completion, the solvent was removed under reduced pressure
(compound 2a has been isolated and analysed), and the residue
was stirred in a mixture of DMF/concd. HCl (1.2 mL, v/v =
2 : 1) at 100 ◦C overnight. The product was extracted by a mixture
of ethyl acetate and petroleum ether (v/v = 1 : 1, 4 mL ¥ 3) and
washed with saturated sodium bicarbonate solution (5 mL) and
brine (5 mL). The organic layer was dried over anhydrous Na2SO4,
concentrated and the residue was purified by flash chromatography
on silica gel (EtOAc/petroleum ether) to give a-cyano ketone 3.
(m, 2H), 2.18 (s, 3H), 1.70 (qd, J = 4.0, 12.8 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3): d = 196.4, 193.4, 139.4, 138.5, 129.8,
127.9, 127.4, 127.0, 126.2, 126.0, 125.3, 114.4, 75.1, 53.7, 51.3,
50.1, 47.2, 46.7, 30.2, 29.7, 28.9, 28.6 ppm; ESI-HRMS: calcd. for
C22H19NO2S+Na 384.1034, found 384.1067.
Compound 3e. 42% yield; dr = 75 : 25, determined by 1H NMR
1
analysis; H NMR (400 MHz, CDCl3): d = 7.45-7.22 (m, 10H),
3.48 (s, 1H), 3.32 (d, J = 6.8 Hz, 1H), 2.94-2.84 (m, 1H), 2.87 (d,
J = 11.6 Hz, 1H), 2.37 (dd, J = 2.0, 11.2 Hz, 1H), 1.99 (s, 3H), 0.87
(d, J = 1.6 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): d = 203.6,
198.4, 137.2, 136.3, 129.0, 128.8, 128.8, 128.2, 128.1, 126.5, 115.9,
74.2, 60.5, 53.7, 53.0, 42.6, 41.1, 19.2, 12.5 ppm; ESI-HRMS:
calcd. for C23H21NO2 + Na 366.1470, found 366.1468.
Compound 2a. 66% yield; dr > 95 : 5, determined by 1H NMR
1
analysis; H NMR (400 MHz, CDCl3): d = 7.40-7.10 (m, 9H),
5.50 (s, 2H), 3.39 (d, J = 4.4 Hz, 1H), 2.97-2.82 (m, 2H), 2.52-2.49
(m, 1H), 2.48 (d, J = 9.2 Hz, 1H), 2.35-2.29 (m, 1H), 2.32 (s,
3H), 2.18 (dd, J = 1.6, 8.8 Hz, 1H), 1.75 (qd, J = 4.8, 12.8 Hz,
1H) ppm; 13C NMR (50 MHz, CDCl3): d = 208.4, 163.7, 137.6,
137.3, 134.7, 128.9, 128.4, 128.3, 127.8, 127.1, 126.6, 117.3, 68.2,
58.9, 56.7, 53.9, 50.0, 30.4, 30.3, 27.1 ppm; ESI-HRMS: calcd. for
C24H22N2O+H 355.1810, found 355.1819.
Compound 3f. 39% yield; dr = 91 : 9, determined by 1H NMR
1
analysis; H NMR (400 MHz, CDCl3): d = 7.37-7.22 (m, 6H),
7.06-7.04 (m, 1H), 7.02-6.99 (m, 1H), 3.38-3.32 (m, 1H), 3.08 (dd,
J = 8.8, 11.2 Hz, 1H), 2.77 (s, 1H), 2.62 (dd, J = 5.6, 14.4 Hz, 1H),
2.52-2.47 (m, 1H), 2.04 (s, 3H), 0.91 (d, J = 6.8 Hz, 3H) ppm; 13
C
Compound 3a. 69% yield; dr > 95 : 5, determined by 1H NMR
NMR (100 MHz, CDCl3): d = 211.8, 209.2, 149.2, 141.7, 128.9,
127.6, 127.2, 127.1, 124.1, 124.0, 118.4, 57.4, 54.7, 54.6, 49.4, 42.3,
30.2, 19.1, 12.2 ppm; ESI-HRMS: calcd. for C21H19NO2S+Na
372.1034, found 372.1005.
1
analysis; H NMR (400 MHz, CDCl3): d = 7.39-7.20 (m, 9H),
3.87 (s, 1H), 3.48 (d, J = 6.8 Hz, 1H), 2.95-2.79 (m, 2H), 2.70-2.64
(m, 1H), 2.62 (d, J = 11.6 Hz, 1H), 2.36 (dd, J = 1.6, 11.2 Hz,
1H), 2.25-2.20 (m, 1H), 1.99 (s, 3H), 1.68 (qd, J = 4.4, 12.8 Hz,
1H) ppm; 13C NMR (50 MHz, CDCl3): d = 203.2, 198.6, 138.7,
136.3, 132.7, 129.8, 128.9, 128.8, 128.2, 127.8, 127.0, 126.1, 114.8,
75.1, 58.7, 54.0, 48.7, 47.2, 44.9, 30.3, 29.9, 28.9 ppm; ESI-HRMS:
calcd. for C24H21NO2 + Na 378.1470, found 378.1490. ent-3a 69%
yield; [a]2D0 = +31.1 (c = 0.75 in CHCl3); 97% ee, determined by
HPLC analysis [Daicel chiralpak AD, n-hexane/i-PrOH = 60/40,
1.0 mL min-1, l = 254 nm, t (major) = 9.5 min, t (minor) =
6.6 min].
General procedure for the synthesis of multiply substituted
cyclopentanes 4
Allylic substrate 1 (0.1 mmol), nBu3SnH (88 mg, 0.3 mmol) and
AIBN (5.0 mg, 0.03 mmol) in dry benzene (1.0 mL) were refluxed
under Ar, and monitored by TLC analysis. After completion, the
solvent was removed under reduced pressure and the residue was
purified by flash chromatography on silica gel (EtOAc/petroleum
ether) to give cyclopentane 4.
Compound 3b. 70% yield; dr > 95 : 5, determined by 1H NMR
analysis; H NMR (400 MHz, CDCl3): d = 7.30-7.20 (m, 6H),
Compound 4a. 63% yield; dr > 95 : 5, determined by 1H NMR
analysis; H NMR (400 MHz, CDCl3): d = 7.43-7.24 (m, 7H),
1
1
7.07-7.02 (m, 2H), 3.88 (s, 1H), 3.53 (d, J = 6.8 Hz, 1H), 2.96-2.81
(m, 2H), 2.63-2.58 (m, 1H), 2.59 (d, J = 11.6 Hz, 1H), 2.38 (dd,
J = 1.6, 11.2 Hz, 1H), 2.24-2.20 (m, 1H), 2.03 (s, 3H), 1.68 (qd,
J = 4.0, 12.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): d =
202.9, 198.7, 162.4 (d, JC,F = 246.2 Hz), 138.6, 132.4, 132.0 (d,
JC,F = 3.2 Hz), 130.6 (d, JC,F = 8.2 Hz), 129.8, 127.9, 127.0, 126.1,
115.7 (d, JC,F = 21.3 Hz), 114.7, 74.9, 57.2, 54.0, 49.9, 47.3, 44.9,
30.2, 29.8, 28.8 ppm; ESI-HRMS: calcd. for C24H20FNO2 + Na
396.1376, found 396.1401.
7.08-7.04 (m, 1H), 6.95-6.93 (m, 1H), 4.27 (s, 1H), 4.17 (dd, J =
2.8, 12.4 Hz, 1H), 3.95 (dd, J = 1.6, 12.4 Hz, 1H), 3.53-3.46 (m,
1H), 3.26 (t, J = 11.2 Hz, 1H), 2.73-2.67 (m, 2H), 2.61 (dd, J =
8.8, 14.0 Hz, 1H), 1.80 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 206.9, 153.6, 139.2, 129.9, 129.3, 128.0, 127.8, 127.2, 122.9,
122.7, 118.5, 112.1, 111.5, 62.3, 56.9, 51.1, 50.4, 44.8, 40.9, 35.3,
30.3 ppm; ESI-HRMS: calcd. for C23H20N2O2 + Na 379.1422,
found 379.1431.
Compound 4b. 55% yield; dr > 95 : 5, determined by 1H NMR
Compound 3c. 69% yield; dr = 67 : 33, determined by 1H NMR
1
analysis; H NMR (400 MHz, CDCl3): d = 7.56-7.54 (m, 1H),
1
analysis; H NMR (400 MHz, CDCl3): d = 7.33-7.09 (m, 6H),
7.41-7.25 (m, 8H), 4.30 (s, 1H), 3.78-3.71 (m, 1H), 3.04-2.93 (m,
4H), 2.75 (dd, J = 7.2, 14.0 Hz, 1H), 2.43-2.32 (m, 1H), 1.86 (s,
3H) ppm; 13C NMR (50 MHz, CDCl3): d = 207.5, 139.0, 135.9,
135.1, 129.7, 129.7, 129.3, 128.6, 128.0, 127.5, 127.0, 112.9, 111.5,
56.6, 55.4, 55.0, 49.8, 38.9, 35.5, 30.9, 30.8 ppm; ESI-HRMS:
calcd. for C23H20N2OS+Na 395.1194, found 395.1159. ent-4b 61%
yield; [a]2D0 = +12.2 (c = 1.1 in CHCl3); 97% ee, determined by
HPLC analysis [Daicel chiralcel OD, n-hexane/i-PrOH = 70/30,
1.0 mL min-1, l = 254 nm, t (major) = 13.1 min, t (minor) =
16.1 min.
6.92-6.85 (m, 2H), 3.86 (s, 1H), 3.80 (d, J = 6.4 Hz, 1H), 3.80 (s,
3H), 2.97-2.67 (m, 2H), 2.65-2.58 (m, 1H), 2.59 (d, J = 12.0 Hz,
1H), 2.34 (dd, J = 1.6, 11.6 Hz, 1H), 2.22-2.18 (m, 1H), 1.99 (s,
3H), 1.66 (qd, J = 4.4, 8.8 Hz, 1H) ppm; 13C NMR (100 MHz,
CDCl3): d = 203.4, 198.7, 159.3, 138.6, 132.7, 130.0, 129.7, 128.5,
127.8, 126.9, 126.1, 114.5, 114.1, 75.1, 58.0, 55.2, 54.0, 50.8, 47.0,
44.9, 30.2, 28.8, 22.1 ppm; ESI-HRMS: calcd. for C25H23NO3 + H
386.1756, found 386.1751.
Compound 3d. 69% yield; dr > 95 : 5, determined by 1H NMR
1
analysis; H NMR (400 MHz, CDCl3): d = 7.32-7.19 (m, 5H),
Compound 4c. 43% yield; dr > 95 : 5, determined by 1H NMR
1
7.01-6.96 (m, 2H), 3.87 (s, 1H), 3.86 (d, J = 7.2 Hz, 1H), 3.00-2.81
(m, 2H), 2.72-2.68 (m, 1H), 2.54 (d, J = 12.0 Hz, 1H), 2.39-2.31
analysis; H NMR (400 MHz, CDCl3): d = 7.37-7.24 (m, 5H),
4.09 (s, 1H), 3.48-3.43 (m, 1H), 3.32 (td, J = 5.6, 9.6 Hz, 1H),
Org. Biomol. Chem., 2010, 8, 2840–2844 | 2843
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