

DOI: 10.1021/acs.joc.7b02546 J. Org. Chem. 2018, 83, 1518−1524

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The Journal of Organic Chemistry Table 1. Optimization of the Reaction Conditionsa

Scheme 1. Representative Nucleophilic Additions to Acylsilanes

addition, if protonation of the generated tetrahedral intermediate (alkoxide) occurs faster than [1,2]-anionic migration, the addition products would be generated, and the [1,2]-Brook rearrangement would not proceed.8 Consequently, we wondered whether a bifunctional organocatalyst could be used for activating both the allyl aryl ketone9 and the acylsilane,3f,8e providing the vinylogous aldol products with γselectivity. Due to the difficulty of controlling the regioselectivity between α- and γ-addition, it is a great challenge to develop a vinylogous aldol reaction with a linear product. Herein, we report an organocatalytic asymmetric vinylogous aldol reaction10 of allyl aryl ketones to silyl glyoxylates, affording α-hydroxysilane products with excellent enantioselectivities (up to 95% ee). To the best of our knowledge, this new nucleophilic addition model of acylsilanes has not been reported up until now. To examine the feasibility of the desired reaction, we began our investigations with the asymmetric vinylogous aldol reaction of allyl phenyl ketone 1a with silyl glyoxylate 2a. Compared to the NEt3 or thiourea I as the achiral catalyst (Table 1, entries 1−3), the reaction was strongly accelerated and 3a was isolated in 68% yield when achiral bifunctional organocatalyst II was added to the system (Table 1, entry 4). As shown in Table 1, the reaction was first performed in dichloromethane at room temperature using chiral bifunctional catalyst III, and the desired product 3a was obtained in a good yield with a high enantioselectivity (Table 1, entry 5). It is important to note that the bifunctional catalyst promoted the asymmetric vinylogous aldol reaction with γ-selectivity (no αselectivity), and only E-selectivity of the double bond was observed. To our delight, no Brook rearrangement product was detected. It should be noted that when 1-phenylbut-2-en-1-one (1a′) was used as the substrate, only a trace amount of the desired product was observed under the same catalytic

entry

catalyst

solvent

time (h)

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17d 18e

NEt3 I NEt3 + I II III III III III III III III IV V VI VII VIII III III

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 ClCH2CH2Cl CHCl3 toluene THF CH3CN DMF THF THF THF THF THF THF THF

18 18 18 18 18 18 18 18 18 18 18 18 18 18 18 18 12 48

trace trace 12 68 64 13 trace 18 65 36 56 47 39 NR trace trace 77 65

89 90 ND 93 95 96 95 93 −72 ND ND ND 95 95

a Reactions were performed with 0.15 mmol of 1a, 0.10 mmol of 2a, and 10 mol % of the catalyst (I−VIII) in 1.0 mL of the solvent at room temperature. bIsolated yield after purification by column chromatography. cDetermined by chiral HPLC analysis. d3 equiv of allyl phenyl ketone 1a was used. e5 mol % of the catalyst was used. NR = no reaction. ND = no detection.

conditions, possibly due to the higher pKa of the nucleophile. Subsequently, we further optimized the reaction conditions in different solvents (Table 1, entries 6−11). Among all of the solvents examined, THF was found to be the ideal solvent both in terms of the yield and enantioselectivity (Table 1, entry 9). Encouraged by this result, we next screened other bifunctional catalysts IV−VII, and the results revealed that the catalytic activity varied greatly with the different structures of the catalysts (Table 1, entries 12−15). Particularly, poor reactivities were observed when VI and VII were used as catalysts (Table 1, entries 14 and 15). Cinchona alkaloid VIII was also examined to test the catalytic reactivity, but only a trace amount of product was obtained without the assistance of thiourea (Table 1, entry 16). Further investigation showed that the isolated yield increased to 77% when 3 equiv of allyl phenyl ketone 1a was used in the reaction (Table 1, entry 17). In addition, no improvement of the yield or enantioselectivity was observed using 5 mol % of the catalyst (entry 18). With the optimal reaction conditions in hand, we turned our focus to the substrate scope. As summarized in Scheme 2, a series of silyl glyoxylates bearing different ester groups were first investigated. The reaction of halogen-substituted substrates 1519

DOI: 10.1021/acs.joc.7b02546 J. Org. Chem. 2018, 83, 1518−1524

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The Journal of Organic Chemistry Scheme 2. Enantioselective Direct Vinylogous Aldol Reaction of Allyl Phenyl Ketone 1a to Silyl Glyoxylates 2a

Scheme 3. Enantioselective Direct Vinylogous Aldol Reaction of Silyl Glyoxylate 2a with Allyl Aryl Ketonesa

a Reactions were performed with 0.30 mmol of 1a, 0.10 mmol of 2, and 10 mol % of catalyst III in 1.0 mL of THF at room temperature. TMS = trimethylsilyl. TES = triethylsilyl. TBS = tert-butyldimethylsilyl. TIPS = triisopropylsilyl.

(2b−d) with 1a all proceeded smoothly, generating the vinylogous aldol products 3b−d with excellent enantioselectivities (90−92% ee) in moderate to high yields (48−83%). A silyl glyoxylate containing a cyclohexyl-based group also functioned as a suitable substrate, delivering the corresponding adduct 3e in 96% yield and 88% ee. It is noteworthy that the reaction with silyl glyoxylate containing a strong electron-donating group (MeO) on the phenyl ring of the ester moiety in 2f was welltolerated and afforded the corresponding product 3f with an excellent enantioselectivity (90% ee). On the contrary, the reaction of silyl glyoxylate with a strong electron-withdrawing group (NO2) at the para-position of the phenyl ring in ester moiety was sluggish. The silyl glyoxylate with a less steric hindrance group, such as TMS or TES, was also conducted in the reaction, affording the corresponding products 3g−h with excellent enantioselectivities (92−93% ee). However, when a bulky TIPS group was introduced to the silyl glyoxylate, no desired product 3i was obtained. To further investigate the reaction scope, we turned our attention to the reaction of allyl aryl ketones 1 with silyl glyoxylate 2a. As shown in Scheme 3, a variety of allyl aryl ketones were tested under the optimized conditions. In general, we found that all of the allyl aryl ketones with different substituents on the phenyl rings successfully reacted with 2a, generating the products with good enantioselectivities. The allyl aryl ketones with an alkyl group, such as Me, iPr, or tBu, attached to the phenyl ring afforded the desired products (3j− m) with excellent enantioselectivities (90−92% ee). We were delighted to observe that all of the halogen substituents (F, Cl, or Br) on the phenyl rings gave the corresponding products (3n−s) with excellent enantioselectivities (91−94% ee). Product 3s proved to crystallize easily, and the absolute configuration was determined via single-crystal X-ray diffraction. The X-ray structural analysis indicated that the absolute configuration of 3s was (R)-type11 (Supporting Information). Next, the strong electron-donating and electron-withdrawing groups, such as MeO and CF3, were introduced into the phenyl ring of the allyl aryl ketones. The reactions also proceeded well, furnishing the desired products (3t−w) with good enantioselectivities. Notably, only 77% ee was obtained when an orthoMeO group was introduced into the allyl aryl ketone. 2-Thienyl

a Reactions were performed with 0.30 mmol of 1, 0.10 mmol of 2a, and 10 mol % of catalyst III in 1.0 mL of THF at room temperature.

ketone was well-tolerated, providing the corresponding product (3x) with a high enantioselectivity (93% ee). Based on the above experimental results, a plausible catalytic cycle for the organocatalytic vinylogous aldol reaction of allyl aryl ketones to silyl glyoxylates is illustrated in Scheme 4. The Scheme 4. Proposed Reaction Mechanism

initial deprotonation of an acidic proton of allyl aryl ketone 1a with the amino group of catalyst III undergoes to generate an enolate intermediate, 4, which attacks the silyl glyoxylate 2a with the assistance of the thiourea group of catalyst III via the strong hydrogen bonding. The density functional theory (DFT) calculations10,12 showed that the less stable synconformation of 2a can form the most favored Si-syn-C1 with the lowest Gibbs free energy (Supporting Information, computational study). In this process, the two carbonyl groups of silyl glyoxylate 2a can be activated by the two N−H bonds of the thiourea moiety. Moreover, two nonclassical C−H···O hydrogen bonds between the catalyst and carbonyl groups of 1520

DOI: 10.1021/acs.joc.7b02546 J. Org. Chem. 2018, 83, 1518−1524

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The Journal of Organic Chemistry

propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 20.170 min, tR (major) = 21.466 min. (R,E)-4-Fluorobenzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo6-phenylhex-4-enoate (3b): white solid (22.5 mg, 51% yield); mp 43.8−45.7 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.45 (t, J = 8.0 Hz, 2H), 7.30−7.33 (m, 2H), 6.99 (t, J = 8.0 Hz, 2H), 6.82−6.89 (m, 2H), 6.77 (d, J = 16.0 Hz, 1H), 5.23 (d, J = 12.0 Hz, 1H), 5.06 (d, J = 12.0 Hz, 1H), 2.99 (s, 1H), 2.74−2.84 (m, 2H), 0.93 (s, 9H), 0.16 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.4, 177.4, 162.8 (d, J = 246 Hz), 142.8, 137.6, 132.7, 130.9 (d, J = 8 Hz), 128.6, 128.5, 115.7 (d, J = 21 Hz), 73.3, 67.0, 39.2, 27.2, 18.3, −6.8, −7.5; HRMS (ESI) calcd for [C25H31FO4Si + H]+ 443.2054, found 443.2051; [α]23 D −45.0 (c 0.4, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 27.770 min, tR (major) = 16.342 min. (R,E)-2-Fluorobenzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo6-phenylhex-4-enoate (3c): white solid (21.2 mg, 48% yield); mp 58.7−60.3 °C; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 2H), 7.54−7.58 (m, 1H), 7.45 (t, J = 8.0 Hz, 2H), 7.34−7.38 (m, 1H), 7.28−7.32 (m, 1H), 7.02−7.10 (m, 2H), 6.83−6.90 (m, 1H), 6.78 (d, J = 16.0 Hz, 1H), 5.30 (d, J = 12.0 Hz, 1H), 5.18 (d, J = 12.0 Hz, 1H), 3.00 (s, 1H), 2.74−2.85 (m, 2H), 0.93 (s, 9H), 0.16 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.5, 177.4, 161.3 (d, J = 247 Hz), 142.9, 137.7, 132.6, 131.4 (d, J = 4 Hz), 130.9 (d, J = 9 Hz), 129.4, 128.7, 128.5, 124.2 (d, J = 3 Hz), 122.1 (d, J = 15 Hz), 115.6 (d, J = 21 Hz), 73.4, 61.6 (d, J = 4 Hz), 39.3, 27.1, 18.3, −7.0, −7.5; HRMS (ESI) calcd for [C25H31FO4Si + H]+ 443.2054, found 443.2051; [α]23 D −70.0 (c 0.3, CH2Cl2). The ee value is 90%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 20.152 min, tR (major) = 15.192 min. (R,E)-4-Bromobenzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo6-phenylhex-4-enoate (3d): white solid (41.7 mg, 83% yield); mp 44.4−47.5 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.43−7.48 (m, 4H), 7.21 (d, J = 8.0 Hz, 2H), 6.83−6.90 (m, 1H), 6.78 (d, J = 16.0 Hz, 1H), 5.21 (d, J = 12.0 Hz, 1H), 5.04 (d, J = 12.0 Hz, 1H), 2.98 (s, 1H), 2.75−2.85 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.3, 177.4, 142.7, 137.6, 131.9, 129.4, 128.6, 128.5, 122.9, 73.3, 67.0, 39.2, 27.2, 18.3, −6.8, −7.4; HRMS (ESI) calcd for [C25H31BrO4Si + H]+ 503.1253, found 503.1248; [α]23 D −57.5 (c 0.4, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 38.076 min, tR (major) = 19.723 min. (R,E)-Cyclohexyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo-6phenylhex-4-enoate (3e): yellow oil (39.9 mg, 96% yield); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.0 Hz, 2H), 7.53−7.57 (m, 1H), 7.46 (t, J = 8.0 Hz, 2H), 6.87−6.89 (m, 2H), 4.83−4.89 (m, 1H), 3.07 (s, 1H), 2.76−2.82 (m, 2H), 1.86−1.97 (m, 2H), 1.65−1.73 (m, 3H), 1.34−1.51 (m, 6H), 0.97 (s, 9H), 0.19 (s, 3H), 0.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.7, 177.1, 143.2, 137.7, 132.6, 129.6, 128.6, 128.5, 74.7, 73.0, 39.4, 31.9, 31.6, 27.3, 23.7, 23.6, 18.4, −6.8, −7.3; HRMS (ESI) calcd for [C24H36O4Si + H]+ 417.2461, found 417.2457; [α]23 D −61.3 (c 0.75, CH2Cl2). The ee value is 88%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 10.469 min, tR (major) = 12.248 min. (R,E)-4-Methoxybenzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6oxo-6-phenylhex-4-enoate (3f): yellow oil (17.2 mg, 38% yield); 1 H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 2H), 7.56 (t, J = 8.0 Hz, 1H), 7.45 (t, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.81− 6.89 (m, 3H), 6.74 (d, J = 12.0 Hz, 1H), 5.22 (d, J = 12.0 Hz, 1H), 5.03 (d, J = 12.0 Hz, 1H), 3.74 (s, 3H), 3.03 (broad s, 1H), 2.73−2.83 (m, 2H), 0.16 (s, 3H), 0.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.5, 177.5, 159.9, 143.0, 137.6, 130.6, 129.4, 128.6, 128.4, 127.0, 114.0, 73.3, 67.6, 55.2, 39.2, 27.2, 18.3, −6.8, −7.5; HRMS (ESI) calcd for [C26H34O5Si + H]+ 455.2254, found 455.2253; [α]23 D −45.0 (c 0.2,

silyl glyoxylate 2a were observed. (See the computational study in the Supporting Information for more detail.) Since the thiourea can stabilize the negative charge on the oxygen more effectively, the tetrahedral intermediate 5 takes the proton from the amino group of the catalyst to afford the addition product 3a and the [1,2]-Brook rearrangement is significantly suppressed without the assistance of a base. Further application of this protocol and investigation of this detailed reaction mechanism are underway in our laboratory. In summary, a novel organocatalytic vinylogous aldol reaction of allyl aryl ketones to silyl glyoxylates was realized for the highly enantioselective synthesis of α-hydroxysilanes (up to 95% ee). This developed methodology offers an opportunity to tackle the problems associated with the nucleophilic addition reaction of acylsilanes. To overcome the steric hindrance of the silicon moiety of the acylsilane in this unprecedented transformation, allyl aryl ketones with less steric hindrance were employed as nucleophiles. Moreover, the low activity of the carbonyl group in the acylsilane was activated by thiourea via strong hydrogen bonding. In addition, the utilized bifunctional catalyst was an ideal organocatalyst for activating both the allyl aryl ketones and the acylsilanes for this asymmetric vinylogous aldol reaction. In light of this new addition model of acylsilanes, further studies of new reactions of acylsilanes are currently underway in our laboratory.

■

EXPERIMENTAL SECTION

General Information. General 1H and 13C NMR spectra were recorded on a Bruker 400 MHz NMR spectrometer. Chemical shifts were reported in ppm, and the coupling constants (J) are given in hertz (Hz). Tetramethylsilane (TMS, δ = 0.00 ppm) or CHCl3 (δ = 7.27 ppm) served as an internal standard for 1H NMR, while CDCl3 was used as an internal standard (δ = 77.0 ppm) 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) instrument. Enantiomeric excess values were determined by chiral HPLC analysis on Agilent 1100 HPLC workstations. Optical rotations were determined with a 0.2 dm tube using 589 nm. X-ray crystallography analysis was performed on a PANalytical X’Pert PRO MPD system (PW3040/60). Melting points were determined on a digital melting point apparatus, and temperatures were uncorrected. 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 gel (200−300 mesh). Catalysts I−VIII were purchased from commercial suppliers. Silyl glyoxylates were prepared according to the literature procedures. The racemic vinylogous aldol products were prepared by using the achiral bifunctional organocatalyst II. General Procedure for Asymmetric Vinylogous Aldol Reaction. Substrate 2a (27.8 mg, 0.10 mmol) and catalyst III (5.1 mg, 0.01 mmol) were dissolved in THF (1.0 mL). Then, allyl ketone 1a (43.8 mg, 0.30 mmol) was added at room temperature. After the reaction was stirred for 12 h at this temperature, the solvent was removed under a vacuum, and the residue was further purified by silica gel chromatography (petroleum ether/EtOAc = 30/1 as the eluent) to afford the desired product 3a (77% yield, 95% ee). (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo-6-phenylhex-4-enoate (3a): yellow oil (32.6 mg, 77% yield); 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 2H), 7.56 (t, J = 8.0 Hz, 1H), 7.44 (t, J = 4.0 Hz, 2H), 7.29−7.35 (m, 5H), 6.83−6.91 (m, 1H), 6.77 (d, J = 12.0 Hz, 1H), 5.27 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 3.02 (s, 1H), 2.75−2.86 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.5, 177.5, 142.9, 137.6, 132.6, 129.4, 128.8, 128.7, 128.6, 128.5, 73.3, 67.8, 39.3, 27.2, 18.3, −6.8, −7.4; HRMS (ESI) calcd for [C25H32O4Si + H]+ 425.2148, found 425.2146; [α]23 D −166.0 (c 0.5, CH2Cl2). The ee value is 95%, determined by HPLC with a Daicel chiral ODH column, n-hexane/21521

DOI: 10.1021/acs.joc.7b02546 J. Org. Chem. 2018, 83, 1518−1524

Note

The Journal of Organic Chemistry

(R,E)-Benzyl 6-(4-(tert-Butyl)phenyl)-2-(tert-butyldimethylsilyl)-2hydroxy-6-oxohex-4-enoate (3m): white solid (32.6 mg, 68% yield); mp 78.7−80.4 °C; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.36−7.29 (m, 5H), 6.90−6.83 (m, 1H), 6.77 (d, J = 16.0 Hz, 1H), 5.26 (d, J = 12.0 Hz, 1H), 5.11 (d, J = 12.0 Hz, 1H), 3.02 (s, 1H), 2.86−2.75 (m, 2H), 1.36 (s, 9H), 0.95 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.1, 177.5, 156.4, 142.3, 135.0, 134.8, 128.8, 128.6, 125.4, 73.4, 67.8, 39.3, 35.1, 31.1, 27.2, 18.3, −6.8, −7.4; HRMS (ESI) calcd for [C29H40O4Si + H]+ 481.2774, found 481.2761; [α]23 D −45.1 (c 0.18, MeOH). The ee value is 91%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 10.168 min, tR (major) = 11.972 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-6-(4-fluoro-phenyl)-2-hydroxy-6-oxohex-4-enoate (3n): white solid (34.5 mg, 78% yield); mp 67.8−68.6 °C; 1H NMR (400 MHz, CDCl3) δ 7.82−7.85 (m, 2H), 7.28−7.36 (m, 5H), 7.08−7.13 (m, 2H), 6.82−6.89 (m, 1H), 6.72 (d, J = 12.0 Hz, 1H), 5.28 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.02 (s, 1H), 2.74−2.86 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 188.8, 177.5, 177.4, 165.5 (d, J = 252 Hz), 143.1, 134.8, 133.9, 131.2 (d, J = 9 Hz), 129.0, 128.8, 128.7, 128.6, 115.5 (d, J = 21 Hz), 73.3, 67.8, 39.2, 27.2, 18.3, −6.8, −7.5; HRMS (ESI) calcd for [C25H31FO4Si + H]+ 443.2054, found 443.2046; [α]23 D −105.0 (c 0.8, CH2Cl2). The ee value is 91%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 10.338 min, tR (major) = 15.483 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-6-(3-fluoro-phenyl)-2-hydroxy-6-oxohex-4-enoate (3o): light yellow oil (33.1 mg, 75% yield); 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 1H), 7.49−7.52 (m, 1H), 7.39−7.42 (m, 1H), 7.23−7.36 (m, 6H), 6.85− 6.92 (m, 1H), 6.70 (d, J = 16.0 Hz, 1H), 5.28 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.75−2.86 (m, 2H), 0.95 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.0 (d, J = 3 Hz), 177.4, 162.7 (d, J = 246 Hz), 143.8, 139.7 (d, J = 9 Hz), 134.8, 130.1 (d, J = 7 Hz), 128.9, 128.8, 128.7, 128.6, 124.3 (d, J = 3 Hz), 119.6 (d, J = 21 Hz), 115.4 (d, J = 22 Hz), 73.3, 67.8, 39.2, 27.2, 18.3, −6.9, −7.5; HRMS (ESI) calcd for [C25H31FO4Si + NH4]+ 460.2319, found 460.2315; [α]23 D −82.7 (c 0.5, CH2Cl2). The ee value is 93%, determined by HPLC with a Daicel chiral ODH column, nhexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 9.912 min, tR (major) = 11.520 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-6-(4-chloro-phenyl)-2-hydroxy-6-oxohex-4-enoate (3p): white solid (33.9 mg, 74% yield); mp 86.7−88.7 °C; 1H NMR (400 MHz, CDCl3) δ 7.72−7.76 (m, 2H), 7.40−7.42 (m, 2H), 7.29−7.34 (m, 5H), 6.81−6.89 (m, 1H), 6.70 (d, J = 16.0 Hz, 1H), 5.28 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.01 (s, 1H), 2.74−2.86 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.1, 143.5, 139.1, 134.8, 130.0, 129.0, 128.8, 128.76, 128.70, 128.67, 73.3, 67.8, 39.2, 27.2, 18.3, −6.8, −7.5; HRMS (ESI) calcd for [C25H31ClO4Si + H]+ 459.1758, found 459.1747; [α]23 D −148.9 (c 0.65, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 11.841 min, tR (major) = 17.794 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-6-(3-chloro-phenyl)-2-hydroxy-6-oxohex-4-enoate (3q): white solid (20.6 mg, 45% yield); mp 61.3−61.5 °C; 1H NMR (400 MHz, CDCl3) δ 7.78−7.79 (m, 1H), 7.66−7.68 (m, 1H), 7.51−7.54 (m, 1H), 7.28−7.40 (m, 6H), 6.84−6.91 (m, 1H), 6.69 (d, J = 16.0 Hz, 1H), 5.29 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.75−2.86 (m, 2H), 0.95 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.0, 177.4, 144.0, 139.2, 132.5, 129.8, 128.9, 128.71, 128.67, 128.66, 126.7, 73.3, 67.8, 39.2, 27.2, 18.3, −6.9, −7.5; HRMS (ESI) calcd for [C25H31ClO4Si + H]+ 459.1758, found 459.1743; [α]23 D −89.3 (c 0.75, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 11.294 min, tR (major) = 14.095 min.

CH2Cl2). The ee value is 90%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 5.143 min, tR (major) = 94.857 min. (R,E)-Benzyl 2-Hydroxy-6-oxo-6-phenyl-2-(trimethylsilyl)hex-4enoate (3g): light yellow oil (24.8 mg, 65% yield); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 2H), 7.46 (t, J = 8.0 Hz, 1H), 7.36 (t, J = 8.0 Hz, 2H), 7.25−7.18 (m, 5H), 6.82−6.89 (m, 1H), 6.75 (d, J = 16.0 Hz, 1H), 5.11 (dd, J = 12.0, 16.0 Hz, 2H), 2.94 (s, 1H), 2.75 (dd, J = 8.0, 16.0 Hz, 1H), 2.63 (dd, J = 8.0, 16.0 Hz, 1H), 0.00 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 190.4, 176.9, 143.3, 137.7, 132.6, 129.1, 128.78, 128.63, 128.61, 128.59, 128.43, 73.9, 67.6, 37.8, −4.1; HRMS (ESI) calcd for [C22H26O4Si + H]+ 383.1679, found 383.1673; [α]23 D −33.3 (c 0.30, MeOH). The ee value is 93%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 30.315 min, tR (major) = 33.881 min. (R,E)-Benzyl 2-Hydroxy-6-oxo-6-phenyl-2-(triethylsilyl)hex-4enoate (3h): light yellow oil (24.6 mg, 58% yield); 1H NMR (400 MHz, CDCl3) δ 7.81−7.83 (m, 2H), 7.55 (t, J = 8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 2H), 7.36−7.28 (m, 5H), 6.93−6.86 (m, 1H), 6.78 (d, J = 16.0 Hz, 1H), 5.25 (d, J = 12.0 Hz, 1H), 5.14 (d, J = 12.0 Hz, 1H), 3.01 (s, 1H), 2.83 (dd, J = 8.0, 16.0 Hz, 1H), 2.75 (d, J = 8.0, 16.0 Hz, 1H), 0.98 (t, J = 8.0 Hz, 9H), 0.69 (dd, J = 8.0, 16.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 190.5, 177.2, 143.2, 137.7, 132.6, 129.2, 128.8, 128.7, 128.6, 128.4, 73.4, 67.7, 38.7, 7.4, 1.8; HRMS (ESI) calcd for [C25H32O4Si + H]+ 425.2148, found 425.2142; [α]23 D −36.7 (c 0.20, MeOH). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 16.729 min, tR (major) = 23.525 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo-6-(ptolyl)hex-4-enoate (3j): light yellow oil (22.3 mg, 51% yield); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 2H), 7.33−7.36 (m, 5H), 7.27 (d, J = 16.0 Hz, 2H), 6.84−6.91 (m, 1H), 6.79 (d, J = 16.0 Hz, 1H), 5.26 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.76−2.84 (m, 2H), 2.44 (s, 3H), 0.96 (s, 9H), 0.18 (s, 3H), 0.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.9, 177.5, 143.5, 142.3, 135.1, 134.8, 129.4, 129.2, 128.8, 128.7, 73.3, 67.8, 39.3, 27.2, 21.6, 18.3, −6.8, −7.4; HRMS (ESI) calcd for [C26H34O4Si + Na]+ 461.2124, found 461.2119; [α]23 D −60.0 (c 0.45, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 15.705 min, tR (major) = 19.514 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo-6-(mtolyl)hex-4-enoate (3k): light yellow oil (24.9 mg, 57% yield); 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.30−7.34 (m, 7H), 6.82−6.92 (m, 1H), 6.76 (d, J = 16.0 Hz, 1H), 5.26 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.75−2.83 (m, 2H), 2.41 (s, 3H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.7, 177.5, 142.7, 137.7, 133.4, 129.6, 129.2, 128.8, 128.6, 128.3, 125.8, 73.3, 67.8, 39.3, 27.2, 21.3, 18.3, −6.8, −7.5; HRMS (ESI) calcd for [C26H34O4Si + H]+ 439.2305, found 439.2300; [α]23 D −55.0 (c 0.8, CH2Cl2). The ee value is 90%, determined by HPLC with a Daicel chiral ODH column, nhexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 23.133 min, tR (major) = 18.362 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-(4-isopropylphenyl)-6-oxohex-4-enoate (3l): light yellow oil (34.0 mg, 73% yield); 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.34− 7.28 (m, 7H), 6.91−6.83 (m, 1H), 6.78 (d, J = 16.0 Hz, 1H), 5.26 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 3.05 (s, 1H), 3.01−2.92 (m, 1H), 2.86−2.75 (m, 2H), 1.29 (s, 3H), 1.27 (s, 3H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.0, 177.4, 154.2, 142.3, 135.4, 134.8, 129.4, 128.9, 128.7, 128.6, 128.5, 73.3, 67.7, 39.2, 34.2, 27.1, 23.6, 18.2, −6.9, −7.5; HRMS (ESI) calcd for [C28H38O4Si + H]+ 467.2618, found 467.2607; [α]23 D −36.7 (c 0.50, MeOH). The ee value is 90%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 10.148 min, tR (major) = 11.670 min. 1522

DOI: 10.1021/acs.joc.7b02546 J. Org. Chem. 2018, 83, 1518−1524

Note

The Journal of Organic Chemistry (R,E)-Benzyl 6-(3-Bromophenyl)-2-(tert-butyldimethylsilyl)-2-hydroxy-6-oxohex-4-enoate (3r): white solid (39.1 mg, 78% yield); mp 58.2−58.8 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.66− 7.72 (m, 2H), 7.28−7.36 (m, 6H), 6.83−6.91 (m, 1H), 6.68 (d, J = 16.0 Hz, 1H), 5.29 (d, J = 12.0 Hz, 1H), 5.08 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.74−2.85 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 188.9, 177.4, 144.0, 139.4, 135.4, 134.7, 131.6, 130.0, 128.7, 127.1, 122.7, 73.3, 67.8, 39.2, 27.2, 18.3, −6.9, −7.5; HRMS (ESI) calcd for [C25H31BrO4Si + H]+ 503.1253, found 503.1243; [α]23 D −73.0 (c 1.0, CH2Cl2). The ee value is 94%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 11.871 min, tR (major) = 15.176 min. (R,E)-Benzyl 6-(4-Bromophenyl)-2-(tert-butyldimethylsilyl)-2-hydroxy-6-oxohex-4-enoate (3s): white solid (38.6 mg, 77% yield); mp 57.7−59.2 °C; 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.28−7.35 (m, 5H), 6.81−6.89 (m, 1H), 6.69 (d, J = 16.0 Hz, 1H), 5.28 (d, J = 12.0 Hz, 1H), 5.08 (d, J = 12.0 Hz, 1H), 3.02 (s, 1H), 2.74−2.86 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.3, 177.4, 143.6, 136.3, 134.8, 131.7, 130.1, 128.9, 128.8, 128.7, 128.6, 127.7, 73.3, 67.8, 39.2, 27.2, 18.3, −6.9, −7.5; HRMS (ESI) calcd for [C25H31BrO4Si + H]+ 503.1253, found 503.1237; [α]23 D −107.7 (c 0.65, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 13.699 min, tR (major) = 19.749 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-(2-methoxyphenyl)-6-oxohex-4-enoate (3t): light yellow oil (29.1 mg, 64% yield); 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.0 Hz, 2H), 7.29− 7.36 (m, 5H), 6.99 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.64− 6.71 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 5.21 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.82 (s, 3H), 2.96 (s, 1H), 2.69−2.81 (m, 2H), 0.93 (s, 9H), 0.14 (s, 3H), 0.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 193.3, 177.4, 157.7, 142.1, 134.0, 132.4, 130.0, 128.8, 128.7, 128.6, 120.5, 111.4, 73.3, 67.7, 55.6, 39.1, 27.1, 18.2, −6.9, −7.5; HRMS (ESI) calcd for [C26H34O5Si + H]+ 455.2254, found 455.2248; [α]23 D −65.0 (c 0.4, CH2Cl2). The ee value is 77%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/ 2, 1.0 mL/min, detection at 220 nm: tR (minor) = 20.995 min, tR (major) = 33.756 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-(4-methoxyphenyl)-6-oxohex-4-enoate (3u): light yellow oil (24.5 mg, 54% yield); 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 12.0 Hz, 2H), 7.29−7.34 (m, 5H), 6.90−6.94 (m, 2H), 6.82−6.87 (m, 1H), 6.78 (d, J = 16.0 Hz, 1H), 5.26 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 3.88 (s, 3H), 2.74−2.86 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 188.7, 177.5, 163.3, 141.7, 134.8, 130.9, 129.2, 128.7, 128.6, 113.7, 73.4, 67.8, 55.4, 39.2, 27.2, 18.3, −6.8, −7.5; HRMS (ESI) calcd for [C26H34O5Si + H]+ 455.2254, found 455.2258; [α]23 D −60.0 (c 0.8, CH2Cl2). The ee value is 91%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 44.151 min, tR (major) = 50.736 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-(3-methoxyphenyl)-6-oxohex-4-enoate (3v): light yellow oil (33.1 mg, 73% yield); 1H NMR (400 MHz, CDCl3) δ 7.28−7.39 (m, 8H), 7.09−7.11 (m, 1H), 6.84−6.91 (m, 1H), 6.75 (d, J = 12.0 Hz, 1H), 5.26 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.0 Hz, 1H), 3.86 (s, 3H), 3.02 (s, 1H), 2.75−2.85 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.2, 177.4, 159.7, 143.0, 139.0, 134.7, 129.4, 128.8, 128.6, 121.2, 119.3, 112.8, 73.3, 67.8, 55.4, 39.2, 27.1, 18.2, −6.9, −7.5; HRMS (ESI) calcd for [C26H34O5Si + H]+ 455.2254, found 455.2248; [α]23 D −66.4 (c 1.25, CH2Cl2). The ee value is 92%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 32.024 min, tR (major) = 25.291 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo-6-(4(trifluoromethyl)phenyl)hex-4-enoate (3w): white solid (37.4 mg, 76% yield); mp 33.2−35.1 °C; 1H NMR (400 MHz, CDCl3) δ 7.86

(d, J = 8.0 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.28−7.33 (m, 5H), 6.83−6.90 (m, 1H), 6.70 (d, J = 12.0 Hz, 1H), 5.30 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.76−2.87 (m, 2H), 0.95 (s, 9H), 0.17 (s, 3H), 0.09 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.7, 177.4, 144.5, 140.5, 134.8, 133.9 (q, J = 32 Hz), 129.1, 128.9, 128.8, 128.7, 125.5 (q, J = 4 Hz), 123.6 (q, J = 271 Hz), 73.3, 67.8, 39.2, 27.2, 18.3, −6.9, −7.5; HRMS (ESI) calcd for [C26H31F3O4Si + H]+ 493.2022, found 493.2011; [α]23 D −68.8 (c 0.8, CH2Cl2). The ee value is 91%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 220 nm: tR (minor) = 9.513 min, tR (major) = 13.664 min. (R,E)-Benzyl 2-(tert-Butyldimethylsilyl)-2-hydroxy-6-oxo-6-(thiophen-2-yl)hex-4-enoate (3x): light yellow oil (32.2 mg, 75% yield); 1 H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 4.0 Hz, 1H), 7.60 (d, J = 4.0 Hz, 1H), 7.26−7.36 (m, 5H), 7.12 (t, J = 4.0 Hz, 1H), 6.90−6.98 (m, 1H), 6.70 (d, J = 16.0 Hz, 1H), 5.27 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 3.03 (s, 1H), 2.74−2.85 (m, 2H), 0.94 (s, 9H), 0.17 (s, 3H), 0.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 181.8, 177.4, 144.9, 142.0, 134.8, 133.8, 132.1, 128.8, 128.7, 128.6, 128.1, 73.3, 67.8, 39.1, 27.2, 18.3, −6.9, −7.5; HRMS (ESI) calcd for [C23H30O4SSi + H]+ 431.1712, found 431.1709; [α]23 D −70.0 (c 0.8, CH2Cl2). The ee value is 93%, determined by HPLC with a Daicel chiral ODH column, n-hexane/2-propanol = 95/5, 1.0 mL/min, detection at 220 nm: tR (minor) = 44.584 min, tR (major) = 24.519 min. Brook Rearrangement of 3a to 6. To the solution of aldol product adduct 3a (84.8 mg, 0.2 mmol) in 2 mL of toluene were added catalyst C (7.0 mg, 0.02 mmol) and Cs2CO3 (130 mg, 0.4 mmol), and the reaction mixture was stirred at 10 °C for 48 h. The residue was purified by silica gel chromatography to afford the desired product 6. (E)-Benzyl 2-((tert-Butyldimethylsilyl)oxy)-6-oxo-6-phenylhex-4enoate (6): colorless oil (26.7 mg, 63% yield); 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.0 Hz, 2H), 7.56 (t, J = 8.0 Hz, 1H), 7.46 (t, J = 8.0 Hz, 2H), 7.29−7.34 (m, 5H), 6.95−7.03 (m, 1H), 6.89 (d, J = 16.0 Hz, 1H), 5.18 (dd, J = 12.0, 24.0 Hz, 2H), 4.42 (dd, J = 4.0, 4.0 Hz, 1H), 2.69−2.81 (m, 2H), 0.87 (s, 9H), 0.06 (s, 3H), 0.03 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 190.5, 172.4, 143.8, 137.7, 135.4, 132.7, 128.9, 128.58, 128.57, 128.50, 128.45, 71.3, 66.9, 38.5, 25.6, 18.2, −5.0, −5.4; HRMS (ESI) calcd for [C25H32O4Si + H]+ 425.2148, found 425.2146. The ee value is 54%, determined by HPLC with a Daicel chiral IC column, n-hexane/2-propanol = 98/2, 1.0 mL/min, detection at 254 nm: tR (minor) = 18.752 min, tR (major) = 20.125 min.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02546. Brook rearrangement of 3a to 6, crystal data for enantiopure 3s, computational study for the reaction mechanism, Cartesian Coordinates, and copies of 1H and 13 C NMR spectra of all new compounds (PDF) X-ray crystallographic data of compound 3s (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Lei Wang: 0000-0001-6580-7671 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge the National Natural Science Foundation of China (nos. 21602073 and 21372095) and the Natural Science Foundation of Anhui (no. 1708085QB39) for financial support of this work. We also thank Mr. Chao-Xian 1523

DOI: 10.1021/acs.joc.7b02546 J. Org. Chem. 2018, 83, 1518−1524

Note

The Journal of Organic Chemistry Yan and Dr. Pan-Pan Zhou at Lanzhou University for the help of calculations.

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REFERENCES

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