Pd(II)-Catalyzed Coupling-Cyclization of R- or â-Amino Allenes
1 H), 4.66 (brs, 1 H), 3.41-3.27 (m, 2 H), 2.33 (s, 3 H), 1.84-
1.72 (m, 2 H), 1.52 (d, J ) 2.7 Hz, 3 H), 1.26-1.15 (m, 4 H),
0.78 (t, J ) 6.9 Hz, 3 H); 13C NMR (CDCl3, 75.4 MHz): δ )
199.38, 143.20, 136.86, 129.50, 127.01, 95.92, 94.21, 45.53,
31.02, 28.45, 21.99, 21.39, 16.74, 13.75; MS (m/z) 293 (M+,
1.25), 155 (100); IR (neat) 3283, 1969, 1599 cm-1. Anal. Calcd
for C16H23NO2S: C, 65.49; H, 7.90; N, 4.77. Found: C, 65.90;
H, 7.73; N, 4.62.
2.38 (dd, J ) 7.5, 16.5 Hz, 1 H), 2.32 (s, 3 H), 1.85-1.72 (m, 1
H), 1.53-1.20 (m, 1 H), 1.45 (s, 3 H). 1.33-0.94 (m, 4 H), 0.78
(t, J ) 7.2 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ ) 143.03,
134.82, 133.99, 130.85, 129.39, 127.64, 127.18, 115.86, 68.47,
59.04, 32.56, 29.45, 25.07, 22.64, 21.37, 14.04, 11.09; MS
(m/z) 333 (M+, 0.26), 276 (100); IR (neat) 1637, 1608 cm-1
.
Anal. Calcd for C19H27NO2S: C, 68.43; H, 8.16; N, 4.20.
Found: C, 68.03; H, 8.27; N, 4.40.
P a lla d iu m (II)-Ca ta lyzed Cou p lin g-Cycliza tion of r-
Am in o Allen es 2a -n w ith Allylic Ha lid es. Syn th esis of
2,5-Dih yd r op yr r ole P r od u ct s 7. 3-Allyl-4-b en zyl-1-(p -
tolu en esu lfon yl)-2,5-d ih yd r o-1H-p yr r ole (7a ). Typical pro-
cedure: A mixture of R-amino allene 2a (0.048 g, 0.15 mmol),
allyl bromide (0.112 g, 0.93 mmol), and PdCl2 (5 mol %) was
stirred at 25 °C in 1 mL of DMA for 4 h. When the reaction
was complete, ether was added. The reaction mixture was
washed with brine (three times) and dried over Na2SO4. After
evaporation, the residue was subjected to column chromatog-
raphy on silica gel (petroleum ether/ ether ) 5/1) to produce
P a lla d iu m (II)-Ca ta lyzed Cou p lin g-Cycliza tion of â-
Am in o Allen es 6a -l w ith Allylic Ha lid es. Syn th esis of
1,2,3,6-Tetr a h yd r op yr id in e P r od u cts 9. 5-Allyl-4-bu tyl-
3-m et h yl-1-(p -t olu en esu lfon yl)-1,2,3,6-t et r a h yd r op yr i-
d in e (9a ). The reaction of 6a (0.083 g, 0.27 mmol), allyl
bromide (0.167 g, 1.38 mmol), and PdCl2 (5 mol %) in 1.6 mL
of DMA at 25 °C for 12 h produced 0.085 g (91%) of 9a : liquid;
1H NMR (300 MHz, CDCl3) δ 7.59 (d, J ) 8.1 Hz, 2 H), 7.24
(d, J ) 8.1 Hz, 2 H), 5.70-5.50 (m, 1 H), 5.02-4.89 (m, 2 H),
3.56 (d, J ) 15.5 Hz, 1 H), 3.15 (dd, J ) 11.1 and 3.6 Hz, 1 H),
3.06 (d, J ) 15.5 Hz, 1 H), 2.80-2.65 (m, 2 H), 2.53 (dd, J )
15.3 and 6.3 Hz, 1 H), 2.36 (s, 3 H), 2.32-2.18 (m, 1 H), 2.17-
2.00 (m, 1 H), 1.90-1.65 (m, 1 H), 1.40-1.05 (m, 4 H), 1.04 (d,
J ) 6.8 Hz, 3 H), 0.80 (t, J ) 6.8 Hz, 3 H); 13C NMR (75.4
MHz, CDCl3) δ 143.35, 136.03, 135.32, 133.16, 129.57, 127.71,
123.40, 115.79, 49.76, 47.63, 34.78, 32.45, 30.84, 29.68, 22.86,
21.51, 17.84, 13.98; MS (m/z) 347 (M+, 3.46), 306 (100); IR
(neat) 1633 cm-1; HRMS calcd for C20H29NO2S 347.1919, found
347.1924.
1
0.033 g (61%) of 7a : solid; mp 71-73 °C (hexane); H NMR
(300 MHz, CDCl3) δ 7.65 (d, J ) 8.2 Hz, 2 H), 7.40-7.10 (m,
5 H), 7.08-6.95 (m, 2 H), 5.79-5.59 (m, 1 H), 5.15-4.90 (m, 2
H), 4.10 (s, 2 H), 3.98 (s, 2 H), 3.35 (s, 2 H), 2.88 (d, J ) 6.2
Hz, 2 H), 2.45 (s, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 143.56,
138.11, 134.24, 134.18, 130.77, 129.95, 129.92, 128.84, 128.51,
127.63, 126.72, 117.03, 57.58, 57.48, 32.63, 30.86, 21.80; MS
(m/z) 353 (M+, 3.87), 91 (100); IR (KBr) 1640 cm-1. Anal. Calcd
for C21H23NO2S: C, 71.35; H, 6.56; N, 3.96. Found: C, 71.26;
H, 6.45; N, 3.77.
Compounds 9b-l were prepared similarly.
Mech a n istic Stu d y. (1) The reaction of amino allene 2b
(0.052 g, 0.16 mmol) and bis(η3-allyl)-di-µ-chlorodipalladium
(0.055 g, 0.15 mmol) in DMA (1.0 mL) at room temperature
for 48 h afforded 0.019 g (34%) of 7b and 15 (7b/15 ) 45:55)
as a mixture.
N-Allyl-N-(2-ben zylbu ta -2,3-d ien yl)-p-tolu en esu lfon a -
m id e 8a . When K2CO3 was added as the base, the reaction of
amino allene 2a (0.046 g, 0.15 mmol), allyl bromide (0.111 g,
0.92 mmol), K2CO3 (0.033 g, 0.24 mmol), and PdCl2 (5 mol %)
at 25 °C in 2.5 mL of THF for 23 h produced 0.023 g (44%) of
7a and 0.009 g (17%) of N-allylation product 8a : liquid; 1H
NMR (300 MHz, CDCl3) δ 7.64-7.56 (m, 2 H), 7.30-7.10 (m,
7 H), 5.55-5.40 (m, 1 H), 5.05-4.96 (m, 2 H), 4.62-4.55 (m, 2
H), 3.75 (d, J ) 6.7 Hz, 2 H), 3.68 (s, 2 H), 3.23 (s, 2 H), 2.36
(s, 3 H); MS (m/z) 353 (M+, 8.43), 224 (100); IR (neat) 1637
cm-1; HRMS calcd for C21H23NO2S 353.1450, found 353.1446.
Compounds 7b-n were prepared similarly.
(2) The reaction of amino allene 2b (0.108 g, 0.34 mmol)
and bis(1-methyl-η3-allyl)di-µ-chlorodipalladium (0.146 g, 0.37
mmol) in DMA (2.0 mL) at room temperature for 96 h afforded
0.044 g (38%) of 7o and 15 (7o/15 ) 47:53) as a mixture.
(3) The reaction of amino allene 2b (0.089 g, 0.28 mmol),
3-chlorobut-1-ene (0.506 g, 5.59 mmol), and bis(η3-allyl)di-µ-
chlorodipalladium (0.100 g, 0.27 mmol) in DMA (2.0 mL) at
room temperature for 32 h afforded 0.075 g (75%) of 7b, 7o
and 15 (7b/7o/15 ) 6:67:27) as a mixture.
(S)-3-Allyl-2-m eth yl-4-bu tyl-1-(p-tolu en esu lfon yl)-2,5-
d ih yd r o-1H-p yr r ole ((S)-7m ). The reaction of (S)-2m (0.093
g, 0.32 mmol, 87% ee), allyl bromide (0.14 mL, 1.58 mmol),
and PdCl2 (5 mol %) at 25 °C in 2 mL of DMA for 2 h produced
0.097 g (92%) of (S)-7m : liquid; 86% ee (detemined by HPLC
analysis, Chiralcel AS, 5% i-PrOH in hexane, 230 nm), tR 16.73
Syn th esis of Au th en tic 15.8,19 The reaction of 2b (0.072
g, 0.22 mmol) and AgNO3 (20 mol %) at 25 °C in 2.5 mL of
acetone for 5 h produced 0.069 g (96%) of 15.
2-H exyl-4-m et h yl-1-(p -t olu en esu lfon yl)-2,5-d ih yd r o-
1H-p yr r ole (15): liquid; 1H NMR (300 MHz, CDCl3) δ 7.70
(d, J ) 8.2 Hz, 2 H), 7.29 (d, J ) 8.2 Hz, 2 H), 5.22-5.16 (m,
1 H), 4.45-4.34 (m, 1 H), 4.05-3.92 (m, 2 H), 2.41 (s, 3 H),
1.85-1.60 (m, 2 H), 1.73 (s, 3 H), 1.42-1.19 (m, 8 H), 0.87 (t,
J ) 6.7 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ 143.42, 135.08,
134.30, 129.84, 127.58, 123.87, 67.94, 58.75, 36.60, 32.08,
29.55, 24.79, 22.86, 21.75, 14.35, 14.18; MS (m/z) 321 (M+,
(S-isomer), 20.67 (R-isomer); [R]20 +101.4 (c ) 1.04, CHCl3);
D
1H NMR (300 MHz, CDCl3) δ 7.66 (d, J ) 8.1 Hz, 2 H), 7.26
(d, J ) 8.7 Hz, 2 H), 5.53-5.37 (m, 1 H), 4.90 (dd, J ) 1.5,
10.2 Hz, 1 H), 4.78 (dd, J ) 1.5, 17.1 Hz, 1 H), 4.37 (t, J ) 5.1
Hz, 1 H), 4.08-3.90 (m, 2 H), 2.80 (dd, J ) 4.8, 15.3 Hz, 1 H),
2.53 (dd, J ) 7.2, 15.6 Hz, 1 H), 2.39 (s, 3 H), 1.93 (t, J ) 6.6
Hz, 2 H), 1.33 (d, J ) 6.6 Hz, 3 H). 1.28-0.98 (m, 4 H), 0.79 (t,
J ) 6.9 Hz, 3 H); 13C NMR (75.4 MHz, CDCl3) δ ) 143.15,
134.58, 134.29, 132.85, 131.08, 129.45, 127.29, 116.03, 64.80,
56.50, 29.78, 29.36, 25.62, 22.10, 21.41, 21.22, 13.79; MS
11.96), 236 (100); IR (neat) 1598 cm-1; HRMS calcd for C18H27
NO2S 321.1763, found 321.1807.
-
Ack n ow led gm en t. We are grateful to the Major
State Basic Research Development Program (Grant No.
G2000077500) and the National Natural Science Foun-
dation of China, Chinese Academy of Sciences, for
financial support. S.M. is the recipient of 1999 Qiu Shi
Award for Young Chinese Scientific Workers issued by
the Hong Kong Qiu Shi Foundation of Science and
Technology (1999-2003).
(m/z) 333 (M+, 0.79), 318 (100); IR (neat) 1638, 1598 cm-1
.
Anal. Calcd for C19H27NO2S: C, 68.43; H, 8.16; N, 4.20.
Found: C, 68.80; H, 8.29; N, 4.67.
(R)-3-Allyl-2-bu tyl-4-m eth yl-1-(p-tolu en esu lfon yl)-2,5-
d ih yd r o-1H-p yr r ole ((R)-7n ). The reaction of (R)-2n (0.020
g, 0.07 mmol, 78% ee), allyl bromide (0.03 mL, 0.34 mmol),
and PdCl2 (5 mol %) at 25 °C in 1.5 mL of DMA for 3 h
produced 0.02 g (88%) of (R)-7n : liquid; 76% ee (detemined
by HPLC analysis, Chiralcel OC, 3% i-PrOH in hexane, 230
nm), tR 17.53 (R-isomer), 20.41 (S-isomer); [R]20 -81.0 (c )
D
Su p p or tin g In for m a tion Ava ila ble: Analytical data and
1H NMR and 13C NMR spectra. This material is available free
1
0.55, CHCl3); H NMR (300 MHz, CDCl3) δ 7.59 (d, J ) 8.1
Hz, 2 H), 7.19 (d, J ) 7.8 Hz, 2 H), 5.41-5.31 (m, 1 H), 4.82
(dd, J ) 1.2, 10.2 Hz, 1 H), 4.69 (dd, J ) 1.8, 16.8 Hz, 1 H),
4.35 (s, 1 H), 3.90 (s, 2 H), 2.74 (dd, J ) 4.8, 15.3 Hz, 1 H),
J O0342469
J . Org. Chem, Vol. 68, No. 15, 2003 5949