ACHTUNGTRENNUNG[3+2] Annulations with a,b-Unsaturated Ketones
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140.6, 138.0, 137.0, 134.6, 132.2, 132.0, 131.7, 130.1, 123.8, 121.3, 64.3,
60.8, 53.7, 36.6, 27.1, 26.8, 14.2 ppm; IR: n˜max =2938, 1698, 1621, 1486,
1243, 1231, 1177, 1072, 1006, 825, 813, 758 cmÀ1; HRMS (ESI): m/z: calcd
for C25H22Br2NaO3 [M+Na]+: 550.9833; found: 550.9830; HPLC analysis:
Daicel CHIRACEL OD, iPrOH/n-heptane (10%), 1 mLminÀ1, 305 nm,
retention times: 8.3 min (major) and 29.0 min (minor).
Daicel CHIRACEL IC, EtOH/n-heptane (10%), 1 mLminÀ1, 230 nm, re-
tention times: 7.5 min (major) and 30.8 min (minor).
Compound 12d: This compound was obtained in 48% yield and 93% ee;
Rf =0.4 (20% EtOAc/heptanes); [a]2D4 =+226 (c=1.3, CHCl3); 1H NMR
(500 MHz, CDCl3): d=7.15 (d, J=8.5 Hz, 4H), 6.96 (d, J=8.5 Hz, 4H),
6.86 (m, 2H), 4.19 (q, J=7.0 Hz, 4H), 3.79 (m, 2H), 3.57 (dt, J=9.0,
6.5 Hz, 2H), 3.04 (ddt, J=19.0, 9.0, 2.5 Hz, 2H), 2.51 (ddt, J=19.0, 6.0,
2.5 Hz, 2H), 1.30 ppm (t, J=7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3):
d=207.3, 164.3, 144.2, 143.4, 134.3, 132.7, 129.0, 128.4, 64.8, 60.7, 46.0,
42.3, 14.5 ppm; IR: n˜max =2933, 1705, 1634, 1492, 1366, 1299, 1245, 1082,
Ethyl
(E)-4-(furan-2-yl)-7-(furan-2-ylmethylene)-6-oxospiroACTHNGUTERNNU[G 4.4]non-1-
ene-1-carboxylate (10d): This compound was obtained in 53% yield and
84% ee, >20:1 regioselectivity; Rf 0.3 (5% AcOEt/toluene); [a]2D4 =+65
(c=0.5, CHCl3); 1H NMR (300 MHz, CDCl3): d=7.53 (d, J=1.5 Hz,
1H), 7.33–7.23 (m, 2H), 6.99 (t, J=2.4 Hz, 1H), 6.61 (d, J=3.6 Hz, 1H),
6.49 (dd, J=3.3, 1.8 Hz, 1H), 6.29 (dd, J=3.0, 1.8 Hz, 1H), 6.10 (d, J=
3.3 Hz, 1H), 4.12 (q, J=7.2 Hz, 2H), 3.90 (t, J=9.0 Hz, 1H), 2.95–2.75
(m, 3H), 2.10–1.95 (m, 3H), 1.20 ppm (t, J=7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=209.6, 163.5, 153.7, 152.8, 144.9, 144.3, 142.0, 140.9,
134.2, 119.6, 116.0, 112.6, 110.5, 107.5, 64.4, 60.7, 47.7, 35.5, 27.2, 26.5,
14.2 ppm; IR: n˜max =2360, 1707, 1620, 1476, 1236, 1181, 1092, 1019,
748 cmÀ1; HRMS (ESI): m/z: calcd for C21H20NaO5 [M+Na]+: 375.1208;
found: 375.1204; HPLC analysis: Daicel CHIRACEL OD, iPrOH/n-hep-
tane (5%), 1 mLminÀ1, 300 nm, retention times: 9.9 min (major) and
25.5 min (minor).
1009, 818, 748 cmÀ1
; HRMS (ESI): m/z: calcd for C29H28Cl2NaO5
[M+Na]+: 549.1211; found: 549.1219; HPLC analysis: Daicel CHIRA-
CEL AD-H, iPrOH/n-heptane (2%), 1 mLminÀ1
, 230 nm, retention
times: 14.7 min (major) and 33.7 min (minor).
Compound 12e: This compound was obtained in 53% yield and 92% ee;
Rf 0.4 (EtOAc/heptanes 20%); [a]2D4 =+227 (c=0.93, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.00–6.85 (m, 10H), 4.19 (q, J=7.2 Hz, 4H), 3.89
(m, 2H), 3.57 (m, 2H), 2.98 (m, 2H), 2.52 (m, 2H), 2.31 (s, 6H),
1.29 ppm (t, J=7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=208.1,
164.5, 144.5, 141.9, 136.1, 134.4, 129.4, 126.9, 64.3, 60.5, 46.3, 42.3, 21.2,
14.5 ppm; IR: n˜max =2980, 2924, 1706, 1635, 1514, 1371, 1241, 1181, 1085,
1031, 811, 749 cmÀ1; HRMS (ESI): m/z: calcd for C31H34NaO5 [M+Na]+:
509.2304; found: 509.2296; HPLC analysis: Daicel CHIRACEL IC,
iPrOH/n-heptane (5%), 1 mLminÀ1, 205 nm, retention times: 8.9 min
(major) and 36.9 min (minor).
Ethyl (E)-7-benzylidene-6-oxo-4-phenylspiroACTHNUTRGNE[NUG 4.5]dec-1-ene-1-carboxylate
(11): This compound was obtained in 35% yield and 85% ee, 20:1 regio-
selectivity; Rf =0.3 (AcOEt/heptanes 10%). [a]2D4 =+306 (c=1.3, CHCl3).
NMR data for this compound have been reported in ref. [6b]. HRMS
(ESI): m/z: calcd for C26H26NaO3 [M+Na]+: 409.1780; found: 409.1766;
HPLC analysis: Daicel CHIRACEL OD, iPrOH/n-heptane (5%),
Compound 12 f: This compound was obtained in 50% yield and 93% ee;
Rf =0.4 (EtOAc/heptanes 20%); [a]2D4 =+236 (c=0.6, CHCl3); 1H NMR
(500 MHz, CDCl3): d=7.10 (d, J=4.5 Hz, 2H), 6.91 (s, 2H), 6.85 (t, J=
3.5 Hz, 2H), 6.81 (s, 2H), 4.18 (q, J=7.0 Hz, 4H), 4.12 (m, 2H), 4.03 (m,
2H), 3.11 (dd, J=18.5, 9.0 Hz, 2H), 2.67 (dt, J=18.5, 2.5 Hz, 2H),
1.28 ppm (t, J=7.5 Hz, 6H); 13C NMR (125 MHz, CDCl3): d=207.6,
164.2, 148.4, 144.2, 134.3, 126.8, 124.5, 123.9, 65.1, 60.7, 42.9, 42.3, 29.8,
1 mLminÀ1
(minor).
, 305 nm, retention times: 7.9 min (major) and 12.2 min
c) Synthesis of d-menthyl (4S,5R)-5-cinnamoyl-4-phenylcyclopent-1-enyl-
carboxylate (7j, Scheme 6): d-Menthyl but-2-ynoate (0.10 mg, 0.45 mmol)
was added to a mixture of dba (35 mg, 0.15 mmol) and FerroPHANE I
(7.1 mg, 0.015 mmol) in degassed toluene (0.5 mL). The mixture was
stirred at 1208C for 18 h. After evaporation of the solvent, the final prod-
uct was purified by chromatography on silica gel with AcOEt/heptane
(5%) as the eluent (Rf 0.3). Compound 7j was obtained as a pale yellow
solid in 75% yield (51 mg) and as a single regioisomer, in 90% de. Rf =
0.30 (EtOAc/heptanes 5%); [a]2D4 =+150 (c=1, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.40–7.15 (m, 11H), 6.96 (m, 1H), 6.66 (d, J=
15.9 Hz, 1H), 4.63 (td, J=10.8, 4.5 Hz, 1H), 4.30 (m, 1H), 3.52 (dt, J=
9.0, 6.3 Hz, 1H), 3.08 (ddt, J=18.9, 9.0, 2.7 Hz, 1H), 2.66 (ddt, J=18.9,
6.0, 2.1 Hz, 1H), 1.95 (dm, J=12.0 Hz, 1H), 1.80–1.70 (m, 1H), 1.63–1.48
(m, 2H), 1.45–1.30 (m, 1H), 1.30–1.15 (m, 1H), 1.00–0.70 (m, 3H), 0.79
(d, J=6.9 Hz, 3H), 0.73 (d, J=6.9 Hz, 3H), 0.65 ppm (d, J=6.9 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=200.1, 163.9, 144.8, 144.0, 135.9, 134.7,
130.6, 129.01, 128.96, 128.5, 127.2, 127.1, 125.6, 74.7, 63.4, 49.0, 47.2, 41.9,
41.0, 34.3, 31.5, 26.1, 23.3, 22.1, 21.0, 16.2 ppm; IR: n˜max =2952, 2358,
1704, 1607, 1448, 1242, 1091, 980, 752, 698 cmÀ1; HPLC analysis: Daicel
CHIRACEL IA, EtOH/n-heptane (1%), 1 mLminÀ1, 290 nm, retention
times: 10.3 min (minor) and 43.6 min (major).
14.4 ppm; IR: n˜max =2978, 1705, 1634, 1368, 1250, 1078, 1029, 707 cmÀ1
;
HRMS (ESI): m/z: calcd for C25H26NaO5S2 [M+Na]+: 493.1119; found:
493.1106; HPLC analysis: Daicel CHIRACEL IA, iPrOH/n-heptane
(1%), 1 mLminÀ1
36.9 min (minor).
, 230 nm, retention times: 28.9 min (major) and
Compound 12g: This compound was obtained in 43% yield and 90% ee;
Rf =0.13 (30% Et2O/heptanes); [a]2D4 =+191 (c=1.6, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.20–7.13 (m, 3H), 7.08 (d, J=8.4 Hz, 2H), 7.05–
6.99 (m, 2H), 6.93 (d, J=8.4 Hz, 2H), 6.90–6.85 (m, 2H), 4.18 (q, J=
7.2 Hz, 4H), 3.84 (m, 2H), 3.58 (m, 2H), 3.03 (m, 2H), 2.55 (m, 2H),
1.29 ppm (t, J=7.1 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=207.6,
164.4, 164.3, 144.9, 144.5, 144.2, 143.3, 134.4, 134.2, 132.4, 129.0, 128.9,
128.4, 127.0, 126.8, 64.6, 64.5, 60.62, 60.59, 46.6, 46.0, 42.4, 42.2, 14.4 ppm;
IR: n˜max =2980, 1704, 1635, 1492, 1241, 1089, 1013, 972, 825, 750,
700 cmÀ1
;
HRMS (ESI): m/z: calcd for C29H29ClNaO5 [M+Na]+:
515.1601; found: 515.1594; HPLC analysis: Daicel CHIRACEL AD-H,
iPrOH/n-heptane (5%), 1 mLminÀ1, 250 nm, retention times: 8.2 min
(major) and 15.6 min (minor).
Representative procedure for the [3+2] annulations on cyclopentenylcar-
boxylates 7 (Scheme 3 and Table 5)
Compound 13: This compound was obtained in 58% yield and 90% dr;
1
Rf = 0.4 (EtOAc/heptanes 20%); [a]2D4 =+194 (c=1.0, CHCl3); H NMR
(300 MHz, CDCl3): d=7.18–7.10 (m, 6H), 7.06–6.98 (m, 4H), 6.95–6.87
(m, 2H), 4.76 (dt, J=10.8, 4.5 Hz, 1H), 4.20 (q, J=7.0 Hz, 2H), 3.98–
3.82 (m, 2H), 3.68–3.58 (m, 2H), 3.03 (ddt, J=18.9, 9.3, 2.4 Hz, 2H),
2.60–2.48 (m, 2H), 2.14–2.02 (m, 1H), 2.00–1.88 (m, 1H), 1.75–1.60 (m,
3H), 1.60–0.75 ppm (m, 16H); 13C NMR (75 MHz, CDCl3): d=207.6,
207.3, 164.3, 164.0, 145.1, 144.9, 144.8, 144.4, 134.8, 134.3, 128.8, 127.0,
126.9, 126.7, 74.4, 64.4, 64.2, 60.6, 47.4, 46.8, 46.3, 42.3, 42.1, 41.1, 34.6,
31.6, 26.5, 23.7, 22.2, 20.9, 16.6, 14.5 ppm; IR: n˜max =2953, 2926, 1704,
1241, 1086, 962, 754, 697 cmÀ1; HRMS (ESI): m/z: calcd for C37H44NaO5
[M+Na]+: 591.3086; found: 591.3087; HPLC analysis: Daicel CHIRA-
Synthesis of 12a: A mixture of cyclopentenylcarboxylate 7a (52 mg,
0.15 mmol), ethyl buta-2,3-dienoate (52 mL, 50 mg, 0.45 mmol) and PPh3
(4.0 mg, 10 mol%) in toluene was stirred under argon at RT for 24 h.
The final product 12a was purified by chromatography on silica gel with
EtOAc/heptane (20%) as the eluent (Rf 0.4). Yield: 45 mg (66%). The
final product displays the same enantiomeric excess as that of the starting
cyclopentene 7a (92% ee). [a]2D4 =+233 (c=1.3, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.20–7.10 (m, 6H), 7.05–6.95 (m, 4H), 6.90 (m,
2H), 4.19 (q, J=7.2 Hz, 4H), 3.95–3.88 (m, 2H), 3.63 (dt, J=9.3, 6.0 Hz,
2H), 3.03 (ddt, J=18.6, 9.0, 2.7 Hz, 2H), 2.54 (ddt, J=18.6, 5.7, 2.4 Hz,
2H), 1.29 ppm (t, J=7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=208.0
(C), 164.4 (2C), 144.8 (2C), 144.6 (2ꢃCH), 134.4 (2C), 128.8 (4ꢃCH),
127.0 (4ꢃCH), 126.7 (2ꢃCH), 64.3 (2ꢃCH), 60.6 (2ꢃCH2), 46.7 (2ꢃ
CH), 42.2 (2ꢃCH2), 14.5 ppm (2ꢃCH3); IR: n˜max =2980, 1699, 1326,
1241, 1196, 1088, 1029, 747, 698 cmÀ1; HRMS (ESI): m/z: calcd for
C29H30NaO5 [M+Na]+: 481.1991; found: 481.1988; HPLC analysis:
CEL AD-H, iPrOH/n-heptane (1%), 1 mLminÀ1
, 230 nm, retention
times: 17.8 min (major) and 23.0 min (minor).
Synthesis of 16: (2,4-Dinitrophenyl)hydrazine (26 mg, 0.13 mmol,
1.5 equiv) and H2SO4 (0.5n, 87 mL, 0.5 equiv) were added to a solution of
7j (40 mg, 0.087 mmol, 1.0 equiv) in ethanol (0.4 mL). The red heteroge-
neous mixture was heated at reflux for 2 h, and further (2,4-dinitrophe-
Chem. Eur. J. 2010, 16, 1033 – 1045
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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