Tandem Addition â-Lithiation-Alkylation Sequence
J . Org. Chem., Vol. 66, No. 4, 2001 1393
before.53 The concentration of PhLi was determined by reaction
with diphenylacetic acid.54 All glassware, syringes, and needles
were dried in a vacuum oven and cooled in a desiccator.
Compounds 3a ,55 4a ,56 5a ,57 and 1358 were identified spectro-
scopically and characterized by their melting points against
samples independently prepared by reported methods. The
physical constants and spectroscopic data of compounds 4c,59
5b,60 5c,61 and 1262 were in agreement with the literature data.
The new alkyl-substituted dihydrochalcones were synthesized
according to the general procedure previously described.1
Isotop e Exch a n ge Rea ction s. (a ) Typ ica l P r oced u r e
for th e Ad d ition in THF . A total of 15 mL of 0.2 M PhLi in
anhydrous THF was placed in a septum-capped round-bot-
tomed reaction flask under a nitrogen atmosphere at room
temperature. Then 132 mg (1 mmol) of (E)-cinnamaldehyde
was added at once to the stirred solution. After 7 h, 20 mg (1
mmol) of D2O was added. The solution was dried with Na2-
SO4, diluted to volume with distilled methanol, and quantified
by GC. The product was isolated by TLC and identified by
(E)-2-Meth yl-1-p h en yl-2-p en ten -1-ol (3d ). Oil.1H NMR
(500 MHz, CDCl3) δ 1.00 (t, 3H, J ) 7.6 Hz), 1.47 (s, 3H), 2.07
(m, 2H) 5.10 (s, 1H), 5.63 (t, 1H, J ) 7.1 Hz), 7.24 (m, 1H),
7.33 (m, 4H). 13C NMR (125 MHz, CDCl3) δ 11.77, 13.98, 20.90,
79.24, 126.19, 127.17, 128.16, 128.86, 136.14, 142.49. HRMS
m/z for C12H16O calcd 176.1201, found 176.1205.
(E)-2-Meth yl-1,3-d ip h en yl-p r op en on e (4b). Oil.1H NMR
(200 MHz, CDCl3) δ 1.93 (s, 3H), 7.26 (m, 3H), 7.54 (m, 5H),
7.69 (s, 1H), 7.90 (d, 2H, J ) 7.4 Hz). 13C NMR (125 MHz,
CDCl3) δ 14.30, 126.82, 128.55, 128.75, 129.90, 130.58, 131.23,
134.85, 136.03, 139.90, 200.09. HRMS m/z for C16H14O calcd
222.1045, found 222.1050.
1,3-Dip h en yl-[3-2H]-p r op a n -1-on e (5a -d 1). White solid,
1
mp 69 °C. H NMR (200 MHz, CDCl3) δ 3.07 (t, 1H, J ) 7.1
Hz), 3.29 (d, 2H, J ) 7.5 Hz), 7.27 (m, 5H), 7.47 (m, 3H), 7.95
(dd, 2H, J ) 1.1 and 8.1 Hz). 13C NMR (125 MHz, CDCl3) δ
29.81 (t, J C-D)19.7 Hz), 40.32,126.08, 128.00, 128.37, 128.48,
128.53, 132.98, 136.92, 141.23, 157.38, 199.15. MS m/z: 211
(M+), 106 (M+ - PhC2H3D), 105 (M+ - PhCO), 92 (M+
-
1
melting point, H and 13C NMR spectroscopy, and HRMS. A
PhCOCH2). HRMS m/z for C15H13DO calcd 211.1108, found
211.1103.
95% yield of 5a -d1 was determined.
(b) Typ ica l P r oced u r e for th e Ad d ition in THF -d 8. To
1 mL of 1.5 M PhLi in THF-d8 99% was added 66 mg (0.5
mmol) of (E)-cinnamaldehyde, and the mixtures was allowed
to react for 7 h and then quenched with excess of D2O. The
organic layer was dried with Na2SO4, and a determination
procedure similar to that described in (a) above gave 70% yield
of compound 5a -d3.
1,3-Diph en yl-[2,2,3-2H3]-pr opan -1-on e (5a-d3). White crys-
tals, mp 64 °C. 1H NMR (200 MHz, CDCl3) δ 3.05 (s, 1H), 7.27
(m, 5H), 7.49 (m, 3H), 7.95 (dd, 2H, J ) 1.5 and 8.1 Hz). 13C
NMR (125 MHz, CDCl3) δ 29.68 (m), 30.87 (m), 126.11, 128.03,
128.26, 128.39, 128.51, 128.59, 130.03, 132.37, 133.03, 136.03,
141.22, 199.23. MS m/z: 213 (M+), 105 (M+ - PhCHD3), 92
(M+ - PhCOCHD2). HRMS m/z for C15H11D3O calcd 213.1233,
found 213.1240.
(E)-1,3-Dip h en yl-1-tr im eth ylsilyloxy-2-p r op en e (6). Oil.
1H NMR (500 MHz, CDCl3) δ 0.0 (s, 9H), 5.20 (d, 1H, J ) 6.2
Hz), 6.17 (dd, 1H, J ) 6.2 and 15.7 Hz), 6.47 (d, 1H, J ) 15.7
Hz), 7.18 (m, 10H). 13C NMR (125 MHz, CDCl3) δ 0.27, 75.52,
126.19, 126.54, 127.19, 127.46, 128.26, 128.48, 129.26, 132.87,
136.86, 143.55. HRMS m/z for C18H22OSi calcd 282.1440, found
282.1445.
13C NMR Sp ectr u m of th e In ter m ed ia te III. The 13C
NMR spectra for the intermediate were determined using a
Bruker 500 spectrometer at 125 MHz. The spectra were
determined as follows. To a solution of 84 mg (1 mmol) of PhLi
in 1 mL of THF-d8 in a 5-mm NMR tube capped with a septum
at 0 °C under a nitrogen atmosphere was added 44 mg (0.3
mmol) of freshly distilled (E)-cinnamaldehyde. The solution
was vigorously shaken to ensure complete mixing. After 7 h,
the sample was allowed to equilibrate to the temperature of
the probe over 15 min before the 1H decoupled 13C NMR
spectrum was obtained. The center peak of the downfield
quintet of the THF-d8 was used as the reference peak and was
set to be at δ ) 67.50. 13C NMR (125 MHz, THF-d8) δ 72.49,
108.25, 109.14, 116.34, 119.25, 127.58, 128.06, 128.58, 128.93,
129.28, 144.07, 147.60.
1,3-Dip h en yl-3-t r im et h ylsilyl-1-p r op a n on e (7). White
1
crystals, mp 84-84.5 °C. H NMR (500 MHz, CDCl3) δ 0.0 (s,
9H), 2.90 (dd, 1H, J ) 5.1 and 9.5 Hz), 3.29 (dd, 1H, J ) 5.1
and 16.8 Hz), 3.54 (dd, 1H, J ) 9.5 and 16.8 Hz), 7.07 (d, 3H,
J ) 7.3 Hz), 7.2 (m, 2H), 7.45 (m, 3H), 7.90 (d, 2H, J ) 7.0
Hz). 13C NMR (125 MHz, CDCl3) δ -2.89, 31.24, 39.03, 124.57,
127.37, 127.89, 128.05, 128.43, 132.68, 137.21, 143.17, 199.12.
HRMS m/z for C18H22OSi calcd 282.1440, found 282.1444.
(E)-1-(2-Meth oxy-p h en yl)-3-p h en yl-2-p r op en -1-ol (9).
Oil. 1H NMR (500 MHz, CDCl3) δ 2.91 (br s, 1H), 3.85 (s, 3H),
5.58 (d,1H, J ) 6.0 Hz), 6.46 (dd, 1H, J ) 6.1 and 16.0 Hz),
6.64 (d, 1H, J ) 16.0 Hz), 6.89 (d, 1H, J ) 8.2 Hz), 6.96 (t, 1H,
J ) 7.4 Hz), 7.21 (m, 2H), 7.28(m, 3H), 7.36 (m, 3H). 13C NMR
(125 MHz, CDCl3) δ 55.42, 71.31, 110.79, 120.94, 126.50,
127.43, 127.45, 128.44, 128.76, 129.89, 130.96, 136.96, 156.70.
HRMS m/z for C16H16O2 calcd 240.1150, found 240.1155.
(E)-1-(2-Met h oxy-p h en yl)-3-p h en yl-p r op en on e (10).
White crystals, mp 65-66 °C. 1H NMR (200 MHz, CDCl3) δ
3.76 (s, 3H), 6.84 (d, 1H, J ) 15.9 Hz), 7.23 (m, 7H), 7.44 (m,
1H), 7.58 (d, 1H, J ) 16 Hz), 7.86 (d, 1H, J ) 7.5 Hz) 13C NMR
(60 MHz, CDCl3) δ 55.57, 114.00, 121.15, 124.01, 127.60,
128.64, 128.75, 129.87, 131.05, 134.90, 135.23, 142.80, 158.82,
191.56. HRMS m/z for C16H14O2 calcd 238.0994, found 238.0996.
1-(2-Meth oxy-ph en yl)-3-ph en yl-pr opan -1-on e (11). White
(E)-2-Meth yl-1,3-d ip h en yl-2-p r op en -1-ol (3b). Oil. 1H
NMR (500 MHz, CDCl3) δ 1.74 (d, 3H, J ) 1.3 Hz), 5.29 (s,
1H), 6.78 (s, 1H), 7.21 (m, 1H), 7.32 (m, 7H), 7.44 (dd, 2H, J )
1.0 and 7.7 Hz). 13C NMR (125 MHz, CDCl3) δ 13.92, 79.34,
125.84, 126.40, 127.41, 128.02, 128.28, 128.95, 137.50, 139.62,
142.17. HRMS m/z for C16H16O calcd 224.1201, found 224.1205.
(E)-1-P h en yl-2-p en ten -1-ol (3c). Oil.1H NMR (500 MHz,
CDCl3) δ 1.01 (t, 3H, J ) 7.4 Hz), 2.08 (m, 2H), 5.17 (d, 1H, J
) 6.8 Hz), 5.67 (ddt, 1H, J ) 1.6, 6.8 and 15.5 Hz), 5.81 (dt,
1H, J ) 6.0 and 15.5 Hz), 7.27 (m, 1H), 7.36 (m, 4H). 13C NMR
(125 MHz, CDCl3) δ 13.30, 25.19, 75.26, 126.16, 127.49, 128.46,
131.34, 134.31, 143.45. HRMS m/z for C11H14O calcd 162.1045,
found 162.1049.
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1
crystals, mp 84-85 °C. H NMR (500 MHz, CDCl3) δ 3.02 (t,
2H, J ) 7.8 Hz), 3.30 (t, 2H, J ) 7.8 Hz), 3.87 (s, 3H), 6.95 (d,
1H, J ) 8.2 Hz), 6.99 (t, 1H, J ) 7.5 Hz), 7.23 (m, 5H), 7.44
(dt, 1H, J ) 1.8 and 7.5 Hz), 7.68 (dd, 1H, J ) 1.8 and 7.8
Hz). 13C NMR (125 MHz, CDCl3) δ 30.48, 45.38, 55.48, 111.51,
120.67, 125.87, 128.37, 128.43, 130.33, 133.35, 141.72, 158.52,
201.70. HRMS m/z for C16H16O2 calcd 240.1150, found 240.1153.
1,3-Dip h en yl-1-octa n on e (15). White crystals, mp 59-60
°C. 1H NMR (500 MHz, CDCl3) δ 0.82 (t, 3H, J ) 6.6 Hz), 1.22
(m, 6H), 1.64 (m, 1H), 1.71 (m, 1H), 3.22 (dd, 1H, J ) 7.4 and
16.3 Hz), 3.27 (dd, 1H, J ) 6.4 and 16.4 Hz), 3.32 (m, 1H),
7.17 (t, 1H, J ) 7.2 Hz), 7.22 (d, 2H, J ) 6.9 Hz), 7.27 (t, 2H,
J ) 7.6 Hz), 7.41 (t, 2H, J ) 7.7 Hz), 7.52 (t, 1H, J ) 7.3 Hz),
7.89 (d, 2H, J ) 7.3 Hz). 13C NMR (125 MHz, CDCl3) δ 13.99,
22.47, 27.13, 31.75, 36.29, 41.33, 45.99, 126.19, 127.55, 128.03,
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