Article pubs.acs.org/joc
Yttrium-Catalyzed Tandem Intermolecular Hydroalkoxylation/ Claisen Rearrangement Bo Zhou,† Long Li,† Xin Liu,† Tong-De Tan,† Jinxian Liu,‡ and Long-Wu Ye*,†,§ †
State Key Laboratory of Physical Chemistry of Solid Surfaces & Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China ‡ College of Chemistry & Materials Science, Longyan University, Fujian 364000, China § State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China S Supporting Information *
ABSTRACT: An efficient yttrium-catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement has been developed, providing various γ,δ-unsaturated amides in generally good to excellent yields. Importantly, high Z/E selectivity and diastereoselectivity were achieved. Other notable features of this method include widespread availability of the substrates, compatibility with a broad range of functional groups, and mild reaction conditions.
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INTRODUCTION Claisen rearrangement is a powerful reaction in the construction of carbon−carbon bonds.1 Recently, transitionmetal-catalyzed tandem intermolecular hydroalkoxylation/ Claisen rearrangement has attracted much interest in organic synthesis due to its high bond-forming efficiency and atom economy.2,3 For example, Aponick and co-workers reported an elegant protocol that gold could effectively catalyze intermolecular hydroalkoxylation of alkynes with allylic alcohols and subsequent Claisen rearrangement, leading to the formation of γ,δ-unsaturated ketones.2a Subsequently, Nolan and co-workers significantly improved this reaction to be more efficient and environmentally friendly.2b Very recently, a major breakthrough was achieved by Feng and Liu, who developed its asymmetric tandem sequence by merging gold-catalyzed hydroalkoxylation with a chiral Lewis acid-catalyzed Claisen rearrangement.2d The relevant one-pot rearrangement reactions have also been well explored by Zhang, Gagosz, Maulide and others.4 Despite these remarkable achievements, these intermolecular tandem reactions have been mainly limited to noble-metal catalysis. In recent years, ynamides have become prevalent in organic synthesis and have attracted considerable attention.5 In particular, they could undergo a variety of various useful transformations under non-noble metal catalysis or under metal-free conditions. In 2002, Hsung and co-workers reported a Brønsted acid-catalyzed stereoselective Ficini-Claisen rearrangement, leading to high diastereoselectivity for various allylic alcohols and chiral ynamides (Scheme 1a).6a In addition, they also extended this reaction to stereoselective Saucy-Marbet rearrangement by replacement of the allylic alcohols with propargyl alcohols.6b In a related study, Gaunt and co-workers disclosed such a zinc-catalyzed tandem sequence (Scheme 1b).7 However, the structure of ynamides in these cases is limited to © 2017 American Chemical Society
Scheme 1. Catalytic Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement Based on Ynamides
the oxazolidinone type ynamide, which may severely hamper the further synthetic applications of this methodology. Therefore, the development of novel intermolecular hydroalkoxylation/Claisen rearrangement reactions is still highly desirable. In our recent study on ynamide chemistry,8 we developed a yttrium-catalyzed intramolecular hydroalkoxylation/Claisen rearrangement of allyl alcohol-tethered ynamides, allowing the facile synthesis of various highly functionalized medium-sized lactams.9 Inspired by these results, we envisioned Received: June 29, 2017 Published: August 28, 2017 10149
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
Article
The Journal of Organic Chemistry
failed to improve the yield (entries 14 and 15). It should be mentioned that without the use of yttrium catalyst, no desired product 3a was observed. With the optimized reaction conditions in hand (Table 1, entry 1), the scope of this hydroalkoxylation/Claisen rearrangement reaction was then examined. As shown in Table 2, the
that this non-noble metal-catalyzed tandem sequence might be extended into its intermolecular version. Herein, we report the yttrium-catalyzed intermolecular hydroalkoxylation/Claisen rearrangement sequence, providing a variety of γ,δ-unsaturated amides in generally good to excellent yields with high Z/E selectivity (Scheme 1c). Moreover, high diastereoselectivity was achieved by employing chiral ynamides as substrates, and the formed chiral amides could be readily converted into the corresponding synthetically useful chiral γ,δ-carboxylic acids.
Table 2. Reaction Scope for the Formation of γ,δUnsaturated Amides 3a
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RESULTS AND DISCUSSION Our initial experiments focused on the reaction of ynamide 1a with MBH alcohol 2a, and some of the results are listed in Table 1. To our delight, the reaction proceeded smoothly to Table 1. Optimization of Reaction Conditionsa
yield (%)b entry
catalyst
reaction conditions
3a
3aa
1 2 3c 4d 5 6 7 8 9 10e 11e 12 13 14 15 16
Y(OTf)3 Y(OTf)3 Y(OTf)3 Y(OTf)3 Zn(OTf)2 Cu(OTf)2 Sc(OTf)3 ln(OTf)3 Yb(OTf)3 Ph3PAuNTf2 IPrAuNTf2 PNBSA HOTf Y(OTf)3 Y(OTf)3 Y(OTf)3
5 Å MS, PhCl, 80 °C, 3 h PhCl, 80 °C, 3 h 3 Å MS, PhCl, 80 °C, 3 h 4 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, PhCl, 80 °C, 3 h 5 Å MS, toluene, 80 °C, 3 h 5 Å MS, DCE, 80 °C, 3 h 5 Å MS, PhCl, 60 °C, 12 h
88 12 30 55 82 29 46 4 78 62 66 26 8 75 61 72
10/1) and over 15/1 Z/E ratio (entries 1−7). Importantly, these results indicate that the reaction is proposed to occur by tandem hydroalkoxylation/Claisen rearrangement but not allylic cation pathway, which is distinctively different from Liu’s protocol.12 Of note, the reaction of the S-MBH alcohol with S-ynamide 4aa also proceeded well to produce the corresponding 6a′ in good yield but with slightly decreased dr (entry 8). The absolute configuration of 6 was further confirmed by comparison of the optical rotation after hydrolysis to the acids, as shown below. Further synthetic transformation of the as-synthesized chiral amides 6 was also explored, as outlined in Scheme 2. To our delight, the treatment of amides 6 with 5 equiv of LiOH at room temperature could afford the corresponding carboxylic acids 7 in good yields. Importantly, ee well matched the diastereomeric ratio of amides 6. In addition, the chiral amide 6 could be readily transformed into the corresponding chiral δlactone. For example, chiral amide 6a was converted into the desired carboxylic acid 6aa, which underwent subsequent condensation to deliver the final chiral δ-lactone 6ab. The absolute configuration of 6ab was further determined by X-ray analysis (for details, see the Supporting Information).13
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CONCLUSION In summary, we have developed a novel yttrium-catalyzed intermolecular hydroalkoxylation/Claisen rearrangement reaction of ynamides with MBH alcohols. Importantly, high Z/E selectivity and high diastereoselectivity were achieved by this non-noble metal-catalyzed rearrangement reaction. Further research on the Lewis acid-catalyzed tandem reaction of ynamides is ongoing in our laboratories.
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EXPERIMENTAL SECTION
General Information. Ethyl acetate (ACS grade), hexanes (ACS grade) and anhydrous chlorobenzene (ACS grade) were obtained commercially and used without further purification. Methylene chloride, tetrahydrofuran and diethyl ether were purified according to standard methods unless otherwise noted. Commercially available reagents were used without further purification. High-resolution mass spectra were obtained using electrospray ionization using an ICR analyzer (ESI-MS). 1 H NMR spectra were recorded in chloroform-d3. Chemical shifts are reported in ppm with the internal TMS signal at 0.0 ppm as a standard. The data are being reported as (s = singlet, d = doublet, t = triplet, m = multiplet or unresolved, brs = broad singlet, coupling constant(s) in Hz, integration). 10151
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
Article
The Journal of Organic Chemistry 13
134.8, 134.7, 129.5, 128.7, 128.3, 128.0, 127.6, 73.3, 70.9, 55.5, 31.3, 28.7, 28.2, 22.5, 21.6, 18.3, 14.0. N-Benzyl-4-methoxy-N-(phenylethynyl)benzenesulfonamide (1i). This compound is known and the spectroscopic data match those reported.15 Yellow solid (256.7 mg, 68%). 1H NMR (500 MHz, CDCl3) δ 7.85−7.81 (m, 2H), 7.36−7.28 (m, 5H), 7.24−7.22 (m, 5H), 6.99−6.95 (m, 2H), 4.58 (s, 2H), 3.87 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 163.6, 134.5, 131.1, 129.9, 129.2, 128.8, 128.5, 128.3, 128.2, 127.6, 122.8, 114.2, 82.8, 71.3, 55.7, 55.6. (R)-4-Bromo-N-(1-phenylethyl)-N-(phenylethynyl)benzenesulfonamide (4a). Pale yellow oil (268.2 mg, 61%). [α]D20 = −45.288° (c = 1.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ 7.58−7.52 (m, 2H), 7.51−7.45 (m, 2H), 7.36−7.32 (m, 2H), 7.31−7.26 (m, 5H), 7.25−7.21 (m, 3H), 5.23 (q, 1H, J = 7.2 Hz), 1.61 (d, 3H, J = 7.2 Hz); 13 C NMR (100 MHz, CDCl3) δ 139.5, 137.1, 131.9, 131.2, 128.9, 128.4, 128.3, 128.2, 128.1, 127.8, 126.7, 122.6, 79.8, 73.5, 59.4, 20.0; IR (neat) 3062, 2981, 2233, 1573, 1367, 1172, 1068, 755, 740, 615; HRESIMS Calcd for [C22H18BrNNaO2S]+ (M + Na+) 462.0134, found 462.0132. (S)-4-Bromo-N-(1-phenylethyl)-N-(phenylethynyl)benzenesulfonamide (4aa). Pale yellow oil (268.2 mg, 61%). [α]D20 = +35.458° (c = 1.0, CHCl3). (R)-4-Bromo-N-((4-fluorophenyl)ethynyl)-N-(1-phenylethyl)benzenesulfonamide (4b). Pale yellow oil (298.0 mg, 65%). [α]D20 = −48.904° (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.57−7.49 (m, 4H), 7.34−7.30 (m, 2H), 7.28−7.21 (m, 5H), 7.02−6.97 (m, 2H), 5.23 (q, J = 7.0 Hz, 1H), 1.61 (d, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 162.3 (d, J = 248.8 Hz), 139.5, 137.1, 133.4 (d, J = 8.8 Hz), 132.0, 128.9, 128.5, 128.2, 126.8, 118.7 (d, J = 3.8 Hz), 115.6 (d, J = 21.3 Hz), 79.4, 72.4, 59.4, 20.0; IR (neat) 2927, 2853, 2235, 1573, 1508, 1368, 1173, 1087, 835, 736, 618, 566; HRESIMS Calcd for [C22H17BrFNNaO2S]+ (M + Na+) 480.0040, found 480.0045. (R)-4-Bromo-N-((4-chlorophenyl)ethynyl)-N-(1-phenylethyl)benzenesulfonamide (4c). Pale yellow oil (332.3 mg, 70%). [α]D20 = −49.372° (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.57−7.49 (m, 4H), 7.29−7.22 (m, 9H), 5.23 (q, J = 7.0 Hz, 1H), 1.62 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 139.4, 137.1, 133.9, 132.4, 132.1, 128.9, 128.6, 128.5, 128.4, 128.2, 126.8, 121.2, 80.8, 72.6, 59.5, 20.0; IR (neat) 2981, 2929, 2234, 1573, 1491, 1369, 1172, 1087, 825, 741, 699, 615; HRESIMS Calcd for [C22H17BrClNNaO2S]+ (M + Na+) 495.9744, found 495.9745. (R)-4-Bromo-N-(1-phenylethyl)-N-(p-tolylethynyl)benzenesulfonamide (4d). Pale yellow oil (313.0 mg, 69%). [α]D20 = −44.358° (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H), 7.30−7.20 (m, 7H), 7.11 (d, J = 8.0 Hz, 2H), 5.22 (q, J = 7.0 Hz, 1H), 2.34 (s, 3H), 1.61 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 139.6, 138.2, 137.1, 131.9, 131.4, 129.0, 128.9, 128.4, 128.3, 128.1, 126.8, 119.5, 79.1, 73.5, 59.4, 21.4, 20.1; IR (neat) 3028, 2923, 2251, 1573, 1358, 1171, 1069, 1010, 742, 698, 614; HRESIMS Calcd for [C23H20BrNNaO2S]+ (M + Na+) 476.0290, found 476.0290. (R)-4-Bromo-N-((4-methoxyphenyl)ethynyl)-N-(1-phenylethyl)benzenesulfonamide (4e). Pale yellow oil (338.2 mg, 72%). [α]D20 = −45.034° (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.35−7.20 (m, 7H), 6.84 (d, J = 8.5 Hz, 2H), 5.22 (q, J = 7.0 Hz, 1H), 3.81 (s, 3H), 1.61 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 159.6, 139.7, 137.2, 133.4, 131.9, 129.0, 128.4, 128.3, 128.1, 126.8, 114.6, 114.0, 78.3, 73.2, 59.4, 55.3, 20.0; IR (neat) 2979, 2932, 2234, 1573, 1511, 1366, 1248, 1172, 1029, 831, 699, 618; HRESIMS Calcd for [C23H20BrNNaO3S]+ (M + Na+) 492.0239, found 492.0238. General Procedure for the Synthesis of MBH-Alcohols 2a− f.16a To a round-bottomed flask charged with arylaldehyde (1 mmol) and methyl acrylate (4 mL) was added 1,4-diaza-bicyclo[2.2.2]octane (135.4 mg, 1.2 mmol) and the solution was stirred for 48−96 h. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography (eluent: hexanes/ethyl acetate = 5/1) to afford the desired MBH-alcohol 2. Methyl-2-(hydroxy(phenyl)methyl)acrylate (2a). This compound is known and the spectroscopic data match those reported.16a Pale
C NMR spectra were recorded in chloroform-d3. Chemical shifts are reported in ppm with the internal chloroform signal at 77.0 ppm as a standard. General Procedure for the Synthesis of N-Sulfonyl Ynamides 1a−k and 4a−e.8e CuSO4·5H2O (0.1 mmol, 25.0 mg), 1,10-phenanthroline (0.2 mmol, 36.0 mg), amide (1.0 mmol), and K2CO3 (3.0 mmol, 414.6 mg) were added to a flame-dried 10 mL round-bottomed flask. The flask was purged with nitrogen, and a solution of alkynyl bromide (1.2 mmol) in toluene (5 mL) was added. The mixture was allowed to stir at 80 °C overnight and was then cooled to rt. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography (eluent: hexanes/ethyl acetate = 15/1) to afford the desired N-sulfonyl ynamide 1 or 4. The data of the following ynamides 1 (1a, 1j, 1k) were reported in our previous work.8e,f N-Benzyl-N-((4-fluorophenyl)ethynyl)-4-methylbenzenesulfonamide (1b). This compound is known and the spectroscopic data match those reported.14 Pale yellow oil (265.6 mg, 70%). 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 8.5 Hz, 2H), 7.35−7.28 (m, 7H), 7.23− 7.18 (m, 2H), 6.96−6.90 (m, 2H), 4.57 (s, 2H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 162.2 (J = 247.5 Hz), 144.7, 134.6, 134.4, 133.1 (J = 8.3 Hz), 129.7, 128.8, 128.5, 128.3, 127.7, 118.7 (J = 3.5 Hz), 115.4 (J = 21.9 Hz), 82.2, 70.3, 55.6, 21.6. N-Benzyl-N-((4-chlorophenyl)ethynyl)-4-methylbenzenesulfonamide (1c). This compound is known and the spectroscopic data match those reported.14 Pale yellow oil (296.9 mg, 75%). 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 8.5 Hz, 2H), 7.34−7.29 (m, 7H), 7.22− 7.18 (m, 2H) 7.15−7.11 (m, 2H), 4.57 (s, 2H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 144.7, 134.6, 134.3, 133.5, 132.2, 129.7, 128.8, 128.5, 128.4, 128.3, 127.7, 121.3, 83.5, 70.4, 55.6, 21.6. N-Benzyl-N-((4-bromophenyl)ethynyl)-4-methylbenzenesulfonamide (1d). Pale yellow oil (291.1 mg, 66%). 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.38−7.28 (m, 9H), 7.06 (d, J = 8.0 Hz, 2H), 4.57 (s, 2H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 144.8, 134.6, 134.2, 132.4, 131.4, 129.7, 128.8, 128.5, 128.4, 127.7, 121.7, 121.6, 83.7, 70.6, 55.6, 21.6; IR (neat) 3032, 2920, 2291, 1594, 1488, 1356, 1166, 1088, 1071, 813, 587, 546; HRESIMS Calcd for [C22H18BrNNaO2S]+ (M + Na+) 462.0134, found 462.0135. N-Benzyl-4-methyl-N-(p-tolylethynyl)benzenesulfonamide (1e). This compound is known and the spectroscopic data match those reported.14 Pale yellow oil (255.3 mg, 68%). 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.35−7.28 (m, 7H), 7.13 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 4.57 (s, 2H), 2.44 (s, 3H), 2.31 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 144.5, 137.8, 134.7, 134.5, 131.2, 129.7, 128.9, 128.8, 128.5, 128.2, 127.7, 119.6, 81.9, 71.3, 55.7, 21.6, 21.4. N-Benzyl-4-methyl-N-(m-tolylethynyl)benzenesulfonamide (1f). Pale yellow oil (263.0 mg, 70%). 1H NMR (500 MHz, CDCl3) δ 7.79 (d, J = 10.5 Hz, 2H), 7.36−7.28 (m, 7H), 7.15−7.10 (m, 1H), 7.07−7.01 (m, 3H), 4.57 (s, 2H), 2.44 (s, 3H), 2.28 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 144.6, 137.8, 134.7, 134.5, 131.7, 129.7, 128.8, 128.5, 128.4, 128.3, 128.2, 128.1, 127.7, 122.6, 82.3, 71.4, 55.7, 21.6, 21.2; IR (neat) 3031, 2922, 2350, 1596, 1354, 1166, 1088, 701, 580, 545; HRESIMS Calcd for [C23H21NNaO2S]+ (M + Na+) 398.1185, found 398.1188. N-Benzyl-N-((4-methoxyphenyl)ethynyl)-4-methylbenzenesulfonamide (1g). This compound is known and the spectroscopic data match those reported.14 Yellow solid (254.5 mg, 65%). 1H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.36−7.27 (m, 7H), 7.19 (d, J = 8.5 Hz, 2H), 6.77 (d, J = 8.5 Hz, 2H), 4.56 (s, 2H), 3.77 (s, 3H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 159.4, 144.5, 134.7, 134.6, 133.1, 129.6, 128.8, 128.4, 128.2, 127.7, 114.7, 113.8, 81.1, 70.9, 55.7, 55.2, 21.6. N-Benzyl-4-methyl-N-(oct-1-yn-1-yl)benzenesulfonamide (1h). This compound is known and the spectroscopic data match those reported.15 Pale yellow oil (214.3 mg, 58%). 1H NMR (500 MHz, CDCl3) δ 7.76−7.72 (m, 2H), 7.31−7.27 (m, 7H), 4.44 (s, 2H), 2.43 (s, 3H), 2.16 (t, J = 7.0 Hz, 2H), 1.39−1.31 (m, 2H), 1.27−1.16 (m, 6H), 0.86 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 144.2, 10152
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
Article
The Journal of Organic Chemistry
mL) at room temperature. The reaction mixture was stirred at 80 °C and the progress of the reaction was monitored by TLC. The reaction typically took 3 h. Upon completion, the mixture was then concentrated and the residue was purified by chromatography on silica gel (eluent: hexanes/ethyl acetate = 8/1) to afford the desired product 3. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-5-oxo-4-phenylpentanoate (3a). Pale yellow oil (137.8 mg, 83%). 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 7.5 Hz, 2H), 7.28− 7.20 (m, 11H), 7.16 (d, J = 8.0 Hz, 2H), 7.00−6.93 (m, 4H), 6.32 (s, 1H), 5.18 (d, J = 16.5 Hz, 1H), 4.78 (d, J = 17.0 Hz, 1H), 4.36−4.28 (m, 1H), 3.44 (s, 3H), 3.03 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.55 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.8, 168.9, 144.5, 138.2, 136.9, 136.5, 136.1, 135.7, 129.6, 129.2, 128.7(2), 128.6(9), 128.2, 128.0, 127.9, 127.8(1), 127.7(8), 127.5, 127.4, 126.7, 51.4, 50.5, 49.2, 40.4, 21.5; IR (neat) 3029, 2949, 1702(s), 1454, 1357, 1168, 1117, 750, 697, 544; HRESIMS Calcd for [C33H31NNaO5S]+ (M + Na+) 576.1815, found 576.1817. N-Benzyl-2-phenyl-N-tosylacetamide (3aa). This compound is known and the spectroscopic data match those reported.8e Pale yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.5 Hz, 2H), 7.37− 7.27 (m, 5H), 7.26−7.19 (m, 5H), 7.00−6.96 (m, 2H), 5.06 (s, 2H), 3.86 (s, 2H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) 13C NMR (126 MHz, CDCl3) δ 171.2, 144.8, 136.5, 136.4, 133.1, 129.6, 129.2, 128.6, 128.5, 127.9, 127.7, 127.6, 127.1, 49.6, 42.8, 21.5. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-4-(4-fluorophenyl)-5-oxopentanoate (3b). Pale yellow oil (159.5 mg, 93%). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2H), 7.28−7.21 (m, 8H), 7.15 (d, J = 8.0 Hz, 2H), 7.01−6.97 (m, 2H), 6.95−6.90 (m, 2H), 6.89−6.84 (m, 2H), 6.33 (s, 1H), 5.14 (d, J = 16.5 Hz, 1H), 4.85 (d, J = 16.5 Hz, 1H), 4.47−4.37 (m, 1H), 3.48 (s, 3H), 3.00 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 2.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 173.0, 169.1, 162.0 (d, J = 245.1 Hz), 144.7, 138.2, 136.4, 136.2, 135.6, 132.7 (d, J = 3.1 Hz), 129.7 (d, J = 8.0 Hz), 129.5, 129.4, 128.7, 128.1, 128.0, 127.9(5), 127.9(3), 127.6, 126.9, 115.5 (d, J = 21.2 Hz), 51.5, 49.7, 49.4, 40.6, 21.6; IR (neat) 3030, 2949, 1703(s), 1508, 1356, 1225, 1168, 735, 697, 586, 544; HRESIMS Calcd for [C33H30FNNaO5S]+ (M + Na+) 594.1721, found 594.1708. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-4-(4-chlorophenyl)-5-oxopentanoate (3c). Pale yellow oil (160.6 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 2H), 7.30−7.21 (m, 8H), 7.17−7.11 (m, 4H), 7.02−6.97 (m, 2H), 6.88 (d, J = 8.0 Hz, 2H), 6.35 (s, 1H), 5.14 (d, J = 16.5 Hz, 1H), 4.85 (d, J = 16.5 Hz, 1H), 4.48−4.39 (m, 1H), 3.48 (s, 3H), 3.00 (dd, J = 5.5 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.5 Hz, J = 14.0 Hz, 1H), 2.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.7, 169.0, 144.7, 138.2, 136.3, 136.2, 135.6, 135.5, 133.4, 129.5, 129.4, 128.7(2), 128.6(7), 128.1, 128.0, 127.9(3), 127.8(9), 127.5, 126.9, 51.5, 49.9, 49.4, 40.5, 21.5; IR (neat) 3029, 2925, 1702(s), 1492, 1357, 1168, 1090, 812, 732, 586, 543; HRESIMS Calcd for [C33H30ClNNaO5S]+ (M + Na+) 610.1425, found 610.1426. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-4-(4-bromophenyl)-5-oxopentanoate (3d). Pale yellow oil (163.2 mg, 86%). 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.27−7.22 (m, 8H), 7.15 (d, J = 8.0 Hz, 2H), 7.02−6.98 (m, 2H), 6.82 (d, J = 8.5 Hz, 2H), 6.36 (s, 1H), 5.14 (d, J = 16.5 Hz, 1H), 4.85 (d, J = 17.0 Hz, 1H), 4.48−4.37 (m, 1H), 3.48 (s, 3H), 3.00 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.7, 169.1, 144.7, 138.3, 136.3, 136.2, 136.1, 135.6, 131.7, 129.7, 129.4, 128.7, 128.0(8), 128.0(6), 127.9(8), 127.9(3), 127.6, 126.9, 121.5, 51.5, 49.9, 49.4, 40.5, 21.6; IR (neat) 2924, 2853, 1709(s), 1593, 1495, 1355, 1261, 1160, 695, 670; HRESIMS Calcd for [C33H30BrNNaO5S]+ (M + Na+) 654.0920, found 654.0920. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-5-oxo-4-(p-tolyl)pentanoate (3e). Pale yellow oil (155.0 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 8.0 Hz, 2H), 7.28− 7.22 (m, 8H), 7.17 (d, J = 8.0, 2H), 7.03−6.97 (m, 4H), 6.84 (d, J = 8.0 Hz, 2H), 6.33 (s, 1H), 5.18 (d, J = 17.0 Hz, 1H), 4.76 (d, J = 17.0
yellow oil (153.8 mg, 80%). 1H NMR (500 MHz, CDCl3) δ 7.38−7.31 (m, 4H), 7.30−7.25 (m, 1H), 6.33 (s, 1H), 5.83 (t, J = 1.0 Hz, 1H), 5.55 (d, J = 4.5 Hz, 1H), 3.71 (s, 3H), 3.12 (d, J = 5.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 166.7, 141.9, 141.2, 128.4, 127.8, 126.5, 126.1, 73.1, 51.9. Methyl-2-((4-fluorophenyl)(hydroxy)methyl)acrylate (2b). This compound is known and the spectroscopic data match those reported.16a Pale yellow oil (195.5 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 7.36−7.28 (m, 2H), 7.04−6.97 (m, 2H), 6.32 (s, 1H), 5.83 (s, 1H), 5.53 (s, 1H), 3.71 (s, 3H), 3.21 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 166.6, 162.3 (J = 244.6 Hz), 141.9, 137.1, 128.2 (J = 8.1 Hz), 125.9, 115.2 (J = 21.4 Hz), 72.5, 51.9. Methyl-2-((4-chlorophenyl)(hydroxy)methyl)acrylate (2c). This compound is known and the spectroscopic data match those reported.16a Pale yellow oil (204.0 mg, 90%). 1H NMR (500 MHz, CDCl3) δ 7.31−7.27 (m, 4H), 6.32 (s, 1H), 5.83 (s, 1H), 5.50 (s, 1H), 3.71 (s, 3H), 3.30 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 166.5, 141.6, 139.8, 133.5, 128.5, 127.9, 126.2, 72.5, 52.0. Methyl-2-((4-bromophenyl)(hydroxy)methyl)acrylate (2d). This compound is known and the spectroscopic data match those reported.16a Pale yellow oil (238.6 mg, 88%). 1H NMR (500 MHz, CDCl3) δ 7.49−7.45 (m, 2H), 7.28−7.25 (m, 2H), 6.34 (s, 1H), 5.83 (s, 1H), 5.52 (d, J = 5.5 Hz, 1H), 3.73 (s, 3H), 3.08 (d, J = 5.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 166.6, 141.5, 140.3, 131.5, 128.3, 126.5, 121.8, 72.8, 52.1. Methyl-2-(hydroxy(p-tolyl)methyl)acrylate (2e). This compound is known and the spectroscopic data match those reported.16a Pale yellow oil (154.7 mg, 75%). 1H NMR (500 MHz, CDCl3) δ 7.24 (d, J = 7.5 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.31 (s, 1H), 5.85 (s, 1H), 5.52 (s, 1H), 3.70 (s, 3H), 3.04 (s, 1H), 2.33 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 166.7, 142.0, 138.3, 137.5, 129.1, 126.5, 125.7, 72.9, 51.8, 21.1. Methyl-2-(hydroxy(4-methoxyphenyl)methyl)acrylate (2f). This compound is known and the spectroscopic data match those reported.16a Pale yellow oil (155.6 mg, 70%). 1H NMR (500 MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 6.31 (s, 1H), 5.86 (s, 1H), 5.51 (s, 1H), 3.78 (s, 3H), 3.70 (s, 3H), 3.08 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 166.7, 159.1, 142.1, 133.4, 127.8, 125.4, 113.7, 72.6, 55.1, 51.8. 1,2-Diphenylprop-2-en-1-ol (2g). This compound is known and the spectroscopic data match those reported.16b Pale yellow oil (189.3 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.38−7.33 (m, 2H), 7.31− 7.26 (m, 4H), 7.25−7.18 (m, 4H), 5.65 (s, 1H), 5.49−5.46 (m, 1H), 5.45−5.43 (m, 1H), 2.30 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 150.3, 141.8, 139.3, 128.4, 128.2, 127.7, 127.6, 127.0, 126.9, 114.0, 75.8. Compounds 5a−c were prepared according to the known procedures.11 (S)-Methyl-2-(hydroxy(phenyl)methyl)acrylate (5a). This compound is known and the spectroscopic data match those reported.11,16a Pale yellow oil (115.3 mg, 60%, 2 steps). 89% ee (determined by HPLC: Chiralpak IC Column, 5/95 i-PrOH/hexane, 1.0 mL/min, 220 nm; tR = 14.53 min (major), 27.28 min (minor)). (S)-Methyl-2-((4-fluorophenyl)(hydroxy)methyl)acrylate (5b). This compound is known and the spectroscopic data match those reported.11,16a Pale yellow oil (111.4 mg, 53%, 2 steps). 84% ee (determined by HPLC: Chiralpak IC Column, 5/95 i-PrOH/hexane, 1.0 mL/min, 220 nm; tR = 10.46 min (major), 19.59 min (minor)). (S)-Methyl-2-(hydroxy(m-tolyl)methyl)acrylate (5c). This compound is known and the spectroscopic data match those reported.11,16a Pale yellow oil (103.1 mg, 50%, 2 steps). 90% ee (determined by HPLC: Chiralpak IC Column, 5/95 i-PrOH/hexane, 1.0 mL/min, 220 nm; tR = 16.28 min (major), 29.80 min (minor)). 1H NMR (400 MHz, CDCl3) δ 7.26−7.11 (m, 3H), 7.08 (d, J = 7.6 Hz, 1H), 6.32 (s, 1H), 5.84 (s, 1H), 5.51 (s, 1H), 3.70 (s, 3H), 3.08 (s, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.7, 142.0, 141.2, 138.0, 128.5, 128.2, 127.2, 125.8, 123.6, 73.1, 51.8, 21.3. General Procedure for the Synthesis of 3. Five Å MS (90 mg) and Y(OTf)3 (16.1 mg, 0.03 mmol) were added to a solution of the ynamide 1 (0.30 mmol) and MBH alcohol 2 (0.45 mmol) in PhCl (6.0 10153
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
Article
The Journal of Organic Chemistry Hz, 1H), 4.28−4.19 (m, 1H), 3.42 (s, 3H), 3.01 (dd, J = 14.0 Hz, J = 6.5 Hz, 1H), 2.52 (dd, J = 13.5 Hz, J = 7.0 Hz, 1H), 2.39 (s, 3H), 2.31 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.9, 168.9, 144.4, 138.1, 137.2, 136.6, 136.3, 135.8, 134.0, 129.9, 129.4, 129.2, 128.7, 128.3, 128.1, 127.8(2), 127.7(9), 127.7(6), 127.5, 126.7, 51.4, 50.2, 49.2, 40.4, 21.6, 21.0; IR (neat) 3027, 2924, 1703(s), 1356, 1168, 1117, 1088, 811, 696, 586; HRESIMS Calcd for [C34H33NNaO5S]+ (M + Na+) 590.1972, found 590.1971. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-5-oxo-4-(m-tolyl)pentanoate (3f). Pale yellow oil (141.4 mg, 83%). 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 8.0 Hz, 2H), 7.30− 7.21 (m, 8H), 7.16 (d, J = 8.0 Hz, 2H), 7.12−7.07 (m, 1H), 7.05−6.97 (m, 3H), 6.79 (d, J = 7.0 Hz, 1H), 6.64 (s, 1H), 6.34 (s, 1H), 5.18 (d, J = 17.0 Hz, 1H), 4.79 (d, J = 16.5 Hz, 1H), 4.32−4.22 (m, 1H), 3.44 (s, 3H), 3.02 (dd, J = 13.5, J = 5.5 Hz, 1H), 2.52 (dd, J = 13.5, J = 7.5 Hz, 1H), 2.37 (s, 3H), 2.20 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.8, 169.0, 144.4, 138.4, 138.2, 136.9, 136.6, 136.3, 135.9, 129.8, 129.2, 128.7, 128.6, 128.3(3), 128.3(0), 128.2(6), 128.1, 127.8(4), 127.7(8), 127.5, 126.8, 125.1, 51.4, 50.5, 49.3, 40.4, 21.6, 21.3; IR (neat) 3028, 2923, 1702(s), 1435, 1356, 1168, 1118, 697, 587, 552; HRESIMS Calcd for [C34H33NNaO5S]+ (M + Na+) 590.1972, found 590.1944. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-benzylidene-4-(4-methoxyphenyl)-5-oxopentanoate (3g). Pale yellow oil (150.6 mg, 86%). 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 8.5 Hz, 2H), 7.27−7.22 (m, 8H), 7.16 (d, J = 8.0 Hz, 2H), 7.01−6.97 (m, 2H), 6.90−6.85 (m, 2H), 6.75−6.70 (m, 2H), 6.32 (s, 1H), 5.17 (d, J = 17.0 Hz, 1H), 4.79 (d, J = 16.5 Hz, 1H), 4.29−7.20 (m, 1H), 3.77 (s, 3H), 3.43 (s, 3H), 3.00 (ddd, J = 13.5, J = 6.0 Hz, J = 0.5 Hz, 1H), 2.52 (dd, J = 13.5, J = 7.0 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 173.1, 169.0, 158.9, 144.5, 138.1, 136.6, 136.3, 135.8, 129.8, 129.2, 129.1, 128.9, 128.7, 128.3, 128.1, 127.9, 127.8, 127.5, 126.7, 114.1, 55.2, 51.4, 49.7, 49.2, 40.4, 21.6; IR (neat) 3029, 2950, 1701(s), 1511, 1356, 1252, 1167, 737, 697, 545; HRESIMS Calcd for [C34H33NNaO6S]+ (M + Na+) 606.1921, found 606.1922. (Z)-Methyl-4-(benzyl(tosyl)carbamoyl)-2-benzylidenedecanoate (3h). Pale yellow oil (102.8 mg, 61%). 1H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 7.5 Hz, 2H), 7.33−7.27 (m, 6H), 7.12−7.05 (m, 4H), 6.38 (s, 1H), 5.27 (d, J = 16.5 Hz, 1H), 5.07 (d, J = 16.5 Hz, 1H), 3.61 (s, 3H), 3.27−3.14 (m, 1H), 2.60 (dd, J = 5.0 Hz, J = 13.0 Hz, 1H), 2.36 (dd, J = 8.0 Hz, J = 13.5 Hz, 1H), 2.34 (s, 3H), 1.45−1.25 (m, 4H), 1.18−1.10 (m, 2H), 1.05−0.91 (m, 4H), 0.82 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 176.4, 169.7, 144.4, 137.1, 136.8, 136.7, 135.7, 130.5, 129.4, 128.6, 128.1, 128.0(9), 128.0(4), 127.9, 127.6, 127.5, 51.7, 49.4, 44.5, 38.1, 32.7, 31.5, 29.1, 26.6, 22.4, 21.5, 14.0; IR (neat) 2925, 2854, 1707(s), 1454, 1357, 1166, 1089, 696, 587, 543; HRESIMS Calcd for [C33H39NNaO5S]+ (M + Na+) 584.2441, found 584.2444. (Z)-Methyl-5-(N-benzyl-4-methoxyphenylsulfonamido)-2-benzylidene-5-oxo-4-phenylpentanoate (3i). Pale yellow oil (157.2 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.8 Hz, 2H), 7.27− 7.18 (m, 11H), 7.01−6.95 (m, 4H), 6.81 (d, J = 9.2 Hz, 2H), 6.34 (s, 1H), 5.17 (d, J = 17.2 Hz, 1H), 4.77 (d, J = 17.2 Hz, 1H), 4.32 (t, J = 6.0 Hz, 1H), 3.81 (s, 3H), 3.43 (s, 3H), 3.04 (dd, J = 6.0 Hz, J = 13.6 Hz, 1H), 2.56 (dd, J = 7.2 Hz, J = 13.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 172.7, 168.9, 163.5, 138.3, 137.0, 136.5, 135.7, 130.6, 130.4, 129.6, 128.7, 128.6, 128.0, 127.9, 127.8, 127.7, 127.5, 127.4, 126.6, 113.7, 55.5, 51.4, 50.5, 49.1, 40.4; IR (neat) 3027, 2947, 1701(s), 1594, 1496, 1356, 1161, 1089, 748, 697, 554; HRESIMS Calcd for [C33H31NNaO6S]+ (M + Na+) 592.1764, found 592.1766. (Z)-Methyl-5-(N-benzyl-4-bromophenylsulfonamido)-2-benzylidene-5-oxo-4-phenylpentanoate (3j). Pale yellow oil (172.6 mg, 93%). 1H NMR (500 MHz, CDCl3) δ 7.60 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 8.5 Hz, 2H), 7.29−7.20 (m, 11H), 7.00−6.92 (m, 4H), 6.32 (s, 1H), 5.18 (d, J = 17.0 Hz, 1H), 4.82 (d, J = 17.0 Hz, 1H), 4.28 (t, J = 6.5 Hz, 1H), 3.44 (s, 3H), 3.03 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.5 Hz, J = 13.5 Hz,1H); 13C NMR (125 MHz, CDCl3) δ 172.9, 169.0, 138.4, 138.0, 136.7, 136.2, 135.6, 131.8, 129.9, 129.4, 128.9, 128.8, 128.7, 128.0, 127.9(5), 127.9(4), 127.8, 127.7, 126.7, 51.5, 50.6, 49.3, 40.4; IR (neat) 3027, 2923, 1702(s), 1572, 1493,
1454, 1362, 1167, 1113, 752, 695, 597; HRESIMS Calcd for [C32H28BrNNaO5S]+ (M + Na+) 640.0764, found 640.0765. (Z)-Methyl-2-benzylidene-5-(N-benzylmethylsulfonamido)-5oxo-4-phenylpentanoate (3k). Pale yellow oil (113.2 mg, 79%). 1H NMR (500 MHz, CDCl3) δ 7.37−7.22 (m, 13H), 7.07 (d, J = 7.0 Hz, 2H), 6.49 (s, 1H), 5.08 (d, J = 17.0 Hz, 1H), 4.80 (d, J = 17.0 Hz, 1H), 4.46−4.37 (m, 1H), 3.49 (s, 3H), 3.18 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 3.04 (s, 3H), 2.69 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 173.8, 169.2, 138.2, 136.9, 136.2, 135.6, 129.7, 129.0, 128.8, 128.1, 128.0, 127.9(7), 127.9(4), 127.8, 127.7, 126.9, 51.5, 50.6, 48.6, 42.5, 40.8; IR (neat) 3028, 2924, 1693(s), 1454, 1353, 1163, 1117, 955, 752, 696, 514; HRESIMS Calcd for [C27H27NNaO5S]+ (M + Na+) 500.1502, found 500.1500. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-(4-fluorobenzylidene)-5-oxo-4-phenylpentanoate (3l). Pale yellow oil (135.5 mg, 79%). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2H), 7.27−7.16 (m, 10H), 7.00−6.91 (m, 6H), 6.30 (s, 1H), 5.18 (d, J = 16.5 Hz, 1H), 4.75 (d, J = 17.0 Hz, 1H), 4.37−4.23 (m, 1H), 3.44 (s, 3H), 3.01 (dd, J = 6.0 Hz, J = 13.0 Hz, 1H), 2.55 (dd, J = 7.5 Hz, J = 14.0 Hz, 1H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.7, 168.6, 162.3 (d, J = 246.3 Hz), 144.6, 137.7, 136.9, 136.5, 136.2, 131.8 (d, J = 3.4 Hz), 130.0 (d, J = 8.1 Hz), 129.6, 129.3, 128.8, 128.7, 128.3, 127.9, 127.6, 127.5, 126.7, 114.8 (d, J = 21.5 Hz), 51.5, 50.6, 49.3, 40.4, 21.6; IR (neat) 3031, 2922, 1702(s), 1600, 1507, 1357, 1225, 1168, 1117, 700, 585, 543; HRESIMS Calcd for [C33H30FNNaO5S]+ (M + Na+) 594.1721, found 594.1720. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-(4-chlorobenzylidene)-5-oxo-4-phenylpentanoate (3m). Pale yellow oil (132.3 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 7.6 Hz, 2H), 7.29−7.13 (m, 12H), 6.99−6.89 (m, 4H), 6.29 (s, 1H), 5.16 (d, J = 16.8 Hz, 1H), 4.75 (d, J = 16.8 Hz, 1H), 4.38−4.27 (m, 1H), 3.45 (s, 3H), 3.01 (dd, J = 13.6 Hz, J = 5.6 Hz, 1H), 2.55 (dd, J = 13.6 Hz, J = 7.2 Hz, 1H), 2.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.6, 168.4, 144.6, 137.4, 136.8, 136.5, 136.1, 134.2, 133.6, 130.2, 129.4, 129.2, 128.8, 128.7, 128.2, 128.0, 127.9, 127.6, 127.5, 126.6, 51.5, 50.5, 49.2, 40.3, 21.5; IR (neat) 2924, 2853, 1701(s), 1490, 1357, 1211, 1168, 1090, 813, 700, 586, 545; HRESIMS Calcd for [C33H30ClNNaO5S]+ (M + Na+) 610.1425, found 610.1406. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-(4-bromobenzylidene)-5-oxo-4-phenylpentanoate (3n). Pale yellow oil (159.4 mg, 84%). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.27−7.15 (m, 10H), 6.96−6.92 (m, 2H), 6.85 (d, J = 8.5 Hz, 2H), 6.26 (s, 1H), 5.17 (d, J = 17.0 Hz, 1H), 4.74 (d, J = 16.5 Hz, 1H), 4.35−4.25 (m, 1H), 3.44 (s, 3H), 3.01 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.6, 168.4, 144.6, 137.4, 136.8, 136.5, 136.1, 134.6, 130.9, 130.3, 129.7, 129.2, 128.8, 128.7, 128.2, 127.9, 127.6, 127.5, 126.7, 121.9, 51.5, 50.5, 49.2, 40.3, 21.6; IR (neat) 2924, 2853, 1701(s), 1486, 1454, 1357, 1167, 1118, 811, 700, 545; HRESIMS Calcd for [C33H30BrNNaO5S]+ (M + Na+) 654.0920, found 654.0918. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-(4-methylbenzylidene)-5-oxo-4-phenylpentanoate (3o). Pale yellow oil (155.0 mg, 91%). 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 8.0 Hz, 2H), 7.30−7.14 (m, 10H), 7.05 (d, J = 7.5 Hz, 2H), 6.97−6.93 (m, 2H), 6.89 (d, J = 8.0 Hz, 2H), 6.27 (s, 1H), 5.17 (d, J = 17.0 Hz, 1H), 4.78 (d, J = 17.0 Hz, 1H), 4.35−4.25 (m, 1H), 3.45 (s, 3H), 3.01 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 2.38 (s, 3H), 2.32 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.9, 169.1, 144.5, 138.4, 137.8, 137.0, 136.6, 136.2, 132.8, 129.7, 129.3, 128.8, 128.7, 128.6, 128.3, 128.2, 128.0, 127.5, 126.7, 51.4, 50.6, 49.2, 40.5, 21.6, 21.2; IR (neat) 3029, 2924, 1701(s), 1495, 1454, 1358, 1168, 1118, 811, 700, 585; HRESIMS Calcd for [C34H33NNaO5S]+ (M + Na+) 590.1972, found 590.1944. (Z)-Methyl-5-(N-benzyl-4-methylphenylsulfonamido)-2-(4-methoxybenzylidene)-5-oxo-4-phenylpentanoate (3p). Pale yellow oil (124.3 mg, 71%). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2H), 7.29−7.14 (m, 10H), 6.99 (d, J = 8.5 Hz, 2H), 6.96−6.93 (m, 2H), 6.78 (d, J = 8.5 Hz, 2H), 6.26 (s, 1H), 5.17 (d, J = 17.0 Hz, 1H), 4.78 (d, J = 17.0 Hz, 1H), 4.35−4.26 (m, 1H), 3.78 (s, 3H), 3.46 (s, 10154
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
Article
The Journal of Organic Chemistry
(R,Z)-Methyl-2-benzylidene-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-5-oxo-4-(p-tolyl)pentanoate (6d). Pale yellow oil (145.5 mg, 75%). 1H NMR (500 MHz, CDCl3) δ 7.44−7.40 (m, 4H), 7.35−7.31 (m, 2H), 7.28−7.22 (m, 6H), 7.02 (d, J = 7.5 Hz, 2H), 7.00−6.96 (m, 2H), 6.84 (d, J = 8.0 Hz, 2H), 6.37 (s, 1H), 5.60 (q, J = 7.0 Hz, 1H), 4.51 (t, J = 7.0 Hz, 1H), 3.58 (s, 3H), 3.06 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.58 (dd, J = 7.5 Hz, J = 14.0 Hz, 1H), 2.31 (s, 3H), 1.62 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 173.3, 169.5, 139.4, 138.8, 138.2, 137.2, 135.8, 133.8, 131.7, 129.8, 129.7, 129.4, 128.4, 128.3, 128.0, 127.9(7), 127.9(0), 127.8(7), 127.5, 127.0, 56.9, 51.5, 50.9, 40.8, 21.0, 17.7; IR (neat) 2924, 2853, 1707(s), 1573, 1359, 1170, 1069, 742, 696, 613; HRESIMS Calcd for [C34H32BrNNaO5S]+ (M + Na+) 668.1077, found 668.1077. (R,Z)-Methyl-2-benzylidene-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-4-(4-methoxyphenyl)-5-oxopentanoate (6e). Pale yellow oil (121.3 mg, 61%). 1H NMR (500 MHz, CDCl3) δ 7.46−7.42 (m, 4H), 7.35−7.31 (m, 2H), 7.27−7.20 (m, 6H), 6.98 (d, J = 7.0 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 6.76−6.70 (m, 2H), 6.35 (s, 1H), 5.61 (q, J = 7.0 Hz, 1H), 4.46 (t, J = 7.0 Hz, 1H), 3.77 (s, 3H), 3.58 (s, 3H), 3.04 (dd, J = 6.5 Hz, J = 14.0 Hz, 1H), 2.56 (dd, J = 7.0 Hz, J = 14.0 Hz, 1H), 1.64 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 173.5, 169.5, 158.9, 139.4, 138.8, 138.2, 135.8, 131.7, 129.8, 129.6, 129.1, 128.8, 128.4, 128.3, 128.0, 127.9, 127.8, 127.4, 127.0, 114.0, 56.8, 55.2, 51.5, 50.4, 40.8, 17.8; IR (neat) 3027, 2949, 1706(s), 1573, 1511, 1358, 1251, 1170, 1069, 742, 697, 614; HRESIMS Calcd for [C34H32BrNNaO6S]+ (M + Na+) 684.1026, found 684.1028. (R,Z)-Methyl-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-2-(4-fluorobenzylidene)-5-oxo-4-phenylpentanoate (6f). Pale yellow oil (134.7 mg, 69%). 1H NMR (500 MHz, CDCl3) δ 7.49−7.39 (m, 4H), 7.35−7.30 (m, 2H), 7.24−7.19 (m, 6H), 6.98−6.93 (m, 6H), 6.31 (s, 1H), 5.59 (q, J = 7.0 Hz, 1H), 4.55 (t, J = 7.0 Hz, 1H), 3.60 (s, 3H), 3.05 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.59 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 1.61 (d, J = 7.0 Hz, 3H); 13 C NMR (125 MHz, CDCl3) δ 173.0, 169.1, 162.3 (J = 246.5 Hz), 139.3, 138.7, 137.6, 136.9, 131.8, 129.9 (J = 8.1 Hz), 129.8, 129.5, 128.7, 128.5, 128.3, 128.0, 127.5, 126.9, 114.9 (J = 21.5 Hz), 56.9, 51.6, 51.2, 40.8, 17.6; IR (neat) 3030, 2948, 1708(s), 1573, 1507, 1389, 1360, 1226, 1171, 1010, 742, 699; HRESIMS Calcd for [C33H29BrFNNaO5S]+ (M + Na+) 672.0826, found 672.0827. (R,Z)-Methyl-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-2-(3-methylbenzylidene)-5-oxo-4-phenylpentanoate (6g). Pale yellow oil (98.9 mg, 51%). 1H NMR (500 MHz, CDCl3) δ 7.44−7.40 (m, 4H), 7.35−7.30 (m, 2H), 7.24−7.20 (m, 6H), 7.17−7.12 (m, 1H), 7.05 (d, J = 7.5 Hz, 1H), 6.98−6.93 (m, 2H), 6.80−6.77 (m, 2H), 6.30 (s, 1H), 5.60 (q, J = 7.0 Hz, 1H), 4.55 (t, J = 7.0 Hz, 1H), 3.58 (s, 3H), 3.06 (dd, J = 13.5 Hz, J = 6.0 Hz, 1H), 2.58 (dd, J = 13.5 Hz, J = 7.0 Hz, 1H), 2.30 (s, 3H), 1.62 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 173.1, 169.6, 139.3, 138.7, 138.3, 137.5, 136.9, 135.6, 131.8, 129.8, 129.3, 128.7, 128.5, 128.3, 128.0, 127.8, 127.4(2), 127.4(1), 127.0, 125.0, 56.8, 51.5, 51.2, 40.8, 21.3, 17.6; IR (neat) 3029, 2946, 1706(s), 1573, 1359, 1170, 1069, 742, 698, 612; HRESIMS Calcd for [C34H32BrNNaO5S]+ (M + Na+) 668.1077, found 668.1078. (R,Z)-Methyl-2-benzylidene-5-(4-bromo-N-((S)-1-phenylethyl)phenylsulfonamido)-5-oxo-4-phenylpentanoate (6a′). Pale yellow oil (132.8 mg, 70%). 1H NMR (500 MHz, CDCl3) δ 7.49−7.45 (m, 4H), 7.30−7.13 (m, 9H), 7.05 (d, J = 7.0 Hz, 2H), 7.00 (d, J = 7.0 Hz, 2H), 6.96 (d, J = 7.5 Hz, 2H), 6.37 (s, 1H), 5.48 (q, J = 7.0 Hz, 1H), 4.59 (t, J = 7.5 Hz, 1H), 3.55 (s, 3H), 2.94 (dd, J = 13.5 Hz, J = 6.0 Hz, 1H), 2.64 (dd, J = 13.5 Hz, J = 6.5 Hz, 1H), 1.85 (d, J = 7.0 Hz, 3H); 13 C NMR (125 MHz, CDCl3) δ 172.8, 169.3, 138.7, 138.6, 137.9, 137.1, 135.8, 132.0, 130.0, 129.7, 128.8, 128.6, 128.3, 128.1, 128.0, 127.9, 127.5, 127.3, 127.1, 57.2, 51.9, 51.5, 40.6, 18.1; IR (neat) 3027, 2925, 1706(s), 1573, 1389, 1360, 1171, 1069, 742, 697, 611; HRESIMS Calcd for [C33H30BrNNaO5S]+ (M + Na+) 654.0920, found 654.0921. (R,Z)-4-(Methoxycarbonyl)-2,5-diphenylpent-4-enoic acid (7a). Compound 7a was prepared according to the known procedure.17 Pale yellow oil (47.2 mg, 76%). [α]D20 = −55.3° (c = 1.0, CHCl3). 84% ee (determined by HPLC: Chiralpak ADH Column, 15/85 i-
3H), 3.00 (dd, J = 6.0 Hz, J = 14.0 Hz, 1H), 2.53 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.9, 169.1, 159.4, 144.5, 138.4, 137.1, 136.6, 136.2, 129.9, 129.3, 128.7, 128.3, 128.1, 127.9, 127.4(8), 127.4(7), 126.7, 113.3, 55.2, 51.4, 50.7, 49.2, 40.6, 21.6; IR (neat) 2950, 2926, 1702(s), 1605, 1510, 1356, 1255, 1168, 813, 700, 544; HRESIMS Calcd for [C34H33NNaO6S]+ (M + Na+) 606.1921, found 606.1892. (Z)-N-Benzyl-2,4,5-triphenyl-N-tosylpent-4-enamide (3q). Colorless oil (145.8 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 8.0 Hz, 2H), 7.22−7.12 (m, 11H), 7.08−7.04 (m, 2H), 7.01−6.96 (m, 3H), 6.90−6.85 (m, 2H), 6.84−6.80 (m, 2H), 6.69−6.64 (m, 2H), 6.07 (s, 1H), 4.90 (d, J = 16.8 Hz, 1H), 4.72 (d, J = 16.8 Hz, 1H), 3.96 (t, J = 6.8 Hz, 1H), 3.18 (dddd, J = 14.4 Hz, J = 13.6 Hz, J = 7.6 Hz, J = 6.8 Hz, 1H), 2.72 (dd, J = 14.4 Hz, J = 6.8 Hz, 1H), 2.37 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 173.1, 144.4, 139.7, 138.3, 137.2, 136.8, 136.4, 136.3, 129.3, 129.2, 128.9, 128.7, 128.6, 128.5, 128.4, 128.1, 128.0, 127.6, 127.4, 127.3, 127.1, 126.7, 126.2, 49.4, 49.2, 44.9, 21.5; IR (neat) 3028, 2923, 1698(s), 1597, 1494, 1356, 1167, 1088, 755, 733, 698; HRESIMS Calcd for [C37H33NNaO3S]+ (M + Na+) 594.2073, found 594.2070. (2S,3S)-N-Benzyl-2,3-diphenyl-N-tosylpent-4-enamide (3r). Pale yellow oil (117.5 mg, 79%). 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.36−7.28 (m, 5H), 7.18 (d, J = 8.4 Hz, 2H), 7.04− 6.92 (m, 6H), 6.83−6.77 (m, 2H), 6.75−6.70 (m, 2H), 5.69 (dddd, J = 18.4 Hz, J = 10.4 Hz, J = 8.0 Hz, J = 1.2 Hz, 1H), 5.17 (d, J = 16.4 Hz, 1H), 4.88−4.76 (m, 3H), 4.47 (d, J = 10.4 Hz, 1H), 3.90 (dd, J = 10.8 Hz, J = 2.8 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 172.6, 144.6, 140.3, 138.3, 136.6, 136.5, 135.3, 129.4, 128.7, 128.6, 128.1, 128.0, 127.9, 127.6, 127.5, 127.0, 126.2, 116.6, 56.3, 54.7, 49.4, 21.5; IR (neat) 3029, 2923, 1697(s), 1495, 1454, 1356, 1167, 1088, 759, 698, 584, 544; HRESIMS Calcd for [C31H29NNaO3S]+ (M + Na+) 518.1760, found 518.1762. (R,Z)-Methyl-2-benzylidene-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-5-oxo-4-phenylpentanoate (6a). Pale yellow oil (132.8 mg, 70%). 1H NMR (500 MHz, CDCl3) δ 7.46−7.40 (m, 4H), 7.35−7.30 (m, 2H), 7.28−7.19 (m, 9H), 6.99−6.93 (m, 4H), 6.35 (s, 1H), 5.60 (q, J = 7.0 Hz, 1H), 4.55 (t, J = 7.0 Hz, 1H), 3.59 (s, 3H), 3.07 (dd, J = 13.5 Hz, J = 6.0 Hz, 1H), 2.60 (dd, J = 13.5 Hz, J = 6.5 Hz, 1H), 1.62 (d, J = 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 173.2, 169.5, 139.3, 138.7, 138.4, 136.9, 135.8, 131.8, 129.8, 129.5, 128.7, 128.5, 128.4, 128.1, 128.0(1), 127.9(7), 127.9, 127.5, 127.4, 127.0, 56.9, 51.6, 51.3, 40.8, 17.7; IR (neat) 3027, 2925, 1706(s), 1573, 1389, 1360, 1171, 1069, 742, 697, 611; HRESIMS Calcd for [C33H30BrNNaO5S]+ (M + Na+) 654.0920, found 654.0920. (R,Z)-Methyl-2-benzylidene-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-4-(4-fluorophenyl)-5-oxopentanoate (6b). Pale yellow oil (97.6 mg, 50%). 1H NMR (500 MHz, CDCl3) δ 7.56−7.46 (m, 4H), 7.32−7.24 (m, 5H), 7.23−7.19 (m, 3H), 6.99−6.93 (m, 2H), 6.88−6.82 (m, 4H), 6.31 (s, 1H), 5.66 (q, J = 7.0 Hz, 1H), 4.45 (t, J = 7.0 Hz, 1H), 3.59 (s, 3H), 3.00 (dd, J = 6.5 Hz, J = 13.5 Hz, 1H), 2.54 (dd, J = 7.0 Hz, J = 13.5 Hz, 1H), 1.70 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 173.6, 169.5, 162.0 (J = 245.3 Hz), 139.3, 138.7, 138.6, 135.6, 132.5 (J = 3.1 Hz), 131.9, 129.8, 129.7 (J = 8.0 Hz), 129.2, 128.7, 128.5, 128.0(2), 128.0(0), 127.6, 126.9, 115.4 (J = 15.0 Hz), 56.6, 51.6, 50.5, 41.0, 18.0; IR (neat) 2925, 2853, 1704(s), 1573, 1507, 1359, 1227, 1170, 1069, 742, 696; HRESIMS Calcd for [C33H29BrFNNaO5S]+ (M + Na+) 672.0826, found 672.0827. (R,Z)-Methyl-2-benzylidene-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-4-(4-chlorophenyl)-5-oxopentanoate (6c). Pale yellow oil (108.1 mg, 54%). 1H NMR (500 MHz, CDCl3) δ 7.56−7.48 (m, 4H), 7.31−7.25 (m, 5H), 7.23−7.19 (m, 3H), 7.15−7.12 (m, 2H), 6.99−6.94 (m, 2H), 6.80 (d, J = 8.5 Hz, 2H), 6.33 (s, 1H), 5.67 (q, J = 7.0 Hz, 1H), 4.45 (t, J = 7.0 Hz, 1H), 3.59 (s, 3H), 2.99 (dd, J = 6.5 Hz, J = 13.5 Hz, 1H), 2.53 (dd, J = 6.5 Hz, J = 13.5 Hz, 1H), 1.71 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 173.4, 169.5, 139.3, 138.7, 138.6, 135.6, 135.3, 133.3, 132.0, 129.8, 129.4, 129.1, 128.7, 128.6, 128.5, 128.1, 128.0, 127.6, 126.9, 56.6, 51.6, 50.7, 40.9, 18.0; IR (neat) 2924, 2853, 1707(s), 1492, 1361, 1170, 1069, 742, 696, 614; HRESIMS Calcd for [C33H29BrClNNaO5S]+ (M + Na+) 688.0531, found 688.0500. 10155
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
The Journal of Organic Chemistry
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PrOH/hexane, 1.0 mL/min, 220 nm; tR = 8.97 min (major), 12.36 min (minor)). 1H NMR (500 MHz, CDCl3) δ 7.34−7.30 (m, 4H), 7.28−7.21 (m, 4H), 7.11−7.07 (m, 2H), 6.58 (s, 1H), 3.93 (t, J = 7.5 Hz, 1H), 3.56 (s, 3H), 3.17 (ddd, J = 14.0 Hz, J = 7.5 Hz, J = 0.5 Hz, 1H), 2.83 (ddd, J = 14.0 Hz, J = 7.5 Hz, J = 0.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 178.5, 169.3, 137.5, 137.4, 135.8, 130.3, 128.7, 128.2, 128.0(2), 128.0(1), 127.9, 127.7, 51.6, 50.6, 38.8; IR (neat) 2925, 2853, 1709(s), 1494, 1435, 1232, 1180, 1117, 750, 697; HRESIMS Calcd for [C19H18NaO4]+ (M + Na+) 333.1097, found 333.1095. (R,Z)-4-(Methoxycarbonyl)-5-phenyl-2-(p-tolyl)pent-4-enoic acid (7b). Compound 7b was prepared according to the known procedure.17 Pale yellow oil (46.7 mg, 72%). [α]D20 = −63.1° (c = 1.0, CHCl3). 82% ee (determined by HPLC: Chiralpak ADH Column, 15/85 i-PrOH/hexane, 1.0 mL/min, 220 nm; tR = 9.04 min (major), 11.77 min (minor)). 1H NMR (500 MHz, CDCl3) δ 7.29−7.19 (m, 5H), 7.15−7.08 (m, 4H), 6.60 (s, 1H), 3.89 (t, J = 7.5 Hz, 1H), 3.56 (s, 3H), 3.15 (dd, J = 14.0 Hz, J = 8.0 Hz, 1H), 2.81 (dd, J = 14.0 Hz, J = 7.0 Hz, 1H), 2.31 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 178.7, 169.4, 137.3, 137.2, 135.8, 134.5, 130.5, 129.4, 128.0(4), 128.0(1), 127.9(9), 127.8, 51.6, 50.2, 38.8, 21.0; IR (neat)2924, 2853, 1709(s), 1513, 1435, 1231, 1179, 1114, 1075, 749, 695; HRESIMS Calcd for [C20H20NaO4]+ (M + Na+) 347.1254, found 347.1259. (R,Z)-5-(4-Fluorophenyl)-4-(methoxycarbonyl)-2-phenylpent-4enoic acid (7c). Compound 7c was prepared according to the known procedure.17 Pale yellow oil (52.5 mg, 80%). [α]D20 = −36.6° (c = 0.5, CHCl3). 76% ee (determined by HPLC: Chiralpak ADH Column, 15/ 85 i-PrOH/hexane, 1.0 mL/min, 220 nm; tR = 8.92 min (major), 13.28 min (minor)). 1H NMR (500 MHz, CDCl3) δ 7.34−7.30 (m, 4H), 7.29−7.26 (m, 1H), 7.11−7.05 (m, 2H), 6.97−6.90 (m, 2H), 6.54 (s, 1H), 3.93 (t, J = 7.5 Hz, 1H), 3.59 (s, 3H), 3.16 (dd, J = 14.0 Hz, J = 7.5 Hz, 1H), 2.82 (dd, J = 14.0 Hz, J = 7.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 178.0, 169.0, 162.4 (d, J = 246.3 Hz), 137.5, 136.6, 131.8 (d, J = 3.8 Hz), 130.3, 129.9 (d, J = 8.8 Hz), 128.7, 128.2, 127.7, 115.0 (d, J = 22.5 Hz), 51.6, 50.6, 38.9; IR (neat) 2925, 2854, 1710(s), 1513, 1493, 1435, 1378, 1231, 1115, 811, 749, 696; HRESIMS Calcd for [C19H17FNaO4]+ (M + Na+) 351.1003, found 351.1005. (R,Z)-5-Benzylidene-3-phenyltetrahydro-2H-pyran-2-one (6ab). Compound 6ab was prepared according to the known procedure.18 White solid (mp 152−154 °C, 31.2 mg, 59%, 3 steps). For details on X-ray crystallography information, see the Supporting Information. [α]D 20 = +15.7° (c = 1.0, CHCl3). 86% ee (determined by HPLC: Chiralcel AD-H Column, 10/90 i-PrOH/hexane, 1.0 mL/min, 254 nm, 25 °C; tR = 19.23 min (minor), 16.23 min (major)). 1H NMR (400 MHz, CDCl3) δ 7.42−7.21 (m, 8H), 7.11−7.05 (m, 2H), 6.58− 6.52 (m, 1H), 5.19−5.12 (m, 2H), 3.99 (dd, J = 9.2 Hz, 6.8 Hz, 1H), 3.14−3.04 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 172.7, 136.7, 135.5, 130.5, 128.7, 128.5, 128.4, 128.0, 127.6, 127.4, 68.2, 46.4, 35.4; IR (neat) 2926, 1736(s), 1443, 1252, 1156, 1051, 1021, 973, 745, 697; HRESIMS Calcd for [C18H16NaO2]+ (M + Na+) 287.1043, found 287.1030.
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ACKNOWLEDGMENTS We are grateful for financial support from the National Natural Science Foundation of China (21622204 and 21572186), the President Research Funds from Xiamen University (20720150045), NFFTBS (J1310024), and XMU Training Program of Innovation and Enterpreneurship for Undergraduates (2016G10384076).
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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.7b01612. 1 H and 13C NMR spectra for all described compounds (PDF) Crystal data (CIF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Long-Wu Ye: 0000-0003-3108-2611 Notes
The authors declare no competing financial interest. 10156
DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
Article
The Journal of Organic Chemistry Y.-F.; Liu, S.; Zhao, T.; Zhang, W.; Lu, X.; Ye, L.-W. Chem. Sci. 2015, 6, 1265. (9) Zhou, B.; Li, L.; Zhu, X.-Q.; Yan, J.-Z.; Guo, Y.-L.; Ye, L.-W. Angew. Chem., Int. Ed. 2017, 56, 4015. (10) For recent selected examples, see: (a) Fustero, S.; SánchezRoselló, M.; Aceña, J. L.; Fernández, B.; Asensio, A.; Sanz-Cervera, J. F.; del Pozo, C. J. Org. Chem. 2009, 74, 3414. (b) Virolleaud, M. A.; Menant, C.; Fenet, B.; Piva, O. Tetrahedron Lett. 2006, 47, 5127. (c) Hutton, T. K.; Muir, K.; Procter, D. Org. Lett. 2002, 4, 2345. (d) Agatsuma, T.; Ogawa, H.; Akasaka, K.; Asai, A.; Yamashita, Y.; Mizukami, T.; Akinaga, S.; Saitoh, Y. Bioorg. Med. Chem. 2002, 10, 3445. (11) Feng, X.; Yuan, Y.-Q.; Cui, H.-L.; Jiang, K.; Chen, Y.-C. Org. Biomol. Chem. 2009, 7, 3660. (12) During the preparation of our manuscript, a beautiful study on the gold-catalyzed 1,4-carbooxygenation of 3-en-1-ynamides via a nonClaisen pathway was reported by Liu and co-workers; see: Giri, S. S.; Lin, L.-H.; Jadhav, P. D.; Liu, R.-S. Adv. Synth. Catal. 2017, 359, 590. (13) CCDC 1557608 (6ab) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre. (14) (a) Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew. Chem., Int. Ed. 2009, 48, 4381. (b) Yang, Y.; Zhang, X.; Liang, Y. Tetrahedron Lett. 2012, 53, 6557. (c) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, 1151. (15) Dunetz, J. R.; Danheiser, R. L. Org. Lett. 2003, 5, 4011. (16) (a) Hoen, R.; Tiemersma-Wegman, T.; Procuranti, B.; Lefort, L.; de Vries, J. G.; Minnaard, A. J.; Feringa, B. L. Org. Biomol. Chem. 2007, 5, 267. (b) Jeong, Y.; Ryu, J.-S. J. Org. Chem. 2010, 75, 4183. (c) Bunescu, A.; Wang, Q.; Zhu, J.-P. Org. Lett. 2015, 17, 1890. (17) Bauer, T.; Gajewiak, J. Synthesis 2004, 1, 20. (18) (a) Li, J.-Q.; Liu, J.; Krajangsri, S.; Chumnanvej, N.; Singh, T.; Andersson, P. G. ACS Catal. 2016, 6, 8342. (b) Cheikh, A. B.; Craine, L. E.; Recher, S. G.; Zemlicka, J. J. Org. Chem. 1988, 53, 929.
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DOI: 10.1021/acs.joc.7b01612 J. Org. Chem. 2017, 82, 10149−10157
