Novel Class of Tunable Zinc Reagents (RXZnCH2Y)
stirring, a solution of trans-â-methylstyrene (0.06 g, 0.5 mmol)
in CH2Cl2 (0.5 mL) was added. The reaction mixture was then
stirred at room temperature. Samples were taken over the
course of the reaction and analyzed by GC to determine the
conversion.
tr a n s-1,2-Dih exylcyclop r op a n e (Ta ble 3, En tr y 5): IR
1
(film) 1465, 1458 cm-1; H NMR (300 MHz, CDCl3) δ 1.38-
1.14 (m, 20H), 0.88 (t, J ) 6.7 Hz, 6H), 0.38 (m, 2H), 0.13 (t,
J ) 6.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 34.6, 32.2, 29.9,
29.5, 23.0, 19.0, 14.4, 12.0. Anal. Calcd for C15H30: C, 85.63;
H, 14.37. Found: C, 85.76; H, 14.13.
R ep r esen t a t ive Cyclop r op a n a t ion P r oced u r e Usin g
CF 3CO2Zn CH2I (Meth od B). To freshly distilled CH2Cl2 (20
mL) was added Et2Zn (1.0 M in hexanes) (20.0 mL, 20.0 mmol)
under N2 (it is best to use an inlet adapter for the nitrogen
line since needles often become clogged). The solution was
cooled in an ice bath and a solution of trifluoroacetic acid (1.54
mL, 20.0 mmol) in CH2Cl2 (10 mL) was then dripped very
slowly into the reaction mixture via syringe. Upon stirring for
20 min, a solution of CH2I2 (1.61 mL, 20.0 mmol) in CH2Cl2
(10 mL) was added. After an additional 20 min of stirring, a
solution of the TBS ether of cinnamyl alcohol (2.60 g, 10.0
mmol) in CH2Cl2 (10 mL) was added, and the ice bath was
removed. After an additional 30 min of stirring, the reaction
mixture was quenched with 0.1 N HCl (50 mL) (alternatively
with saturated aqueous NH4Cl or Et3N followed by saturated
aqueous NaHCO3) and hexanes (25 mL), and the layers were
separated. The aqueous layer was extracted with hexanes. The
combined organic layers were washed with saturated NaHCO3,
H2O, and brine and then dried (Na2SO4), filtered, concentrated,
and purified by column chromatography (hexanes/ether )
50/1) to yield the cyclopropane product (2.61 g, 95%).
Rep r esen ta tive P r oced u r e for Lew is Acid -Ca ta lyzed
Cyclop r op a n a tion (Ta ble 2). To a solution of Et2Zn (1.0 M
in hexane) (1.0 mL, 1.0 mmol) in CH2Cl2 (1 mL) at -78 °C
under N2 was added a solution of CH2I2 (0.53 g, 2.0 mmol) in
CH2Cl2 (0.5 mL). After the reaction mixture was stirred at -15
°C for 1-2 h, a solution of ClCH2CH2OH (0.079 g, 1.0 mmol)
in CH2Cl2 (1 mL) was added. After 30-45 min of stirring, a
solution of trans-â-methylstyrene (0.06 g, 0.5 mmol) in
CH2Cl2 (0.5 mL) was added. After an additional 15 min of
stirring, Lewis acid (0.15 mmol) was added. The reaction
mixture was then stirred at room temperature for the indicated
time, poured into diluted HCl, extracted with hexanes, washed
with saturated NaHCO3, H2O, brine, dried (Na2SO4), and
concentrated. The crude product was then analyzed by GC and/
or 1H NMR to determine the conversion.
cis-1-Meth yl-2-P h en ylcyclop r op a n e (Ta ble 3, En tr y 6):
46
IR (film) 1497 cm-1 1H NMR (300 MHz, CDCl3) δ 7.29-
;
7.12 (m, 5H), 2.08 (td, J ) 8.7, 6.3 Hz, 1H), 1.17-1.07 (m, 1H),
0.97 (td, J ) 8.7, 4.8 Hz, 1H), 0.80 (d, J ) 6.3 Hz, 3H), 0.58 (q,
J ) 5.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 139.6, 129.4,
127.9, 125.7, 21.4, 13.9, 13.0, 11.2.
cis-1,2-Dip h en ylcyclop r op a n e (Ta ble 3, En tr y 7):47 IR
(film) 1602, 1497, 696 cm-1 1H NMR (300 MHz, CDCl3) δ
;
7.10-6.92 (m, 10H), 2.48 (dd, J ) 8.6, 6.2 Hz, 2H), 1.46 (td, J
) 8.6, 5.4 Hz, 1H), 1.37 (td, J ) 6.2, 5.4 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ 138.6, 129.2, 127.9, 125.8, 24.6, 11.6.
Ben zo[2,3]bicyclo[3.1.0]h exa n e (Ta ble 3, En tr y 8).4i IR
(film) 1475 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.31-7.26 (m,
1H), 7.16-7.02 (m, 3H), 3.19 (dd, J ) 16.8, 6.6 Hz, 1H), 2.95
(d, J ) 16.8 Hz, 1H), 2.38-2.28 (m, 1H), 1.88-1.78 (m, 1H),
1.05 (td, J ) 8.1, 4.5 Hz, 1H), 0.06 (q, J ) 3.9 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 147.1, 142.0, 126.0, 125.54, 125.46,
123.5, 35.7, 24.2, 17.0, 16.3. Anal. Calcd for C10H10: C, 92.26;
H, 7.74. Found C, 92.12; H, 7.89.
Ben zo[2,3]bicyclo[5.1.0]octa n e (Ta ble 3, En tr y 9):48 IR
(film) 1450 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.33-7.28 (m,
1H), 7.19-7.09 (m, 2H), 7.06-7.00 (m, 1H), 3.35 (td, J ) 12.6,
7.2 Hz, 1H), 2.54 (dd, J ) 13.2, 5.7 Hz, 1H), 2.08-1.91 (m,
2H), 1.90-1.77 (m, 1H), 1.58-1.44 (m, 1H), 1.12-0.86 (m, 2H),
0.54-0.37 (m, 1H), 0.27-0.18 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 139.9, 130.8, 128.2, 126.6, 126.5, 31.5, 27.1, 24.2, 17.6,
12.5, 12.4. Anal. Calcd for C12H14: C, 91.08; H, 8.92. Found:
C, 90.88; H, 9.07.
1-P h en ylbicyclo[4.1.0]h ep ta n e (Ta ble 3, En tr y 10):49
IR (film) 1601, 1494, 1448, 698 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.27-7.24 (m, 4H), 7.14 (m, 1H), 2.12-1.86 (m, 3H),
1.66 (m, 1H), 1.50-1.18 (m, 5H), 0.93 (dd, J ) 9.3, 4.5 Hz,
1H), 0.62 (dd, J ) 5.4, 4.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 149.9, 128.4, 127.7, 125.6, 31.8, 24.8, 24.3, 22.0, 21.9, 19.2,
18.6. Anal. Calcd for C13H16: C, 90.64; H, 9.36. Found: C,
90.46; H, 9.30.
tr a n s-1-Meth yl-2-p h en ylcyclop r op a n e (Ta ble 3, En tr y
1):2b,8 IR (film) 1605, 1495, 696 cm-1 1H NMR (300 MHz,
;
Ben zo[3,4]-1-m eth ylbicyclo[3.1.0]h exa n e (Ta ble 3,
En tr y 11):50 IR (film) 1477 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.22-7.17 (m, 1H), 7.11-6.98 (m, 3H), 3.01 (d, J ) 16.8 Hz,
1H), 2.93 (d, J ) 16.8 Hz, 1H), 2.06 (ddd, J ) 7.8, 3.3, 0.9 Hz,
1H), 1.37 (s, 3H), 0.95 (dd, J ) 7.8, 4.2 Hz, 1H), 0.23 (dd, J )
4.2, 3.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 148.0, 142.6,
125.9, 125.3, 125.2, 123.1, 41.8, 31.2, 24.3, 24.0, 22.0.
Ben zo[2,3]-1-p h en ylbicyclo[3.1.0]h exa n e (Ta ble 3,
En tr y 12):51 IR (film) 1477 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.48-7.02 (m, 9H), 3.40 (dd, J ) 16.8, 6.6 Hz, 1H), 3.03 (d,
J ) 16.8 Hz, 1H), 2.05-1.94 (m, 1H), 1.77 (dd, J ) 8.1, 4.5
Hz, 1H), 0.59 (dd, J ) 4.8, 4.2 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ 149.1, 142.0, 141.3, 129.2, 128.4, 126.5, 126.1, 125.8,
125.6, 123.9, 39.8, 35.8, 26.7, 22.0. Anal. Calcd for C16H14: C,
93.16; H, 6.84. Found: C, 92.90; H, 6.68.
CDCl3) δ 7.27-7.20 (m, 2H), 7.15-7.08 (m, 1H), 7.05-7.00 (m,
2H), 1.56 (dt, J ) 8.8, 4.6 Hz, 1H), 1.18 (d, J ) 5.7 Hz, 3H),
1.04 (m, 1H), 0.88 (m, 1H), 0.73 (m, 1H); 13C NMR (75 MHz,
CDCl3) δ 144.3, 128.4, 125.7, 125.4, 24.6, 19.3, 18.2, 17.8.
(tr a n s-2-P h en ylcyclop r op yl)m eth a n ol (Ta ble 3, En tr y
2):43f,h IR (film) 3341, 1604, 1497, 1020, 697 cm-1 1H NMR
;
(300 MHz, CDCl3) δ 7.25 (m, 2H), 7.15 (m, 1H), 7.06 (m, 2H),
3.63 (dd, J ) 11.4, 6.6 Hz, 1H), 3.59 (dd, J ) 11.4, 6.6 Hz,
1H), 1.82 (dt, J ) 8.4, 4.8 Hz, 1H), 1.56 (m, 1H), 1.45 (m, 1H),
0.96 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 142.7, 128.6, 126.1,
125.9, 66.8, 25.5, 21.5, 14.1.
tr a n s-1-[(ter t-Bu tyld im eth ylsiloxy)m eth yl]-2-p h en yl-
cyclop r op a n e (Ta ble 3, En tr y 3): IR (film) 1606, 1497, 1097,
836, 696 cm-1 1H NMR (300 MHz, CDCl3) δ 7.28-7.03 (m,
;
Ben zo[2,3]-1-eth ylbicyclo[4.1.0]h ep ta n e (Ta ble 3,
En tr y 13): IR (film) 1491 cm-1; 1H NMR (300 MHz, CDCl3) δ
7.42 (d, J ) 7.8 Hz, 1H), 7.21-7.12 (m, 1H), 7.08-6.99 (m,
2H), 2.68-2.36 (m, 3H), 2.06-1.94 (m, 1H), 1.90-1.74 (m, 1H),
1.33-1.23 (m, 1H), 1.21-1.04 (m, 1H), 0.95 (t, J ) 6.9 Hz, 3H),
5H), 3.72 (dd, J ) 10.8, 5.7 Hz, 1H), 3.62 (dd, J ) 10.8, 6.3
Hz, 1H), 1.80 (dt, J ) 8.5, 5.0 Hz, 1H), 1.33 (m, 1H), 0.98-
0.89 (m, 2H), 0.90 (s, 9H), 0.07 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 143.3, 128.5, 126.1, 125.6, 66.1, 26.2, 25.5, 21.0, 18.7,
13.9, -4.9. Anal. Calcd for C16H26OSi: C, 73.22; H, 9.98.
Found: C, 73.19; H, 9.71.
(46) Casey, C. P.; Polichnowski, S. W.; Shusterman, A. J .; J ones, C.
R. J . Am. Chem. Soc. 1979, 101, 7282.
(47) Kawabata, N.; Kamemura, I.; Naka, M. J . Am. Chem. Soc. 1979,
101, 2139.
(48) Hahn, R. C.; Howard, P. H.; Kong, S.-M.; Lorenzo, G. A.; Miller,
N. L. J . Am. Chem. Soc. 1969, 91, 3558.
(49) Balsamo, A.; Battistini, C.; Crotti, P.; Macchia, B.; Macchia, F.
J . Org. Chem. 1975, 40, 3233.
tr a n s-1,2-Dip h en ylcyclop r op a n e (Ta ble 3, En tr y 4):45
1
IR (film) 1603, 1498, 696 cm-1; H NMR (300 MHz, CDCl3) δ
7.32-7.12 (m, 10H), 2.16 (dd, J ) 7.5, 6.9 Hz, 2H), 1.45 (dd, J
) 7.5, 6.9 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 142.8, 128.6,
126.0, 126.0, 28.3, 18.5.
(45) (a) Hildebrand, J . P.; Marsden, S. P. Synlett 1996, 893. (b) Zhou,
S.-M.; Deng, M.-Z.; Xia, L.-J .; Tang, M.-H. Angew. Chem., Int. Ed. 1998,
37, 2845. (c) Yao, M.-L.; Deng, M.-Z. Synthesis 2000, 1095.
(50) O’Leary, M. A.; Wege, D. Tetrahedron 1981, 37, 801.
(51) Lamberts, J . J . M.; Laarhoven, W. H. J . Org. Chem. 1983, 48,
2202.
J . Org. Chem, Vol. 69, No. 2, 2004 333