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DOI: 10.1055/s-0034-1378786
Practical and Highly Stereoselective Synthesis of Trisubstituted (E)-α,β-Unsaturated Esters
Publication History
Received: 15 April 2015
Accepted after revision: 04 June 2015
Publication Date:
24 July 2015 (online)
Abstract
Trisubstituted (E)-α,β-unsaturated esters bearing various substituents were synthesized with high geometrical selectivity by using three reactions: an aldol reaction, acetylation of the hydroxy group at the β-position, and an E1cB reaction induced by 1,8-diazabicyclo[5.4.0]undec-7-ene. The method does not require separation of the diastereoisomeric mixture of β-hydroxy ester intermediates before the E1cB reaction, and is usable for gram-scale syntheses of trisubstituted (E)-α,β-unsaturated esters.
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Key words
stereoselective synthesis - enoates - aldol reactions - acylations - elimination reactionsTrisubstituted (E)-α,β-unsaturated esters are among the most important substrates for organic reactions such as the Michael addition or the Diels–Alder reaction.[1] Because of their potent biological and pharmaceutical activities, natural products having appropriate structures for use as partial units have attracted the attention of organic chemists and biologists.[2] It is well known that the geometry of α,β-unsaturated esters is often reflected in the stereochemistry of the chiral centers of the products of organic reactions. Moreover, the biological activities of natural products can be dramatically affected by the geometry of the carbon–carbon double bond in the α,β-unsaturated ester moiety.[2a] [d] [3] The Wittig reaction and the Horner–Wadsworth–Emmons reaction are reliable methods for the preparation of α,β-unsaturated carbonyl compounds; however, those reactions necessitate the preliminary preparation of moisture-sensitive ylide derivatives and they generate large amounts of phosphonate or phosphine oxide byproducts.[4]
Many reports have been published on geometrically selective syntheses of trisubstituted (E)-α,β-unsaturated carbonyl compounds. For example, Kowalski and Shindo independently reported E-selective syntheses of trisubstituted (E)-α,β-unsaturated esters by using ynolate intermediates.[5] [6] Verkade and colleagues reported a synthesis of trisubstituted (E)-α,β-unsaturated esters by using expensive proazaphosphatrane as a strong base but they found that the method was not applicable to the synthesis of α,β-unsaturated esters bearing an aliphatic chain in the β-position.[7] Recently, a nickel complex catalyzed carbonylation of alkyne was reported by Ma and colleagues.[8] In that reaction, a decrease in regioselectivity was observed in several cases depending on the chemical properties of the substituents. Although syntheses by stereoselective dehydration reactions of α-substituted β-hydroxy carbonyl compounds have been reported by several groups, some problems in achieving high geometrical selectivity remain, including difficulties in preliminary preparation of substrates and the need to use a single diastereomer of a β-hydroxy carbonyl compound as the substrate for the elimination reaction.[9] [10] [11] [12] The Baylis–Hillman reaction can be used as a key reaction for the preparation of trisubstituted (E)-α,β-unsaturated esters, as reported by several research groups,[2f] [13] [14] [15] [16] but it requires a long reaction time, which hampers easy access to the desired compounds.
In our studies on the development of novel asymmetric reactions, we required trisubstituted (E)-α,β-unsaturated esters bearing various substituents with high E/Z ratios as substrates. In general, simple reactions are desirable for the synthesis of target molecules. Here we report a practical and highly geometrically selective synthesis of trisubstituted (E)-α,β-unsaturated esters, containing various substituents, that involves a combination of an aldol reaction, acetylation of a hydroxy group at the β-position, and an E1cB reaction under basic conditions (Scheme [1]).
a Selectivities were determined by 1H NMR spectroscopy.
b 15 equiv of DBU were used in the elimination reaction.
c Yield over two steps.
First, we examined the synthesis of trisubstituted (E)-α,β-unsaturated esters having an aromatic ring at the β-position, as shown in Table [1] (entries 1–9). The aldol reaction of esters 1–5 with benzaldehyde derivatives having either an electron-donating group or an electron-withdrawing group on the aromatic ring provided α-substituted β-hydroxy esters 6a–i in good yields but with low diastereoselectivities (1.1:1 to 4.7:1). Subsequent acetylation of the hydroxy group of diastereomeric mixtures 6a–i gave the corresponding products 7a–i in excellent yields (92–98%) in all cases. Finally, the acetylated diastereomeric mixtures 7a–i were subjected to an E1cB reaction using 1,8-diazabicyclo[5.4.0]undec-7-ene as the base in refluxing toluene to provide the desired trisubstituted (E)-α,β-unsaturated esters 8a–i in 88–99% yields with good to high stereoselectivities (E/Z = 84:16 to 99:1). Note that use of an acetyl group as the leaving group was essential for obtaining the high geometric selectivity in the elimination step. According to the literature, elimination reactions that use either a tosyl group or a mesyl group as the leaving group show lower selectivities.[1e] [17] The acetyl group is a milder leaving group than tosyl or mesyl group, so that the E1cB reaction proceeds in preference to the E2 reaction when the acetyl group is used as the leaving group. The geometry of the carbon–carbon double bond in compounds 8a–o was determined by means of NOE analysis in the 1H NMR spectroscopy of 8a and was confirmed by comparison of the 1H NMR chemical shifts of our synthesized 8a–o with those reported in the literature.[16a] [18]
Next, we conducted the synthesis of 8j–l, which bear a heteroaromatic ring in the β-position (Table [1], entries 10–12). The aldol reaction of tert-butyl propionate (1) with the appropriate aldehydes gave the desired products 6j–l in good yields (80–83%) but low diastereoselectivities (1.2:1 to 1.4:1). Subsequent acetylation of 6j and 6k gave the acetylated compounds 7j and 7k in excellent yields, respectively. The final elimination reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene in refluxing toluene afforded trisubstituted (E)-α,β-unsaturated esters 8j and 8k in 95% and 97% yield, respectively, with almost complete E-selectivity (entries 10 and 11). On the other hand, the acetylation of 6l spontaneously afforded the trisubstituted (E)-α,β-unsaturated ester 8l in 74% yield with predominant E-selectivity (Table [1], entry 12). Finally, we explored the applicability of the synthesis to compounds bearing an aliphatic substituent, of which there have been few previous reports[15] (Table [1], entries 13–15). The aldol reaction gave aldol products 6m–o in 68–80% yield and low diastereoselectivities (1.1:1 to 2.0:1); subsequent acetylation of the diastereomeric mixtures 6m–o gave the corresponding acetates 7m–o in good to excellent yields (88–99%). The E1cB reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene in refluxing toluene gave the desired trisubstituted (E)-α,β-unsaturated esters 8m–o in 63–82% yields and high geometric selectivities (entries 13–15).
In conclusion, we have developed a practical and highly stereoselective method for the synthesis of trisubstituted (E)-α,β-unsaturated esters bearing various substituents, such as aromatic rings, heteroaromatic rings, or aliphatic groups. The present method involves three simple reactions: an aldol reaction, acetylation of the hydroxy group, and an E1cB reaction using 1,8-diazabicyclo[5.4.0]undec-7-ene in refluxing toluene. Moreover, diastereomeric mixtures of the aldol products can be used in our method, and trisubstituted (E)-α,β-unsaturated esters can be synthesized on a gram scale. Further studies on asymmetric syntheses using those compounds will be reported in due course.
1H NMR spectra were recorded at 400 MHz and 13C NMR spectra were recorded at 100 MHz on Varian Unity INOVA-400 or JEOL JNM ECS-400 spectrometers. Chemical shifts are reported in ppm relative to TMS as internal reference. IR spectra were recorded in CHCl3 on a Shimadzu FTIR-8300 spectrometer. Mass spectra were recorded on a JEOL JMS-SX 102A QQ or a JEOL JMS-GC-mate spectrometer. Melting points were determined on a micro hot-stage apparatus (Yanagimoto) and are uncorrected. Elemental analysis was performed on a PerkinElmer Series II CHNS/O Analyzer 2400. Flash column chromatography was performed on 63–210 μm silica gel. TLC analysis and preparative TLC were performed on commercial glass plates with 0.25 or 0.5 mm thick layers of silica gel, respectively. When necessary, compounds were further purified by recycling HPLC (JAI LC-908) on a silica gel column (Kusano Si-10) after column chromatography on silica gel.
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tert-Butyl 3-Phenylpropanoate (3)
A solution of 3-phenylpropionyl chloride (5.02 g, 29.8 mmol) in toluene (20 mL) was added dropwise to a solution of t-BuOH (8.54 mL, 89.3 mmol) and DIPEA (6.12 mL, 35.7 mmol) in toluene (80 mL) at 0 °C, and the mixture was stirred for 45 min at r.t. and then for another 1.5 h at 50 °C. The mixture was poured into a sat. aq NaHCO3 (200 mL), and extracted with EtOAc (3 × 100 mL). The organic layer was washed successively with a sat. aq NH4Cl (80 mL) and brine (80 mL), then dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (20:1)] to give a colorless oil; yield: 3.83 g (62%). Spectral data for the synthesized 3 were identical to the reported values.[19]
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(E)-α-Substituted α,β-Unsaturated Esters 8
Pure (E)-α-substituted α,β-unsaturated ester 8 were isolated from E,Z-mixtures of 8 by either recycling HPLC on a silica gel column or by recrystallization. The three-step procedure for the synthesis of compound 8a from 6a is reported as a typical procedure.
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tert-Butyl 3-(4-Chlorophenyl)-3-hydroxy-2-methylpropanoate (6a); Typical Procedure
A 1.11 M solution of LDA in 5:1 hexane–THF (26.7 mL, 29.7 mmol) was added dropwise to a solution of tert-butyl propionate (1: 2.97 g, 22.8 mmol) in THF (30 mL) at –78 °C, and the mixture was stirred for 30 min. A solution of 4-chlorobenzaldehyde (3.27 g, 23.3 mmol) in THF (5 mL) was added dropwise to the enolate solution at –78 °C, and the mixture was stirred for 30 min at –78 °C. When the reaction was complete, the mixture was poured into a sat. aq NH4Cl (150 mL) and the pH was adjusted to 5–7 with 1 M aq HCl. The resulting mixture was extracted with EtOAc (3 × 100 mL), and the organic layer was washed with brine (80 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (5:1)] to give a colorless oil; yield: 4.83 g (78%, 1.1:1 diastereomeric mixture).
IR (CHCl3): 3519, 3039, 2979, 2937, 1720, 1591, 1525, 1490, 1458, 1394, 1153, 1014 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.34–7.26 (m, 4 Hmajor, 4 Hminor), 5.03 (br t, J = 3.8 Hz, 1 Hminor), 4.68 (dd, J = 7.8, 5.0 Hz, 1 Hmajor), 3.33 (d, J = 5.0 Hz, 1 Hmajor), 3.23 (d, J = 2.9 Hz, 1 Hminor), 2.66 (quin, J = 7.4 Hz, 1 Hmajor), 2.63 (dq, J = 7.1, 4.0 Hz, 1 Hminor), 1.43 (s, 9 Hmajor), 1.42 (s, 9 Hminor), 1.07 (d, J = 7.1 Hz, 3 Hminor), 1.03 (d, J = 7.4 Hz, 1 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.3, 175.1, 140.4, 140.0, 133.5, 133.0, 128.5 (2 C), 128.3 (2 C), 128.0 (2 C), 127.5 (2 C), 81.5, 81.4, 75.6, 73.0, 47.5, 46.8, 27.99 (3 C), 27.96 (3 C), 14.6, 10.8.
MS (CI): m/z = 271 (100) [M + H]+.
HRMS: m/z calcd for C14H20ClO3 [M + H]+: 271.1101; found: 271.1105.
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tert-Butyl 3-(Acetyloxy)-3-(4-chlorophenyl)-2-methylpropanoate (7a); Typical Procedure
Ac2O (155 μL, 1.64 mmol) was added dropwise to a solution of a diastereomeric mixture of hydroxy ester 6a (222 mg, 0.820 mmol) in pyridine (1.1 mL) containing DMAP (catalytic amount) at 0 °C, and the mixture was stirred for 1 h at r.t. The reaction was quenched with MeOH (0.5 mL) at 0 °C, and the solvent was removed under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (10:1)] to give colorless crystals; yield: 247 mg (96%, diastereomeric mixture); mp 34–40 °C (hexane–EtOAc).
IR (CHCl3): 3043, 3057, 3006, 2979, 1730, 1598, 1525, 1517, 1494, 1458, 1369, 1286, 1259, 1091, 1026, 1014 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.34–7.25 (m, 4 Hmajor, 4 Hminor), 5.91 (d, J = 7.9 Hz, 1 Hminor), 5.74 (d, J = 10.1 Hz, 1 Hmajor), 2.84–2.78 (m, 1 Hmajor, 1 Hminor), 2.07 (s, 3 Hminor), 2.01 (s, 3 Hmajor), 1.46 (s, 9 Hmajor), 1.29 (s, 9 Hminor), 1.19 (d, J = 7.0 Hz, 3 Hminor), 0.93 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 172.8, 171.9, 169.8, 169.4, 137.2, 136.6, 134.2, 133.9, 128.9 (2 C), 128.7 (2 C), 128.5 (2 C), 128.4 (2 C), 80.95, 80.88, 76.9, 75.8, 46.5, 46.4, 27.9 (3 C), 27.8 (3 C), 21.0, 20.9, 13.9, 13.1.
MS (EI, 20 eV): m/z (%) = 312 (1) [M]+, 256 (72), 239 (11), 213 (100), 152 (45), 117 (50), 57 (40).
HRMS: m/z [M+] calcd for C16H21ClO4: 312.1128; found: 312.1130.
Anal. Calcd for C16H21ClO4: C, 61.44; H, 6.77. Found: C, 61.59; H, 6.77.
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tert-Butyl (2E)-3-(4-Chlorophenyl)-2-methylacrylate (8a); Typical Procedure
DBU (9.58 ml, 64.2 mmol) was added to a solution of a diastereomeric mixture of esters 7a (4.02 g, 12.8 mmol) in toluene (20 mL), and the mixture was refluxed for 2.5 h. The mixture was then poured into sat. aq NH4Cl (200 mL), and the pH was adjusted to 5–7 with 1 M aq HCl. The resulting mixture was extracted with EtOAc (3 × 100 mL). The organic layer was washed with brine (80 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (10:1)] to give colorless crystals; yield: 3.10 g (96%, E/Z = 99:1); mp 66–67 °C (hexane–EtOAc).
IR (CHCl3): 2981, 1697, 1635, 1593, 1490, 1369, 1284, 1215, 1168, 1093, 1014 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.53 (br d, J = 1.5 Hz, 1 H), 7.35 (br dt, J = 8.6, 2.1 Hz, 2 H), 7.30 (br dt, J = 8.6, 2.1 Hz, 2 H), 2.04 (d, J = 1.5 Hz, 3 H), 1.54 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 167.6, 136.4 (2 C), 134.6, 133.9, 130.8 (2 C), 128.5 (2 C), 80.7, 28.1 (3 C), 14.0.
MS (EI, 70 eV): m/z (%) = 254 (5) [M + 2]+, 252 (14) [M+], 196 (100), 179 (13), 161 (22), 150 (20), 57 (9).
HRMS: m/z [M+] calcd for C14H17ClO2: 252.0917; found: 252.0920.
Anal. Calcd for C14H17ClO2: C, 66.53; H, 6.78. Found: C, 66.67; H, 6.64.
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tert-Butyl 3-Hydroxy-2-methyl-3-[4-(trifluoromethyl)phenyl]propanoate (6b)
Colorless oil; yield: 3.09 g (84%, dr = 1.5:1).
IR (CHCl3): 3496, 3028, 2981, 2906, 1706, 1622, 1458, 1369, 1325, 1166, 1130, 1068, 1016 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.61 (d, J = 8.1 Hz, 2 Hmajor), 7.60 (d, J = 8.1 Hz, 2 Hminor), 7.47 (d, J = 8.1 Hz, 2 Hminor), 7.46 (d, J = 8.1 Hz, 2 Hmajor), 5.13 (br t, J = 3.4 Hz, 1 Hminor), 4.76 (dd, J = 7.2, 5.5 Hz, 1 Hmajor), 3.48 (d, J = 5.5 Hz, 1 Hmajor), 3.39 (br d, J = 3.4 Hz, 1 Hminor), 2.70 (quin, J = 7.2 Hz, 1 Hmajor), 2.67 (dq, J = 7.2, 3.4 Hz, 1 Hminor), 1.43 (s, 9 Hminor), 1.42 (s, 9 Hmajor), 1.07 (d, J = 7.1 Hz, 3 Hmajor), 1.06 (d, J = 7.1 Hz, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.3, 175.0, 146.4, 145.5, 129.9 (q, 2 J C–F = 32.4 Hz), 129.5 (q, 2 J C–F = 32.4 Hz), 126.9 (2 C), 126.4 (2 C), 125.2 (q, 3 J C–F = 3.8 Hz, 2 C), 125.1 (q, 3 J C–F = 3.8 Hz, 2 C), 124.1 (q, 1 J C–F = 272 Hz), 124.0 (q, 1 J C–F = 272 Hz), 81.6, 81.5, 75.6, 72.9, 47.4, 46.6, 27.91 (3 C), 27.90 (3 C), 14.5, 10.6.
MS (CI): m/z (%) = 305 (2) [M + H]+.
HRMS: m/z [M + H]+ calcd for C15H20F3O3: 305.1365; found: 305.1363.
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tert-Butyl 3-(Acetyloxy)-2-methyl-3-[4-(trifluoromethyl)phenyl]propanoate (7b)
Colorless oil; yield: 2.59 g (95%).
IR (CHCl3): 3028, 2981, 2939, 1730, 1622, 1458, 1369, 1325, 1238, 1168, 1132, 1068, 1018 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.61 (d, J = 8.6 Hz, 2 Hmajor), 7.59 (d, J = 8.1 Hz, 2 Hminor), 7.47 (d, J = 8.1 Hz, 2 Hminor), 7.45 (d, J = 8.6 Hz, 2 Hmajor), 6.00 (d, J = 7.5 Hz, 1 Hminor), 5.82 (d, J = 9.9 Hz, 1 Hmajor), 2.88–2.80 (m, 1 Hmajor, 1 Hminor), 2.10 (s, 3 Hmajor), 2.03 (s, 3 Hminor), 1.47 (s, 9 Hmajor), 1.29 (s, 9 Hminor), 1.19 (d, J = 7.0 Hz, 3 Hminor), 0.95 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 172.7, 171.9, 169.9, 169.5, 142.8, 142.2, 130.6 (q, 2 J C–F = 32.4 Hz), 130.4 (q, 2 J C–F = 32.4 Hz), 127.9 (2 C), 127.5 (2 C), 125.6 (q, 3 J C–F = 3.8 Hz, 2 C), 125.4 (q, 3 J C–F = 3.8 Hz, 2 C), 124.1 (q, 1 J C–F = 272 Hz), 124.0 (q, 1 J C–F = 272 Hz), 81.2, 81.1, 77.5, 75.9, 46.52, 46.49, 28.0 (3 C), 27.8 (3 C), 21.0, 20.9, 13.9, 12.9.
MS (CI): m/z (%) = 347 (4) [M + H]+.
HRMS: m/z [M + H]+ calcd for C17H22F3O4: 347.1470; found: 347.1472.
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tert-Butyl (2E)-2-Methyl-3-[4-(trifluoromethyl)phenyl]acrylate (8b)
Colorless crystals; yield: 2.03 g (97%, E/Z = 96:4); mp 67–69 °C (hexane–EtOAc).
IR (CHCl3): 2979, 2931, 1701, 1616, 1456, 1369, 1326, 1276, 1163, 1068 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.2 Hz, 2 H), 7.58 (br s, 1 H), 7.46 (d, J = 8.2 Hz, 2 H), 2.05 (d, J = 1.5 Hz, 3 H), 1.55 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 167.3, 139.8, 136.1, 132.4, 129.7 (q, 2 J C–F = 31.0 Hz), 129.6 (2 C), 125.2 (q, 3 J C–F = 3.8 Hz, 2 C), 124.0 (q, 1 J C–F = 272 Hz), 81.0, 28.1 (3 C), 14.5.
MS (EI, 70 eV): m/z (%) = 286 (11) [M+], 230 (100), 213 (18), 184 (25), 161 (23), 57 (19).
HRMS: m/z [M+] calcd for C15H17F3O2: 286.1180; found: 286.1183.
Anal. Calcd for C15H17F3O2: C, 62.93; H, 5.99. Found: C, 63.08; H, 5.80.
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tert-Butyl 3-Hydroxy-2-methyl-3-(4-nitrophenyl)propanoate (6c)
Pale-yellow oil; yield: 330 mg (71%, dr = 1.1:1).
IR (CHCl3): 3520, 2981, 1705, 1606, 1521, 1458, 1369, 1350, 1153 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 8.21 (br d, J = 9.0 Hz, 2 Hmajor), 8.20 (br d, J = 8.8 Hz, 2 Hminor), 7.54 (br d, J = 8.8 Hz, 2 Hminor), 7.53 (br d, J = 9.0 Hz, 2 Hmajor), 5.19 (br t, J = 2.6 Hz, 1 Hminor), 4.81 (br t, J = 6.1 Hz, 1 Hmajor), 3.71 (d, J = 6.1 Hz, 1 Hmajor), 3.58 (d, J = 2.6 Hz, 1 Hminor), 2.75–2.66 (m, 1 Hmajor, 1 Hminor), 1.45 (s, 9 Hmajor), 1.41 (s, 9 Hminor), 1.12 (d, J = 7.1 Hz, 3 Hminor), 1.04 (d, J = 7.3 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.2, 174.7, 149.4, 148.8, 147.4, 147.2, 127.4 (2 C), 126.9 (2 C), 123.5 (2 C), 123.4 (2 C), 81.9, 81.8, 75.2, 72.5, 47.2, 46.3, 27.94 (3 C), 27.91 (3 C), 14.6, 10.4.
MS (EI, 20 eV): m/z (%) = 281 (3) [M+], 225 (52), 208 (18), 164 (8), 151 (11), 130 (87), 74 (100), 57 (62).
HRMS: m/z [M+] calcd for C14H19NO5: 281.1263; found: 281.1269.
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tert-Butyl 3-(Acetyloxy)-2-methyl-3-(4-nitrophenyl)propanoate (7c)
Pale-yellow oil; yield: 320 mg (98%).
IR (CHCl3): 3018, 2981, 1732, 1608, 1525, 1458, 1369, 1350, 1234, 1153 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 8.22 (br d, J = 8.8 Hz, 2 Hmajor), 8.20 (br d, J = 8.8 Hz, 2 Hminor), 7.53 (br d, J = 8.8 Hz, 2 Hminor), 7.51 (br d, J = 8.8 Hz, 2 Hmajor), 6.04 (d, J = 7.3 Hz, 1 Hminor), 5.85 (d, J = 9.7 Hz, 1 Hmajor), 2.89–2.81 (m, 1 Hmajor, 1 Hminor), 2.12 (s, 3 Hminor), 2.05 (s, 3 Hmajor), 1.47 (s, 9 Hmajor), 1.32 (s, 9 Hminor), 1.20 (d, J = 7.1 Hz, 3 Hminor), 0.96 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 172.2, 171.5, 169.7, 169.4, 147.8, 147.6, 146.0, 145.3, 128.3 (2 C), 127.9 (2 C), 123.7 (2 C), 123.5 (2 C), 81.33, 81.25, 76.5, 75.4, 46.3, 46.2, 27.9 (3 C), 27.8 (3 C), 20.83, 20.77, 13.7, 12.8.
MS (EI, 20 eV): m/z (%) = 323 (39) [M+], 267 (100), 250 (42), 224 (64), 208 (60), 190 (34), 163 (29), 116 (37), 57 (61).
HRMS: m/z [M+] calcd for C16H21NO6: 323.1369; found: 323.1365.
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tert-Butyl (2E)-2-Methyl-3-(4-nitrophenyl)acrylate (8c)
Pale-yellow crystals; yield: 1.42 g (90%, E/Z = 94:6); mp 98–99 °C (hexane–EtOAc).
IR (CHCl3): 3026, 2981, 2933, 1701, 1639, 1596, 1346, 1276, 1166, 1124 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.25 (br d, J = 8.6 Hz, 2 H), 7.59 (br s, 1 H), 7.51 (br d, J = 8.6 Hz, 2 H), 2.07 (d, J = 1.6 Hz, 3 H), 1.56 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 166.9, 147.0, 142.8, 135.1, 133.7, 130.1 (2 C), 123.5 (2 C), 81.2, 28.0 (3 C), 14.2.
MS (EI, 70 eV): m/z (%) = 263 (20) [M+], 207 (100), 190 (55), 175 (4), 161 (16), 115 (25), 57 (85).
HRMS: m/z [M+] calcd for C14H17NO4: 263.1158; found: 263.1155.
Anal. Calcd for C14H17NO4: C, 63.87; H, 5.32. Found: C, 64.13; H, 5.36.
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tert-Butyl 3-Hydroxy-2-methyl-3-(4-tolyl)propanoate (6d)
Colorless oil; yield: 3.76 g (77%, dr = 1.5:1).
IR (CHCl3): 3502, 3008, 2981, 2937, 1716, 1514, 1458, 1369, 1153, 1014 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.23 (d, J = 8.1 Hz, 2 Hminor), 7.22 (d, J = 8.0 Hz, 2 Hmajor), 7.15 (d, J = 8.0 Hz, 2 Hmajor), 7.14 (d, J = 8.1 Hz, 2 Hminor), 4.98 (br d, J = 2.8 Hz, 1 Hminor), 4.66 (dd, J = 8.2, 4.1 Hz, 1 Hmajor), 3.09 (d, J = 4.1 Hz, 1 Hmajor), 3.05 (br d, J = 2.8 Hz, 1 Hminor), 2.72–2.62 (m, 1 Hmajor, 1 Hminor), 2.34 (s, 3 Hmajor), 2.33 (s, 3 Hminor), 1.45 (s, 9 Hmajor), 1.40 (s, 9 Hminor), 1.10 (d, J = 7.1 Hz, 3 Hminor), 0.99 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.4 (2 C), 138.8, 138.5, 137.5, 136.9, 129.0 (2 C), 128.8 (2 C), 126.6 (2 C), 126.0 (2 C), 81.05, 80.97, 76.2, 73.7, 47.8, 47.1, 28.0 (3 C), 27.9 (3 C), 21.09, 21.06, 14.6, 11.1.
MS (EI, 20 eV): m/z (%) = 250 (15) [M+], 194 (65), 177 (29), 121 (100), 57 (4).
HRMS: m/z [M+] calcd for C15H22O3: 250.1569; found: 250.1564.
#
tert-Butyl 3-(Acetyloxy)-2-methyl-3-(4-tolyl)propanoate (7d)
Colorless oil; yield: 4.14 g (95%).
IR (CHCl3): 3028, 2981, 1728, 1458, 1369, 1244, 1153, 1020 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.24 (br d, J = 8.1 Hz, 2 Hmajor), 7.21 (br d, J = 8.1 Hz, 2 Hminor), 7.15 (br d, J = 8.1 Hz, 2 Hmajor), 7.12 (br d, J = 8.1 Hz, 2 Hminor), 5.94 (d, J = 7.7 Hz, 1 Hminor), 5.74 (d, J = 10.3 Hz, 1 Hmajor), 2.88–2.79 (m, 1 Hmajor, 1 Hminor), 2.33 (s, 3 Hmajor), 2.32 (s, 3 Hminor), 2.06 (s, 3 Hminor), 1.99 (s, 3 Hmajor), 1.47 (s, 9 Hmajor), 1.29 (s, 9 Hminor), 1.18 (d, J = 7.0 Hz, 3 Hminor), 0.93 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 173.2, 172.2, 169.9, 169.5, 138.2, 137.8, 135.6, 135.0, 129.1 (2 C), 128.9 (2 C), 127.5 (2 C), 127.0 (2 C), 80.7, 77.6, 77.2, 76.4, 46.6 (2 C), 27.9 (3 C), 27.8 (3 C), 21.2, 21.13, 21.05, 21.02, 14.0, 13.0.
MS (EI, 20 eV): m/z (%) = 292 (2) [M+], 236 (100), 219 (4), 193 (37), 163 (17), 121 (5), 57 (0.3).
HRMS: m/z [M+] calcd for C17H24O4: 292.1675; found: 292.1681.
#
tert-Butyl (2E)-2-Methyl-3-(4-tolyl)acrylate (8d)
Colorless oil; yield: 3.05 g (94%, E/Z = 99:1).
IR (CHCl3): 2981, 2927, 1693, 1631, 1512, 1369, 1317, 1278, 1168, 1124 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.57 (br s, 1 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.19 (d, J = 8.0 Hz, 2 H), 2.36 (s, 3 H), 2.07 (d, J = 1.5 Hz, 3 H), 1.54 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 168.0, 138.1, 137.8, 133.3, 129.6 (2 C), 129.3, 129.0 (2 C), 80.4, 28.1 (3 C), 21.3, 14.1.
MS (EI, 70 eV): m/z (%) = 232 (15) [M+], 176 (100), 161 (27), 130 (41), 115 (18), 91 (12), 57 (10).
HRMS: m/z [M+] calcd for C15H20O2: 232.1463; found: 232.1465.
#
tert-Butyl 3-Hydroxy-3-(4-methoxyphenyl)-2-methylpropanoate (6e)
Colorless oil; yield: 3.89 g (75%, dr = 1.4:1).
IR (CHCl3): 3523, 3008, 2981, 2937, 1716, 1612, 1514, 1458, 1369, 1249, 1153, 1035 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.26 (d, J = 8.8 Hz, 2 Hminor), 7.25 (d, J = 8.6 Hz, 2 Hmajor), 6.88 (d, J = 8.6 Hz, 2 Hmajor), 6.87 (d, J = 8.8 Hz, 2 Hminor), 4.94 (br dd, J = 4.5, 2.1 Hz, 1 Hminor), 4.65 (dd, J = 8.2, 4.2 Hz, 1 Hmajor), 3.80 (s, 3 Hmajor), 3.79 (s, 3 Hminor), 3.10 (d, J = 4.2 Hz, 1 Hmajor), 3.00 (br d, J = 2.1 Hz, 1 Hminor), 2.71–2.62 (m, 1 Hmajor, 1 Hminor), 1.45 (s, 9 Hmajor), 1.39 (s, 9 Hminor), 1.11 (d, J = 7.1 Hz, 3 Hminor), 0.98 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.4, 175.3, 159.2, 158.9, 134.0, 133.8, 127.8 (2 C), 127.4 (2 C), 113.7 (2 C), 113.5 (2 C), 81.1, 80.9, 75.9, 73.6, 55.2 (2 C), 47.8, 47.2, 28.0 (3 C), 27.9 (3 C), 14.6, 11.4.
MS (EI, 20 eV): m/z (%) = 266 (19) [M+], 209 (18), 193 (14), 137 (100), 57 (2).
HRMS: m/z [M+] calcd for C15H22O4: 266.1518; found: 266.1522.
#
tert-Butyl 3-(Acetyloxy)-3-(4-methoxyphenyl)-2-methylpropanoate (7e)
Colorless crystals; yield: 221 mg (93%); mp 80–84 °C (hexane–EtOAc).
IR (CHCl3): 3041, 2985, 2970, 2937, 1728, 1612, 1514, 1458, 1369, 1263, 1176, 1153, 1024 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.28 (br dt, J = 8.8, 2.2 Hz, 2 Hmajor), 7.27 (br dt, J = 8.8, 1.9 Hz, 2 Hminor), 6.87 (br dt, J = 8.8, 2.2 Hz, 2 Hmajor), 6.85 (br dt, J = 8.8, 1.9 Hz, 2 Hminor), 5.88 (d, J = 8.1 Hz, 1 Hminor), 5.74 (d, J = 10.4 Hz, 1 Hmajor), 3.80 (s, 3 Hmajor), 3.79 (s, 3 Hminor), 2.87–2.81 (m, 1 Hmajor, 1 Hminor), 2.05 (s, 3 Hminor), 1.99 (s, 3 Hmajor), 1.47 (s, 9 Hmajor), 1.27 (s, 9 Hminor), 1.20 (d, J = 6.9 Hz, 3 Hminor), 0.92 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 173.2, 172.2, 170.0, 169.5, 159.6, 159.4, 130.8, 130.1, 128.8 (2 C), 128.5 (2 C), 113.8 (2 C), 113.6 (2 C), 80.6, 77.3 (2 C), 76.3, 55.2 (2 C), 46.65, 46.60, 27.9 (3 C), 27.7 (3 C), 21.1, 21.0, 14.0, 13.4.
MS (EI, 20 eV): m/z (%) = 308 (10) [M+], 252 (43), 248 (25), 192 (100), 179 (56), 148 (74), 137 (91), 57 (9).
HRMS: m/z [M+] calcd for C17H24O5: 308.1624; found: 308.1622.
Anal. Calcd for C17H24O5: C, 66.21; H, 7.84. Found: C, 66.45; H, 7.66.
#
tert-Butyl (2E)-3-(4-Methoxyphenyl)-2-methylacrylate (8e)
Colorless oil; yield: 160 mg (94%, E/Z = 98:2).
IR (CHCl3): 2981, 2936, 1693, 1606, 1510, 1369, 1276, 1164, 1122, 1033 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.55 (br d, J = 1.5 Hz, 1 H), 7.36 (br dt, J = 8.6, 1.7 Hz, 2 H), 6.92 (br dt, J = 8.6, 1.7 Hz, 2 H), 3.83 (s, 3 H), 2.08 (d, J = 1.5 Hz, 3 H), 1.54 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 168.2, 159.4, 137.4, 131.2 (2 C), 128.8, 128.0, 113.7 (2 C), 80.3, 55.3, 28.2 (3 C), 14.1.
MS (EI, 70 eV): m/z (%) = 248 (31) [M+], 192 (100), 175 (8), 147 (16), 57 (3).
HRMS: m/z [M+] calcd for C15H20O3: 248.1412; found: 248.1414.
#
Methyl 2-[Hydroxy(phenyl)methyl]butanoate (6f)
Colorless oil; yield: 199 mg (70%, dr = 1.2:1).
IR (CHCl3): 3508, 3028, 3010, 2937, 2877, 1728, 1494, 1456, 1436, 1363, 1296, 1197, 1170 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.38–7.24 (m, 5 Hmajor, 5 Hminor), 4.94 (br dd, J = 5.7, 1.6 Hz, 1 Hmajor), 4.79 (dd, J = 8.2, 4.8 Hz, 1 Hminor), 3.71 (s, 3 Hminor), 3.60 (s, 3 Hmajor), 2.88–2.82 (br s, 1 Hmajor, 1 Hminor), 2.72–2.63 (m, 1 Hmajor, 1 Hminor), 1.81–1.62 (m, 2 Hmajor), 1.65–1.50 (m, 1 Hminor), 1.40–1.29 (m, 1 Hminor), 0.87 (t, J = 7.5 Hz, 3 Hmajor), 0.84 (t, J = 7.3 Hz, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.7, 175.3, 142.0, 141.6, 128.5 (2 C), 128.3 (2 C), 128.0, 127.6, 126.4 (2 C), 126.1 (2 C), 75.3, 74.0, 54.7, 54.5, 51.7, 51.5, 22.7, 20.2, 12.0, 11.6.
MS (EI, 70 eV): m/z (%) = 208 (22) [M+], 107 (76), 102 (100), 87 (82), 79 (43).
HRMS: m/z [M+] calcd for C12H16O3: 208.1100; found: 208.1094.
#
Methyl 2-[(Acetyloxy)(phenyl)methyl]butanoate (7f)
Colorless oil; yield: 66.5 mg (96%).
IR (CHCl3): 3100, 2980, 1735, 1460, 1375, 1242, 1097 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.36–7.25 (m, 5 Hmajor, 5 Hminor), 5.94 (d, J = 8.6 Hz, 1 Hmajor), 5.82 (d, J = 10.4 Hz, 1 Hminor), 3.73 (s, 3 Hminor), 3.49 (s, 3 Hmajor), 2.88–2.82 (m, 1 Hmajor, 1 Hminor), 2.08 (s, 3 Hmajor), 1.99 (s, 3 Hminor), 1.80–1.68 (m, 2 Hmajor), 1.53–1.41 (m, 1 Hminor), 1.26–1.16 (m, 1 Hminor), 0.91 (t, J = 7.4 Hz, 3 Hmajor), 0.81 (t, J = 7.4 Hz, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 173.7, 172.8, 169.8, 169.5, 138.5, 138.1, 128.51 (2 C), 128.47, 128.3 (2 C), 128.2, 127.4 (2 C), 126.9 (2 C), 76.8, 75.7, 53.6, 53.0, 51.7, 51.5, 22.0, 21.9, 21.02, 20.96, 11.6, 11.4.
MS (EI, 20 eV): m/z (%) = 250 (10) [M+], 207 (76), 175 (13), 159 (14), 149 (46), 107 (100), 102 (60).
HRMS: m/z [M+] calcd for C14H18O4: 250.1205; found: 250.1208.
#
Methyl (2E)-2-Ethyl-3-phenylacrylate (8f)
Colorless oil; yield: 250 mg (97%, E/Z = >99:1).
IR (CHCl3): 3016, 1706, 1635, 1434, 1288, 1242, 1128 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.65 (s, 1 H), 7.41–7.31 (m, 5 H), 3.82 (s, 3 H), 2.55 (br q, J = 7.4 Hz, 2 H), 1.18 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.8, 138.6, 135.7, 134.7, 129.2 (2 C), 128.4 (2 C), 128.3, 51.9, 20.8, 13.8.
MS (EI, 70 eV): m/z (%) = 190 (81) [M+], 158 (44), 131 (100), 121 (20), 115 (58), 91 (55).
HRMS: m/z [M+] calcd for C12H14O2: 190.0994; found: 190.0991.
#
tert-Butyl 2-Benzyl-3-hydroxy-3-phenylpropanoate (6g)
Colorless oil; yield: 4.54 g (79%, dr = 1.1:1).
IR (CHCl3): 3489, 3030, 3010, 2981, 1712, 1602, 1494, 1454, 1369, 1151 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.42–7.10 (m, 10 Hmajor, 10 Hminor), 4.96 (br d, J = 2.5 Hz, 1 Hminor), 4.77 (dd, J = 7.2, 5.8 Hz, 1 Hmajor), 3.41 (d, J = 7.2 Hz, 1 Hmajor), 3.07 (br d, J = 2.5 Hz, 1 Hminor), 3.00–2.77 (m, 3 Hmajor, 3 Hminor), 1.17 (s, 9 Hmajor), 1.09 (s, 9 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 174.0, 173.5, 142.2, 141.4, 139.2, 138.5, 129.07 (2 C), 129.05 (2 C), 128.3 (2 C), 128.2 (3 C), 128.1 (2 C), 127.7, 127.6, 126.5 (2 C), 126.4 (2 C), 126.1 (3 C), 81.3, 81.0, 74.5, 74.4, 55.4, 54.9, 36.0, 33.6, 27.7 (3 C), 27.6 (3 C).
MS (EI, 20 eV): m/z (%) = 312 (4) [M+], 294 (8), 256 (27), 238 (73), 221 (17), 206 (26), 193 (41), 165 (70), 150 (100), 107 (44), 57 (13).
HRMS: m/z [M+] calcd for C20H24O3: 312.1726; found: 312.1733.
#
tert-Butyl 3-(Acetyloxy)-2-benzyl-3-phenylpropanoate (7g)
Colorless crystals; yield: 4.78 g (92%); mp 61–62 °C (hexane–EtOAc).
IR (CHCl3): 3030, 2981, 1733, 1602, 1496, 1456, 1369, 1240, 1151 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.45–7.03 (m, 10 Hmajor, 10 Hminor), 5.94 (d, J = 9.0 Hz, 1 Hminor), 5.87 (d, J = 10.1 Hz, 1 Hmajor), 3.17–3.08 (m, 1 Hmajor, 1 Hminor), 3.00 (dd, A part of AB, J AB = 13.6 Hz, J = 4.6 Hz, 1 Hminor), 2.96 (dd, B part of AB, J AB = 13.6 Hz, J = 10.3 Hz, 1 Hminor), 2.69 (dd, A part of AB, J AB = 13.6 Hz, J = 11.4 Hz, 1 Hmajor), 2.45 (dd, B part of AB, J AB = 13.6 Hz, J = 4.3 Hz, 1 Hmajor), 2.06 (s, 3 Hminor), 2.00 (s, 3 Hmajor), 1.27 (s, 9 Hmajor), 1.02 (s, 9 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 171.5, 170.7, 169.9, 169.4, 138.6, 138.1, 138.00, 137.97, 129.0 (2 C), 128.9 (2 C), 128.59 (2 C), 128.56, 128.3, 128.20 (2 C), 128.18 (2 C), 128.16 (2 C), 127.55 (2 C), 127.51 (2 C), 126.4, 126.3, 80.8, 80.7, 77.1, 76.5, 54.4, 54.2, 35.4, 35.1, 27.7 (3 C), 27.4 (3 C), 21.1, 20.9.
MS (EI, 20 eV): m/z (%) = 354 (0.1) [M+], 294 (14), 238 (39), 193 (100), 132 (7), 57 (22).
HRMS: m/z [M+] calcd for C22H26O4: 354.1831; found: 354.1838.
Anal. Calcd for C22H26O4: C, 74.55; H, 7.39. Found: C, 74.60; H, 7.46.
#
tert-Butyl (2E)-2-Benzyl-3-phenylacrylate (8g)
Colorless oil; yield: 3.73 g (94%, E/Z = 93:7).
IR (CHCl3): 3016, 1706, 1635, 1434, 1288, 1242, 1128 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.83 (s, 1 H), 7.38–7.24 (m, 7 H), 7.20–7.16 (m, 3 H), 3.89 (s, 2 H), 1.38 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 167.3, 139.9, 139.6, 135.7, 132.7, 129.0 (2 C), 128.5 (2 C), 128.4, 128.3 (2 C), 127.9 (2 C), 125.9, 80.7, 33.3, 27.9 (3 C).
MS (EI, 70 eV): m/z (%) = 190 (81) [M+], 158 (44), 131 (100), 121 (20), 115 (58), 91 (55).
HRMS: m/z [M+] calcd for C12H14O2: 190.0994; found: 190.0991.
#
Methyl 2-[Hydroxy(phenyl)methyl]-3-methylbutanoate (6h)
Pale-yellow oil; yield: 1.69 g (88%, dr = 4.7:1).
Spectral data for the synthesized 6h were identical to those reported in the literature.[20]
Methyl 2-[(Acetyloxy)(phenyl)methyl]-3-methylbutanoate (7h)
Yield: 1.02 g (98%).
#
Major Isomer
Colorless crystals; mp 47.0–47.4 °C (hexane–EtOAc).
IR (CHCl3): 3028, 2966, 1735, 1436, 1371, 1234, 1168, 1024 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.23 (m, 5 H), 5.99 (d, J = 10.6 Hz, 1 H), 3.41 (s, 3 H), 2.96 (dd, J = 10.6, 4.8 Hz, 1 H), 2.23–2.12 (m, 1 H), 2.03 (s, 3 H), 1.03 (d, J = 10.4 Hz, 3 H), 1.01 (d, J = 10.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.6, 169.8, 138.9, 128.30 (2 C), 128.29, 127.5 (2 C), 74.2, 57.2, 51.0, 27.5, 21.3, 21.0, 17.8.
MS (EI, 70 eV): m/z (%) = 264 (5) [M+], 221 (45), 116 (50), 107 (100), 101 (43), 91 (16), 77 (17).
HRMS: m/z [M+] calcd for C15H20O4: 264.1362; found: 264.1358.
Anal. Calcd for C15H20O4: C, 68.16; H, 7.63. Found: C, 68.26; H, 7.72.
#
Minor Isomer
Colorless oil.
IR (CHCl3): 3028, 1735, 1436, 1373, 1240, 1170, 1020 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.30 (m, 5 H), 6.00 (d, J = 10.4 Hz, 1 H), 3.70 (s, 3 H), 2.90 (dd, J = 10.4, 4.4 Hz, 1 H), 1.98 (s, 3 H), 1.63–1.50 (m, 1 H), 0.91 (d, J = 6.8 Hz, 3 H), 0.89 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 172.5, 169.7, 138.2, 128.6 (2 C), 128.5, 127.5 (2 C), 75.4, 56.8, 51.3, 26.9, 21.6, 20.9, 17.7.
MS (EI, 70 eV): m/z (%) = 264 (5) [M+], 221 (48), 149, (45), 116 (62), 107 (100), 101 (49), 91 (18), 77 (17).
HRMS: m/z [M+] calcd for C15H20O4: 264.1362; found: 264.1358.
#
Methyl (2E)-2-Isopropyl-3-phenylacrylate (8h)
Colorless oil; yield: 164 mg (88%, E/Z = 84:16).
IR (CHCl3): 3028, 2962, 1708, 1492, 1434, 1247, 1139, 1033 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.55 (s, 1 H), 7.41–7.36 (m, 2 H), 7.33–7.29 (m, 3 H), 3.80 (s, 3 H), 3.15 (sept, J = 7.0 Hz, 1 H), 1.24 (d, J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 168.4, 139.1, 138.0, 136.1, 128.9 (2 C), 128.4 (2 C), 128.0, 51.4, 27.5, 21.1 (2 C).
MS (EI, 70 eV): m/z (%) = 204 (27) [M+], 145 (100), 129 (37), 91 (21), 77 (8).
HRMS: m/z [M+] calcd for C13H16O2: 204.1150; found: 204.1148.
#
Methyl 3-Hydroxy-2,3-diphenylpropanoate (6i)
Colorless crystals; yield: 1.40 g (71%, dr = 2.6:1).
Spectral data for the synthesized 6i were identical to those reported in the literature.[21]
#
Methyl 3-(Acetyloxy)-2,3-diphenylpropanoate (7i)
Yield: 1.05 g (98%).
#
Major Isomer
Colorless crystals; mp 103–105 °C (hexane–EtOAc).
IR (CHCl3): 3031, 1739, 1497, 1456, 1435, 1373, 1271, 1230, 1205, 1165, 1022 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.17–7.08 (m, 10 H), 6.25 (d, J = 11.0 Hz, 1 H), 4.06 (d, J = 11.0 Hz, 1 H), 3.74 (s, 3 H), 2.05 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.8, 169.4, 137.4, 133.7, 128.7 (br s, 2C), 128.5 (br), 128.0 (br s, 4C), 127.2 (br s, 3C), 77.1, 57.6, 52.2, 21.0.
MS (EI, 20 eV): m/z (%) = 298 (0.8) [M+], 239 (3), 192 (100), 150 (89), 118 (19), 107 (18), 77 (2).
HRMS: m/z [M+] calcd for C18H18O4: 298.1205; found: 298.1211.
Anal. Calcd for C18H18O4: C, 72.47; H, 6.08. Found: C, 72.31; H, 5.84.
#
Minor Isomer
Colorless crystals; mp 136–137 °C (hexane–EtOAc).
IR (CHCl3): 3089, 3066, 3031, 3012, 2952, 1739, 1603, 1587, 1496, 1456, 1434, 1371, 1236, 1197, 1163, 1024 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 7.6 Hz, 4 H), 7.36–7.30 (m, 6 H), 6.41 (d, J = 10.2 Hz, 1 H), 4.11 (d, J = 10.2 Hz, 1 H), 3.49 (s, 3 H), 1.78 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.0, 169.4, 138.2, 135.0, 128.4 (br s, 5 C), 127.8 (br s, 3 C), 127.4 (br s, 2 C), 75.4, 57.8, 52.0, 20.7.
MS (EI, 20 eV): m/z (%) = 298 (0.4) [M+], 192 (100), 150 (80), 118 (14), 107 (13), 90 (2), 77 (1).
HRMS: m/z [M+] calcd for C18H18O4: 298.1205; found: 298.1203.
Anal. Calcd for C18H18O4: C, 72.47; H, 6.08. Found: C, 72.34; H, 5.90.
#
Methyl (2E)-2,3-Diphenylacrylate (8i)
Colorless crystals; yield: 180 mg (99%, E/Z = 86:14); mp 76–77 °C (hexane–EtOAc).
IR (CHCl3): 3014, 2953, 1708, 1624, 1493, 1448, 1435, 1257, 1193, 1168 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.86 (s, 1 H), 7.38–7.36 (m, 3 H), 7.23–7.13 (m, 5 H), 7.04 (br d, J = 7.2 Hz, 2 H), 3.80 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.4, 140.6, 135.9, 134.6, 132.4, 130.6 (2 C), 129.7 (2 C), 129.1, 128.7 (2 C), 128.2 (2 C), 127.8, 52.3.
MS (EI, 70 eV): m/z (%) = 238 (100) [M+], 205 (13), 179 (90), 152 (13), 121 (68), 77 (7).
HRMS: m/z [M+] calcd for C16H14O2: 238.0994; found: 238.0998.
Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found: C, 80.40; H, 5.71.
#
tert-Butyl 3-(2-Furyl)-3-hydroxy-2-methylpropanoate (6j)
Pale-yellow oil; yield: 289 mg (82%, dr = 1.2:1).
IR (CHCl3): 3510, 3015, 2982, 2937, 2881, 1722, 1458, 1369, 1251, 1224, 1151, 1010 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.38–7.35 (m, 1 Hmajor, 1 Hminor), 6.34 (d, J = 2.0 Hz, 1 Hminor), 6.33 (d, J = 2.0 Hz, 1 Hmajor), 6.28 (br d, J = 3.2 Hz, 1 Hmajor, 1 Hminor), 4.94 (t, J = 5.2 Hz, 1 Hminor), 4.72 (t, J = 7.3 Hz, 1 Hmajor), 3.31 (br d, J = 7.3 Hz, 1 Hmajor), 3.12 (br d, J = 5.2 Hz, 1 Hminor), 2.91 (quint, J = 7.3 Hz, 1 Hmajor), 2.87 (dq, J = 7.2, 5.2 Hz, 1 Hminor), 1.46 (s, 9 Hmajor), 1.43 (s, 9 Hminor), 1.18 (t, J = 7.3 Hz, 3 Hmajor), 1.11 (t, J = 7.2 Hz, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 174.8, 174.1, 154.5 (2 C), 142.0, 141.6, 110.0 (2 C), 107.1, 106.6, 81.1, 81.0, 69.7, 68.8, 45.1, 44.9, 27.84 (3 C), 27.78 (3 C), 14.1, 12.1.
MS (EI, 20 eV): m/z (%) = 226 (3) [M+], 170 (53), 153 (13), 97 (100), 57 (6).
HRMS: m/z [M+] calcd for C12H18O4: 226.1205; found: 226.1200.
#
tert-Butyl 3-(Acetyloxy)-3-(2-furyl)-2-methylpropanoate (7j)
Pale-yellow oil; yield: 254 mg (97%).
IR (CHCl3): 3018, 2981, 2937, 1730, 1458, 1369, 1236, 1153, 1012 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.39–7.37 (br m, 1 Hmajor, 1 Hminor), 6.41 (br dd, J = 3.2, 0.4 Hz, 1 Hmajor), 6.34–6.32 (br m, 1 Hmajor, 2 Hminor), 6.04 (d, J = 8.4 Hz, 1 Hminor), 5.94 (d, J = 10.4 Hz, 1 Hmajor), 3.12 (dq, J = 10.4, 7.2 Hz, 1 Hmajor), 3.04 (dq, J = 8.4, 6.8 Hz, 1 Hminor), 2.08 (s, 3 Hminor), 2.01 (s, 3 Hmajor), 1.45 (s, 9 Hmajor), 1.34 (s, 9 Hminor), 1.24 (d, J = 6.8 Hz, 3 Hminor), 1.00 (d, J = 7.2 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 172.5, 171.8, 169.8, 169.4, 151.2, 150.2, 142.7, 142.3, 110.3, 110.2, 110.1, 108.7, 80.8, 80.7, 69.9, 69.3, 43.8 (2 C), 27.8 (3 C), 27.7 (3 C), 20.79, 20.77, 13.7, 13.3.
MS (EI, 20 eV): m/z (%) = 268 (0.5) [M+], 212 (100), 169 (93), 151 (33), 139 (14), 124 (35), 57 (10).
HRMS: m/z [M+] calcd for C14H20O5: 268.1311; found: 268.1306.
#
tert-Butyl (2E)-3-(2-Furyl)-2-methylacrylate (8j)
Colorless oil; yield: 1.79 g (95%); E/Z = 99:1.
IR (CHCl3): 3045, 2983, 1693, 1602, 1521, 1456, 1369, 1284, 1164, 1122 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.51 (d, J = 1.6 Hz, 1 H), 7.36 (d, J = 1.0 Hz, 1 H), 6.57 (d, J = 3.4 Hz, 1 H), 6.48 (dd, J = 3.4, 1.6 Hz, 1 H), 2.17 (d, J = 1.0 Hz, 3 H), 1.53 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 167.7, 152.1, 143.6, 126.7, 124.9, 114.1, 111.9, 80.4, 28.1 (3 C), 14.1.
MS (EI, 70 eV): m/z (%) = 208 (18) [M+], 152 (100), 135 (15), 124 (12), 107 (14), 57 (13), 56 (41).
HRMS: m/z [M+] calcd for C12H16O3: 208.1099; found: 208.1097.
#
tert-Butyl 3-Hydroxy-2-methyl-3-(2-thienyl)propanoate (6k)
Pale-yellow oil; yield: 171 mg (80%, dr = 1.4:1).
IR (CHCl3): 3528, 2983, 2937, 1716, 1521, 1458, 1369, 1153, 3030, 3010, 2981, 1712, 1602, 1494, 1454, 1369, 1151 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.26 (dd, J = 4.8, 1.4 Hz, 1 Hmajor), 7.23 (dd, J = 4.6, 1.7 Hz, 1 Hminor), 6.98–6.94 (m, 2 Hmajor, 2 Hminor), 5.22 (br t, J = 3.8 Hz, 1 Hminor), 4.96 (dd, J = 7.2, 5.4 Hz, 1 Hmajor), 3.84 (d, J = 5.4 Hz, 1 Hmajor), 3.26 (d, J = 3.8 Hz, 1 Hminor), 2.77 (quin, J = 7.2 Hz, 1 Hmajor), 2.76 (dq, J = 7.1, 4.7 Hz, 1 Hminor), 1.44 (s, 9 Hmajor), 1.41 (s, 9 Hminor), 1.21 (d, J = 7.2 Hz, 3 Hmajor), 1.12 (d, J = 7.1 Hz, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 174.9, 174.7, 146.0, 145.4, 126.6, 126.5, 125.0, 124.6, 124.4, 123.8, 81.5, 81.4, 72.3, 70.9, 47.9, 47.4, 28.0 (3 C), 27.9 (3 C), 14.7, 11.7.
MS (EI, 70 eV): m/z (%) = 242 (2) [M+], 186 (29), 169 (13), 124 (100), 113 (80), 97 (30), 91 (11), 57 (32), 56 (86).
HRMS: m/z [M+] calcd for C12H18O3S: 242.0976; found: 242.0980.
#
tert-Butyl 3-(Acetyloxy)-2-methyl-3-(2-thienyl)propanoate (7k)
Pale-yellow oil; yield: 151 mg (95%).
IR (CHCl3): 2981, 1728, 1369, 1236, 1153, 1020 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.29 (br d, J = 5.0 Hz, 1 Hmajor), 7.25 (dd, J = 5.1, 1.3 Hz, 1 Hminor), 7.10 (br dd, J = 3.6, 1.1 Hz, 1 Hmajor), 7.05 (br d, J = 3.6 Hz, 1 Hminor), 6.96 (dd, J = 5.0, 3.6 Hz, 1 Hmajor), 6.94 (dd, J = 5.1, 3.6 Hz, 1 Hminor), 6.23 (d, J = 8.2 Hz, 1 Hminor), 6.13 (d, J = 10.3 Hz, 1 Hmajor), 2.96–2.87 (m, 1 Hmajor, 1 Hminor), 2.07 (s, 3 Hmajor), 2.00 (s, 3 Hminor), 1.46 (s, 9 Hmajor), 1.31 (s, 9 Hminor), 1.25 (d, J = 6.9 Hz, 3 Hminor), 1.04 (d, J = 7.1 Hz, 3 Hmajor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 172.5, 171.9, 169.8, 169.3, 141.4, 140.6, 127.3, 126.5, 126.4, 126.2, 125.9, 125.3, 80.92, 80.87, 72.7, 71.9, 47.11, 47.06, 27.9 (3 C), 27.7 (3 C), 20.93, 20.91, 14.1, 13.6.
MS (EI, 20 eV): m/z (%) = 284 (1) [M+], 228 (100), 211 (9), 185 (85), 167 (21), 151 (28), 140 (13), 113 (29), 57 (9).
HRMS: m/z [M+] calcd for C14H20O4S: 284.1082; found: 284.1079.
#
tert-Butyl (2E)-2-Methyl-3-(2-thienyl)acrylate (8k)
Pale-yellow oil; yield: 109 mg (97%, E/Z = 99:1).
IR (CHCl3): 2976, 2895, 2399, 1693, 1477, 1423, 1242, 1045 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.76 (br s, 1 H), 7.46 (d, J = 5.1 Hz, 1 H), 7.25 (br d, J = 3.7 Hz, 1 H), 7.10 (dd, J = 5.1, 3.7 Hz, 1 H), 2.17 (d, J = 1.3 Hz, 3 H), 1.54 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 167.7, 139.5, 131.2, 130.6, 128.6, 127.2, 126.7, 80.5, 28.1 (3 C), 14.3.
MS (EI, 70 eV): m/z (%) = 224 (15) [M+], 168 (100), 151 (25), 123 (47), 97 (10).
HRMS: m/z [M+] calcd for C12H16O2S: 224.0871; found: 224.0869.
#
tert-Butyl 3-Hydroxy-2-methyl-3-(1-methyl-1H-indol-3-yl)propanoate (6l)
Pale-yellow oil; yield: 376 mg (83%, dr = 1.3:1).
IR (CHCl3): 3502, 3006, 2979, 2935, 1716, 1616, 1550, 1475, 1367, 1325, 1272, 1155 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 7.77 (br d, J = 8.0 Hz, 1 Hminor), 7.65 (br d, J = 8.0 Hz, 1 Hmajor), 7.32–7.20 (m, 2 Hmajor, 2 Hminor), 7.15–7.09 (m, 1 Hmajor, 1 Hminor), 7.08 (s, 1 Hmajor), 7.04 (s, 1 Hminor), 5.84 (br d, J = 3.2 Hz, 1 Hmajor), 5.03 (dd, J = 8.6, 3.4 Hz, 1 Hminor), 3.76 (s, 3 Hmajor, 3 Hminor), 3.06–2.88 (m, 2 Hmajor, 2 Hminor), 1.48 (s, 9 Hminor), 1.36 (s, 9 Hmajor), 1.21 (d, J = 7.2 Hz, 3 Hmajor), 1.05 (d, J = 7.2 Hz, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.7, 175.4, 137.1, 136.9, 126.9, 126.6, 126.2, 126.0, 121.7, 121.6, 119.8, 119.3, 119.2, 119.0, 115.43, 115.37, 109.3, 109.2, 80.8, 80.6, 70.4, 68.8, 47.1, 46.3, 32.3 (2 C), 28.0 (3 C), 27.8 (3 C), 15.0, 11.9.
MS (EI, 20 eV): m/z (%) = 289 (44) [M+], 271 (12), 215 (12), 160 (100).
HRMS: m/z [M+] calcd for C17H23NO3: 289.1678; found: 289.1676.
#
tert-Butyl (2E)-2-Methyl-3-(1-methyl-1H-indol-3-yl)acrylate (8l)
Pale-yellow crystals; yield: 2.20 g (74%, E/Z = >99:1); mp 80–82 °C (hexane–EtOAc).
IR (CHCl3): 3041, 2979, 1685, 1622, 1529, 1475, 1367, 1323, 1272, 1170, 1112 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96 (br s, 1 H), 7.79 (br d, J = 7.8 Hz, 1 H), 7.35–7.19 (m, 4 H), 3.84 (s, 3 H), 2.14 (d, J = 1.1 Hz, 3 H), 1.57 (s. 9 H).
13C NMR (100 MHz, CDCl3): δ = 168.4, 136.4, 129.9, 129.0, 128.4, 123.8, 122.6, 120.3, 119.0, 111.9, 109.4, 79.9, 33.2, 28.3 (3 C), 15.1.
MS (EI, 70 eV): m/z (%) = 271 (70) [M+], 215 (100), 198 (15), 170 (27), 144 (40).
HRMS: m/z [M+] calcd for C17H21NO2: 271.1572; found: 271.1569.
Anal. Calcd for C17H21NO2: C, 75.25; H, 7.80; N, 5.16. Found: C, 75.20; H, 7.85; N, 5.12.
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tert-Butyl 3-Hydroxy-2-methylnonanoate (6m)
Colorless oil; yield: 815 mg (80%, dr = 1.6:1).
IR (CHCl3): 3517, 2931, 2858, 1706, 1458, 1369, 1153 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 3.83 (br s, 1 Hmajor), 3.59 (br s, 1 Hminor), 2.70 (br s, 1 Hminor), 2.65 (br s, 1 Hmajor), 2.45–2.38 (m, 1 Hmajor, 1 Hminor), 1.62–1.20 (m, 10 Hmajor, 10 Hminor), 1.47 (s, 9 Hmajor, 9 Hminor), 1.18 (d, J = 7.1 Hz, 3 Hminor), 1.14 (d, J = 7.1 Hz, 3 Hmajor), 0.88 (t, J = 6.8 Hz, 3 Hmajor, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 175.8, 175.6, 80.9, 80.8, 73.4, 71.8, 45.7, 44.9, 34.8, 33.7 (2 C), 31.7, 29.2 (2 C), 28.02 (3 C), 28.00 (3 C), 25.9, 25.5, 22.6 (2 C), 14.4, 14.0 (2 C), 10.8.
MS (CI): m/z (%) = 245 (72) [M + H]+.
HRMS: m/z [M + H]+ calcd for C14H29O3: 245.2117; found: 245.2119.
#
tert-Butyl 3-(Acetyloxy)-2-methylnonanoate (7m)
Colorless oil; yield: 264 mg (99%).
IR (CHCl3): 3028, 2956, 2931, 2860, 1728, 1458, 1369, 1249, 1157 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 5.14 (dt, J = 7.1, 5.5 Hz, 1 Hmajor), 5.09 (dt, J = 7.1, 4.3 Hz, 1 Hminor), 2.64 (quin, J = 7.1 Hz, 1 Hminor), 2.55 (dq, J = 7.1, 5.5 Hz, 1 Hmajor), 2.04 (s, 3 Hmajor), 2.03 (s, 3 Hminor), 1.61–1.20 (m, 10 Hmajor, 10 Hminor), 1.44 (s, 9 Hmajor, 9 Hminor), 1.11 (d, J = 7.1 Hz, 3 Hmajor), 1.10 (d, J = 7.1 Hz, 3 Hminor), 0.88 (t, J = 7.1 Hz, 3 Hmajor, 3 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 173.0, 172.9, 170.5, 170.3, 80.6, 80.5, 74.8, 74.4, 44.2, 44.0, 31.9, 31.6 (2 C), 31.0, 29.1, 29.0, 27.9 (6 C), 25.3, 24.9, 22.5 (2 C), 21.05, 20.99, 14.0 (2 C), 12.8, 11.8.
MS (CI): m/z (%) = 287 (20) [M + H]+.
HRMS: m/z [M + H]+ calcd for C16H31O4: 287.2222; found: 287.2226.
#
tert-Butyl (2E)-2-Methylnon-2-enoate (8m)
Colorless oil; yield: 107 mg (82%, E/Z = 92:8).
IR (CHCl3): 3028, 2929, 2858, 1697, 1647, 1456, 1369, 1284, 1255, 1145, 1101 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.66 (tq, J = 7.4, 1.1 Hz, 1 H), 2.13 (br qq, J = 7.4, 1.1 Hz, 2 H), 1.78 (br q, J = 1.1 Hz, 3 H), 1.54–1.24 (m, 8 H), 1.48 (s, 9 H), 0.89 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.7, 141.4, 129.0, 79.9, 31.7, 29.1, 28.7, 28.6, 28.1 (3 C), 22.6, 14.1, 12.3.
MS (EI, 70 eV): m/z (%) = 226 (1.4) [M+], 171 (77), 153 (41), 97 (26), 57 (100).
HRMS: m/z [M+] calcd for C14H26O2: 226.1933; found: 226.1941.
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tert-Butyl 3-Cyclohexyl-3-hydroxy-2-methylpropanoate (6n)
Yield: 201 mg (75%, dr = 2.0:1).
#
Major Isomer
Colorless oil.
IR (CHCl3): 3550, 3026, 2929, 1705, 1521, 1450, 1369, 1153 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.29 (dt, J = 7.9, 5.7 Hz, 1 H), 2.70 (d, J = 7.9 Hz, 1 H), 2.57 (dt, J = 7.1, 5.7 Hz, 1 H), 1.86–1.63 (m, 6 H), 1.46 (s, 9 H), 1.42–1.30 (m, 1 H), 1.26–1.00 (m, 4 H), 1.20 (d, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 176.0, 80.9, 77.9, 42.4, 41.6, 29.9, 28.0 (3 C), 27.5, 26.38, 26.34, 26.1, 15.0.
MS (CI): m/z (%) = 243 (3) [M + H]+.
HRMS: m/z [M + H]+ calcd for C14H27O3: 243.1960; found: 243.1966.
#
Minor Isomer
Colorless oil.
IR (CHCl3): 3560, 3006, 2929, 2854, 1705, 1450, 1369, 1155 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.57 (dd, J = 8.1, 3.5 Hz, 1 H), 2.66 (br s, 1 H), 2.54 (dq, J = 7.1, 3.5 Hz, 1 H), 2.10–2.04 (m, 1 H), 1.80–1.51 (m, 4 H), 1.46 (s, 9 H), 1.41–1.08 (m, 4 H), 1.13 (d, J = 7.1 Hz, 3 H), 1.03–0.93 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 176.3, 80.8, 75.7, 41.9, 40.4, 29.03, 28.98, 28.0 (3 C), 26.3, 26.1, 25.9, 10.2.
MS (CI): m/z (%) = 243 (19) [M + H]+.
HRMS: m/z [M + H]+ calcd for C14H27O3: 243.1960; found: 243.1957.
tert-Butyl 3-(Acetyloxy)-3-cyclohexyl-2-methylpropanoate (7n)
Yield: 401 mg (97%).
#
Major Isomer
Colorless crystals; mp 59–60 °C (hexane–EtOAc).
IR (CHCl3): 3022, 2931, 2856, 1728, 1450, 1369, 1253, 1153 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.96 (dd, J = 7.2, 5.3 Hz, 1 H), 2.70 (quin, J = 7.2 Hz, 1 H), 2.04 (s, 3 H), 1.76–1.56 (m, 6 H), 1.43 (s, 9 H), 1.27–0.93 (m, 5 H), 1.10 (d, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 173.0, 170.4, 80.4, 78.3, 42.3, 39.0, 29.9, 27.9 (3 C), 26.9, 26.23, 26.16, 26.0, 20.9, 13.9.
MS (FAB) m/z (%) = 285 (M++H, 23).
HRMS: m/z [M + H]+ calcd for C16H29O4: 285.2066; found: 285.2071.
#
Minor Isomer
Colorless oil.
IR (CHCl3): 2981, 2931, 2854, 1728, 1456, 1369, 1247, 1149 cm–1.
1H NMR (400 MHz, CDCl3): δ = 5.08 (dd, J = 7.1, 5.5 Hz, 1 H), 2.65 (dq, J = 7.0, 5.5 Hz, 1 H), 2.04 (s, 3 H), 1.76–1.43 (m, 6 H), 1.42 (s, 9 H), 1.27–0.98 (m, 5 H), 1.09 (d, J = 7.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 173.3, 170.4, 80.6, 77.5, 41.7, 39.7, 29.4, 28.0, 27.9 (3 C), 26.2, 26.0, 25.9, 20.9, 11.3.
MS (CI): m/z (%) = 285 (33) [M + H]+.
HRMS: m/z [M + H]+ calcd for C16H29O4: 285.2066; found: 285.2062.
#
tert-Butyl (2E)-3-Cyclohexyl-2-methylacrylate (8n)
Colorless oil; yield: 109 mg (79%); E/Z = 95:5.
IR (CHCl3): 3053, 2976, 2929, 2852, 1693, 1645, 1521, 1448, 1392, 1367, 1301, 1278, 1147, 1101 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.48 (dq, J = 9.5, 1.5 Hz, 1 H), 2.32–2.24 (m, 1 H), 1.79 (d, J = 1.5 Hz, 3 H), 1.78–1.61 (m, 5 H), 1.48 (s, 9 H), 1.32–1.12 (m, 5 H).
13C NMR (100 MHz, CDCl3): δ = 168.0, 146.2, 127.2, 79.8, 37.7, 32.0 (2 C), 28.1 (3 C), 25.9, 25.7 (2 C), 12.4.
MS (EI, 20 eV): m/z (%) = 224 (0.4) [M+], 168 (100), 150 (26), 87 (98), 57 (27), 56 (33).
HRMS: m/z [M+] calcd for C14H24O2: 224.1776; found: 224.1781.
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tert-Butyl 3-Hydroxy-2,4,4-trimethylpentanoate (6o)
Yield: 1.13 g (68%, dr = 1.1:1).
#
Major Isomer
Colorless oil.
IR (CHCl3): 3462, 2979, 2937, 2873, 1701, 1479, 1458, 1369, 1251, 1151, 1055 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.60 (t, J = 4.1 Hz, 1 H), 2.59 (dq, J = 7.1, 4.1 Hz, 1 H), 2.30 (d, J = 4.1 Hz, 1 H), 1.45 (s, 9 H), 1.20 (d, J = 7.1 Hz, 3 H), 0.95 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 176.7, 80.5, 78.0, 41.9, 35.5, 28.0 (3 C), 26.6 (3 C), 12.9.
MS (CI): m/z (%) = 217 (4.7) [M + H]+.
HRMS: m/z [M + H]+ calcd for C12H25O3: 217.1804; found: 217.1801.
#
Minor Isomer
Colorless oil.
IR (CHCl3): 3520, 3028, 2977, 2908, 2873, 1716, 1674, 1458, 1369, 1251, 1151 cm–1.
1H NMR (400 MHz, CDCl3): δ = 4.03 (d, J = 9.3 Hz, 1 H), 3.13 (dd, J = 9.3, 1.8 Hz, 1 H), 2.60 (dq, J = 7.1, 1.8 Hz, 1 H), 1.46 (s, 9 H), 1.34 (d, J = 7.1 Hz, 3 H), 0.91 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 177.3, 82.8, 81.3, 38.8, 36.1, 27.9 (3 C), 26.3 (3 C), 18.4.
MS (CI): m/z (%) = 217 (3.7) [M + H]+.
HRMS: m/z [M + H]+ calcd for C12H25O3: 217.1804; found: 217.1810.
#
tert-Butyl 3-(Acetyloxy)-2,4,4-trimethylpentanoate (7o)
Colorless oil; yield: 329 mg (88%).
IR (CHCl3): 3026, 2976, 2939, 2873, 1728, 1458, 1369, 1247, 1151, 1022 cm–1.
1H NMR (400 MHz, CDCl3): δ (mixture of diastereomers) = 5.05 (d, J = 6.4 Hz, 1 Hminor), 4.74 (d, J = 4.8 Hz, 1 Hmajor), 2.75 (dq, J = 7.1, 4.8 Hz, 1 Hmajor), 2.63 (dq, J = 7.1, 6.4 Hz, 1 Hminor), 2.08 (s, 3 Hminor), 2.06 (s, 3 Hmajor), 1.45 (s, 9 Hminor), 1.44 (s, 9 Hmajor), 1.19 (d, J = 7.1 Hz, 3 Hmajor), 1.07 (d, J = 7.1 Hz, 3 Hminor), 0.95 (s, 9 Hmajor), 0.93 (s, 9 Hminor).
13C NMR (100 MHz, CDCl3): δ (mixture of diastereomers) = 174.3, 173.0, 170.51, 170.48, 81.6, 80.5, 80.2, 79.4, 42.0, 41.0, 35.4 (2), 27.94 (3 C), 27.87 (3 C), 26.3 (3 C), 26.2 (3 C), 20.9, 20.7, 17.4, 13.8.
MS (CI): m/z (%) = 259 (1.9) [M + H]+.
HRMS: m/z [M + H]+ calcd for C14H27O4: 259.1909; found: 259.1911.
#
tert-Butyl (2E)-2,4,4-Trimethylpent-2-enoate (8o)
Colorless oil; yield: 319 mg (63%, E/Z = >99:1).
IR (CHCl3): 2964, 2935, 2869, 1693, 1639, 1475, 1458, 1392, 1367, 1296, 1253, 1164, 1116, 1014 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.70 (q, J = 1.4 Hz, 1 H), 1.90 (d, J = 1.4 Hz, 3 H), 1.48 (s, 9 H), 1.17 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 168.6, 150.1, 128.0, 80.0, 32.7, 30.1 (3 C), 28.1 (3 C), 13.3.
MS (CI)” m/z (%) = 199 (0.3) [M + H]+.
HRMS: m/z [M + H]+ calcd for C12H23O2: 199.1698; found: 199.1693.
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#
Acknowledgment
This research was financially supported in part by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, a Grant-in-Aid for Scientific Research (C) (22590024) from the Japan Society for the Promotion of Science (JSPS).
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0034-1378786.
- Supporting Information
-
References
- 1a Davies SG, Ichihara O, Walters AS. J. Chem. Soc., Perkin Trans. 1 1994; 1141
- 1b Villa M.-J, Warren S. J. Chem. Soc., Perkin Trans. 1 1994; 1569
- 1c Sturm T, Weissensteiner E, Spindler F. Adv. Synth. Catal. 2003; 345: 160
- 1d Huang J, Corey EJ. Org. Lett. 2003; 5: 3455
- 1e Langenhan JM, Gellman SH. J. Org. Chem. 2003; 68: 6440
- 2a Watanabe T, Hayashi K, Yoshimatsu S, Sakai K, Takeyama S, Takashima K. J. Med. Chem. 1980; 23: 50
- 2b D’Auria MA, Minale L, Riccio R. Chem. Rev. 1993; 93: 1839
- 2c Senokuchi K, Nakai H, Nakayama Y, Odagaki Y, Sakaki K, Kato M, Maruyama T, Miyazaki T, Ito H, Kamiyasu K, Kim S, Kawamura M, Hamanaka N. J. Med. Chem. 1995; 38: 2521
- 2d Senokuchi K, Nakai H, Nakayama Y, Odagaki Y, Sakaki K, Kato M, Maruyama T, Miyazaki T, Ito H, Kamiyasu K, Kim S, Kawamura M, Hamanaka N. J. Med. Chem. 1995; 38: 4508
- 2e Franklin AS. J. Chem. Soc., Perkin Trans. 1 1999; 3537
- 2f Basavaiah D, Krishnamacharyulu M, Hyma RS, Sarma PK. S, Kumaragurabaran N. J. Org. Chem. 1999; 64: 1197
- 3 Marfat A, McGuirk PR, Helquist P. J. Org. Chem. 1979; 44: 3888
- 4a Mouloungui Z, Elmestour R, Delmas M, Gaset A. Tetrahedron 1992; 48: 1219
- 4b Kojima S, Takagi R, Akiba K. J. Am. Chem. Soc. 1997; 119: 5970
- 4c Ando K. J. Org. Chem. 1997; 62: 1934
- 4d Sano S, Yokoyama K, Fukushima M, Yagi T, Nagao Y. Chem. Commun. 1997; 559
- 5 Kowalski CJ, Sakdarat S. J. Org. Chem. 1990; 55: 1977
- 6 Shindo M, Sato Y, Shishido K. Tetrahedron Lett. 1998; 39: 4857
- 7 Kisanga P, D’Sa B, Verkade J. Tetrahedron 2001; 57: 8047
- 8 Li S, Yuan W, Ma S. Angew. Chem. Int. Ed. 2011; 50: 2578
- 9 Sai H, Ohmizu H. Tetrahedron Lett. 1999; 40: 5019
- 10 Concellón JM, Pérez-Andrés JA, Rodrígues-Solla H. Angew. Chem. Int. Ed. 2000; 39: 2773
- 11 Bartoli G, Bellucci MC, Petrini M, Marcantoni E, Sambri L, Torregiani E. Org. Lett. 2000; 2: 1791
- 12a Feuillet FJ. P, Robinson DE. J. E, Bull SD. Chem. Commun. 2003; 2184
- 12b Feuillet FJ. P, Cheeseman M, Mahon MF, Bull SD. Org. Biomol. Chem. 2005; 3: 2976
- 13 Basavaiah D, Sarma PK. S, Bhavani AK. D. J. Chem. Soc., Chem. Commun. 1994; 1091
- 14 Ravichandran S. Synth. Commun. 2001; 31: 2055
- 15 Fernades L, Bortoluzzi AJ, Sá MM. Tetrahedron 2004; 60: 9983
- 16a Das B, Chowdhury N, Banerjee J, Majhi A. Tetrahedron Lett. 2006; 47: 6615
- 16b Das B, Banerjee J, Chowdhury N, Majhi A. Chem. Pharm. Bull. 2006; 54: 1725
- 17 Heissler D, Jenn T, Nagano H. Tetrahedron Lett. 1991; 32: 7587
- 18a Guindon Y, Rancourt J. J. Org. Chem. 1998; 63: 6554
- 18b Tsoi Y.-T, Zhou Z, Chen AS. C, Yu W.-Y. Org. Lett. 2010; 12: 4506
- 19 Lerebours R, Wolf C. Org. Lett. 2007; 9: 2737
- 20 Taniguchi M, Fujii H, Oshima K, Utimoto K. Tetrahedron 1993; 49: 11169
- 21 McNulty J, Nair JJ, Vurgun N, DiFrancesco BR, Brown CE, Tsoi B, Crankshaw DJ, Holloway AC. Bioorg. Med. Chem. Lett. 2012; 22: 718
-
References
- 1a Davies SG, Ichihara O, Walters AS. J. Chem. Soc., Perkin Trans. 1 1994; 1141
- 1b Villa M.-J, Warren S. J. Chem. Soc., Perkin Trans. 1 1994; 1569
- 1c Sturm T, Weissensteiner E, Spindler F. Adv. Synth. Catal. 2003; 345: 160
- 1d Huang J, Corey EJ. Org. Lett. 2003; 5: 3455
- 1e Langenhan JM, Gellman SH. J. Org. Chem. 2003; 68: 6440
- 2a Watanabe T, Hayashi K, Yoshimatsu S, Sakai K, Takeyama S, Takashima K. J. Med. Chem. 1980; 23: 50
- 2b D’Auria MA, Minale L, Riccio R. Chem. Rev. 1993; 93: 1839
- 2c Senokuchi K, Nakai H, Nakayama Y, Odagaki Y, Sakaki K, Kato M, Maruyama T, Miyazaki T, Ito H, Kamiyasu K, Kim S, Kawamura M, Hamanaka N. J. Med. Chem. 1995; 38: 2521
- 2d Senokuchi K, Nakai H, Nakayama Y, Odagaki Y, Sakaki K, Kato M, Maruyama T, Miyazaki T, Ito H, Kamiyasu K, Kim S, Kawamura M, Hamanaka N. J. Med. Chem. 1995; 38: 4508
- 2e Franklin AS. J. Chem. Soc., Perkin Trans. 1 1999; 3537
- 2f Basavaiah D, Krishnamacharyulu M, Hyma RS, Sarma PK. S, Kumaragurabaran N. J. Org. Chem. 1999; 64: 1197
- 3 Marfat A, McGuirk PR, Helquist P. J. Org. Chem. 1979; 44: 3888
- 4a Mouloungui Z, Elmestour R, Delmas M, Gaset A. Tetrahedron 1992; 48: 1219
- 4b Kojima S, Takagi R, Akiba K. J. Am. Chem. Soc. 1997; 119: 5970
- 4c Ando K. J. Org. Chem. 1997; 62: 1934
- 4d Sano S, Yokoyama K, Fukushima M, Yagi T, Nagao Y. Chem. Commun. 1997; 559
- 5 Kowalski CJ, Sakdarat S. J. Org. Chem. 1990; 55: 1977
- 6 Shindo M, Sato Y, Shishido K. Tetrahedron Lett. 1998; 39: 4857
- 7 Kisanga P, D’Sa B, Verkade J. Tetrahedron 2001; 57: 8047
- 8 Li S, Yuan W, Ma S. Angew. Chem. Int. Ed. 2011; 50: 2578
- 9 Sai H, Ohmizu H. Tetrahedron Lett. 1999; 40: 5019
- 10 Concellón JM, Pérez-Andrés JA, Rodrígues-Solla H. Angew. Chem. Int. Ed. 2000; 39: 2773
- 11 Bartoli G, Bellucci MC, Petrini M, Marcantoni E, Sambri L, Torregiani E. Org. Lett. 2000; 2: 1791
- 12a Feuillet FJ. P, Robinson DE. J. E, Bull SD. Chem. Commun. 2003; 2184
- 12b Feuillet FJ. P, Cheeseman M, Mahon MF, Bull SD. Org. Biomol. Chem. 2005; 3: 2976
- 13 Basavaiah D, Sarma PK. S, Bhavani AK. D. J. Chem. Soc., Chem. Commun. 1994; 1091
- 14 Ravichandran S. Synth. Commun. 2001; 31: 2055
- 15 Fernades L, Bortoluzzi AJ, Sá MM. Tetrahedron 2004; 60: 9983
- 16a Das B, Chowdhury N, Banerjee J, Majhi A. Tetrahedron Lett. 2006; 47: 6615
- 16b Das B, Banerjee J, Chowdhury N, Majhi A. Chem. Pharm. Bull. 2006; 54: 1725
- 17 Heissler D, Jenn T, Nagano H. Tetrahedron Lett. 1991; 32: 7587
- 18a Guindon Y, Rancourt J. J. Org. Chem. 1998; 63: 6554
- 18b Tsoi Y.-T, Zhou Z, Chen AS. C, Yu W.-Y. Org. Lett. 2010; 12: 4506
- 19 Lerebours R, Wolf C. Org. Lett. 2007; 9: 2737
- 20 Taniguchi M, Fujii H, Oshima K, Utimoto K. Tetrahedron 1993; 49: 11169
- 21 McNulty J, Nair JJ, Vurgun N, DiFrancesco BR, Brown CE, Tsoi B, Crankshaw DJ, Holloway AC. Bioorg. Med. Chem. Lett. 2012; 22: 718
