Yttrium-catalyzed tandem intermolecular hydroalkoxylation/ claisen rearrangement

Article abstract of DOI:10.1021/acs.joc.7b01612

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.

Full text of DOI:10.1021/acs.joc.7b01612

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Article
Yttrium-Catalyzed Tandem Intermolecular
Hydroalkoxylation/Claisen Rearrangement
Bo Zhou, Long Li, Xin Liu, Tong-De Tan, Jinxian Liu, and Long-Wu Ye
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01612 • Publication Date (Web): 28 Aug 2017
Downloaded from http://pubs.acs.org on August 29, 2017
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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
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Claisen rearrangement is a powerful reaction in the construction of carbon-carbon bonds.1 Recently,
transition-metal-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 ꢀ,/-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 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
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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 that this non-noble metal-catalyzed tandem sequence might be extended into its
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intermolecular
version.
Herein,
we
report
the
yttrium-catalyzed
intermolecular
hydroalkoxylation/Claisen rearrangement sequence, providing a variety of ꢀ,/-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 ꢀ,/-carboxylic acids.
Scheme 1. Catalytic Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement Based on
Ynamides
a) Brønsted acid-catalyzed tandem hydroalkoxylation/Claisen rearrangement (Hsung)
O
O
O
1
1' O
O
R3
OH
2
O
3
O
O
2'
N
R3
N
R1
N
R3
PNBSA
3'
R1
R1
R2
R2
R2
b) Zinc-catalyzed tandem hydroalkoxylation/Claisen rearrangement (Gaunt)
O
O
O
1
O
1'O
2'
R2
OH
O
2
3
O
O
N
R2
N
R1
N
R2
[Zn]
3'
1
1
Me Me
Me
R
Me
Me Me
R
c) Yttrium-catalyzed tandem hydroalkoxylation/Claisen rearrangement (this work)
OH
MeO2C
CO2Me
O
PG
R2
2
3
1
1'O
N
R1
PG
Ph
N
R2
PG R1 CO2Me
2'
N
R2
[Y]
Ph
3'
Ph R1
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 afford the corresponding
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yield (%)b
4
5
6
entry
catalyst
reaction conditions
5 Å MS, PhCl, 80 oC, 3 h
3a 3aa
88 <5
1
Y(OTf)3
7
8
9
PhCl, 80 oC, 3 h
2
Y(OTf)3
Y(OTf)3
Y(OTf)3
Zn(OTf)2
Cu(OTf)2
12 72
3 Å MS, PhCl, 80 oC, 3 h
30
7
3c
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4 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
55 29
82 11
4d
5
6
7
5 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
29
47
46 40
Sc(OTf)3
8
4
77
12
9
In(OTf)3
Yb(OTf)3
9
78
62
10e
Ph3PAuNTf2
IPrAuNTf2
5 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
5 Å MS, PhCl, 80 oC, 3 h
11e
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66 20
26 55
PNBSA
HOTf
8
90
5 Å MS, toluene, 80 oC, 3 h
5 Å MS, DCE, 80 oC, 3 h
5 Å MS, PhCl, 60 oC, 12 h
Y(OTf)3
Y(OTf)3
Y(OTf)3
75 15
61 25
72 12
a Reactions run in vials; [1a] = 0.05 M. b Estimated by 1H NMR using
diethyl phthalate as internal reference.
unreacted after 20 h. d 15% of 1a remained unreacted after 20 h. e
c
60% of 1a remained
5
mol % of catalyst was used.
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 reaction
proceeded well with various aryl-substituted ynamides 1, affording the desired ꢀ,/-unsaturated amides
3a-3g in good to excellent yields (entries 1Þ7). In addition, it was found that alkyl-substituted ynamide
1h was also a suitable substrate for this tandem reaction to produce the corresponding 3h in 61% yield
(entry 8). Different sulfonyl protected ynamides were then examined to deliver the desired amides 3i-3k
in 79-93% yields (entries 9Þ11). Finally, various substituted MBH alcohols 2 were screened, and the
reaction furnished the desired products 3l-3p in generally good to excellent yields (entries 12Þ16).
Importantly, high Z/E ratio (over 15/1) was achieved in all these cases. Thus, this yttrium-catalyzed
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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.
Experimental Section
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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).
1H 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).
13C 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.8h CuSO4đ5H2O (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.8h,8i
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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) / 7.78 (d, J = 8.5 Hz, 2H), 7.35 œ 7.28 (m, 7H), 7.23 œ 7.18 (m, 2H), 6.96 œ 6.90 (m, 2H), 4.57
(s, 2H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3) / 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.
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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) / 7.78 (d, J = 8.5 Hz, 2H), 7.34 œ 7.29 (m, 7H), 7.22 œ 7.18 (m, 2H) 7.15 œ 7.11 (m, 2H), 4.57 (s,
2H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) / 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) / 7.78 (d, J = 8.0 Hz, 2H), 7.38 œ 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) / 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)
/ 7.78 (d, J = 8.0 Hz, 2H), 7.35 œ 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) / 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.
1
N-benzyl-4-methyl-N-(m-tolylethynyl)benzenesulfonamide (1f). Pale yellow oil (263.0 mg, 70%). H
NMR (500 MHz, CDCl3) / 7.79 (d, J = 10.5 Hz, 2H), 7.36 œ 7.28 (m, 7H), 7.15 œ 7.10 (m, 1H), 7.07 œ
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7.01 (m, 3H), 4.57 (s, 2H), 2.44 (s, 3H), 2.28 (s, 3H); 13C NMR (125 MHz, CDCl3) / 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.
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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) / 7.78 (d, J = 8.0 Hz, 2H), 7.36 œ 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) / 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)
/ 7.76 œ 7.72 (m, 2H), 7.31 œ 7.27 (m, 7H), 4.44 (s, 2H), 2.43 (s, 3H), 2.16 (t, J = 7.0 Hz, 2H), 1.39 œ
1.31 (m, 2H), 1.27 œ 1.16 (m, 6H), 0.86 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) / 144.2, 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)
/ 7.85 œ 7.81 (m, 2H), 7.36 œ 7.28 (m, 5H), 7.24 œ 7.22 (m, 5H), 6.99 œ 6.95 (m, 2H), 4.58 (s, 2H), 3.87
(s, 3H); 13C NMR (125 MHz, CDCl3) / 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,
1
61%). [.]D20 = -45.288º (c = 1.0, CHCl3). H NMR (400 MHz, CDCl3) / 7.58 œ 7.52 (m, 2H), 7.51 œ
7.45 (m, 2H), 7.36 œ 7.32 (m, 2H), 7.31 œ 7.26 (m, 5H), 7.25 œ 7.21 (m, 3H), 5.23 (q, 1H, J = 7.2 Hz),
1.61 (d, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) / 139.5, 137.1, 131.9, 131.2, 128.9, 128.4, 128.3,
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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.
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(S)-4-bromo-N-(1-phenylethyl)-N-(phenylethynyl)benzenesulfonamide (4aa). Pale yellow oil (268.2
mg, 61%). [.]D20 = +35.458º (c = 1.0, CHCl3).
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(R)-4-bromo-N-((4-fluorophenyl)ethynyl)-N-(1-phenylethyl)benzenesulfonamide (4b). Pale yellow oil
(298.0 mg, 65%). [.]D20 = -48.904º (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) / 7.57 œ 7.49 (m, 4H),
7.34 œ 7.30 (m, 2H), 7.28 œ 7.21 (m, 5H), 7.02 œ 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) / 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%). [.]D20 = -49.372º (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) / 7.57 œ 7.49 (m, 4H),
7.29 œ 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) /
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%). [.]D20 = -44.358º (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) / 7.54 (d, J = 8.5 Hz, 2H), 7.48
(d, J = 8.5 Hz, 2H), 7.30 œ 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) / 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.
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(R)-4-bromo-N-((4-methoxyphenyl)ethynyl)-N-(1-phenylethyl)benzenesulfonamide (4e). Pale yellow
oil (338.2 mg, 72%). [.]D20 = -45.034º (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) / 7.54 (d, J = 8.5
Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.35 œ 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) / 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.
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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 yellow oil (153.8 mg, 80%). 1H NMR (500 MHz, CDCl3) / 7.38 œ 7.31 (m,
4H), 7.30 œ 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) / 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
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spectroscopic data match those reported.16a Pale yellow oil (195.5 mg, 93%). H NMR (400 MHz,
CDCl3) / 7.36 œ 7.28 (m, 2H), 7.04 œ 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) / 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
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spectroscopic data match those reported.16a Pale yellow oil (204.0 mg, 90%). H NMR (500 MHz,
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CDCl3) / 7.31 œ 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) / 166.5, 141.6, 139.8, 133.5, 128.5, 127.9, 126.2, 72.5, 52.0.
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Methyl-2-((4-bromophenyl)(hydroxy)methyl)acrylate (2d). This compound is known and the
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spectroscopic data match those reported.16a Pale yellow oil (238.6 mg, 88%). H NMR (500 MHz,
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CDCl3) / 7.49 œ 7.45 (m, 2H), 7.28 œ 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) / 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) / 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) / 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
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spectroscopic data match those reported.16a Pale yellow oil (155.6 mg, 70%). H NMR (500 MHz,
CDCl3) / 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) / 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) / 7.38 œ 7.33 (m, 2H), 7.31 œ
7.26 (m, 4H), 7.25 œ 7.18 (m, 4H), 5.65 (s, 1H), 5.49 œ 5.46 (m, 1H), 5.45 œ 5.43 (m, 1H), 2.30 (s, 1H);
13C NMR (100 MHz, CDCl3) / 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:
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(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)).
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(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) / 7.26 œ 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) / 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. 5 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 mL) at
o
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) / 7.65 (d, J = 7.5 Hz, 2H), 7.28 œ 7.20 (m,
11H), 7.16 (d, J = 8.0 Hz, 2H), 7.00 œ 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 œ 4.28 (m, 1H), 3.44 (s, 3H), 3.03 (dd, J = 6.0 Hz, J = 13.5 Hz, 1H), 2.55 (dd, J =
7.0Hz, J = 13.5 Hz, 1H), 2.38 (s, 3H); 13C NMR (125 MHz, CDCl3) / 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,
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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.
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N-benzyl-2-phenyl-N-tosylacetamide (3aa). This compound is known and the spectroscopic data
match those reported.8h Pale yellow oil. 1H NMR (500 MHz, CDCl3) / 7.63 (d, J = 8.5 Hz, 2H), 7.37 œ
7.27 (m, 5H), 7.26 œ 7.19 (m, 5H), 7.00 œ 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) / 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.
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(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) / 7.64 (d, J = 8.0 Hz,
2H), 7.28 œ 7.21 (m, 8H), 7.15 (d, J = 8.0 Hz, 2H), 7.01 œ 6.97 (m, 2H), 6.95 œ 6.90 (m, 2H), 6.89 œ 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 œ 4.37 (m, 1H), 3.48 (s,
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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); C
NMR (125 MHz, CDCl3) / 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) / 7.63 (d, J = 8.0 Hz,
2H), 7.30 œ 7.21 (m, 8H), 7.17 œ 7.11 (m, 4H), 7.02 œ 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 œ 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) / 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,
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1702(s), 1492, 1357, 1168, 1090, 812, 732, 586, 543; HRESIMS Calcd for [C33H30ClNNaO5S]+ (M +
Na+) 610.1425, found 610.1426.
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(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) / 7.62 (d, J = 8.0 Hz,
2H), 7.29 (d, J = 8.0 Hz, 2H), 7.27 œ 7.22 (m, 8H), 7.15 (d, J = 8.0 Hz, 2H), 7.02 œ 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 œ 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) / 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.
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(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) / 7.66 (d, J = 8.0 Hz, 2H), 7.28 œ 7.22 (m,
8H), 7.17 (d, J = 8.0, 2H), 7.03 œ 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 Hz, 1H), 4.28 œ 4.19 (m, 1H), 3.42 (s, 3H), 3.01 (dd, J = 14.0 Hz, J = 6.5 Hz,
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1H), 2.52 (dd, J = 13.5 Hz, J = 7.0 Hz, 1H), 2.39 (s, 3H), 2.31 (s, 3H); C NMR (125 MHz, CDCl3) /
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) / 7.66 (d, J = 8.0 Hz, 2H), 7.30 œ 7.21 (m,
8H), 7.16 (d, J = 8.0 Hz, 2H), 7.12 œ 7.07 (m, 1H), 7.05 œ 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 œ 4.22 (m, 1H), 3.44 (s, 3H),
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NMR (125 MHz, CDCl3) / 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.
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(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) / 7.66 (d, J = 8.5 Hz,
2H), 7.27 œ 7.22 (m, 8H), 7.16 (d, J = 8.0 Hz, 2H), 7.01 œ 6.97 (m, 2H), 6.90 œ 6.85 (m, 2H), 6.75 œ 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 œ 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) / 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) / 7.67 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 7.5 Hz, 2H), 7.33 œ 7.27 (m, 6H),
7.12 œ 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
œ 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 œ 1.25 (m, 4H), 1.18 œ 1.10 (m, 2H), 1.05 œ 0.91 (m, 4H), 0.82 (t, J = 7.0 Hz, 3H); 13C NMR
(125 MHz, CDCl3) / 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) / 7.71 (d, J = 8.8 Hz, 2H), 7.27 œ 7.18 (m,
11H), 7.01 œ 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 =
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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) / 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.
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(Z)-methyl-5-(N-benzyl-4-bromophenylsulfonamido)-2-benzylidene-5-oxo-4-phenylpentanoate
(3j).
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Pale yellow oil (172.6 mg, 93%). H NMR (500 MHz, CDCl3) / 7.60 (d, J = 8.5 Hz, 2H), 7.47 (d, J =
8.5 Hz, 2H), 7.29 œ 7.20 (m, 11H), 7.00 œ 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,
13
J = 7.5 Hz, J = 13.5 Hz,1H); C NMR (125 MHz, CDCl3) / 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)-5-oxo-4-phenylpentanoate
(3k).
Pale
yellow oil (113.2 mg, 79%). 1H NMR (500 MHz, CDCl3) / 7.37 œ 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 œ 4.37 (m, 1H), 3.49 (s, 3H),
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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); C NMR
(125 MHz, CDCl3) / 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) / 7.64 (d, J = 8.0
Hz, 2H), 7.27 œ 7.16 (m, 10H), 7.00 œ 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 œ 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
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Hz, J = 14.0 Hz, 1H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) / 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.
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(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) / 7.64 (d, J = 7.6
Hz, 2H), 7.29 œ 7.13 (m, 12H), 6.99 œ 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 œ 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) / 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) / 7.64 (d, J = 8.0
Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.27 œ 7.15 (m, 10H), 6.96 œ 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 œ 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) / 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) / 7.65 (d, J = 8.0
Hz, 2H), 7.30 œ 7.14 (m, 10H), 7.05 (d, J = 7.5 Hz, 2H), 6.97 œ 6.93 (m, 2H), 6.89 (d, J = 8.0 Hz, 2H),
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6.27 (s, 1H), 5.17 (d, J = 17.0 Hz, 1H), 4.78 (d, J = 17.0 Hz, 1H), 4.35 œ 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) / 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.
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(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) / 7.64 (d, J = 8.0
Hz, 2H), 7.29 œ 7.14 (m, 10H), 6.99 (d, J = 8.5 Hz, 2H), 6.96 œ 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 œ 4.26 (m, 1H), 3.78 (s, 3H), 3.46
(s, 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) / 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.
1
(Z)-N-benzyl-2,4,5-triphenyl-N-tosylpent-4-enamide (3q). Colourless oil (145.8 mg, 85%). H NMR
(400 MHz, CDCl3) / 7.52 (d, J = 8.0 Hz, 2H), 7.22 œ 7.12 (m, 11H), 7.08 œ 7.04 (m, 2H), 7.01 œ 6.96 (m,
3H), 6.90 œ 6.85 (m, 2H), 6.84 œ 6.80 (m, 2H), 6.69 œ 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); 13C NMR (100 MHz, CDCl3) /
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.
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(2S,3S)-N-benzyl-2,3-diphenyl-N-tosylpent-4-enamide (3r). Pale yellow oil (117.5 mg, 79%). H
NMR (400 MHz, CDCl3) / 7.57 (d, J = 8.4 Hz, 2H), 7.36 œ 7.28 (m, 5H), 7.18 (d, J = 8.4 Hz, 2H), 7.04
œ 6.92 (m, 6H), 6.83 œ 6.77 (m, 2H), 6.75 œ 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 œ 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) / 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.
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(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) / 7.46 œ 7.40 (m,
4H), 7.35 œ 7.30 (m, 2H), 7.28 œ 7.19 (m, 9H), 6.99 œ 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,
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J = 6.5 Hz, 1H), 1.62 (d, J = 6.5 Hz, 3H); C NMR (125 MHz, CDCl3) / 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)-
1
5-oxopentanoate (6b). Pale yellow oil (97.6 mg, 50%). H NMR (500 MHz, CDCl3) / 7.56 œ 7.46 (m,
4H), 7.32 œ 7.24 (m, 5H), 7.23 œ 7.19 (m, 3H), 6.99 œ 6.93 (m, 2H), 6.88 œ 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) / 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.
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chlorophenyl)-5-oxopentanoate (6c). Pale yellow oil (108.1 mg, 54%). H NMR (500 MHz, CDCl3) /
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7.56 œ 7.48 (m, 4H), 7.31 œ 7.25 (m, 5H), 7.23 œ 7.19 (m, 3H), 7.15 œ 7.12 (m, 2H), 6.99 œ 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) / 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.
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(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) / 7.44 œ 7.40 (m,
4H), 7.35 œ 7.31 (m, 2H), 7.28 œ 7.22 (m, 6H), 7.02 (d, J = 7.5 Hz, 2H), 7.00 œ 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) / 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) /
7.46 œ 7.42 (m, 4H), 7.35 œ 7.31 (m, 2H), 7.27 œ 7.20 (m, 6H), 6.98 (d, J = 7.0 Hz, 2H), 6.84 (d, J = 8.5
Hz, 2H), 6.76 œ 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) / 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,
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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.
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(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) / 7.49 œ 7.39 (m,
4H), 7.35 œ 7.30 (m, 2H), 7.24 œ 7.19 (m, 6H), 6.98 œ 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); 13C NMR (125 MHz, CDCl3) / 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.
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(R,Z)-methyl-5-(4-bromo-N-((R)-1-phenylethyl)phenylsulfonamido)-2-(3-methylbenzylidene)-5-oxo-4-
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phenylpentanoate (6g). Pale yellow oil (98.9 mg, 51%). H NMR (500 MHz, CDCl3) / 7.44 œ 7.40 (m,
4H), 7.35 œ 7.30 (m, 2H), 7.24 œ 7.20 (m, 6H), 7.17 œ 7.12 (m, 1H), 7.05 (d, J = 7.5 Hz, 1H), 6.98 œ 6.93
(m, 2H), 6.80 œ 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) / 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 (6aÅ). Pale yellow oil (132.8 mg, 70%). 1H NMR (500 MHz, CDCl3) / 7.49 œ 7.45 (m,
4H), 7.30 œ 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); 13C NMR (125 MHz,
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CDCl3) / 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.
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(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%). [.]D20 = -55.3º (c = 1.0, CHCl3). 84% ee
(determined by HPLC: Chiralpak ADH Column, 15/85 i-PrOH/hexane, 1.0 mL/min, 220 nm; TR = 8.97
1
min (major), 12.36 min (minor)). H NMR (500 MHz, CDCl3) / 7.34 œ 7.30 (m, 4H), 7.28 œ 7.21 (m,
4H), 7.11 œ 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) / 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%). [.]D20 = -63.1º (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) / 7.29 œ 7.19 (m, 5H), 7.15 œ
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) / 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-4-enoic acid (7c). Compound 7c was
prepared according to the known procedure.17 Pale yellow oil (52.5 mg, 80%). [.]D20 = -36.6º (c = 0.5,
CHCl3). 76% ee (determined by HPLC: Chiralpak ADH Column, 15/85 i-PrOH/hexane, 1.0 mL/min,
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220 nm; TR = 8.92 min (major), 13.28 min (minor)). 1H NMR (500 MHz, CDCl3) / 7.34 œ 7.30 (m, 4H),
7.29 œ 7.26 (m, 1H), 7.11 œ 7.05 (m, 2H), 6.97 œ 6.90 (m, 2H), 6.54 (s, 1H), 3.93 (t, J = 7.5 Hz, 1H),
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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); C NMR
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(125 MHz, CDCl3) / 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.
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(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 oC, 31.2 mg, 59%, 3 steps). For details on
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X-ray crystallography information, see the Supporting Information. [.]D = +15.7º (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
1
oC; tR = 19.23 min (minor), 16.23 min (major)). H NMR (400 MHz, CDCl3) / 7.42 œ 7.21 (m, 8H),
7.11 œ 7.05 (m, 2H), 6.58 œ 6.52 (m, 1H), 5.19 œ 5.12 (m, 2H), 3.99 (dd, J = 9.2 Hz, 6.8 Hz, 1H), 3.14 œ
3.04 (m, 2H); 13C NMR (100 MHz, CDCl3) / 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.
ASSOCIATED CONTENT
1
Supporting Information Available. H and 13C NMR spectra for all described compounds. This
material is available free of charge via the Internet at http://pubs.acs.org.
ORCID
Long-Wu Ye: 0000-0003-3108-2611
Notes
The authors declare no competing financial interest.
Acknowledgment. We are grateful for financial support from the National Natural Science
Foundation of China (21622204 and 21572186), the President Research Funds from Xiamen University
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(20720150045), NFFTBS (J1310024), and XMU Training Program of Innovation and Enterpreneurship
for Undergraduates (2016G10384076).
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