Tandem Intramolecular Carbolithiation-Lithium/Zinc Transmetallation
FULL PAPER
3-(Cyclopentylmethyl)-3,7-dimethylocta-1,6-diene (7b): Rf ϭ 0.81
(38), 84 (30), 83 (35), 82 (99), 81 (43), 80 (19), 79 (54), 77 (26), 69
(hexane). IR (film): ν˜ ϭ 3080, 3056 (CϭCH), 1636 cmϪ1 (CϭC). (54), 68 (28), 67 (100), 66 (20), 65 (15), 55 (31), 53 (25). HRMS for
1H NMR (300 MHz, CDCl3): δ ϭ 0.98 (s, 3 H, CH2CCH3), 1.02
(m, 2 H, CH2), 1.29 (m, 2 H, CH2), 1.49 (m with s at 1.58, 9 H,
CH3CCH3, 3 ϫ CH2), 1.85 (m with s at 1.67, 8 H, CH3CCH3, 2
ϫ CH2, CH), 4.88 (dd, J ϭ 1.4, 17.5 Hz, 1 H, CHHϭ), 4.95 (dd,
J ϭ 1.4, 10.8 Hz, 1 H, CHHϭ), 5.08 [def. t, J ϭ 7.1 Hz, 1 H,
(CH3)2CϭCH], 5.73 (dd, J ϭ 10.8, 17.5 Hz, 1 H, CH2ϭCH) ppm.
13C NMR (75 MHz, CDCl3): δ ϭ 17.6, 22.7 [(CH3)2Cϭ], 22.9, 25.1
(3 ϫ CH2), 25.7 (CH3CHCH2), 35.0, 35.1 (2 ϫ CH2), 36.5
(CH2CHCH2), 40.1 (CH2CCH3), 41.6, 47.8 (2 ϫ CH2), 111.1 (ϭ
CH2), 125.2 [(CH3)2CϭCH], 130.9 [(CH3)2CϭCH], 148.0 (CH2ϭ
CH) ppm. GC-LRMS: m/z (%) ϭ 220 (3.0) [Mϩ], 138 (13), 137
(12), 109 (70), 96 (13), 95 (83), 83 (43), 82 (61), 81 (69), 79 (10), 70
(12), 69 (100), 68 (21), 67 (52), 55 (78), 53 (16). HRMS for C16H28:
calcd. 220.2191; found 220.2199 [Mϩ].
C16H26: calcd. 218.2035; found 218.2035 [Mϩ].
Arylation, Vinylation, and Benzylation of Intermediate 5. Isolation
of Compounds 10؊13. General Procedure: 6-Chlorohex-1-ene
(0.138 mL, 1.0 mmol) was added at Ϫ30 °C under an argon atmos-
phere to a stirred green suspension of lithium powder (40 mg,
5.8 mmol) and DTBB (13.3 mg, 0.05 mmol) in THF (4 mL). The
color disappeared after the substrate addition, the reaction mixture
was stirred until the green color was regenerated (40 min), and the
lithium excess was then filtered off under inert conditions. The re-
sulting solution was added at room temperature to a solution of
zinc bromide (260 mg, 1.1 mmol) in THF (5 mL), and the color of
the mixture changed to brown. A solution of Pd(OAc)2(PtBu3)2
[prepared by dissolving palladium() acetate (11.3 mg, 0.05 mmol)
and tri-tert-butylphosphane (22 mg, 0.1 mmol) in THF (7 mL)] was
added to the resulting mixture, and the corresponding aryl halide
(1.1 mmol) was then added. The mixture was heated at reflux for
6 h and was then hydrolyzed with water (10 mL), acidified (2
HCl, 10 mL) and extracted with ethyl acetate (3 ϫ 20 mL). The
organic layer was washed with saturated NH4Cl solution (2 ϫ
15 mL) and dried over MgSO4. The solvents were evaporated
(15 Torr) to yield a residue, which was purified by column chroma-
tography (silica gel, hexane/ethyl acetate) to give compounds
10Ϫ13. Structures and yields are given in Scheme 3 and Table 1;
physical, spectroscopic and analytical data follow.
4-Bromo-3-(cyclopentylmethyl)-1-butene (7c): Rf ϭ 0.67 (hexane).
IR (film): ν˜ ϭ 3076 (CϭCH), 1641 cmϪ1 (CϭC). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.46 (m, 11 H, 5 ϫ CH2, CH2CHCH2),
2.41 (m, 1 H, CHCH2Br), 3.35 (d, J ϭ 2.8 Hz, 1 H, BrCHH), 3.37
(d, J ϭ 2.3 Hz, 1 H, BrCHH), 5.10 (m, 2 H, CH2ϭ), 5.62 (m, 1 H,
CHϭ) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 25.06, 25.09, 32.1,
33.1 (4 ϫ CH2), 37.3 (CH2CHCH2), 38.6, 39.5 (2 ϫ CH2), 44.9
(CHCH2Br), 116.5 (CH2ϭ), 139.8 (CHϭ) ppm. GC-LRMS: m/z
(%) ϭ 189 (1.3) [Mϩ Ϫ (CHϭCH2)], 137 (12), 123 (19), 109 (11),
95 (33), 83 (55), 82 (68), 81 (68), 79 (15), 69 (28), 68 (19), 67 (87),
55 (100), 54 (46), 53 (37). HRMS for C8H12Br: calcd. 189.0279;
found 189.0067 [Mϩ Ϫ (CHϭCH2)].
(Cyclopentylmethyl)benzene (10a):[28] Rf ϭ 0.62 (hexane). IR (film):
ν˜ ϭ 3084, 3062, 3026 (ArCϪH), 1603, 1495 cmϪ1 (ArCϪC). 1H
NMR (300 MHz, CDCl3): δ ϭ 1.19 (m, 2 H, CH2), 1.60 (m, 6 H,
3 ϫ CH2), 2.08 (def. sept, J ϭ 7.6 Hz, 1 H, CH), 2.60 (d, J ϭ
7.3 Hz, 2 H, ArCH2), 7.21 (m, 5 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 24.9, 32.4 (4 ϫ CH2), 42.0 (CH), 42.1
(CH2), 125.5, 128.1, 128.8, 142.4 (ArC) ppm. GC-LRMS: m/z
(%) ϭ 161 (2.9) [Mϩ ϩ 1], 160 (20.2) [Mϩ], 92 (100), 91 (52), 69
(19), 65 (10). HRMS for C12H16: calcd. 160.1252; found 160.1260
[Mϩ].
4-Cyclopentyl-3-phenyl-1,2-butadiene (8a): Rf ϭ 0.70 (hexane). IR
(film): ν˜ ϭ 3059, 3027 (CϭCϭCϪH), 1940 cmϪ1 (CϭCϭC). 1H
NMR (300 MHz, CDCl3): δ ϭ 1.22 (m, 2 H, CH2), 1.56 (m, 4 H,
2 ϫ CH2), 1.81 (m, 2 H, CH2), 2.10 (sept, J ϭ 7.6 Hz, 1 H, CH),
2.41 (t, J ϭ 3.2 Hz, 1 H, CHHCϭCϭ), 2.43 (t, J ϭ 3.5 Hz, 1 H,
CHHCϭCϭ), 5.04 (d, J ϭ 3.0 Hz, 1 H, CHHϭ), 5.05 (d, J ϭ
3.1 Hz, 1 H, CHHϭ), 7.18 (t, J ϭ 7.3 Hz, 1 H, ArH), 7.30 (m, 2
H, ArH), 7.40 (d, J ϭ 7.6 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 25.2, 32.7, 36.4 (5 ϫ CH2), 38.2 (CH), 77.6 (CH2ϭ),
104.6 (CH2ϭCϭC), 126.0, 126.5, 128.3, 136.6 (ArC), 209.2 (CH2ϭ
CϭC) ppm. GC-LRMS: m/z (%) ϭ 199 (0.7) [Mϩ ϩ1], 198 (4.1)
[Mϩ], 131 (14), 130 (100), 129 (72), 128 (28), 127 (11), 115 (49), 91
(11). HRMS for C15H18: calcd. 198.1409; found 198.1406 [Mϩ].
p-(Cyclopentylmethyl)toluene (10b): Rf ϭ 0.71 (hexane). IR (film):
1
ν˜ ϭ 3047, 3018, 3003 (ArCϪH), 1514 cmϪ1 (ArCϪC). H NMR
(300 MHz, CDCl3): δ ϭ 1.17 (m, 2 H, CH2), 1.59 (m, 6 H, 3 ϫ
CH2), 2.05 (sept, J ϭ 7.6 Hz, 1 H, CHCH2), 2.30 (s, 3 H, CH3),
2.55 (d, J ϭ 7.5 Hz, 2 H, ArCH2), 7.06 (m, 4 H, ArH) ppm. 13C
NMR (75 MHz, CDCl3): δ ϭ 21.0 (CH3), 24.9, 32.4, 41.6 (5 ϫ
CH2), 42.1 (CHCH2), 128.6, 128.8, 134.8, 139.3 (ArC) ppm. GC-
LRMS: m/z (%) ϭ 175 (2.6) [Mϩ ϩ1], 174 (26.8) [Mϩ], 106 (86),
105 (100), 91 (23). HRMS for C13H18: calcd. 174.1409; found
174.1406 [Mϩ].
3-(Cyclopentylmethyl)-1,2-octadiene (8b): Rf ϭ 0.88 (hexane). IR
1
(film): ν˜ ϭ 3046 (CϭCϭCϪH), 1957 cmϪ1 (CϭCϭC). H NMR
(300 MHz, CDCl3): δ ϭ 0.89 (t, J ϭ 6.6 Hz, 3 H, CH3), 1.56 (m,
19 H, 9 ϫ CH2, CH), 4.62 (m, 2 H, ϭCH2) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 14.1 (CH3), 22.6, 25.3, 27.3, 31.6, 32.2, 32.7,
39.1 (9 ϫ CH2), 38.1 (CH), 74.8 (CϭCϭCH2), 102.9 (CϭCϭCH2),
206.3 (CϭCϭCH2) ppm. GC-LRMS: m/z (%) ϭ 192 (0.7) [Mϩ],
121 (43), 109 (15), 107 (24), 95 (42), 94 (18), 93 (35), 91 (18), 82
(12), 81 (34), 80 (14), 79 (39), 77 (16), 69 (31), 68 (100), 67 (69), 55
(23), 53 (14). HRMS for C14H24: calcd. 192.1878; found 192.1860
[Mϩ].
p-(Cyclopentylmethyl)anisole (10c):[29] Rf ϭ 0.26 (hexane). IR
(film): ν˜ ϭ 3060, 3030 (ArCϪH), 1612, 1583, 1512 (ArCϪC), 1246,
1
1040 cmϪ1 (CϪO). H NMR (300 MHz, CDCl3): δ ϭ 1.17 (m, 2
H, CH2), 1.53 (m, 2 H, CH2), 1.67 (m, 4 H, 2 ϫ CH2), 2.04 (def.
sept, J ϭ 7.5 Hz, 1 H, CH2CH), 2.54 (d, J ϭ 7.5 Hz, 2 H, ArCH2),
3.78 (s, 3 H, OCH3), 6.81 (d, J ϭ 8.6 Hz, 2 H, 2 ϫ ArH), 7.08 (d,
J ϭ 8.4 Hz, 2 H, 2 ϫ ArH) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 24.9, 32.4 (4 ϫ CH2), 41.1 (ArCH2), 42.2 (CH), 55.2 (CH3),
113.5, 129.6, 134.5, 157.5 (6 ϫ ArC) ppm. GC-LRMS: m/z (%) ϭ
191 (1.2) [Mϩ ϩ 1], 190 (8.6) [Mϩ], 122 (13), 121 (100).
2,3-Bis(cyclopentylmethyl)-1,3-butadiene (9):[17] Rf ϭ 0.85 (hexane).
1
IR (film): ν˜ ϭ 3088 (CϭCH), 1629, 1592 cmϪ1 (CϭC). H NMR
(300 MHz, CDCl3): δ ϭ 1.13, 1.60, 1.98 (3 m, 18 H, 8 ϫ CH2, 2
ϫ CH), 2.22 (d, J ϭ 7.3 Hz, 4 H, 2 ϫ CH2Cϭ), 4.88 (s, 2 H, ϭ
CH2), 5.03 (s, 2 H, ϭCH2) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 1-(Cyclopentylmethyl)-p-nitrobenzene (10d):[30] Rf ϭ 0.35 (hexane).
25.1, 32.5, 40.9 (10 ϫ CH2), 38.4 (2 ϫ CH), 112.0 (2 ϫ ϭCH2), IR (film): ν˜ ϭ 3103, 3077, 3048 (CϭCH), 1597 (CϭC), 1517, 1345
147.7 (2 ϫ CϭCH2) ppm. GC-LRMS: m/z (%) ϭ 219 (1.2) [Mϩ cmϪ1 (NO2). 1H NMR (300 MHz, CDCl3): δ ϭ 1.20 (m, 2 H, CH2),
ϩ1], 218 (5.5) [Mϩ], 150 (30), 149 (44), 136 (28), 135 (83), 121 (48), 1.63 (m, 6 H, 3 ϫ CH2), 2.10 (def. sept, J ϭ 7.7 Hz, 1 H, CH),
109 (16), 108 (53), 107 (91), 104 (13), 95 (33), 94 (23), 93 (55), 91
2.72 (d, J ϭ 7.5 Hz, 2 H, ArCH2), 7.32 (d, J ϭ 8.7 Hz, 2 H, ArH),
Eur. J. Org. Chem. 2004, 3833Ϫ3841
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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