Panchaud et al.
mmol). Filtration (hexane then hexane/EtOAc 90:10) and FC
(hexane/EtOAc 95:5) gave 1a (191 mg, 79%) as a colorless oil:
1H NMR (360 MHz, CDCl3) δ 4.15 (q, J ) 7.3 Hz, 2H), 3.35-
3.27 (m, 1H), 2.50-2.31 (m, 2H), 1.95-1.81 (m, 1H), 1.80-
1.64 (m, 1H), 1.62-1.21 (m, 10H), 1.26 (t, J ) 7.3 Hz, 3H),
0.89 (t, J ) 6.8 Hz, 3H); 13C NMR (90 MHz, CDCl3) 173.0, 62.2,
60.5, 34.4, 31.6, 30.9, 29.5, 29.0, 26.0, 22.5, 14.2, 14.0; IR (film)
2099, 1738 cm-1; MS (CI, CH4) m/z 242 (MH+, 20), 214 (100),
199 (88), 168 (30), 143 (27), 126 (13), 113 (7), 70 (18). Anal.
Calcd for C12H23N3O2 (241.33): C, 59.72; H, 9.61; N, 17.41.
Found: C, 59.77; H, 9.56; N, 17.36.
SCHEME 4. P r ep a r a tion of Sp ir ola cta m 12, a
Bu ild in g Block for th e Syn th esis of
(()-Desm eth yla m in o F R901483
(b) Prepared according to general procedure A from ethyl
2-bromoacetate (167 mg, 1.0 mmol), 1-octene (0.31 mL, 2.0
mmol), PhSO2N3 (550 mg, 3.0 mmol), Bu6Sn2 (0.76 mL, 1.5
mmol), and DTBHN (16 mg, 0.09 mmol). Filtration (hexane
then hexane/EtOAc 90:10) and FC (hexane/EtOAc 95:5) gave
1a (158 mg, 66%).
(c) Prepared according to general procedure A from ethyl
2-[[(ethyloxy)carbothioyl]sulfanyl]acetate (208 mg, 1.0 mmol,
prepared from ethyl 2-iodoacetate and potassium ethyl xan-
thogenate according to a literature procedure),18 1-octene (0.31
mL, 2.0 mmol), PhSO2N3 (550 mg, 3.0 mmol), Bu6Sn2 (0.76
mL, 1.5 mmol), and DTBHN (31 mg, 0.18 mmol) added by 3%
portions every 90 min. Filtration (hexane then hexane/EtOAc
90:10) and FC (hexane/EtOAc 95:5) gave 1a (168 mg, 70%).
Eth yl 4-Azid o-7-br om oh ep ta n oa te (4a ). Prepared ac-
cording to general procedure A from ethyl 2-iodoacetate (642
mg, 3.0 mmol), 5-bromo-1-pentene (0.71 mL, 6.0 mmol),
PhSO2N3 (1.65 g, 9.0 mmol), Bu6Sn2 (2.25 mL, 4.5 mmol), and
DTBHN (31 mg, 0.18 mmol). Filtration (hexane then hexane/
EtOAc 90:10) and CC (hexane/Et2O 95:5) gave 4a (645 mg,
77%) as a colorless liquid: 1H NMR (300 MHz, CDCl3) δ 4.15
(q, J ) 7.3 Hz, 2H), 3.44 (t, J ) 6.4 Hz, 2H), 3.41-3.32 (m,
1H), 2.53-2.36 (m, 2H), 2.12-1.60 (m, 6H), 1.27 (t, J ) 7.3
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 172.7, 61.2, 60.5, 33.0,
32.8, 30.6, 29.4, 29.0, 14.1; IR (film) 2102, 1732 cm-1; MS (EI,
70ev) m/z 280 (M+, 0.1), 278 (M+, 0.1), 232 (2), 189 (1), 162
(10), 143 (17), 124 (18), 100 (15), 81 (39), 70 (100), 55 (45), 41
(98). Anal. Calcd for C9H16BrN3O2 (278.15): C, 38.86; H, 5.80;
N, 15.11. Found: C, 38.94; H, 5.87; N, 15.17.
is efficient with nonactivated terminal alkenes and takes
advantage of radical atom or group-transfer processes.
The synthetic utility of this method is demonstrated by
the preparation of various pyrrolidinones, pyrrolizidino-
nes, indolizidinones, and spirolactams, which are impor-
tant building blocks for alkaloid synthesis. The reaction
proves to be particularly efficient for the formation of
aminated quaternary carbon centers.
Exp er im en ta l Section
Caution: Since sulfonyl azides are capable of exploding, it
is strongly recommended to apply standard safety rules and
to use a safety shield.
Hexa h yd r o-3H-p yr r olizin -3-on e (5a ). Prepared according
to general procedure B from azide 4a (556 mg, 2.0 mmol). CC
(CH2Cl2/MeOH 97:3) gave 5a (205 mg, 82%) as a yellowish oil.
Physical and spectral data were in accordance with literature
data.19
Gen er a l P r oced u r e A. DTBHN (5 mg, 0.03 mmol) was
added every 2 h to a solution of radical precursor (1.0 mmol),
olefin (1.0 or 2.0 mmol), PhSO2N3 (550 mg, 3.0 mmol), and
Bu6Sn2 (0.76 mL, 1.5 mmol) in dry C6H6 (2.0 mL) at reflux
under N2. The reaction was monitored by TLC. Upon comple-
tion of the reaction (4-12 h), the solvent was removed under
reduced pressure and the crude product was filtered through
silica gel. Elution with hexane allowed the removal of un-
changed Bu6Sn2, and further elution with hexane/Et2O or
hexane/EtOAc gave a crude product that was purified by FC
(hexane/Et2O or hexane/EtOAc).
Gen er a l P r oced u r e B. Indium powder (230 mg, 2.0 mmol)
and NH4Cl (107 mg, 2.0 mmol) were added to a solution of
azide (2.0 mmol) in dry EtOH (6.0 mL). The reaction mixture
was stirred under reflux for 2 h. Et3N (1.4 mL, 10.0 mmol)
was added, and the reaction mixture was further stirred under
reflux for 4 h. The cooled reaction mixture was then diluted
with EtOAc (10 mL), stirred for 10 min, and filtered through
a short pad of Celite. The solvent was removed under reduced
pressure, and the crude product was purified by FC (CH2Cl2/
MeOH).
Eth yl 3-(1-Azid ocyclop en tyl)p r op a n oa te (6). Prepared
according to general procedure A from methylenecyclopentane
(411 mg, 5.0 mmol), ethyl 2-iodoacetate (1.07 g, 5.0 mmol),
PhSO2N3 (2.75 g, 15.0 mmol), Bu6Sn2 (3.79 mL, 7.5 mmol), and
DTBHN (52 mg, 0.30 mmol). Filtration (hexane then hexane/
EtOAc 90:10) and FC (hexane/EtOAc 98:2) gave 6 (790 mg,
75%) as a yellowish oil: 1H NMR (300 MHz, CDCl3) δ 4.09 (q,
J ) 7.0 Hz, 2H), 2.39-2.36 (m, 2H), 1.95-1.89 (m, 2H), 1.81-
1.65 (m, 6H), 1.55-1.48 (m, 2H), 1.22 (t, J ) 7.0 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) δ 173.2, 72.7, 60.4, 36.7, 33.9, 30.3,
23.6, 14.1; IR (film) 2101, 1727 cm-1; HRMS (ESI) for
C
10H17N3O2Na calcd 234.1218, found 234.1228.
1-Aza sp ir o[4.4]n on a n -2-on e (7). Prepared according to
general procedure C from azide 6 (211 mg, 1 mmol) and 10%
Pd/C (63 mg, 30% w/w). FC (EtOAc) gave 7 (115 mg, 84%) as
a pale brown solid: mp 142-144 °C; 1H NMR (300 MHz,
CDCl3) δ 6.72 (br s, 1H), 2.41-2.36 (m, 2H), 2.04-1.98 (m,
2H), 1.72-1.65 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 66.9,
39.1, 33.8, 30.7, 29.7, 23.1; HRMS (ESI) for C8H14NO calcd
140.1075, found 140.1071.
8-Meth ylen e-1,4-dioxaspir o[4.5]decan e (10). t-BuOK (3.67
g, 30.0 mmol) was added to a solution of CH3PPh3Br (10.72 g,
30.0 mmol) in Et2O (60.0 mL) at rt under N2. The resulting
Gen er a l P r oced u r e C. A solution of azide (2.0 mmol) and
10% Pd/C (10% w/w) in dry EtOH (12.0 mL) was stirred for
36 h at rt under H2 (30 bar). Et3N (1.4 mL, 10.0 mmol) was
added, and the reaction mixture was stirred under reflux for
4 h. The catalyst was filtered off, the solvent removed under
reduced pressure, and the crude product purified by CC
(EtOAc or CH2Cl2/MeOH).
Eth yl 4-Azid od eca n oa te (1a ). (a) Prepared according to
general procedure A from ethyl 2-iodoacetate (214 mg, 1.0
mmol), 1-octene (0.31 mL, 2.0 mmol), PhSO2N3 (550 mg, 3.0
mmol), Bu6Sn2 (0.76 mL, 1.5 mmol), and DTBHN (10 mg, 0.06
(18) Quiclet-Sire, B.; Sortais, B.; Zard, S. Z. Chem. Commun. 2002,
1692.
(19) Murray, A.; Proctor, G. R.; Murray, P. J . Tetrahedron 1996,
52, 3757.
2758 J . Org. Chem., Vol. 69, No. 8, 2004