Synthesis of Electrophilic Acetone Equivalents
J . Org. Chem., Vol. 63, No. 11, 1998 3699
C(O)CH2I); exact mass calcd for C5H9ClO2 227.9647, found
227.9647.
suitable purity (>97% as judged by GC) for use in the next
step although it could be purified via flash column chroma-
tography (SiO2, petroleum ether/EtOAc 10:1).
1-Iod o-2-[[2-(t r im et h ylsilyl)et h oxy]m et h oxy]-2-p r o-
p en e (11b): yield 93.3%. This product was purified via flash
column chromatography (SiO2, petroleum ether/CH2Cl2 7:1) to
give pure 11b with 93.1% yield as a clear oil: 1H NMR (400
MHz, CDCl3) δ 0.00 (s, 9H, Si(CH3)3), 0.95 (A in AA′XX′, J AX
) 9.8 Hz, J A′X ) 7.0 Hz, J AA′ ) -2.9 Hz, J XX′ ) -2.3, 2H,
CH2Si(CH3)3), 3.74 (X in AA′XX′, 2H, OCH2CH2Si(CH3)3), 3.81
(d, J ) 0.7 Hz, 2H, ICH2), 4.32 (dt, J ) 2.4, 0.7 Hz, 1H, (Z)-
H2CdC), 4.44 (d, J ) 2.4 Hz, 1H, (E)-H2CdC), 5.04 (s, 2H,
OCH2O); 13C NMR (100 MHz, CDCl3) δ -1.49 (Si(CH3)3), 4.22
(ICH2), 17.88 (CH2Si(CH3)3), 66.46 (OCH2CH2Si(CH3)3), 87.24
(H2CdC), 92.08 (OCH2O), 155.69 (H2CdC(O)CH2I); exact mass
calcd for C9H19IO2Si 314.0199, found 313.01367 (M - 1).
1-Iod o-2-n -bu toxy-2-p r op en e (11c). The crude product
was purified by flash column chromatography (SiO2, hexane/
Et2O 20:1) to give pure 11c with 83.3% yield as a clear oil: 1H
NMR (400 MHz, CDCl3) δ 0.96 (t, J ) 7.5 Hz, 3H, OCH2CH2-
CH2CH3), 1.47 (tq, J ) 7.5, 7.3 Hz, 2H, OCH2CH2CH2CH3),
1.69 (tt, J ) 7.3, 6.4 Hz, 2H, OCH2CH2CH2CH3), 3.72 (t, J )
6.4 Hz, 2H, OCH2CH2CH2CH3), 3.81 (d, J ) 0.8 Hz, 2H,
ClCH2), 4.01 (dt, J ) 2.4, 0.8 Hz, 1H, (Z)-H2CdC), 4.29 (d, J
) 2.4 Hz, 1H, (E)-H2CdC); 13C NMR (100 MHz, CDCl3) δ 4.57
(ICH2), 14.05 (OCH2CH2CH2CH3), 19.57 (OCH2CH2CH2CH3),
31.03 (OCH2CH2CH2CH3), 68.02 (OCH2CH2CH2CH3), 83.84
(H2CdC), 159.52 (H2CdC(O)CH2I); exact mass calcd for C7H13IO
240.0011, found 240.0010.
4,4-Dicar beth oxy-2-(m eth oxym eth oxy)-1-pen ten e (33a):
yield 87%; H NMR (500 MHz, CDCl3) δ 1.24 (t, 6H, J ) 7.2
1
Hz, COOCH2CH3), 1.41 (s, 3H, OCH3), 2.76 (s, 2H, CH2CdCH2),
3.38 (s, 3H, CH3C(COOC2H5)2), 4.04 (A in ABq, 1H, J ) 1.9
Hz, (E)-CH2dC), 4.17 (ABqq, 4H, J ) 7.1 Hz, J AB ) 10.9 Hz,
δA ) 4.18, δB ) 4.16, COOCH2CH3), 4.20 (B in ABq, 1H, (Z)-
CH2dC), 4.84 (s, 2H, OCH2OCH3); 13C NMR (125 MHz, CDCl3)
δ 13.90 (COOCH2CH3), 19.23 (CH3C(COOCH2CH3)2), 40.63
(CH2CdCH2), 52.29 (CH3C(COOCH2CH3)2), 56.17 (OCH3),
61.09 (OCH2CH3), 87.97 (CH2dC), 93.60 (OCH2O), 156.44
(CdCH2), 171.79 (COOCH2CH3); exact mass calcd for C13H22O6
274.1416, found 274.1412.
4,4-Dicar beth oxy-2-[[2-(tr im eth ylsilyl)eth oxy]m eth oxy]-
1-p en ten e (33b): yield 89%; 1H NMR (500 MHz, CDCl3) 0.03
(s, 9H, Si(CH3)3), 0.92 (A in AA′XX′, 2H, J AX ) 9.8 Hz, J A′X
)
7.0, J AA′ ) -2.9 Hz, J XX′ ) -2.3 Hz, CH2Si), 1.25 (t, 6H, J )
7.1 Hz, COOCH2CH3), 1.40 (s, 3H, CH3C(COOC2H5)2), 2.76 (s,
2H, CH2CdCH2), 3.62 (X in AA′XX′, 2H, OCH2CH2Si), 3.99
(A in ABq, 1H, J ) 1.9 Hz, CH2dC), 4.18 (ABqq, 4H, J ) 7.1
Hz, J AB ) 10.8 Hz, δA ) 4.18, δB ) 4.16, COOCH2CH3), 4.21
(B in ABq, 1H, CH2dC), 4.88 (s, 2H, OCH2O); 13C NMR (125
MHz, CDCl3) δ -1.60 (CH3Si), 13.86 (COOCH2CH3), 17.80
(CH2Si), 19.15 (CH3C(COOCH2CH3)2), 40.62 (CH2CdCH2),
52.24 (CH3C(COOCH2CH3)2), 60.97 (OCH2CH3), 66.12 (OCH2-
CH2Si), 87.75 (CdCH2), 91.91 (OCH2O), 156.48 (CdCH2),
171.69 (COOCH2CH3); exact mass calcd for C17H32O6Si 360.1968,
found 361.2041 (M + 1, CI, CH4 carrier).
1-Iod o-2-(p h en ylm eth oxy)-2-p r op en e (11d ). The crude
product was purified by flash column chromatography (SiO2,
petroleum ether/CH2Cl2 10:1) to give pure 11d in 83.3% yield
as a clear oil: 1H NMR (400 MHz, CDCl3) δ 3.85 (d, J ) 0.8
Hz, 2H, ICH2), 4.11 (dt, J ) 2.7 Hz, 0.8 Hz 1H, (Z)-H2CdC),
4.38 (d, J ) 2.7 Hz, 1H, (E)-H2CdC), 4.80 (s, 2H, OCH2Ph),
7.27-7.43 (AA′BB′C, 5H, C6H5); 13C NMR (100 MHz, CDCl3)
δ 4.21 (ICH2), 70.17 (OCH2Ph), 85.18 (H2CdC), 127.49 (o-
C6H5CH2), 128.09 (p-C6H5CH2), 128.65 (m-C6H5CH2), 136.74
(ipso-C6H5CH2), 159.06 (H2CdC(O)CH2I); exact mass calcd for
4,4-Dica r boeth oxy-2-n -bu toxy-1-p en ten e (33c): yield
87%; 1H NMR (500 MHz, CDCl3) δ 0.89 (t, 3H, J ) 7.3 Hz,
CH3CH2CH2CH2O), 1.22 (t, 6H, J ) 7.2 Hz, COOCH2CH3),
1.341 (sex, 2H, J ) 7.6 Hz, CH3CH2CH2CH2O), 1.34 (s, 3H,
CH3C(COOC2H5)2), 1.55 (quint, J ) 7.06 Hz, CH3CH2CH2CH2O),
2.73 (s, 2H, CH2CdCH2), 3.54 (t, 2H, J ) 6.5 Hz, CH3CH2-
CH2CH2O), 3.88 (ABq, 2H, J ) 1.9 Hz, CH2dC), 4.17 (ABqq,
4H, J ) 7.1 Hz, J AB ) 10.9 Hz, δA ) 4.15, δB ) 4.12,
COOCH2CH3); 13C NMR (125 MHz, CDCl3) δ 13.71 (OCH2-
CH2CH2CH3), 13.89 (COOCH2CH3), 19.13 (OCH2CH2CH2CH3),
19.22 (CH3C(COOCH2CH3)2), 30.77 (OCH2CH2CH2CH3), 40.58
(CH2CdCH2), 52.39 (CH3C(COOCH2CH3)2), 61.01 (COOCH2-
CH3), 67.05 (OCH2CH2CH2CH3), 84.37 (CdCH2), 158.80
(CdCH2), 171.89 (COOCH2CH3); exact mass calcd for C15H26O5
286.1780, found 286.1779.
C
10H11IO 273.9855, found 274.9927 (M + 1).
1-Iodo-2-[(p-m eth oxyph en yl)m eth oxy]-2-pr open e (11e).
The crude product was purified by flash column chromatog-
raphy (SiO2, hexane/CH2Cl2 10:1) to give pure 11e with 72.2%
yield as a clear oil: 1H NMR (400 MHz, CDCl3) δ 3.80 (s, 3H,
OCH3), 3.85 (d, J ) 0.8 Hz, 2H, ICH2), 4.13 (dt, J ) 2.5, 0.8
Hz, 1H, (Z)-H2CdC), 4.38 (d, J ) 2.5 Hz, 1H, (E)-H2CdC), 4.74
(s, 2H, OCH2Ar), 6.90 (A in AA′BB′, J AB ) 8.3 Hz, J AA′ ) 2.3
Hz, J AB′ ) 0.6, 2H, o-CH3OC6H4CH2), 7.30 (B in AA′BB′, 2H,
m-CH3OC6H4CH2); 13C NMR (100 MHz, CDCl3) δ 4.38 (ICH2),
55.47 (OCH3), 70.02 (OCH2Ar), 85.01 (H2CdC), 114.07 (o-
CH3OC6H4CH2), 128.80 (ipso-CH3OC6H4), 129.25 (m-CH3-
OC6H4CH2), 159.16 (ipso-CH2C6H4), 159.56 (H2CdC(O)CH2I);
exact mass calcd for C11H13IO2 303.9960, found 305.0033 (M
+ 1).
1-Iodo-2-[2-(tr im eth ylsilyl)eth oxy]-2-pr open e (11f): yield
102.8% of a light yellow oil of low-boiling 11f. This material
was not purified, as the only contaminant observable by NMR
was a minor amount of solvent, which did not affect the
reactivity of the substrate: 1H NMR (400 MHz, CDCl3) δ 0.06
(s, 9H, Si(CH3)3), 1.06 (A in AA′XX′, J AX ) 8.8 Hz, J A′X ) 7.2
Hz, J AA′ ) -2.8 Hz, J XX′ ) -2.5 Hz, 2H, CH2Si(CH3)3), 3.79
(d, J ) 0.8 Hz, 2H, ICH2), 3.82 (X in AA′XX′, 2H, OCH2-
CH2Si(CH3)3), 4.07 (d, J ) 2.3 Hz, (Z)-H2CdC), 4.24 (d, J )
2.3 Hz, (E)-H2CdC); 13C NMR (100 MHz, CDCl3) δ -1.06
(Si(CH3)3), 4.57 (ICH2), 17.27 (CH2Si(CH3)3), 65.85 (OCH2-
CH2Si(CH3)3), 83.92 (H2CdC), 159.43 (H2CdC(O)CH2I); exact
mass calcd for C8H18IOSi 284.0093, found 282.9987 (M - 1).
Gen er a l P r oced u r e for Aceton yla tion of 32. To a
stirred solution of 32 (0.27 g, 1.56 mmol) in THF (11 mL) under
N2 was added via syringe 1.48 M potassium tert-butoxide/THF
(1.05 mL, 1.55 mmol, 1.01 equiv). After the mixture was
stirred for 20 min, 11 (1.55 mmol) was added via syringe. The
mixture was stirred for 18 h and then poured into water (40
mL) and extracted with CH2Cl2 (4 × 40 mL). The organic
phases were combined, dried (MgSO4), and concentrated in
vacuo to yield essentially pure oil 29. This material was of
4,4-Dica r beth oxy-2-(p h en ylm eth oxy)-1-p en ten e (33d ):
1
yield 91%; H NMR (500 MHz, CDCl3) δ 1.14 (t, 6H, J ) 7.1
Hz, COOCH2CH3), 1.43 (s, 3H, CH3C(COOC2H5)2), 2.82 (s, 2H,
CH2CdCH2), 4.03 (ABqq, 4H, J ) 7.2 Hz, J AB ) 10.9 Hz, δA )
4.04, δB ) 4.00, COOCH2CH3), 4.04 (A in ABq, 1H, J ) 1.8
Hz, (E)-CH2dC), 4.08 (B in ABq, 1H, (Z)-CH2dC), 4.63 (s, 2H,
OCH2Ph), 7.25-7.4 (AA′BB′C, 5H, C6H5); 13C NMR (125 MHz,
CDCl3) δ 13.73 (COOCH2CH3), 19.34 (CH3C(COOCH2CH3)2),
40.63 (CH2CdCH2), 52.30 (CH3C(COOCH2CH3)2), 60.94
(OCH2CH3), 69.94 (OCH2C6H5), 85.53 (CH2dC), 127.67 (o-
C6H5CH2), 127.79 (p-C6H5CH2), 128.13 (m-C6H5CH2), 136.56
(ipso-CH2C6H5), 158.52 (CdCH2), 171.72 (COOCH2CH3); exact
mass calcd for C18H24O5 320.1624, found 320.1623.
4,4-Dica r b et h oxy-2-[(p -m et h oxyp h en yl)m et h oxy]-1-
p en ten e (33e): yield 92%; 1H NMR (500 MHz, CDCl3) δ 1.12
(t, 6H, J ) 7.1 Hz, COOCH2CH3), 1.40 (s, 3H, CH3C-
(COOC2H5)2), 2.78 (s, 2H, CH2CdCH2), 3.78 (s, 3H, C6H4OCH3),
4.00 (ABqq, 4H, J ) 7.2 Hz, J AB ) 10.7 Hz, δA ) 4.02, δB
)
3.98, COOCH2CH3), 3.99 (A in ABq, 1H, J ) 2.0 Hz, (E)-
CH2dC), 4.06 (B in ABq, 1H, (Z)-CH2dC), 4.55 (s, 2H,
OCH2C6H4), 6.87 (A in AA′BB′, 2H, C6H4), 7.24 (B in AA′BB′,
2H, C6H4); 13C NMR (125 MHz, CDCl3) δ 13.77 (COOCH2CH3),
19.36 (CH3C(COOCH2CH3)2), 40.69 (CH2CdCH2), 52.34
(CH3C(COOCH2CH3)2), 55.11 (CH3OC6H5), 60.98 (OCH2CH3),
69.35 (OCH2C6H4OCH3), 85.35 (CH2dC), 113.52 (o-CH3-
OC6H4CH2), 128.75 (ipso-CH3OC6H4), 129.49 (m-CH3OC6H4CH2),
158.60 (ipso-CH2C6H4), 159.23 (CdCH2), 171.79 (COOCH2CH3);
exact mass calcd for C19H26O6 350.1729, found 350.1729.
4,4-Dica r b et h oxy-2-[2-(t r im et h ylsilyl)et h oxy]-1-p en -
ten e (33f): yield 90%; 1H NMR (400 MHz, CDCl3) 0.01 (s, 9H,