102
Vol. 52, No. 1
(67.8 MHz, CDCl3) d: 23.13, 43.64, 43.80, 123.64, 127.65, 127.78, 128.37,
128.54, 128.60, 129.06, 130.26, 131.63, 131.88, 131.93, 132.07, 132.69,
133.16, 137.33, 138.28. MS m/z: 277(Mϩ). Exact mass determination:
277.14670 (Calcd C19H19NO: 277.1469).
ted to preparative TLC (ether–hexane 1 : 2) to give dimethyl 4-benzylidene-
3-methyl-1,2,3,4-tetrahydronaphthalene-2,2-dicarboxylate (14) (97 mg, 45%
yield, 5% e.e.). With (S)-(R)-PPFOMe as a ligand: yield 44%, 10% e.e. (at
70 °C in DME 18 h); (S)-(R)-PPFA: yield 23%, 10% e.e. (reflux in THF,
18 h); (S)-N,N-dimethyl-1-ferrocenylethylamine: yield 41%, 7% e.e. (reflux
in THF, 18 h).
Palladium-Catalyzed Reactions of (R)-6 with N-Methyl-2-iodobenzyl-
amine (19). General Procedure A 25 ml two-necked flask equipped with
a septem inlet and a magnetic stirring bar, and containing Pd(dba)2 (12.0 mg,
0.02 mmol) and PPh3 (11 mg, 0.04 mmol) was flushed with argon and main-
tained under a positive pressure of argon. To the above flask THF (1 ml) was
added and the mixture was stirred for 30 min. A solution of 19 (100 mg,
0.40 mmol) in THF (5 ml) was added and the mixture was stirred at room
temperature for 30 min. Then, a solution of (R)-6 (58 mg, 0.45 mmol) and
Et3N (0.08 mmol) in THF (1 ml) was further added and the reaction mixture
was heated under reflux for 12 h. The reaction mixture was diluted with
ether and filtered. The filtrate was concentrated under reduced pressure. The
residue was submitted to preparative TLC (ether–hexane 1 : 1) to give (S)-
(E)-4-benzylidene-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline (20) (18 mg,
18% yield, 46% e.e.). The e.e. of (S)-20 obtained was determined by HPLC
analysis with SUMICHIRAL OA-4800 (n-hexane–THF–MeOH–trifluo-
roacetic acid 60 : 38 : 2 : 0.2); flow: 0.5 ml/min, retention time: 55, 64 min.
The results obtained under other reaction conditions with other phosphine
ligands are summarized in Table 4.
The e.e. of the product (R)-14 obtained was determined by HPLC analysis
with SUMICHIRAL OA-3100 (i-propanol–hexane 1 : 500; flow rate: 0.5 ml/
min; retention time: 17.1, 18.6 min).
1
14: IR (cmϪ1): 1735 (ester), 1610, 1590 (aromatic). H-NMR (270 MHz,
CDCl3) d: 1.12 (3H, d, Jϭ6.76 Hz, CHCH3), 3.39—3.60 (1H, m, CHCH3),
3.65, 3.72 (2H, d, d, Jϭ7.25, 7.25 Hz, CH2C(CO2CH3)), 3.62, 3.79 (6H, s, s,
C(CO2CH3)2), 6.55 (1H, s, CHϭC), 6.80—7.83 (9H, m, aromatic H). 13C-
NMR (67.8 MHz, CDCl3) d: 15.21, 31.04, 39.40, 43.4, 51.5, 52.6, 52.7,
53.0, 124.9, 126.5, 126.7, 127.6, 128.2, 128.3, 128.4, 128.5, 128.6, 128.7,
128.9, 129.9, 130.5, 139.7. MS m/z: 350 (Mϩ). Exact mass determination:
350.1503 (Calcd C22H22O4: 350.1503).
The Palladium-Catalyzed Asymmetric Reaction of a Chiral Allene,
(R)-6, with 13. General Procedure A 25 ml two-necked flask equipped
with a septem inlet and a magnetic stirring bar, and containing sodium hy-
dride (NaH) (29 mg, 0.594 mmol, 50% oil dispersion) was flushed with
argon and maintained under a positive pressure of argon. THF (1 ml) was
added to the flask and a solution of 13 (214 mg, 0.615mmol) in THF (2 ml)
was added at 0 °C. The mixture was stirred at room temperature for 30 min.
Another 25 ml two-necked flask equipped with a septem inlet and a mag-
netic stirring bar, and containing Pd(dba)2 (14.1 mg, 0.025 mmol) and dppf
(30 mg, 0.054 mmol) was flushed with argon and maintained under a posi-
tive pressure of argon. To the above flask THF (1 ml) was added and the
mixture was stirred for 40 min. This solution was added to the above solu-
tion and the reaction mixture was stirred for 30 min. Then, a solution of (R)-
6 (80 mg, 0.615 mmol) in THF (1 ml) was further added and the reaction
mixture was heated under reflux for 18 h. The reaction mixture was diluted
with ether, and the solution was washed with a 10% aqueous HCl, a satu-
rated aqueous NaHCO3, and a saturated aqueous NaCl, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The residue was submit-
ted to preparative TLC (ether–hexane 1 : 2) to give (R)-(14) (38 mg, 12%
yield, 50% e.e.). The results obtained with other phosphine ligands are sum-
marized in Table 3.
(S)-20: IR (cmϪ1): 1590 (aromatic). 1H-NMR (270 MHz, CDCl3) d: 1.270
(3H, d, Jϭ6.76 Hz, CHCH3), 2.35 (3H, s, NCH3), 3.64—4.12 (3H, m,
CH2NCHCH3), 7.05—7.68 (10H, m, CHϭC, aromatic H). 13C-NMR (67.8
MHz, CDCl3) d: 0.00, 13.88, 42.49, 50.72, 54.25, 124.30, 124.80, 126.52,
126.6, 126.8, 127.51, 128.3, 128.82, 132.78, 133.16, 137.34, 137.5. MS m/z:
249 (Mϩ). Exact mass determination: 249.1517 (Calcd C18H19N: 249.1513).
The Palladium-Catalyzed Intramolecular Carboxylations of an Al-
lene, (R)-6, with 2-Iodobenzoic Acid (21). General Procedure A 25 ml
two-necked flask equipped with a septem inlet and a magnetic stirring bar,
and containing Pd(PPh3)4 (17.0 mg, 0.03 mmol), PPh3 (17 mg, 0.067 mmol),
21 (32 mg, 0.121 mmol), K2CO3 (334 mg, 2.42 mmol), and silver carbonate
(8 mg, 0.03 mmol) was flushed with argon and maintained under a positive
pressure of argon. To the above flask CH3CN (5 ml) was added and the mix-
ture was stirred for 30 min. A solution of (R)-6 (87 mg, 0.67 mmol) in
CH3CN (4 ml) was added and the reaction mixture was heated under reflux
for 18 h. The reaction mixture was diluted with ether and filtered through sil-
ica gel. The filtrate was concentrated under reduced pressure. The residue
was submitted to preparative TLC (ethyl acetate–hexane 1 : 4) to give 4-ben-
zylidene-3-methyl-1-oxo-1,2,3,4-tetrahydro-2-oxanaphthalene (22a, b) (119
mg, 79% yield). The product ratio of 22a, b was determined by 1H-NMR
analysis. The results obtained are summarized in Table 5.
The Palladium-Catalyzed Reactions of (؎)-6 with 2-Bromobenzyl-
amine (15) A 25 ml two-necked flask equipped with a septem inlet and a
magnetic stirring bar, and containing sodium hydride (NaH) (32 mg,
0.677 mmol, 50% oil dispersion) was flushed with argon and maintained
under a positive pressure of argon. THF (2 ml) was added to the flask and a
solution of 15 (115 mg, 0.60 mmol) in THF (2 ml) was added at 0 °C. The
mixture was stirred at room temperature for 30 min.
(E)-22a: IR (cmϪ1): 1600 (aromatic). 1H-NMR (270 MHz, CDCl3) d: 1.62
(3H, d, Jϭ1 Hz, CH3), 5.16 (1H, q, Jϭ1 Hz, OCH), 6.82—8.16 (10H, m,
C6H4, C6H5CH). 13C-NMR (67.8 MHz, CDCl3) d: 14.78, 82.56, 116.10,
123.94, 126.58, 126.85, 127.25, 128.37, 128.52, 128.57, 129.34, 130.30,
130.38, 134.19, 13.73, 137.34, 138.97. MS m/z: 250(Mϩ). Exact mass deter-
mination: 250.0970 (Calcd C17H14O2: 250.0994).
Another 25 ml two-necked flask equipped with a septem inlet and a mag-
netic stirring bar, and containing Pd(dba)2 (17.0 mg, 0.03 mmol) and PPh3
(16 mg, 0.06 mmol) was flushed with argon and maintained under a positive
pressure of argon. To the above flask THF (1.5 ml) was added and the mix-
ture was stirred for 40 min. This solution was added to the above solution
and the reaction mixture was stirred for 30 min. Then, a solution of (Ϯ)-6
(80 mg, 0.615 mmol) in THF (1 ml) was further added and the reaction mix-
ture was heated under reflux for 18 h. The reaction mixture was diluted with
ether and filtered. The filtrate was concentrated under reduced pressure. To a
solution of the residue in CH2Cl2 (7 ml) was added at 0 °C a solution of
acetic anhydride (78 mg, 0.78 mmol), Et3N (0.2 ml, 0.78 mmol), and a cat-
alytic amount of 4-(dimethylamino)pyridine in CH2Cl2 (1 ml) and the reac-
tion mixture was stirred at room temperature for 3 h. The reaction mixture
was diluted with ether, and the solution was washed with a saturated aque-
ous NaHCO3 and a saturated aqueous NaCl, dried over anhydrous Na2SO4,
and concentrated under reduced pressure. The residue was submitted
to preparative TLC (ether) to give (E)-2-acetyl-4-benzylidene-3-methyl-
1,2,3,4-tetrahydroisoquinoline (17b) (10 mg, 6% yield) and N-[2-(1-phenyl-
1,3-butadien-2-yl)benzyl]acetamide (18b) (35 mg, 21% yield).
(Z)-22b: IR (cmϪ1): 1600 (aromatic). 1H-NMR (270 MHz, CDCl3) d: 1.61
(3H, d, Jϭ1 Hz, CH3), 5.74 (1H, q, Jϭ1 Hz, OCH), 6.82—8.16 (10H, m,
C6H4, C6H5CH). MS m/z: 250 (Mϩ). Exact mass determination: 250.1003
(Calcd C17H14O2: 250.0994).
HPLC: CHIRALPAK AD (i-propanol–hexane 1 : 20); flow: 0.5 ml/min;
retention time: 24, 27 (E), 38, 41 (Z) min.
The Palladium-Catalyzed Reactions of an Allene, (R)-6, with 2-
Iodobenzyl Alcohol (23). General Procedure A 25 ml two-necked flask
equipped with a septem inlet and a magnetic stirring bar, and containing
Pd(OAc)2 (14.0 mg, 0.064 mol), PPh3 (34 mg, 0.128 mmol), 23 (150 mg,
0.64 mmol), Na2CO3 (340 mg, 3.21 mmol), and tetra-n-butylammonium
chloride (178 mg, 0.64 mmol) was flushed with argon and maintained under
a positive pressure of argon. To the above flask THF (4 ml) was added and
the mixture was stirred for 30 min. A solution of (R)-6 (92 mg, 0.71 mmol)
in THF (6 ml) was added and the reaction mixture was heated under reflux
for 12 h. The reaction mixture was diluted with ether, and the solution was
washed with a saturated aqueous NH4Cl and a saturated aqueous NaCl, dried
over anhydrous Na2SO4, and concentrated under reduced pressure. The
residue was submitted to preparative TLC (ethyl acetate–hexane 1 : 20) to
give (E)-4-benzylidene-3-methyl-1,2,3,4-tetrahydro-2-oxanaphthalene (24)
(65 mg, 43% yield).
17b: IR (cmϪ1): 1630, 1640 (amide), 1600 (aromatic). 1H-NMR (270
MHz, CDCl3) d: 1.23 (3H, d, Jϭ2.16 Hz, NCHCH3), 2.02 (3H, s, COCH3),
4.52 (2H, d, Jϭ4.32 Hz, CH2N), 6.60 (1H, s, CϭCH), 7.11—7.56 (9H, m,
aromatic H). 13C-NMR (67.8 MHz, CDCl3) d: 23.29, 53.02, 58.02, 77.23,
125.49, 126.01, 126.49, 127.13, 127.33, 127.79, 128.15, 128.24, 128.38,
128.95, 129.14, 129.26, 130.59, 132.81. MS m/z: 277(Mϩ). Exact mass de-
termination: 277.14670 (Calcd C19H19NO: 277.1490).
The results obtained are summarized in Table 6.
24: IR (cmϪ1): 1600 (aromatic). 1H-NMR (270 MHz, CDCl3) d: 1.46 (3H,
d, Jϭ6.4 Hz, CH3), 4.46 (1H, dt, Jϭ6.4, 1.2 Hz, OCH), 4.87 (2H, s, OCH2),
6.54 (1H, s, CϭCH), 6.86—7.41 (9H, m, aromatic). 13C-NMR (67.8 MHz,
18b: IR (cmϪ1): 1630, 1640 (amide), 1590 (aromatic). 1H-NMR (270
MHz, CDCl3) d: 2.00 (3H, s, COCH3), 4.46—4.48 (2H, m, CH2N), 6.40
(1H, m, NHCO), 7.10—7.66 (10H, m, CϭCH, aromatic H). 13C-NMR