1354 J . Org. Chem., Vol. 62, No. 5, 1997
Hand et al.
then with 1:3 EtOAc-CHCl3 to obtain 20 (0.85 g total, 66%)
Meth yl 6-[2-[8-[1-(ter t-Bu tyld im eth ylsiloxy)-2-p h en yl-
eth yl]d iben zofu r a n yl]]-6-oxoh exa n oa te (26). The reagent
was prepared by dropwise addition of 4-bromobutanoyl chlo-
ride (3.5 mL, 30 mmol) to a cold solution of anhydrous MeOH
(5 mL) in dry PhH (10 mL). After 1 h, the solution was diluted
with PhH, washed with ice-water (4×), dried, and evaporated
under reduced pressure to give methyl 4-bromobutanoate as
a colorless liquid which contained ca. 0.35 equiv of PhH (6.2
g, 100%).
The crude alkylation products (from 3.1 g, 7.0 mmol of 6)
were fractionated on silica gel (275 g) with PhH; early fractions
gave 14 as a syrup (0.62 g, 19%): TLC (PhH) Rf 0.75; 1H
NMR19 δ 3.16 (q, CH2CH3), 1.3 (t, CH2CH3). Anal. Calcd for
C29H34O3Si [458.68]: C, 75.94; H, 7.47. Found: C, 75.95; H,
7.52.
1
as a syrup: TLC (1:3 EtOAc-CHCl3) Rf ca. 0.7; H NMR19
δ
3.58 (t, (Z)-NCH2), 3.53 (t, (E)-NCH2), 3.47 [t, ArC(O)CH2], 2.85
[t, CH2C(O)N], 1.65 (m, 4 H, (E)-NCH2CH2 and CH2CH2CH2-
CH2CH2), 1.56 (m, 2H, (Z)-NCH2CH2). Anal. Calcd for C35H43
-
NO4Si + 0.26C6H6 + 0.3H2O [FW 578.61]: C, 73.19; H, 7.64;
N, 2.42. Found: C, 73.19; H, 7.71; N, 2.44.
After trituration with Et2O, compound 21 was obtained as
a colorless solid: mp 148-149 °C; TLC (1:3 EtOAc-CHCl3)
Rf ca. 0.2; 1H NMR (200 MHz)19 δ 4.63 [p, ArC(O)CH], 3.5 and
3.4 (b, 8 H, 2 × CH2NCH2), 2.79 (ABX, 4 H, 2 × CH2CO), 1.5
[b, 12 H, 2 × C(CH2)3C]. Anal. Calcd for C42H54N2O5Si
[694.99]: C, 72.59; H, 7.83; N, 4.03. Found: C, 72.33; H,
7.84: N, 4.01.
N,N-Diisop r op yl 4-[2-[8-[1-(ter t-Bu tyld im eth ylsiloxy)-
2-p h en yleth yl]d iben zofu r a n yl]]-4-oxobu ta n a m id e (22).
The reagent, N,N-diisopropyl bromoacetamide, was prepared
by dropwise addition of (i-Pr)2NH (7.27 g, 72 mmol, 1.8 equiv,
dried over 4 Å molecular sieves)21 dissolved in CH2Cl2 (10 mL)
to a stirred solution of BrCH2COBr (3.5 mL, 40 mmol) in CH2-
Cl2 (30 mL) at 0 °C. After 20 min the mixture was filtered,
and the filtrate was washed with ice-water (4×), NaHCO3 to
give pH 8-9, and ice-water, dried, and evaporated; the orange
residue was triturated with heptane to give the reagent as
colorless, long needles (0.51 g, 63%): mp 64-65.5 °C (lit.20
liquid); 1H NMR δ 3.96 (h, (Z)-NCH), 3.81 (s, BrCH2), 3.43 (h,
(E)-NCH), 1.39 [d, (E)-NCH(CH3)2], 1.25 [d, (Z)-NCH(CH3)2].
Anal. Calcd for C8H16BrNO [222.13]: C, 43.26; H, 7.26; Br,
35.97; N, 6.31. Found: C, 43.31; H, 7.30; Br, 36.05; N, 6.25.
Middle fractions contained 6 and methyl 4-bromobutanoate.
Late fractions gave 26 (1.62 g, 43%), which crystallized from
heptane as a colorless solid: mp 69-71 °C; TLC (PhH) Rf ca.
0.2; 1H NMR19 δ 3.68 (OCH3), 3.12 [t, ArC(O)CH2], 2.42 (t, CH2-
CO2), 1.80 (m, CCH2CH2C). Anal. Calcd for C33H40O5Si
[544.77]: C, 72.76; H, 7.40. Found: C, 72.91; H, 7.44.
N-[4-[2-[8-[1-(ter t-Bu tyld im eth ylsiloxy)-2-(2-p h en yleth -
yl)p h en yleth yl]d iben zofu r a n yl]]-4-oxobu ta n oyl]p yr r oli-
d in e (29). The crude products (from 0.70 g, 1.27 mmol of 12)
were fractionated on silica gel (100 g). CHCl3 eluted the minor
side products, 27 and 28, and 12 (0.12 g, 17%); 1:9 and 1:3
EtOAc-CHCl3 eluted 2919,22 (0.54 g, 64%) as a hygroscopic
syrup, which failed to crystallize from heptane: TLC (1:3
EtOAc-CHCl3) Rf ca. 0.7. Anal. Calcd for C42H49NO4Si +
0.14heptane + 0.2H2O [FW 677.88]: C, 76.19; H, 7.69; N, 2.07.
Found: C, 76.13; H, 7.79; N, 2.06.
N,N-Diisop r op yl 4-[2-[8-[1-(ter t-Bu tyld im eth ylsiloxy)-
2-(2-p h en yleth yl)p h en yleth yl]d iben zofu r a n yl]]-4-oxobu -
ta n a m id e (30). The crude products (from 0.81 g, 1.5 mmol
of 12) were fractionated on silica gel (65 g), eluting with CHCl3,
to give 30 and impure 30, which was rechromatographed. A
heptane solution of the product was left to evaporate to give
3019,22 as a waxy solid (0.88 g, 86%): mp 98-103 °C; TLC
(CHCl3) Rf ca. 0.2. Anal. Calcd for C44H55NO4Si + 0.3H2O
[FW 695.42]: C, 76.00; H, 8.06; N, 2.01. Found: C, 76.03; H,
8.10; N, 1.98.
The filtered, crude alkylation product (from 1.00 g, 2.25
mmol of 6) was purified by chromatography on silica gel (75
g) eluting first with PhH to remove 14, 15, and 6 and then
with CHCl3 to obtain 22, followed by impure 22, which was
rechromatographed (silica gel, 50 g) with 1:33 EtOAc-CHCl3.
The product was obtained as a syrup (0.73 g, 55% total): TLC
1
(1:15 EtOAc-CHCl3) Rf ca. 0.5; H NMR (200 MHz)19 δ 4.17
(h, (Z)-NCH), 3.55 (h, (E)-NCH), 3.49 [t, ArC(O)CH2], 2.82 [t,
CH2C(O)N], 1.40 [d, (E)-NCH(CH3)2], 1.27 [d, (Z)-NCH(CH3)2].
Anal. Calcd for C36H57NO4Si + 0.2Et2O + 0.3H2O [FW 610.90]:
C, 73.14; H, 8.18; N, 2.29. Found: C, 73.19; H 8.13; N, 2.29.
4-[2-[8-[1-(ter t-Bu t yld im et h ylsiloxy)-2-p h en ylet h yl]-
d iben zofu r a n yl]]-4-oxobu ta n en itr ile (23). The crude alky-
lation products were fractionated on silica gel (60 g) with PhH.
The product 23 (0.51 g, 60%) crystallized from Et2O as a
colorless solid: mp 139-140 °C; TLC (PhH) Rf ca. 0.4; 1H NMR
(200 MHz)19 δ 3.52 (t, OdCCH2), 2.85 (t, CH2CN). Anal. Calcd
for C30H33NO3Si [483.69]: C, 74.50; H, 6.88; N, 2.90. Found:
C, 74.41; H, 6.92; N, 2.86.
Meth yl 5-[2-[8-[1-(ter t-Bu tyld im eth ylsiloxy)-2-(2-p h en -
y l e t h y l )p h e n y l e t h y l ]d i b e n z o fu r a n y l ]]-5 -o x o p e n -
ta n oa te (31). The crude products (from 0.76 g, 1.4 mmol of
12) were fractionated on silica gel (60 g); PhH eluted 27 (15
mg, 2%) and 12 (0.12 g, 16%); CHCl3 eluted 3119,22 which was
obtained as a syrup (0.67 g, 76%): TLC (PhH) Rf ca. 0.2. Anal.
Calcd for C40H46O5Si + 0.3H2O [FW 640.30]: C, 75.03; H, 7.34.
Found: C, 75.04; H, 7.38.
Meth yl 5-[2-[8-[1-(ter t-Bu tyld im eth ylsiloxy)-2-p h en yl-
eth yl]d iben zofu r a n yl]]-5-oxop en ta n oa te (24). The re-
agent, methyl 3-iodopropionate, was prepared by stirring a
solution of NaI (5.8 g, 38.7 mmol) and 3-bromopropionate (3.3
mL, 30.2 mmol) in acetone (20 mL) for 2 h, heating the mixture
at 50 °C for 45 min, cooling, and filtering; the filtrate was
concentrated under reduced pressure, diluted with Et2O,
extracted with ice-cold H2O (2×), dried, and evaporated to give
a liquid (6.57 g, ca. 95%) consisting of 19:1 ICH2CH2CO2CH3-
BrCH2CH2CO2CH3, according to a 1H NMR spectrum [δ 3.73
(s, OCH3), 3.59 (t, BrCH2), 3.34 (t, ICH2), 2.99 (t, ICH2CH2),
2.96 (t, BrCH2CH2)].
A heptane solution of the crude alkylation products (from
1.64 g, 3.7 mmol of 6) was partially evaporated to give 24 (0.90
g), mp 69-72 °C. Materials in the mother liquor were
fractionated on silica gel (75 g); PhH eluted side products and
6 (ca. 26%), 1:20 Et2O-PhH eluted 24 (0.47 g), which was
recrystallized from heptane to give a second crop (0.28 g, 60%
total): TLC (PhH) Rf 0.35; 1H NMR (200 MHz)19 δ 3.69 (s,
OCH3), 3.12 [t, ArC(O)CH2], 2.42 (t, CH2CO2), 1.80 (p, CH2CH2-
CH2). Anal. Calcd for C32H38O5Si [530.74]: C, 72.42; H, 7.22.
Found: C, 72.55; H, 7.28.
Rea ction of 6 w ith N,N-Dim eth ylca r ba m oyl Ch lor id e.
A solution of the MMC-adduct formed from 6 (0.78 g, 1.75
mmol), DMF (3 mL), and MMC (4.4 mL, 2 M in DMF, 5 equiv),
was treated with a solution of Me2NCOCl (0.48 mL, 5.25 mmol,
3 equiv) in DMF (0.9 mL) and heated for 40 min at 65 °C and
then at 120 °C for 45 min, cooled, treated with additional Me2-
NCOCl (0.32 mL, 2 equiv), and heated at 115 °C for 1 h. The
cooled orange-red solution was poured into ice-water and
acidified to pH 3 with HCl (5.5 mL, 1.4 N). Filtration gave a
solid (0.94 g) which was fractionated on silica gel (60 g). PhH
eluted 15 (ca. 15 mg), 14 (ca. 15 mg), 6 (0.17 g, 22%), and 32
(tough gum, 0.16 g, 18%); Et2O eluted 34 (glass, 0.12 g, 12%)
and 1:19 MeOH-Et2O eluted 33 (hard glass, 0.17 g, 16%).
Data for 32: TLC (CHCl3) Rf ca. 0.7; MS m/z ) 411 [(M -
1
PhCH2)+, base]; H NMR (200 MHz) (9:1 keto-enol mixture)
δ (keto) 8.57 (H-1), 4.14 (CH2), 3.79 (OCH3); δ (enol) 8.42 (H-
1); 5.79 (dCH), 3.84 (OCH3); CH2 and dCH exchange with
D2O. Anal. Calcd for C30H34O5Si [502.69]: C, 71.68; H, 6.82.
Found: C, 71.79; H, 6.86.
Data for 33: TLC (1:33 MeOH-Et2O) Rf ca. 0.3; MS m/z )
1
499 (M+, 0.2%), 408 [(M - PhCH2)+, base]; H NMR19 δ 7.90
(d, J ) 12.5 Hz, dCHN), 5.86 (d, J ) 12.5 Hz, OdCC(H)d),
In the experiment with methyl 3-bromopropionate (3 + 10.5
equiv), the bis-alkylation product 25 (0.18 g, 17%) was isolated
from the last column eluates (1:20 Et2O-PhH) as a syrup:
TLC (1:20 Et2O-PhH) Rf ca. 0.2. Anal. Calcd for C36H44O7Si
[616.83]: C, 70.10; H, 7.19. Found: C, 70.24; H, 7.15.
ca. 3.18 (b, ca. 3 H, NCH3), ca. 3.0 (b, overlayed by two sharp
(22) Chemical shifts of the amide and ester side chain protons in
29-31 were about the same as in the corresponding compounds 19,
22, and 24.