4534 J . Org. Chem., Vol. 67, No. 13, 2002
Petrini et al.
C23H27NO4 (381.4): C, 72.42; H, 7.13; N, 3.67. Found: C, 72.47;
H, 7.09; N, 3.70.
mo ketone 21 add to sulfones 3, affording the correspond-
ing N-protected â-amino ketones 22, which are valuable
intermediates in organic synthesis.
Eth yl 2-{2-[(ter t-Bu toxyca r bon yl)a m in o]-3-m eth ylbu -
tyl}a cr yla te (13e). Yield: 95%. Oil. IR (cm-1, neat): 3377,
1
1712, 1684. H NMR δ: 0.89 (d, 3H, J ) 7.0 Hz), 0.91 (t, 3H,
Exp er im en ta l Section
J ) 7.0 Hz), 1.29 (t, 3H, J ) 7.3 Hz), 1.37 (s, 9H), 1.68-1.84
(m, 1H), 2.20 (dd, J ) 10,6, 13.9 Hz), 2.51 (dd, 1H, 4.0, 13.2
Hz), 3.53-3.68 (m, 1H), 4.19 (q, 2H, J ) 7.3 Hz), 4.41 (d, 1H,
J ) 8.9 Hz), 5.59 (s, 1H), 6.19 (s, 1H).13C NMR δ: 14.1, 17.5,
19.0, 28.3, 32.4, 34.5, 55.2, 60.7, 78.7, 126.5, 138.0, 155.8, 167.2.
Anal. Calcd for C15H27NO4 (285.4): C, 63.13; H, 9.54; N, 4.91.
Found: C, 63.20; H, 9.52; N, 4.94.
1H NMR spectra were performed at 300 MHz in CDCl3 as
solvent.13C NMR spectra were performed at 75 MHz in CDCl3
as solvent. Tetrahydrofuran was dried by refluxing it over
sodium wire and then distilled. All chemicals used are com-
mercial grade. Sulfones 3,13a 3-bromo-1-acetoxy-1-propene 17,25
and R-bromoacetyl furan 21b32 have been prepared as de-
scribed. Compounds 22b,e,f have been identified by compari-
son with the literature data.33
Gen er a l P r oced u r e for th e P r ep a r a tion of Allyl De-
r iva tives 7, 9, 13, a n d 18. To a suspension of zinc dust (5
mmol) in dry THF (10 mL) was added the corresponding allyl
bromide (3 mmol) at room temperature. After stirring for 30
min, the appropriate sulfone 3 (2 mmol) dissolved in dry THF
(8 mL) was added dropwise. Stirring was continued for 1 h
(24 h for compounds 18) and then the mixture was quenched
by addition of saturated NH4Cl (8 mL). The mixture was
extracted with CH2Cl2 (4 × 15 mL) and dried over MgSO4. The
crude product obtained after removal of the solvent was
purified by column chromatography (7:3 hexanes-ethyl ac-
etate).
a n ti-1-{1-[(Ben zyloxyca r bon yl)a m in o]octyl}a llyl Ac-
1
eta te (a n ti-18a ). Yield: 54%. Oil. IR (cm-1, neat): 1712. H
NMR δ: 0.88 (t, 3H, J ) 6.2 Hz), 1.20-1.55 (m, 12H), 2.06, (s,
3H), 3.82-4.03 (m, 1H), 4.65 (d, 1H, J ) 9.5 Hz), 5.12 (s, 2H),
5.23-5.38 (m, 3H), 5.68-5.90 (m, 1H), 7.32-7.43 (m, 5H).13
C
NMR δ: 14.1, 22.6, 25.9, 29.1, 29.3, 30.6, 31.7, 53.3, 66.7, 76.1,
118.7, 128.0, 128.1, 128.5, 132.3, 156.2, 170.1. Anal. Calcd for
C
21H31NO4 (361.5): C, 69.78; H, 8.64; N, 3.87. Found: C, 69.82;
H, 8.61; N, 3.90.
syn -1-{1-[(Ben zyloxyca r b on yl)a m in o]oct yl}a llyl Ac-
eta te (syn -18a ). Yield: 14%. Oil. IR (cm-1, neat): 1712. 1H
NMR δ: 0.89 (t, 3H, J ) 6.6 Hz), 1.18-1.40 (m, 10H), 1.44-
1.73 (m, 2H), 2.10, (s, 3H), 3.30-3.50 (m, 1H), 4.96-5.18 (m,
3H), 5.20-5.44 (m, 3H), 5.62-5.90 (m, 1H), 7.35-7.45 (m,
5H).13C NMR δ: 14.1, 24.7, 24.9, 28.8, 28.9, 31.7, 35.9, 53.4,
66.9, 76.5, 119.2, 128.1, 128.2, 128.6, 131.6, 155.8, 169.9. Anal.
Calcd for C21H31NO4 (361.5): C, 69.78; H, 8.64; N, 3.87.
Found: C, 69.75; H, 8.65; N, 3.92.
Ben zyl 1-P h en eth ylbu t-3-en ylca r ba m a te (7a ). Yield:
99%. Mp: 55 °C. IR (cm-1, KBr): 3310, 1685. 1H NMR δ:
1.61-1.98 (m, 2H), 2.18-2.41 (m, 2H), 2.61-2.86 (m, 2H),
3.71-3.95 (m, 1H), 4.75 (d, 1H, J ) 8.8 Hz), 5.05-5.19 (m,
2H), 5.15 (s, 2H), 5.70-5.92 (m, 1H), 7.19-7.41 (m, 10H). 13C
NMR δ: 32.4, 36.6, 39.6, 50.5, 66.6, 118.2, 125.9, 128.1, 128.2,
128.3, 128.4, 128.5, 133.9 136,6, 141.7, 156.0. Anal. Calcd for
a n ti-1-{1-[(ter t-Bu toxyca r bon yl)a m in o]-2-m eth ylp r o-
p yl}a llyl Aceta te (a n ti-18b). Yield: 63%. Oil. IR (cm-1
,
neat): 1710. 1H NMR δ: 0.90 (d, 3H, J ) 6.6 Hz), 0.99 (d, 3H,
J ) 6.6 Hz), 1.44 (s, 9H), 1.64-1.80 (m, 1H), 2.06 (s, 3H), 3.62-
3.77 (m, 1H), 4.40 (d, 1H, J ) 10.6 Hz), 5.26-5.38 (m, 2H),
5.72-5.89 (m, 1H). 13C NMR δ: 21.6, 14.6, 22.9, 23.1, 23.6,
52.0, 69.1, 73.9, 113.7, 127.3, 150.7, 164.7. Anal. Calcd for
C
20H23NO2 (309.4): C, 77.64; H, 7.49; N, 4.53. Found: C, 77.70;
H, 7.44; N, 4.57.
Ben zyl 1-Hep tylbu t-3-en ylca r ba m a te (7b). Yield: 80%.
1
Mp: 38 °C. IR (cm-1, KBr): 3305, 1695. H NMR δ: 0.90 (t,
C
14H25NO4 (271.3): C, 61.97; H, 9.29; N, 5.16. Found: C, 62.02;
3H, J ) 6.6 Hz), 1.18-1.56 (m, 12H), 2.11-2.40 (m, 2H), 3.62-
3.84 (m, 1H), 4.66 (d, 1H, J ) 8.8 Hz), 5.05-5.19 (m, 2H), 5.11
(s, 2H), 5.68-5.93 (m, 1H), 7.29-7.43 (m, 5H). 13C NMR δ:
14.1, 22.7, 25.7, 25.9, 28.7, 29.2, 29.5, 29.9, 31.8, 34.6, 36.8,
39.4, 50.7, 66.5, 117.8, 128.0, 128.5, 134.3, 136.7, 156.1. Anal.
Calcd for C19H29NO2 (303.4): C, 75.21; H, 9.63; N, 4.62.
Found: C, 75.29; H, 9.57; N, 4.66.
H, 9.33; N, 5.13.
syn -1-{1-[(ter t-Bu toxycar bon yl)am in o]-2-m eth ylpr opyl}-
a llyl Aceta te (syn -18b). Yield: 7%. Oil. IR (cm-1, neat): 1710.
1H NMR δ: 0.91 (d, 3H, J ) 6.8 Hz), 0.99 (d, 3H, J ) 6.8 Hz),
1.43 (s, 9H), 1.86-2.01 (m, 1H), 2.09 (s, 3H), 3.37-3.46 (m,
1H), 3.77 (d, 1H, J ) 9.8 Hz), 5.25-5.40 (m, 3H), 5.70-5.89
(m, 1H). 13C NMR δ: 13.7, 15.8, 22.9, 23.1, 24.0 53.6, 68.7,
73.6, 113.9, 126.9, 150.5, 154.9.
Ben zyl 1-P h en eth ylbu t-3-yn ylca r ba m a te (9a ). Yield:
1
99%. Oil. IR (cm-1, neat): 3315, 1683. H NMR δ: 1.85-1.99
Gen er a l P r oced u r e for th e P r ep a r a tion of N-Boc
La cta m s 14. To a solution of amino ester 11 (1 mmol) in dry
toluene (9 mL) was added Me3Al (2M in toluene, 2 mmol, 1
mL) at 0 °C, stirring was continued for 1 h at 0 °C, and the
solution was then quenched with brine (6 mL). The mixture
was extracted with CH2Cl2 (4 × 15 mL) and dried over Mg
SO4. The crude product obtained after evaporation of the
solvent was purified by column chromatography (75:25 hex-
anes-ethyl acetate).
(m, 2H), 2.03 (t, 1H, J ) 1.1 Hz), 2.35-2.64 (m, 2H), 2.66-
2.81 (m, 2H), 3.80-4.00 (m, 1H), 4.89-5.02 (m, 1H), 5.15 (s,
2H), 7.12-7.44 (m, 10H). 13C NMR δ: 24.7, 32.4, 35.5, 48.9,
66.8, 71.2, 80.0, 126.0, 128.2, 128.4, 128.5, 128.6, 136.5, 141.3,
155.8. Anal. Calcd for C20H21NO2 (307.4): C, 78.15; H, 6.89;
N, 4.56. Found: C, 78.16; H, 6.94; N, 4.51.
Ben zyl 1-Hep tylbu t-3-yn ylca r ba m a te (9b). Yield: 80%.
1
Mp: 47 °C. IR (cm-1, KBr): 3305, 1695. H NMR δ: 0.90 (t,
ter t-Bu tyl 5-Cycloh exyl-3-m eth ylen e-2-oxop yr r olid in e-
3H, J ) 7.0 Hz), 1.24-1.43 (m, 10H), 1.46-1.70 (m, 2H), 2.01
(t, 1H, J ) 2.5 Hz), 2.31-2.59 (m, 1H), 3.70-3.91 (m, 1H),
4.92 (d, 1H, J ) 8.3 Hz), 5.12 (s, 2H), 7.34-740 (m, 5H). 13C
NMR δ: 13.8, 22.4, 24.2, 25.7, 28.9, 29.1, 31.5, 33,4, 48.9, 66.4,
70.6, 80.0, 127.9, 128.0, 128.3, 136.3, 155.6. Anal. Calcd for
1-ca r boxyla te (14c). Yield: 73%. Oil. IR (cm-1, neat): 1780,
1
1723. H NMR δ: 0.81-1.40 (m, 6H), 1.56 (s, 9H), 1.58-1.96
(m, 5H), 2.63-2.75 (m, 2H), 4.05-4.15 (m, 1H), 5.44 (t, 1H,
J ) 2.2 Hz), 6.14 (t, 1H, J ) 2.5 Hz). 13C NMR δ: 25.8, 25.9,
26.3, 26.4, 26.6, 28.1, 29.4, 41.5, 58.7, 82.8, 119.1, 139.8, 150.8,
165.6. Anal. Calcd for C16H25NO3 (297.4): C, 68.79; H, 9.02;
N, 5.01. Found: C, 68.81; H, 9.00; N, 5.04.
C
19H27NO2 (301.4): C, 75.71; H, 9.03; N, 4.65. Found C, 75.77;
H, 8.98; N, 4.68.
Eth yl 2-{2-[(Ben zyloxycar bon yl)am in o]-4-ph en ylbu tyl}-
a cr yla te (13a ). Yield: 98%. Mp: 72 °C. IR (cm-1, KBr): 3370,
1713, 1685. 1H NMR δ: 1.30 (t, 1H, J ) 7.0 Hz), 1.72-1,96
(m, 2H), 2.38-2.61 (m, 2H) 2.63-2.84 (m, 2H), 3.83-3.98 (m,
1H), 4.21 (q, 2H, J ) 7.0 Hz), 4.83 (d, 1H, J ) 9.1 Hz), 5.11 (s,
2H), 5.59 (s, 1H), 6.23 (s, 1H), 7.10-7.42 (m, 10H). 13C NMR
δ: 14.2, 32.3, 37.2, 37.5, 50.9, 60.9, 66.5, 125.9, 127.5, 128.0,
128.3, 128.4, 128.5, 137.2, 141,6, 156.0, 167.1. Anal. Calcd for
ter t-Bu tyl 3-Meth ylen e-2-oxo-5-p h en eth ylp yr r olid in e-
1-ca r boxyla te (14d ). Yield: 75%. Oil. IR (cm-1, neat): 1784,
1
1722. H NMR δ: 1.54 (s, 9H), 1.58-1.89 (m, 1H), 2.06-2.13
(m, 1H), 2.47-2.80 (m, 3H), 2.83-3.00 (m, 1H), 4.11-4.28 (m,
1H), 5.52 (s, 1H), 6.23 (s, 1H), 7.17-7.34 (m, 5H). 13C NMR δ:
28.2, 29.9, 31.6, 36.6, 54.6, 83.2, 120.6, 126.3, 128.4, 128.7,
138.8, 140.9, 150.6, 166.5. Anal. Calcd for C18H23NO3 (301.4):
C, 71.73; H, 7.69; N, 4.65. Found: C, 71.77; H, 7.65; N, 4.67.
Gen er a l P r oced u r e for N-Boc Clea va ge of of Am in o
Ester s 13. Syn th esis of Am in o Ester 15d a n d La cta m s
16. N-Boc amino ester 13 (1.5 mmol) was dissolved in THF
(10 mL) and 37% HCl (5 mL) was then added at room
(32) Giovannini, R.; Petrini, M. Tetrahedron Lett. 1997, 38, 3781-
3784.
(33) (a) Molander, G. A.; Stengel, P. J . Tetrahedron 1997, 53, 8887-
8912. (b) Gaunt, M. J .; Spencer, J . B. Org. Lett. 2001, 3, 25-28.