The Journal of Organic Chemistry
Article
1H), 6.87 (dt, J = 7.7, 1.1 Hz, 1H), 6.64−6.57 (m, 2H), 5.31 (d, J =
17.0 Hz, 1H), 4.89 (d, J = 17.0 Hz, 1H), 4.02 (d, J = 12.2 Hz, 1H),
3.69 (dddd, J = 12.3, 9.4, 7.9, 3.1 Hz, 1H), 2.68−2.57 (m, 1H), 2.56−
2.42 (m, 2H), 2.14 (ddd, J = 12.4, 7.5, 4.9 Hz, 1H), 2.06 (s, 3H) ppm.
13C{1H} NMR (101 MHz, chloroform-d): δ 201.8, 179.5, 140.4,
137.3, 135.5, 132.2, 132.2, 128.7 (2C), 128.5 (2C), 128.3 (2C),
127.6, 126.82, 125.2 (2C), 122.4, 122.1, 119.9, 59.7, 56.8, 55.8, 45.0,
36.3, 24.3, 18.6 ppm. IR (KBr): ν = 1708 (CO, aldehyde, amide)
cm−1. HRMS (ESI+) m/z: calcd for C27H26NO2 [M + H]+, 396.1960;
found, 396.1958. Rf = 0.28 (hexane/EtOAc - 5:1).
1′-Benzyl-2-(naphthalen-2-yl)-2′-oxospiro[cyclopentane-1,3′-in-
doline]-3-carbaldehyde. The title compounds were synthesized
according to the general procedure (GP4, reaction time: 15 h). The
products were purified by column chromatography (hexane/EtOAc -
4:1 to 3:1) with a diastereomeric ratio of 3m/4m = 1/1.7 and an
overall yield of 3m/4m = 97%.
(1S,2S,3S)-1′-Benzyl-2-(naphthalen-2-yl)-2′-oxospiro-
[cyclopentane-1,3′-indoline]-3-carbaldehyde (3m). Yellow oil. Yield
= 36% (16 mg). 97% ee. The enantiomeric excess of product 3m was
determined by HPLC using a Chiralpak IA column (heptane/i-PrOH
- 80:20, flow rate = 1.0 mL/min, λ = 228 nm); tR = 10.4 min, tR = 13.7
min. [α]2D0 = −105.4 (c = 0.9, CHCl3). 1H NMR (400 MHz,
chloroform-d): δ 9.81 (d, J = 2.1 Hz, 1H), 7.75 (dd, J = 8.2, 1.3 Hz,
1H), 7.66 (dd, J = 8.2, 1.3 Hz, 1H), 7.61−7.57 (m, 1H), 7.54 (d, J =
8.6 Hz, 1H), 7.52−7.48 (m, 1H), 7.45 (ddd, J = 8.2, 6.8, 1.5 Hz, 1H),
7.40 (ddd, J = 8.2, 6.8, 1.5 Hz, 1H), 7.14 (td, J = 7.5, 1.2 Hz, 1H),
7.11−7.01 (m, 2H), 6.92−6.85 (m, 1H), 6.53−6.46 (m, 2H), 6.34−
6.29 (m, 1H), 6.25−6.16 (m, 2H), 5.06−4.94 (m, 1H), 4.47−4.35
(m, 1H), 4.17 (d, J = 16.0 Hz, 1H), 3.98 (d, J = 11.7 Hz, 1H), 2.78−
2.67 (m, 1H), 2.50−2.40 (m, 1H), 2.40−2.28 (m, 2H) ppm. 13C{1H}
NMR (101 MHz, chloroform-d): δ 202.3, 173.7, 142.8, 134.8, 133.2
(2C, overlapped), 132.9, 131.3, 128.7, 128.3, 128.2, 128.1 (2C), 127.9,
127.5, 126.9 (2C, overlapped), 126.4, 126.1 (2C), 126.0, 125.9, 122.8,
122.3, 109.1, 60.2, 56.6, 54.2, 43.3, 35.6, 24.5 ppm. IR (KBr): ν =
1709 (CO, aldehyde, amide) cm−1. HRMS (ESI+) m/z: calcd for
C30H26NO2 [M + H]+, 432.1957; found, 432.1958. Rf = 0.52
(hexane/EtOAc - 3:1).
4.33−4.19 (m, 2H), 3.78 (d, J = 11.7 Hz, 1H), 2.66 (tdd, J = 10.2, 8.0,
5.1 Hz, 1H), 2.47−2.21 (m, 6H) ppm. 13C{1H} NMR (101 MHz,
chloroform-d): δ 202.5, 178.8, 142.8, 137.0, 135.2, 132.4, 131.4, 129.1
(2C), 128.4 (2C), 128.1, 128.0 (2C), 127.1, 126.5 (2C), 122.7, 122.3,
109.1, 60.0, 56.3, 54.2, 43.3, 35.5, 24.4, 21.2 ppm. IR (KBr): ν = 1705
(CO, aldehyde, amide) cm−1. HRMS (ESI+) m/z calcd for
C27H26NO2 [M + H]+, 396.1958; found, 396.1970. Rf = 0.24
(hexane/EtOAc - 6:1).
(1R,2S,3S)-1′-Benzyl-2′-oxo-2-(p-tolyl)spiro[cyclopentane-1,3′-
indoline]-3-carbaldehyde (4n). Colorless oil. Yield = 58% (23 mg).
98% ee. The enantiomeric excess of product 4n was determined by
HPLC using a Chiralpak IA column (heptane/i-PrOH - 80:20, flow
rate = 1.0 mL/min, λ = 208 nm); tR = 9.6 min, tR = 11.5 min. [α]D20
=
1
+73.9 (c = 1.1, CHCl3). H NMR (400 MHz, chloroform-d): δ 9.64
(d, J = 3.1 Hz, 1H), 7.35−7.28 (m, 1H), 7.22−7.09 (m, 3H), 7.09−
6.98 (m, 2H), 6.84 (s, 4H), 6.75 (dq, J = 7.5, 1.0 Hz, 2H), 6.45−6.39
(m, 1H), 5.18−5.04 (m, 1H), 4.50 (d, J = 16.0 Hz, 1H), 3.95 (d, J =
12.2 Hz, 1H), 3.63 (dddd, J = 12.5, 9.7, 7.5, 3.2 Hz, 1H), 2.66−2.54
(m, 1H), 2.54−2.37 (m, 2H), 2.22 (s, 3H), 2.11 (ddd, J = 12.0, 8.0,
4.0 Hz, 1H) ppm. 13C{1H} NMR (101 MHz, chloroform-d): δ 202.5,
178.8, 142.8, 137.0, 135.2, 132.4, 131.4, 129.1 (2C), 128.4 (2C),
128.1, 128.0 (2C), 127.1, 126.5 (2C), 122.7, 122.3, 109.1, 60.0, 56.3,
54.2, 43.3, 35.5, 24.4, 21.2 ppm. IR (KBr): ν = 1716 (CO,
aldehyde, amide) cm−1. HRMS (ESI+) m/z: calcd for C27H26NO2 [M
+ H]+, 396.1958; found, 396.1958. Rf = 0.20 (hexane/EtOAc - 6:1).
1′-Benzyl-2-(4-methoxyphenyl)-2′-oxospiro[cyclopentane-1,3′-
indoline]-3-carbaldehyde. The title compounds were synthesized
according to the general procedure (GP4, reaction time: 46 h). The
products were purified by column chromatography (hexane/EtOAc -
7:1) with a adiastereomeric ratio of 3o/4o = 1/1.1 and an overall
yield of 3o/4o = 87%.
(1S,2S,3S)-1′-Benzyl-2-(4-methoxyphenyl)-2′-oxospiro-
[cyclopentane-1,3′-indoline]-3-carbaldehyde (3o). Colorless oil.
Yield = 41% (17 mg). 98% ee. The enantiomeric excess of product
3o was determined by HPLC using a Chiralpak IA column (heptane/
i-PrOH - 80:20, flow rate = 1.0 mL/min, λ = 208 nm); tR = 10.3 min,
tR = 12.6 min. [α]2D0 = −96.1 (c = 0.8, CHCl3). 1H NMR (400 MHz,
chloroform-d): δ 9.77 (d, J = 2.3 Hz, 1H), 7.45−7.40 (m, 1H), 7.19−
7.07 (m, 5H), 6.98−6.92 (m, 2H), 6.69−6.62 (m, 2H), 6.53−6.47
(m, 2H), 6.43−6.36 (m, 1H), 5.14−5.03 (m, 1H), 4.29 (d, J = 16.0
Hz, 1H), 4.22 (dddd, J = 11.8, 9.5, 7.1, 2.2 Hz, 1H), 3.78−3.73 (m.
4H), 2.71−2.56 (m, 1H), 2.46−2.36 (m, 1H), 2.36−2.22 (m, 2H)
ppm. 13C{1H} NMR (101 MHz, chloroform-d): δ 202.5, 178.9, 159.1,
142.9, 135.1, 131.5, 129.1 (2C), 128.4 (2C), 128.1, 127.4, 127.1,
126.5 (2C), 122.7, 122.3, 113.7 (2C), 109.1, 60.0, 56.1, 55.0, 54.2,
43.2, 35.3, 24.4 ppm. IR (KBr): ν = 1705 (CO, aldehyde, amide)
cm−1. HRMS (ESI+) m/z: calcd for C27H26NO3 [M + H]+, 412.1908;
found, 412.1906. Rf = 0.46 (hexane/EtOAc - 5:1).
(1R,2S,3S)-1′-Benzyl-2-(4-methoxyphenyl)-2′-oxospiro-
[cyclopentane-1,3′-indoline]-3-carbaldehyde (4o). Colorless oil.
Yield = 46% (19 mg). 98% ee. The enantiomeric excess of product
4o was determined by HPLC using a Chiralpak IA column (heptane/
i-PrOH - 80:20, flow rate = 1.0 mL/min, λ = 205 nm); tR = 11.7 min,
tR = 13.6 min. [α]2D0 = +68.9 (c = 0.8, CHCl3). 1H NMR (400 MHz,
chloroform-d): δ 9.65 (d, J = 3.2 Hz, 1H), 7.37−7.31 (m, 1H), 7.22−
7.12 (m, 3H), 7.12−7.00 (m, 2H), 6.90−6.85 (m, 2H), 6.78−6.72
(m, 2H), 6.61−6.56 (m, 2H), 6.48−6.44 (m, 1H), 5.13 (d, J = 16.0
Hz, 1H), 4.52 (d, J = 16.0 Hz, 1H), 3.95 (d, J = 12.4 Hz, 1H), 3.71 (s,
3H), 3.62 (dddd, J = 12.6, 9.7, 7.6, 3.2 Hz, 1H), 2.61 (ddd, J = 12.3,
10.1, 8.4 Hz, 1H), 2.55−2.39 (m, 2H), 2.13 (ddd, J = 12.1, 8.0, 4.1
Hz, 1H) ppm. 13C{1H} NMR (101 MHz, chloroform-d): δ 201.9,
178.5, 159.0, 142.2, 135.1, 131.5, 129.3 (2C), 128.5 (2C), 128.1,
127.3, 127.1, 126.7 (2C), 123.9, 122.3, 113.5 (2C), 109.4, 60.4, 56.3,
55.6, 55.1, 43.7, 35.1, 24.1 ppm. IR (KBr): ν = 1712 (CO,
aldehyde, amide) cm−1. HRMS (ESI+) m/z: calcd for C27H26NO3 [M
+ H]+, 412.1908; found, 412.1907. Rf = 0.42 (hexane/EtOAc - 5:1).
1′-Benzyl-2-(4-nitrophenyl)-2′-oxospiro[cyclopentane-1,3′-indo-
line]-3-carbaldehyde. The title compounds were synthesized
according to the general procedure (GP4, reaction time: 15 h). The
products were purified by column chromatography (hexane/EtOAc -
(1R,2S,3S)-1′-Benzyl-2-(naphthalen-2-yl)-2′-oxospiro-
[cyclopentane-1,3′-indoline]-3-carbaldehyde (4m). Colorless oil.
Yield = 61% (26 mg). 99% ee. The enantiomeric excess of product 4m
was determined by HPLC using a Chiralpak IB column (heptane/i-
PrOH - 90:10, flow rate = 1.0 mL/min, λ = 229 nm); tR = 14.4 min, tR
= 18.6 min. [α]2D0 = +127.2 (c = 1.2, CHCl3). H NMR (400 MHz,
1
chloroform-d): δ 9.71 (d, J = 3.1 Hz, 1H), 7.72 (dd, J = 7.5, 1.9 Hz,
1H), 7.69−7.61 (m, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.49 (d, J = 8.6
Hz, 1H), 7.48−7.38 (m, 3H), 7.10−6.95 (m, 4H), 6.73−6.66 (m,
2H), 6.60−6.50 (m, 2H), 6.40−6.30 (m, 1H), 5.21−5.07 (m, 1H),
4.44 (d, J = 16.0 Hz, 1H), 4.19 (d, J = 12.3 Hz, 1H), 3.82 (dddd, J =
12.5, 9.6, 7.7, 3.1 Hz, 1H), 2.75−2.63 (m, 1H), 2.63−2.51 (m, 2H),
2.19 (ddd, J = 12.1, 7.7, 4.3 Hz, 1H) ppm. 13C{1H} NMR (101 MHz,
chloroform-d): δ 201.6, 178.4, 142.2, 134.8, 133.1, 132.9, 132.8,
131.4, 128.3 (2C), 128.2, 128.0, 127.9, 127.7, 127.4, 127.1, 126.3
(2C), 126.0 (2C, overlapped), 125.6, 124.0, 122.4, 109.5, 60.6, 57.0,
55.5, 43.7, 35.5, 24.3 ppm. IR (KBr): ν = 1716 (CO, aldehyde,
amide) cm−1. HRMS (ESI+) m/z: calcd for C30H26NO2 [M + H]+,
432.1962; found, 432.1958. Rf = 0.46 (hexane/EtOAc - 3:1).
1′-Benzyl-2′-oxo-2-(p-tolyl)spiro[cyclopentane-1,3′-indoline]-3-
carbaldehyde. The title compounds were synthesized according to
the general procedure (GP4, reaction time: 46 h). The products were
purified by column chromatography (hexane/EtOAc - 6:1) with a
diastereomeric ratio of 3n/4n = 1/1.5 and an overall yield of 3n/4n =
96%.
(1S,2S,3S)-1′-Benzyl-2′-oxo-2-(p-tolyl)spiro[cyclopentane-1,3′-
indoline]-3-carbaldehyde (3n). Colorless oil. Yield = 38% (15 mg).
98% ee. The enantiomeric excess of product 3n was determined by
HPLC using a Chiralpak IA column (heptane/i-PrOH - 80:20, flow
rate = 1.0 mL/min, λ = 213 nm); tR = 8.3 min, tR = 13.5 min. [α]D20
=
−113.5 (c = 0.6, CHCl3). 1H NMR (400 MHz, chloroform-d): δ 9.77
(d, J = 2.2 Hz, 1H), 7.50−7.40 (m, 1H), 7.23−7.04 (m, 5H), 6.94 (s,
4H), 6.58−6.48 (m, 2H), 6.46−6.32 (m, 1H), 5.12−4.94 (m, 1H),
K
J. Org. Chem. XXXX, XXX, XXX−XXX