4166 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Guijarro et al.
was stirred at 0 °C for 10 min (Table 7, reaction conditions). The
organozinc reagent was centrifuged (2500 rpm, 2 min), and the content
of the tube was cannulated to a two-necked 100 mL flask containing
copper(I) cyanide (17.9 mg, 0.2 mmol) and lithium bromide (17.4 mg,
0.4 mmol) in anhydrous tetrahydrofuran (10 mL) at -30 °C. 2,3-
Dichloropropene (222 mg, 2.0 mmol) was added immediately to the
flask. After 3 h, temperature was allowed to rise to room temperature
and stirring was maintained for an additional 3 h. After this, hexanes
(50 mL) were added, the mixture was hydrolyzed (1 M hydrobromic
acid) and extracted (hexanes, 2 × 50 mL), the organic phases were
dried over magnesium sulfate, and the solvents were removed (15 Torr,
30 °C). 14 (64%) was purified from the crude reaction mixture by
Kugelrohr distillation: IR (cm-1) 1635, 1453, 910, 884, 761, 735, 701,
647; 1H NMR (300 MHz) 1.61-2.00 (m, 4H, CH2CH2CH2Br), 2.56-
2.70 (m, 2H, CdCClCH2), 2.94-3.10 (m, 1H, PhCH), 3.36 (app t, J
) 6.4 Hz, 2H, CH2Br), 4.99 (app d, J ) 1.0 Hz, 1H, HHCdC), 5.10
(app d, J ) 1.0 Hz, 1H, HHCdC), 7.14-7.38 (m, 5H, ArH); 13C NMR
(75 MHz) 30.55, 33.65, 33.65, 42.5, 46.65, 114.0, 126.55 (2C), 127.45,
128.45 (2C), 140.5, 143.1; HRMS calcd for C13H16BrCl 286.0124, found
286.0128.
was reacted with active zinc (3.0 mmol) at room temperature (3 h)
and the organozinc intermediate was coupled with 2,3-dichloropropene
to afford 17 (96%): IR (cm-1) 2898, 2849, 1629, 1428, 1175, 879,
1
639, 616; H NMR (300 MHz) 1.26-1.40 (m, 4H, CH2CH2CH2CH2-
CH2CH2), 1.50-1.63 (m, 4H, CH2CH2 CH2CH2CH2CH2), 2.33 (t, J )
7.4 Hz, 2H, CdCClCH2), 2.41 (t, J ) 7.4 Hz, 2H, CdCBrCH2), 5.11
(app t, J ) 1.0 Hz, 1H, cis-HHCdCCl), 5.13 (app s, 1H, trans-HHCd
CCl), 5.38 (app d, J ) 1.2 Hz, 1H, cis-HHCdCBr), 5.55 (app d, J )
1.2 Hz, 1H, trans-HHCdCBr); 13C NMR (75 MHz) 26.95, 27.7, 28.0,
28.1, 39.0, 41.25, 111.85, 116.3, 134.7, 142.95; HRMS calcd for C10H16-
Br (M - Cl)+ 215.0435, found 215.0430. Anal. Calcd for C10H16BrCl:
C, 47.74; H, 6.41. Found: C, 47.7; H, 6.6.
Di-tert-butyl (6-Bromo-6-hepten-1-yl)hydrazine-N,N′-dicarboxy-
late (18). Compound 10 was reacted with active zinc using the same
procedure as described for 17. The resulting organozinc was centrifuged
(2500 rpm, 2 min), and the content of the tube was cannulated under
argon atmosphere to a 50 mL flask at 0 °C. Di-tert-butyl azodicar-
boxylate (460.6 mg, 2.0 mmol) in dry tetrahydrofuran (4 mL) was added
to the flask at 0 °C, leaving the mixture to react for 10 min. The reaction
was hydrolyzed (0.2 M phosphate buffer, 10 mL), extracted (ethyl
acetate, 3 × 30 mL), and dried (magnesium sulfate), the solvents were
removed (15 Torr, 30 °C), and the crude reaction mixture was purified
by flash chromatography (Florisil, hexanes/ethyl acetate) to afford 18
(91%): IR (cm-1) 3312, 2971, 2925, 1712, 1630, 1394, 1369, 1254,
4- and 2-Bromo-(2-deuterioethyl)benzene (15). Active zinc (1.3
mL, 2.0 mmol)11a as a tetrahydrofuran suspension (c ) 10 g/100 mL)
was added via disposable syringe under argon atmosphere to a 50 mL
centrifuge tube charged with a 61/39 mixture 4- and 2-bromo-(2-
bromoethyl)benzene (9, 527.9 mg, 2.0 mmol) in anhydrous tetrahy-
drofuran (10 mL) equipped with stirring bar and septum at room
temperature. The reaction was stirred at room temperature for 3 h and
another 1 equiv of active zinc was added in the same way, stirring for
2 h more (Table 7, reaction conditions). Deuterium oxide (48.1 mg,
2.4 mmol) in anhydrous tetrahydrofuran (1 mL) was then added. After
1 h, hexanes (50 mL) were added and the mixture was hydrolyzed (2
M hydrochloric acid) and extracted (hexanes, 2 × 50 mL). The organic
phases were dried over magnesium sulfate and the solvents removed
(15 Torr, 30 °C). The crude product was a 61/39 mixture of 4-Br/2-Br
isomers (1H NMR and GLC). 15 (96%) was purified from the crude
reaction mixture by Kugelrohr distillation for analytical purposes: IR
1
1157, 885, 856, 781, 759; H NMR (300 MHz) 1.20-1.35 (m, 2H,
CH2CH2CH2N), 1.43 (s, 9H, (CH3)3C, 9H), 1.44 (s, (CH3)3C, 9H),
1.48-1.62 (2m, 2 × 2H, CH2CH2CH2CH2N) 2.39 (t, J ) 7.3 Hz, 2H,
CdCBrCH2), 3.40 (br t, J ) 6.2 Hz, 2H, CH2N), 5.35 (app s, 1H,
cis-HHCdCBr), 5.52 (app s, 1H, trans-HHCdCBr), 6.17, 6.35 (2 br
s, 1H, NH); 13C NMR (75 MHz) 25.4, 27.15 (br), 27.5, 28.15 (br, 6C),
42.2, 49.2 (br), 81.0 (br, 2C), 116.4, 134.5, 155.35 (br, 2C); HRMS
calcd for C17H31N2O4BrLi (M + Li)+ 413.1628, found 413.1627.
4-Bromo-(3-chloro-3-buten-1-yl)benzene (19). By adapting the
procedure described for 14 to the reaction conditions described in Table
7, 11 was reacted with active zinc (1.0 mmol) at 0 °C (1 h) and the
organozinc intermediate was coupled with 2,3-dichloropropene to afford
19 (96%): IR (cm-1) 1634, 1489, 1072, 1011, 884, 813, 619; 1H NMR
(300 MHz) 2.60 (app t, J ) 7.5 Hz, 2H, CdCClCH2), 2.85 (app t, J )
7.5 Hz, 2H, ArCH2), 5.05 (app d, J ) 1.0 Hz, 1H, HHCdC), 5.15
(app d, J ) 1.0 Hz, 1H, HHCdC), 7.07 (app d, J ) 8.2 Hz, 2H, ArHo),
7.41 (app d, J ) 8.2 Hz, 2H, ArHm); 13C NMR (75 MHz) 32.95, 40.75,
113.05, 119.95, 130.2 (2C), 131.45 (2C), 139.35, 141.4; HRMS calcd
for C10H10BrCl 243.9654, found 243.9654. Anal. Calcd for C10H10-
BrCl: C, 48.91; H, 4.10. Found: C, 48.9; H, 4.2.
1
(cm-1) 2964, 2936, 1487, 1470, 1073, 1021, 1011, 814, 751, 656; H
NMR (300 MHz), 4-Br (mayor) isomer: 1.15-1.32 (m, 2H, CH2D),
2.61 (app t, J ) 7.3 Hz, 2H, ArCH2), 7.09 (app d, J ) 8.2 Hz, 2H,
ArHo), 7.42 (app d, J ) 8.2 Hz, 2H, ArHm). 2-Br (minor) isomer: 1.15-
1.32 (m, 2H, CH2D), 2.78 (app t, J ) 7.4 Hz, 2H, ArCH2), 7.02-7.11
(m, 1H, 4-ArH), 7.22-7.29 (2m, 2 × 1H, 5- and 6-ArH), 7.55 (app d,
J ) 7.9 Hz, 1H, 3-ArH); 13C NMR (75 MHz) of 4-Br (mayor) isomer
15.85 (t, JCD) 19.2 Hz), 28.95, 119.95, 130.35 (2C), 132.0 (2C), 143.8;
13C NMR (75 MHz) of 2-Br (minor) isomer 14.65 (t, JCD) 19.8 Hz),
30.0, 125.0, 128.05, 128.2, 130.2, 133.35, 143.95; HRMS calcd for
C8H8BrD 184.9949, found 184.9943. Anal. Calcd for C8H8BrD (cor-
rected for D incorporation): C, 51.64; H + D, 4.89. Found: C, 51.6;
H + D, 4.9.
4-Bromobenzyl Phenyl Ketone (20).84 Compound 11 was reacted
with active zinc using the same procedure as described for 19. The
organozinc reagent was then centrifuged (2500 rpm, 2 min), and the
content of the tube was cannulated to a two-necked 100 mL flask
containing copper(I) cyanide (179 mg, 2 mmol) and lithium bromide
(174 mg, 4 mmol) in anhydrous tetrahydrofuran (10 mL) at -30 °C.
The mixture was stirred for 15 min, allowing the temperature to rise
to 0 °C. Then it was cooled back to -30 °C and benzoyl chloride
(281.14 mg, 2.0 mmol) was added. After 3 h, the temperature was
allowed to rise to room temperature. The reaction mixture was
hydrolyzed (aqueous NaHCO3) and extracted (ethyl acetate, 2 × 50
mL and benzene, 2 × 50), the organic phases was dried over magnesium
sulfate, and the solvents were removed (15 Torr, 30 °C). 20 (89%)
was purified from the crude reaction mixture by recrystallization: mp
4- and 2-Bromo-(4-chloro-4-penten-1-yl)benzene (16). Compound
9 was reacted with active zinc using the same procedure as described
for 15. Then, following the procedure described for 14, the organozinc
intermediate was coupled with 2,3-dichloropropene to afford 16 (65%)
as a 61/39 mixture of 4-Br/2-Br isomers: IR (cm-1) 2955, 1634, 1489,
1470, 1073, 1011, 882, 751, 696; 1H NMR (300 MHz) of 4-Br (mayor)
isomer 1.83-1.98 (m, 2H, CH2CH2CH2), 2.37 (app t, J ) 7.3 Hz, 2H,
CdCClCH2), 2.60 (app t, J ) 7.8 Hz, 2H, ArCH2), 5.15 (app s, 1H,
HHCdC), 5.22 (app s, 1H, HHCdC), 7.08 (app d, J ) 8.4 Hz, 2H,
1
1
ArHo), 7.42 (app d, J ) 8.4 Hz, 2H, ArHm); H NMR (300 MHz) of
148-148.5 °C (hexanes/ethyl acetate); H NMR (300 MHz) 4.25 (s,
2-Br (minor) isomer 1.83-1.98 (m, 2H, CH2CH2CH2), 2.44 (app t, J
) 7.4 Hz, 2H, CdCClCH2), 2.77 (app t, J ) 7.8 Hz, 2H, ArCH2),
5.20 (app s, 2 × 1H, H2CdC), 7.05-7.15 (m, 1H, 4-ArH), 7.20-7.30
(2m, 2 × 1H, 5- and 6-ArH), 7.55 (app d, J ) 7.9 Hz, 1H, 3-ArH);
13C NMR (75 MHz) of 4-Br (major) isomer 28.5, 33.9, 38.35, 112.45,
119.6, 130.15 (2C), 131.4 (2C), 140.5, 142.35; 13C NMR (75 MHz) of
2-Br (minor) isomer: 27.25, 34.95, 38.6, 112.35, 124.4, 127.4, 127.65,
130.3, 132.8, 141.0, 142.3; HRMS calcd for C11H12BrCl 257.9811,
found 257.9802. Anal. Calcd for C11H12BrCl: C, 50.90; H, 4.66.
Found: C, 50.9; H, 4.7.
2H, COCH2), 7.14 (app d, J ) 8.6 Hz, 2H, 4-BrArHo), 7.46 (app d, J
) 8.6 Hz, 2H, 4-BrArHm), 7.45-7.52 (m, 2H, PhHm), 7.54-7.63 (m,
1H, PhHp), 7.98-8.05 (m, 2H, PhHo); 13C NMR (75 MHz) 44.7, 120.9,
128.5 (2C), 128.7 (2C), 131.25 (2C), 131.7 (2C), 133.35, 133.4, 136.35,
196.95.
3-(6-Bromo-1,1-dimethylhexyl)cyclohexanone (21). Active zinc
(2.9 mL, 2.2 mmol) as a tetrahydrofuran suspension (c ) 5 g/100 mL)11a
was added via disposable syringe under argon atmosphere to a 50 mL
centrifuge tube charged with anhydrous tetrahydrofuran (10 mL) and
equipped with stirring bar and septum. A solution of 1,6-dibromo-6-
2-Bromo-9-chloro-1,9-decadiene (17). By adapting the procedure
described for 14 to the reaction conditions described in Table 7, 10
(84) Kim, S.-H.; Rieke, R. D. J. Org. Chem. 1998, 63, 6766.