The Journal of Organic Chemistry
Article
3.17 (dd, J = 15.2, 6.6 Hz, 1 H), 2.38 (s, 3 H); 13C NMR (176 MHz,
CDCl3) δ 173.8, 146.4, 145.1, 136.2, 130.1, 129.9, 129.3, 126.6, 123.4,
118.4, 115.0, 113.5, 111.8, 56.8, 52.1, 31.0, 21.6; IR (neat, ATR)
3370,1736, 1601, 1362 cm−1. HRMS (ESI+, magnetic sector) m/z:
[M + H]+ calcd for C21H23N2O4S 399.1379; Found 399.1379.
Methyl 3-Phenyl-2-(phenylamino)butanoate (12). General proce-
dure 4 was used for the rearrangement of 11 (48 mg, 0.18 mmol) with
Side Product (E)-Methyl 5-Phenyl-2-(phenylamino)pent-4-enoate
1
(15c′). H NMR (400 MHz, CDCl3) δ 7.36−7.13 (m, 7 H), 6.78−
6.74 (m, 1 H), 6.64 (d, J = 8.0 Hz, 2 H), 6.51 (d, J = 15.7 Hz, 1 H),
6.17−6.14 (m, 1 H), 4.26−4.24 (m, 2 H), 3.74 (s, 3 H), 2.81−2.71
(m, 2 H).
Methyl-3,3-dimethyl-2-(phenylamino)pent-4-enoate (15d). Gen-
eral procedure 4 was used for the reaction of compound 14d (47 mg,
0.2 mmol) with dibutylboron triflate (0.3 mL, 0.3 mmol) and iPr2NEt
(0.06 mL, 0.34 mmol) in 0.7 mL of dichloromethane. The crude
product was purified using flash column chromatography with 95%
hexanes/diethyl ether as the eluent. This procedure afforded 35 mg
(75%) of a 2:1 mixture of 15d and 15d′, a product resulting from the
aza-[1,2]-Wittig rearrangement. After a second careful chromatog-
raphy, small amounts of each pure compound were isolated for
characterization. Title Compound 15d: White solid, mp 45−47 °C. 1H
NMR (400 MHz, CDCl3) δ 7.14 (dd, J = 7.2, 8.5 Hz, 2 H), 6.71 (t, J =
7.3 Hz, 1 H), 6.64−6.56 (m, 2 H), 5.94 (dd, J = 17.4, 10.8 Hz, 1 H),
5.20−5.06 (m, 2 H), 4.09 (d, J = 9.9 Hz, 1 H), 3.84 (d, J = 9.8 Hz, 1
H), 3.66 (s, 3 H), 1.16 (d, J = 13.7 Hz, 6 H); 13C NMR (176 MHz,
CDCl3) δ 173.4, 147.2, 143.2, 129.3, 118.3, 114.2, 113.6, 64.6, 51.6,
40.2, 24.9, 23.7; IR (neat, ATR) 3384, 1736, 1603 cm−1. HRMS (ESI+,
magnetic sector) m/z: [M + H]+ calcd for C14H20NO2 234.1494; Found
234.1488.
i
dibutylboron triflate (0.58 mL, 0.58 mmol) and Pr2NEt (0.13 mL,
0.72 mmol) in 0.2 mL of dichloromethane. The crude product was
purified using flash column chromatography with 90% hexanes/diethyl
ether as the eluent. This procedure afforded 32 mg (66%) of the title
compound as a white solid, mp 55−57 °C. The diastereoselectivity of
the transformation could not be determined through 1H NMR analysis
of the crude reaction mixture prior to purification due to signal overlap
with boron-containing byproducts; the isolated product was obtained
with 1.6:1 dr following purification. Data are for the mixture. 1H NMR
(500 MHz, CDCl3) δ 7.37−7.20 (m, 5 H), 7.12 (t, J = 7.6 Hz, 2 H),
6.73−6.69 (m, 1 H), 6.58−6.54 (m, 2 H), 4.22−4.17 (m, 1.4 H), 3.90
(d, J = 8.7 Hz, 0.6 H), 3.68 (s, 1.8 H), 3.49 (s, 1.2 H), 3.32−3.29 (m,
0.6 H), 3.22−3.20 (m, 0.4 H), 1.46 (d, J = 7.2 Hz, 1.2 H), 1.40 (d, J =
7.1 Hz, 1.8 H); 13C NMR (176 MHz, CDCl3) δ 173.9, 147.1, 142.0,
129.3, 128.6, 127.8, 127.2, 118.5, 113.8, 63.1, 52.0, 43.0, 18.4; IR (neat,
ATR) 3387, 1734 cm−1. HRMS (ESI+, magnetic sector) m/z: [M + H]+
calcd for C17H20NO2 270.1494; Found 270.1480.
Side Product Methyl-5-methyl-2-(phenylamino)hex-4-enoate
1
(15d′). H NMR (400 MHz, CDCl3) δ 7.20−7.11 (m, 2 H), 6.71
Methyl-2-(phenylamino)pent-4-enoate (15a). General procedure
(t, J = 7.3 Hz, 1 H), 6.59 (d, J = 8.0 Hz, 2 H), 5.11 (t, J = 7.5 Hz, 1 H),
4.08 (t, J = 6.1 Hz, 1 H), 3.70 (s, 3 H), 2.61−2.44 (m, 2 H), 1.71 (s,
3 H), 1.60 (s, 3 H); 13C NMR (176 MHz, CDCl3) δ 174.2, 146.7,
136.0, 129.3, 118.2, 118.1, 113.4, 56.5, 52.1, 31.4, 25.9, 17.9; IR (neat,
ATR) 3369, 1738, 1604 cm−1. HRMS (ESI+, magnetic sector) m/z:
[M + H]+ calcd for C14H20NO2 234.1489; Found 234.1486.
4 was used for the reaction of compound 14a (41 mg, 0.2 mmol) with
i
dibutylboron triflate (0.3 mL, 0.3 mmol) and Pr2NEt (0.06 mL,
0.34 mmol) in 0.7 mL of dichloromethane. The crude product was
purified using flash column chromatography with 95% hexanes/diethyl
ether as the eluent. This procedure afforded 29 mg (70%) of the title
compound as a pale yellow oil. 1H NMR (700 MHz, CDCl3) δ 7.19−
7.14 (m, 2 H), 6.74 (t, J = 7.4 Hz, 1 H), 6.63−6.59 (m, 2 H), 5.78
(ddt, J = 17.2, 10.1, 7.2 Hz, 1 H), 5.19−5.13 (m, 2 H), 4.15 (s, 1 H),
3.72 (s, 3 H), 2.64−2.53 (m, 2 H); 13C NMR (176 MHz, CDCl3) δ
173.9, 146.5, 132.7, 129.3, 119.0, 118.4, 113.4, 56.0, 52.1, 37.0; IR
(neat, ATR) 3400, 1737, 1603 cm−1. HRMS (ESI+, magnetic sector)
m/z: [M + H]+ calcd for C12H16NO2 206.1181; Found 206.1171.
(2S*,3R*)-Methyl-3-methyl-2-(phenylamino)pent-4-enoate
(15b). General procedure 4 was used for the reaction of compound
14b (44 mg, 0.2 mmol) with dibutylboron triflate (0.3 mL, 0.3 mmol)
and iPr2NEt (0.06 mL, 0.34 mmol) in 0.7 mL of dichloromethane. The
crude product was purified using flash column chromatography with
95% hexanes/diethyl ether as the eluent. This procedure afforded
Methyl-4-methyl-2-(phenylamino)pent-4-enoate (15e). General
procedure 4 was used for the reaction of compound 14e (44 mg,
0.2 mmol) with dibutylboron triflate (0.3 mL, 0.3 mmol) and iPr2NEt
(0.06 mL, 0.34 mmol) in 0.7 mL of dichloromethane. The crude
product was purified using flash column chromatography with 95%
hexanes/diethyl ether as the eluent. This procedure afforded 24 mg
1
(55%) of the title compound as a colorless oil. H NMR (700 MHz,
CDCl3) δ 7.24−7.13 (m, 2 H), 6.74 (t, J = 7.3 Hz, 1 H), 6.64−6.58
(m, 2 H), 4.89 (s, 1 H), 4.83 (s, 1 H), 4.17 (q, J = 6.7 Hz, 1 H), 4.06
(s, br, 1 H), 3.71 (s, 3 H), 2.58 (dd, J = 6.1, 13.8 Hz, 1 H), 2.50 (dd,
J = 8.2, 13.8 Hz, 1 H), 1.76 (s, 3 H); 13C NMR (176 MHz, CDCl3) δ
174.4, 146.6, 140.7, 129.3, 118.4, 114.5, 113.3, 55.0, 52.1, 41.2, 21.8; IR
(neat, ATR) 3318, 1738, 1603 cm−1. HRMS (ESI+, magnetic sector)
m/z: [M + H]+ calcd for C13H18NO2 220.1338; Found 220.1325.
(2S*,3R*)-Methyl-2-[(4-methoxyphenyl)amino]-3-vinyloctanoate
(15f). General procedure 4 was used for the reaction of compound 14f
(62 mg, 0.2 mmol) with dibutylboron triflate (0.3 mL, 0.3 mmol) and
iPr2NEt (0.06 mL, 0.34 mmol) in 0.7 mL of dichloromethane. The
1
26 mg (59%) of the title compound as a colorless oil. H NMR (700
MHz, CDCl3) δ 7.19−7.14 (m, 2 H), 6.76−6.71 (m, 1 H), 6.64−6.58
(m, 2 H), 5.76 (ddd, J = 17.6, 10.2, 8.4 Hz, 1 H), 5.19−5.08 (m, 2 H),
4.15 (d, J = 9.6 Hz, 1 H), 4.01 (dd, J = 9.4, 5.8 Hz, 1 H), 3.69 (s, 3 H),
2.67−2.64 (m, 1 H), 1.16 (d, J = 7.0 Hz, 3 H); 13C NMR (176 MHz,
CDCl3) δ 173.4, 146.9, 139.1, 129.3, 118.4, 116.5, 113.6, 61.1, 51.8,
41.4, 16.5; IR (neat, ATR) 3396, 1735, 1602 cm−1. HRMS (ESI+, magnetic
sector) m/z: [M + H]+ calcd for C13H18NO2 220.1338; Found 220.1335.
(2S*,3S*)-Methyl-3-phenyl-2-(phenylamino)pent-4-enoate (15c).
General procedure 4 was used for the reaction of compound 14c
(56.3 mg, 0.2 mmol) with dibutylboron triflate (0.3 mL, 0.3 mmol)
crude product was purified using flash column chromatography with
95% hexanes/diethyl ether as the eluent. This procedure afforded
1
36 mg (58%) of the title compound as a colorless oil. H NMR (400
MHz, CDCl3) δ 6.79−6.70 (m, 2 H), 6.63−6.52 (m, 2 H), 5.66−5.57
(m, 1 H), 5.21−5.05 (m, 2 H), 3.97−3.91 (m, 2 H), 3.73 (s, 3 H), 3.66
(s, 3 H), 2.42−2.38 (m, 1 H), 1.64−1.59 (m, 1 H), 1.43−1.26 (m,
7 H), 0.88 (t, J = 6.8 Hz, 3 H); 13C NMR (176 MHz, CDCl3) δ 173.7,
152.8, 141.0, 137.8, 118.1, 115.3, 114.9, 61.4, 55.7, 51.6, 47.7, 31.7,
30.9, 26.8, 22.5, 14.0; IR (neat, ATR) 3394, 1735, 1512 cm−1. HRMS
(ESI+, magnetic sector) m/z: [M + H]+ calcd for C18H28NO3 306.2069;
Found 306.2062.
i
and Pr2NEt (0.06 mL, 0.34 mmol) in 0.7 mL of dichloromethane.
The crude product was purified using flash column chromatography
with 95% hexanes/diethyl ether as the eluent. This procedure afforded
41 mg (73%) of a 4:1 mixture of 15c and 15c′, a product resulting
from the aza-[1,2]-Wittig rearrangement. After a second careful
chromatography, small amounts of each pure compound were isolated
for characterization.
(2S*,3R*)-Methyl-2-[(4-chlorophenyl)amino]-3-ethylpent-4-
enoate (15g). General procedure 4 was used for the reaction of com-
pound 14g (56.3 mg, 0.2 mmol) with dibutylboron triflate (0.3 mL,
0.3 mmol) and iPr2NEt (0.06 mL, 0.34 mmol) in 0.7 mL of
dichloromethane. The crude product was purified using flash column
chromatography with 95% hexanes/diethyl ether as the eluent. This
procedure afforded 35 mg (62%) of the title compound as a colorless
Title Compound 15c. White solid, mp 71−74 °C. 1H NMR
(500 MHz, CDCl3) δ 7.34−7.30 (m, 2 H), 7.32−7.19 (m, 3 H), 7.21−
7.10 (m, 2 H), 6.73 (t, J = 7.3 Hz, 1 H), 6.60 (d, J = 7.8 Hz, 2 H), 6.15
(ddd, J = 16.9, 10.1, 9.0 Hz, 1 H), 5.26−5.16 (m, 2 H), 4.38 (t, J = 7.6
Hz, 1 H), 3.99 (d, J = 8.1 Hz, 1 H), 3.79 (t, J = 8.1 Hz, 1 H), 3.65 (s, 3
H); 13C NMR (126 MHz, CDCl3) δ 173.2, 146.6, 139.2, 136.8, 129.2,
128.8, 127.9, 127.3, 118.6, 117.7, 113.7, 61.3, 53.2, 51.8; IR (neat,
ATR) 3384, 1737, 1601 cm−1. HRMS (ESI+, magnetic sector) m/z:
[M + H]+ calcd for C18H20NO2 282.1494; Found 282.1491.
1
oil. H NMR (700 MHz, CDCl3) δ 7.12−7.07 (m, 2 H), 6.56−6.49
(m, 2 H), 5.61−5.56 (m, 1 H), 5.20−5.12 (m, 2 H), 4.18 (d, J = 10.0
Hz, 1 H), 4.00 (dd, J = 5.9, 10.0 Hz, 1 H), 3.67 (s, 3 H), 2.34−2.31
L
J. Org. Chem. XXXX, XXX, XXX−XXX