1064 J . Org. Chem., Vol. 64, No. 3, 1999
Notes
J ) 7.07 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 167.7, 145.3,
141.6, 141.1, 129.3, 128.5, 128.1, 126.9, 126.3, 126.1, 125.9, 60.1,
56.0, 23.4, 21.7, 21.1, 13.8; HRMS (FAB) m/z (M+ + 1) found
372.1628, calcd for C21H26O3NS 372.1633.
nucleophilic additions in which the Z/E selectivity is
controlled by Rs and RL groups (s ) small, L ) large).
In conclusion, a novel tandem asymmetric carbon-
carbon formation system has been established, providing
the first approach to the highly stereoselective synthesis
of unusual Baylis-Hillman adducts, â-branched R-(ami-
noalkyl)acrylates. The absolute structure is unambigu-
ously determined by X-ray analysis and by synthetic
conversions to a known sample. The application of this
method to the asymmetric synthesis of biologically im-
portant compounds will be conducted in this laboratory
in the future.
1: colorless oil (0.201 g, 58.6% yield); [R]25D ) +135.6 (c 0.52,
95% EtOH); 1H NMR (200 MHz, CDCl3) δ 7.62 (d, J ) 6.54 Hz,
2 H), 7.24-7.39 (m, 7 H), 6.20 (q, J ) 7.31 Hz, 1 H), 5.31 (d, J
) 7.58 Hz, 1 H), 5.00 (d, J ) 7.58 Hz, 1 H), 3.60 (s, 3 H), 2.42 (s,
3 H), 1.99 (d, J ) 7.31 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ
166.8, 141.7, 141.3, 140.6, 140.5, 133.1, 129.4, 128.4, 127.4, 127.0,
125.7, 60.5, 51.3, 21.4, 15.7; HRMS (FAB) m/z (M+ + 1) found
344.1326, calcd for C19H22O3NS 344.1320.
2: light yellow oil (0.232 g, 58.7% yield); [R]25 ) +85.7 (c
D
0.57, 95% EtOH); 1H NMR (200 MHz, CDCl3) δ 7.61 (d, J ) 8.19
Hz, 2 H), 7.26-7.34 (m, 8 H), 6.92 (s, 1 H), 6.26 (m, 2 H), 5.47
(d, J ) 7.49 Hz, 1 H), 5.05 (d, J ) 7.49 Hz, 1 H), 3.64 (s, 3 H),
2.40 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 168.3, 152.0, 142.7,
141.4, 137.1, 134.9, 132.1, 129.5, 128.5, 128.3, 128.2, 125.9, 125.7,
110.6, 108.1, 55.4, 51.8, 21.3; HRMS (FAB) m/z (M+ + 1) found
396.1276, calcd for C22H22O4NS 396.1269.
Exp er im en ta l Section
All reactions were conducted under nitrogen atmosphere in
oven-dried glassware with magnetic stirring. Diethyl ether and
THF were dried and freshly distilled from sodium and ben-
zophenone under nitrogen protection. Organolithium reagents
(MeLi, PhLi, and n-BuLi in diethyl ether solutions) and Et2AlCl
in hexane solution were purchased from Aldrich Chemical Co.
Other commercial chemicals were used without purification, and
their stoichiometries were calculated on the basis of the reported
purities from the manufacturers. Flash chromatography was
performed on E. Merck silica gel 60 (230-400 mesh). High-
resolution mass spectral analysis was conducted by the Scripps
Research Institute.
5: colorless oil (0.381 g, 77.0% yield); [R]25 ) -71.3 (c 0.24,
D
95% EtOH); 1H NMR (200 MHz, CDCl3) δ 7.60 (d, J ) 8.23 Hz,
2 H), 7.52 (d, J ) 6.94 Hz, 2 H), 7.36-7.13 (m, 15 H), 5.82 (d, J
) 10.36 Hz, 1 H), 5.51 (d, J ) 10.36 Hz, 1 H), 3.71 (q, J ) 7.22
Hz, 2 H), 2.37 (s, 3 H), 0.62 (t, J ) 7.22 Hz, 3 H); 13C NMR (75
MHz, CDCl3) δ 169.5, 151.4, 142.8, 142.3, 140.9, 140.7, 139.7,
131.3, 129.4, 128.9, 128.8, 128.4, 128.3, 127.9, 127.8 127.4, 126.5,
125.7, 60.4, 60.3, 21.3, 13.1; HRMS (FAB) m/z (M++1) found
496.1929, calcd for C31H30O3NS 496.1946.
6: colorless oil (0.351 g, 81.0% yield); [R]25D ) +189.3 (c 0.81,
95% EtOH); 1H NMR (200 MHz, CDCl3) δ 7.63 (d, J ) 8.21 Hz,
2 H), 7.37-7.18 (m, 12 H), 5.93 (d, J ) 8.40 Hz, 1 H), 5.42 (d, J
) 8.40 Hz, 1 H), 3.66 (q, J ) 7.20 Hz, 2 H), 2.36 (s, 3 H), 2.22 (s,
3 H), 0.60 (t, J ) 7.20 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ
169.2, 145.4, 143.6, 141.2, 141.0, 140.3, 131.4, 129.4, 128.3, 128.0,
127.4, 127.2, 126.9, 126.5, 126.0, 60.2, 55.2, 21.6, 21.3, 13.2;
HRMS (FAB) m/z (M+ + 1) found 496.1929, calcd for C31H30O3-
NS 496.1946.
The representative procedure was illustrated by the nucleo-
philic addition of â,â-dimethyl[R-(alkoxycarbonyl)vinyl]cuprate
to p-toluenesulfinimines. Into a dry, nitrogen-flushed flask was
added purified cuprous iodide (0.210 g, 1.10 mmol) and freshly
distilled diethyl ether (9 mL). The resulting solution was cooled
to 0 °C, and a solution of methyllithium in diethyl ether (1.4 M,
1.46 mL, 2.05 mmol) was added via syringe. The resulting
homogeneous gray solution was stirred for 30 min at 0 °C and
then cooled to -23 °C using a CCl4/dry ice bath before a solution
of ethyl 2-butynoate (0.112 g, 1.0 mmol) in Et2O (2 mL) was
added in ca. 10 min. The reaction mixture was stirred at -23
°C for 2 h before a solution of (S)-(+)-benzylidene-p-toluene-
sulfinamide (0.292 g, 1.2 mmol) in diethyl ether (2 mL) and an
Et2AlCl solution (1.0 M solution in hexane, 1.2 mL, 1.2 mmol)
were added via syringe in order. The resulting mixture was
stirred at -23 °C for 12 h and at 0 °C for 1 h. The reaction was
finally quenched by dropwise addition of saturated aqueous NH4-
Cl solution (2 mL). The phases were separated, and the aqueous
phase was extracted with ethyl acetate (3 × 15 mL). The
combined organic layers were washed with 10% aqueous am-
monia and brine, dried over anhydrous magnesium sulfate, and
concentrated to dryness, which was determined by 1H NMR.
Purification by flash chromatography (EtOAc/hexane, 1/10, v/v)
provided product 4 (0.286 g, 77.1% yield) as a colorless solid.
Needle crystals were obtained by using H2O-MeOH (v/v, 3:7)
as crystallization solvent (for X-ray structure of 4, see Figure
7: colorless oil (0.279 g, 66.0% yield); [R]25D ) +174.0 (c 0.54,
95% EtOH); 1H NMR (200 MHz, CDCl3) δ 7.66 (d, J ) 7.72 Hz,
2 H), 7.32-7.18 (m, 8 H), 6.25 (m, 1 H), 6.18 (m, 1 H), 6.02 (d,
J ) 8.40 Hz, 1 H), 5.38 (d, J ) 8.40 Hz, 1 H), 3.75 (q, J ) 7.16
Hz, 2 H), 2.40 (s, 3 H), 2.19 (s, 3 H), 0.69 (t, J ) 7.16 Hz, 3 H);
13C NMR (75 MHz, CDCl3) δ 169.1, 153.1, 146.6, 143.4, 142.0,
141.3, 140.8, 129.5, 128.9, 128.0, 127.4, 126.9, 126.3, 110.4, 107.1,
60.4, 50.3, 21.6, 21.2, 13.2; HRMS (FAB) m/z (M+ + 1) found
396.1276, calcd for C22H22O4NS 396.1269.
Ack n ow led gm en t. We gratefully acknowledge fi-
nancial support from the Robert A. Welch Foundation
(grant D-1361) and the Seed Grant of Texas Tech
University. We would also like to thank J ason Hook and
Sun Hee Kim for their assistance.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for all pure isomers. This material is available free of
1): mp 75.1-77.0 °C; [R]25 ) +128.9 (c 1.22, 95% EtOH); 1H
D
NMR (200 MHz, CDCl3) δ 7.66 (d, J ) 6.52 Hz, 2 H), 7.25-7.63
(m, 7 H), 5.52 (d, J ) 8.91 Hz, 1 H), 5.38 (d, J ) 8.92 Hz, 1 H),
4.00 (m, 2 H), 2.43 (s, 3 H), 2.01 (s, 3 H), 1.68 (s, 3 H), 1.02 (t,
J O981976L