Organocatalytic Addition of b-Ketosulfones to Nitroalkenes
FULL PAPER
(mixture of diastereoisomers): d=7.80–7.77 (m, 2H), 7.68–7.63 (m, 4H),
7.60–7.53 (m, 3H), 7.47–7.42 (m, 8H), 7.40–7.34 (m, 6H), 7.28–7.22 (m,
5H), 5.66 (d, J=7.9 Hz, 1H), 5.60 (dd, J=13.7, 4.0 Hz, 1H), 5.54 (d, J=
5.9 Hz, 1H), 5.24 (dd, J=14.1, 3.5 Hz, 1H), 5.15 (dd, J=13.7, 10.4 Hz,
1H), 5.07 (dd, J=14.1, 9.6 Hz, 1H), 4.65 (ddd, J=9.4, 5.9, 3.5 Hz, 1H),
4.54 ppm (td, J=10.7, 4.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) (mixture
of diastereoisomers): d=191.8, 190.8, 139.9, 139.4, 137.8, 136.9, 136.4,
136.2, 135.1, 134.8, 134.8, 134.3, 130.8 (q, J=32.7 Hz), 130.8 (q, J=
32.7 Hz), 129.5, 129.4, 129.1, 129.0, 128.9, 128.8, 128.8, 128.6, 128.3, 126.4
(q, J=3.7 Hz), 126.1 (q, J=3.7 Hz), 123.7 (q, J=272.3 Hz), 123.6 (q, J=
272.7 Hz), 77.7, 76.6, 70.8, 70.7, 43.0, 42.5 ppm; 19F NMR (282 MHz,
CDCl3): d=À62.90 (s), À63.00 ppm (s); HRMS (TOF-MS ES+): calcd
for C23H18F3NO5S·Na+: 500.0755 [M+Na]+; found: 500.0742.
tained after purification by column chromatography (dichloromethane/
pentane 3:1) as a white solid and a 60:40 mixture of diastereoisomers
(86% yield). 1H NMR (300 MHz, CDCl3) (major diastereoisomer): d=
7.72 (d, J=4.9 Hz, 2H), 7.41 (d, J=8.0 Hz, 2H), 7.36–7.20 (m, 3H), 7.16–
7.10 (m, 2H), 5.47 (dd, J=13.2, 4.1 Hz, 1H), 4.91 (dd, J=13.2, 10.7 Hz,
1H), 4.67–4.59 (m, 1H), 4.22–4.08 (m, 1H), 2.49 (s, 3H), 1.79 ppm (s,
3H); 1H NMR (300 MHz, CDCl3) (minor diastereoisomer): d=7.64 (d,
J=4.9 Hz, 2H), 7.36–7.20 (m, 3H), 7.16–7.10 (m, 2H), 7.01–6.94 (m,
2H), 5.06–5.00 (m, 2H), 4.67–4.59 (m, 1H), 4.22–4.08 (m, 1H), 2.46 (s,
3H), 2.27 ppm (s, 3H); 13C NMR (75 MHz, CDCl3) (mixture of diaste-
reoisomers): d=200.0, 198.3, 146.5, 146.0, 135.7, 134.8, 134.6, 133.2, 130.1,
129.5, 129.4, 129.3, 129.0, 128.8, 128.6, 128.2, 127.5, 125.9, 78.0, 76.5, 76.4,
76.2, 42.3, 42.2, 34.2, 32.1, 21.8, 21.7 ppm; HRMS (TOF-MS ES+): calcd
for C18H19NO5S·Na+: 384.0882; found: 384.0876 [M+Na]+; elemental
analysis (%) calcd for C18H19NO5S (361.41): C 59.82, H 5.30, N 3.88;
found: C 59.41, H 4.98, N 3.71.
ACHTUNGTRENNUNG(2R/2S,3S)-3-[3,5-Bis(trifluoromethyl)phenyl]-4-nitro-1-phenyl-2-(phenyl-
sulfonyl)butan-1-one (3i). According to the general procedure using cata-
lyst 4d, compound 3i was obtained after purification by column chroma-
tography (dichloromethane/pentane 2:1) as a white solid and a 77:23 mix-
ture of diastereoisomers (68% yield). 1H NMR (300 MHz, CDCl3)
(major diastereoisomer): d=7.86–7.20 (m, 13H), 5.57 (d, J=6.7 Hz, 1H),
5.16 (dd, J=14.0, 3.2 Hz, 1H), 5.00 (dd, J=14.1, 9.2 Hz, 1H), 4.75–
AHCTUNGTERG(NNUN 2R/2S,3R)-2-(Naphthalen-2-ylsulfonyl)-4-nitro-1,3-diphenylbutan-1-one
(3m): According to the general procedure using catalyst 4c at room tem-
perature, compound 3m was obtained after purification by column chro-
matography (dichloromethane/pentane 2:1) as a white solid and a 58:42
mixture of diastereoisomers (73% yield). 1H NMR (300 MHz,
[D6]DMSO) (major diastereoisomer): d=8.51 (s, 1H), 8.09 (d, J=8.2 Hz,
2H), 8.06–7.89 (m, 2H), 7.83–7.55 (m, 4H), 7.50 (t, J=7.5 Hz, 2H), 7.32–
7.17 (m, 3H), 7.12–7.01 (m, 3H), 6.58 (d, J=11.1 Hz, 1H), 5.87–5.72 (m,
1H), 5.21 (t, J=12.5 Hz, 1H), 4.16 ppm (td, J=11.1, 3.9 Hz, 1H);
1H NMR (300 MHz, [D6]DMSO) (minor diastereoisomer): d=8.17 (d,
J=7.9 Hz, 2H), 8.06–7.89 (m, 2H), 7.83–7.55 (m, 5H), 7.38 (t, J=7.2 Hz,
2H), 7.32–7.17 (m, 3H), 7.01–6.90 (m, 3H), 6.25 (d, J=9.3 Hz, 1H),
5.04–4.83 (m, 2H), 4.41 ppm (td, J=9.3, 5.2 Hz, 1H); 13C NMR (75 MHz,
[D6]DMSO): d=191.9, 191.1, 136.9, 136.1, 135.7, 135.5, 135.1, 134.6,
134.5, 133.9, 133.4, 131.8, 131.4, 131.2, 130.4, 130.0, 129.7, 129.3, 129.2,
129.1, 128.7, 128.5, 128.4, 128.3, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6,
123.7, 122.4, 78.5, 77.8, 69.3, 68.9, 43.6, 43.3 ppm; HRMS (TOF-MS ES+):
calcd for C26H21NO5S·Na+: 482.1038 [M+Na]+; found: 482.1033.
General procedure for the synthesis of nitrones 5: Activated Zn[15]
(450 mg) and saturated NH4Cl (7.0 mL) were added at room temperature
to an ordinary flask equipped with a magnetic stirring bar charged with
sulfone 3a–m (0.1 mmol) and THF (7.0 mL). The reaction was followed
by TLC analysis (usually 1–30 min), and the crude reaction mixture was
filtered through celite and washed with dichloromethane (30 mL). The
organic phase was separated and the aqueous phase was extracted with
dichloromethane (20 mL). The organic phases are collected, dried over
anhydrous Na2SO4, filtered, and the solvent was removed under reduced
pressure. The residue was purified by column chromatography, thus lead-
ing to the corresponding nitrone 5 as a single diastereoisomer (d.r.>
98:2).
1
4.70 ppm (m, 1H); H NMR (300 MHz, CDCl3) (minor diastereoisomer):
d=7.86–7.20 (m, 13H), 5.7 (d, J=11.2 Hz, 1H), 5.6 (dd, J=14.1, 3.8 Hz,
1H), 4.61 ppm (td, J=10.4, 3.8 Hz, 1H); 13C NMR (75 MHz, CDCl3)
(mixture of diastereoisomer): d=192.1, 192.1, 140.6, 139.8, 139.8, 139.6,
138.1, 138.1, 137.9, 137.4, 137.4, 135.9, 135.4, 135.3, 135.1, 132.3 (q, J=
33.5 Hz), 132.17 (q, J=33.3 Hz), 131.3, 131.3, 130.8, 130.7, 130.6, 130.3,
130.1, 129.7, 129.2, 128.6, 124.1 (q, J=272.3 Hz,), 124.0 (q, J=272.2 Hz),
123.2 (sept, J=3.7 Hz), 122.9 (sept, J=3.7 Hz), 78.2, 78.1, 78.0, 44.4, 44.3,
44.1, 44.0 ppm; 19F NMR (282 MHz, CDCl3): d=À63.00 (s), À63.20 ppm
(s); HRMS (TOF-MS ES+): calcd for C24H17F6NO5S·Na+: 568.0629
[M+Na]+; found: 568.0627.
ACHTUNGTRENNUNG(2R/2S,3S)-4-Nitro-1-phenyl-2-(phenylsulfonyl)-3-(thiophen-2-yl)butan-1-
one (3j): According to the general procedure using catalyst 4d, com-
pound 3j was obtained after purification by column chromatography (di-
chloromethane/pentane 2:1) as a white solid and a 50:50 mixture of dia-
stereoisomers (90% yield). 1H NMR(300 MHz, CDCl3): (mixture of dia-
stereoisomers): d=7.76–7.73 (m, 4H), 7.61–7.57 (m, 3H), 7.55–7.49 (m,
4H), 7.45–7.38 (m, 5H), 7.32 (t, J=7.8, 2H), 7.24, (dd, J=10.6, 4.9 Hz,
2H), 7.11 (brd, J=5.0 Hz, 1H), 7.03 (brd, J=5.1 Hz, 1H), 6.82 (brd, J=
3.3 Hz, 2H), 6.79 (dd, J=5.0, 3.6 Hz, 1H), 6.70 (dd, 5.1, 3.6 Hz, 1H), 5.75
(d, J=11.1 Hz, 1H), 5.56 (d, J=4.8 Hz, 1H), 5.50 (dd, J=13.8, 3.8 Hz,
1H), 5.42 (dd, J=14.1, 3.0 Hz, 1H), 5.18 (dd, J=7.9, 5.9 Hz, 1H), 5.12
(dd, J=8.2, 5.9 Hz, 1H), 4.90 (ddd, J=9.8, 4.6, 3.1 Hz, 1H), 4.82 ppm
(ddd, J=11.0, 9.7, 3.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) (mixture of
diastereoisomers): d=192.0, 190.8, 138.4, 137.8, 137.2, 137.1, 136.5, 136.4,
135.0, 134.8, 134.5, 134.0, 129.9, 129.5, 129.3, 129.1, 128.9, 128.7, 128.6,
128.5, 128.4, 127.4, 127.2, 126.2, 126.1, 78.5, 77.7, 71.7, 71.1, 38.9,
38.1 ppm; HRMS (TOF-MS ES+): calcd for C20H17NO5S2·Na+: 438.0446
[M+Na]+; found: 438.0437.
AHCTUNGTERG(NNUN 3R,4S)-3,5-Diphenyl-4-(phenylsulfonyl)-3,4-dihydro-2H-pyrroline-1-
oxide (5a): According to the general procedure, compound 5a was ob-
tained after purification by column chromatography (hexane/EtOAc 3:1)
as a white solid and a single diastereoisomer (55% yield). Upon a single
recrystallization from CH2Cl2/pentane of a sample (e.r.=97:3, 300 mg),
compound 5a was obtained with e.r.>99.5:0.5 (231 mg, 77%). M.p. 157–
ACHTUNGTRENNUNG(2R/2S,3R)-3-Nitromethyl-1-phenyl-2-(phenylsulfonyl)hexan-1-one (3k):
According to the general procedure using catalyst 4c, compound 3k was
obtained after purification by column chromatography (hexane/EtOAc
3:1) as a yellow gum and a 63:27 mixture of diastereoisomers (82%
yield). 1H NMR (300 MHz, CDCl3) (major diastereoisomer): d=7.76 (d,
J=7.3 Hz, 2H), 7.66–7.20 (m, 8H), 5.26 (d, J=4.4 Hz, 1H), 5.19 (dd, J=
14.3, 3.1 Hz, 1H), 4.46 (dd, J=14.3, 8.1 Hz, 1H), 3.15–3.00 (m, 1H),
1.54–1.34 (m, 2H), 1.28–1.15 (m, 2H), 0.73 ppm (t, J=7.2 Hz, 3H);
1H NMR (300 MHz, CDCl3) (minor diastereoisomer): d=7.68 (d, J=
7.2 Hz, 2H), 7.66–7.20 (m, 8H), 5.59 (d, J=9.1 Hz, 1H), 5.08 (dd, J=
14.5, 5.1 Hz, 1H), 4.89 (dd, J=14.5, 4.2 Hz, 1H), 3.15–3.00 (m, 1H), 1.54–
1.34 (m, 2H), 1.28–1.15 (m, 2H), 0.72 ppm (t, J=6.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3) (mixture of diastereoisomers): d=192.1, 192.0, 137.6,
137.4, 137.0, 136.7, 134.7, 134.5, 134.4, 134.3, 129.5, 129.4, 129.2, 129.1,
129.0, 128.8, 128.7, 128.5, 76.4, 74.7, 69.1 (2C), 36.9, 36.5, 33.1, 31.5, 19.8,
19.7, 13.7, 13.4 ppm; HRMS (TOF-MS ES+): calcd for C19H21NO5S·H+:
376.1213 [M+H]+; found: 376.1212.
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1598C; [a]20D =+16.7 (c=0.21, CHCl3); H NMR (300 MHz, CDCl3): d=
7.94 (d, J=8.7 Hz, 2H), 7.68 (d, J=8.5 Hz, 2H), 7.54 (t, J=7.5 Hz, 1H),
7.38–7.17 (m, 10H), 4.86 (s, 1H), 4.68 (brdd, J=14.3, 7.8 Hz, 1H), 4.28
(d, J=7.7 Hz, 1H), 4.40 ppm (brd, J=14.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=141.0, 137.0, 134.4, 133.7, 130.2, 129.6, 129.2, 120.0, 128.2,
128.1, 127.4, 126.1, 69.9, 37.7, 29.6 ppm; HRMS (TOF-MS ES+): calcd
for C22H19NO3S·H+: 378.1158 [M+H]+; found: 378.1142; elemental anal-
ysis (%) calcd for C22H19NO3S (377.46): C 70.00, H 5.07, N 3.71; found: C
69.77, H 4.79, N 3.53; HPLC analysis on a Chiralcel IB column (hexane/
iPrOH 90:10); flow rate=1.0 mLminÀ1
(e.r.>99.5:0.5).
; tmajor =35.4, tminor =47.9 min
AHCTUNGTERG(NNUN 3S,4R)-3-(4-Methoxyphenyl)-5-phenyl-4-(phenylsulfonyl)-3,4-dihydro-
2H-pyrroline-1-oxide (ent-5b): According to the general procedure, com-
pound ent-5b was obtained after filtration through a short pad of silica
gel as a yellow solid and a single diastereoisomer (84% yield). M.p. 166–
1688C; [a]20D =+6.8 (c=0.10, CH2Cl2); 1H NMR (300 MHz, CDCl3): d=
ACHTUNGTRENNUNG
Chem. Eur. J. 2011, 17, 984 – 992
ꢅ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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