1984 J . Org. Chem., Vol. 63, No. 6, 1998
Davis and Fanelli
mmol), in anhydrous DMF (25 mL). Anhydrous K2CO3 (4.46
g, 32.3 mmol) and 2-bromopropane (2.74 g, 22.3 mmol) were
added to the solution, and the reaction mixture was refluxed
for 3 h. At this time the solution was diluted with H2O (25
mL), the aqueous layer was extracted with EtOAc (3 × 50 mL),
and the combined organic phases were washed with brine (50
mL), dried (Na2SO4), filtered, and concentrated to give a yellow
oil. Flash chromatography (EtOAc:hexane 1.5:8.5) afforded
1.99 g (82%) of 7b as an oil. IR (neat) 2977, 2829, 1721, 1221
cm-1. Anal. Calcd for C21H27NO4S: C, 64.75; H, 6.99; N, 3.60.
Found: C, 64.72; H, 6.92; N, 3.51.
(R)-(+)-N-[3,5-Bis(ben zyloxy)-4-m eth oxyben zylid en e]-
p-tolu en esu lfin a m id e (10c): yield 81% (crystallization 20%
EtOAc/hexane); mp 97-98 °C; [R]25 +6.7 (c 0.75, CHCl3); IR
D
(KBr) 1573 cm-1; H NMR (CDCl3) δ 8.56 (s,1H), 7.61 (d, 2H,
1
J ) 8.5 Hz), 7.45 (d, 2H, J ) 8.5 Hz), 7.40-7.31 (m, 10H),
7.15 (s, 2H), 5.18 (s, 4H), 3.95 (s, 3H), 2.40 (s, 3H); 13C NMR
(CDCl3) δ 160.7, 153.4, 144.0, 142.5, 142.4, 137.2, 130.2, 129.7,
129.3, 128.7, 128.0, 125.5, 109.7, 71.8, 61.7, 22.1. Anal. Calcd
for C29H27NO4S: C, 71.73; H, 5.60; N, 2.88. Found: C, 71.70;
H, 5.59; N, 2.81.
1
cm-1; H NMR (CDCl3) δ 7.20 (s, 2H), 4.51 (m, 2H), 3.80 (s,
3H), 3.79 (s, 3H), 1.28 (d, 12H, 6.5 Hz); 13C NMR δ 167.3, 152.1,
145.9, 125.4, 111.1, 72.2, 61.0, 52.6, 22.7. Anal. Calcd for
C15H22O5: C, 63.81; H, 7.85. Found: C, 63.80; H, 7.83.
Sta n d a r d P r oced u r e for th e Red u ction of Ester s to
Ald eh yd es Usin g DIBAL-H. In a 250 mL single-neck round-
bottom flask equipped with a magnetic stir bar, rubber septum,
and argon-filled balloon was placed the appropriate ester 7
(4.7 mmol) in dry toluene (40 mL). The mixture was cooled to
-78 °C and stirred, and 1.0 M DIBALH in hexane (10.5 mL,
10.5 mmol) was added dropwise via syringe over 15 min. The
reaction mixture was carefully monitored by TLC and quenched
after 15-20 min at -78 °C by addition of 1 N HCl (10 mL).
The solution was diluted with H2O (25 mL), extracted with
EtOAc (3 × 50 mL), dried (Na2SO4), and concentrated to give
the aldehydes 8b-d , which were purified by chromatography
or crystallization.
(R)-(+)-N-(3,5-Bis(t-bu tyld im eth ylsilyloxy)-4-m eth oxy-
ben zylid en e)-p-tolu en esu lfin a m id e (10d ): yield 73% (flash
chromatography 20% EtOAc/hexane); mp 123-124 °C; [R]25
D
+8.14 (c 0.8, CHCl3); IR (neat) 1608 cm-1; 1H NMR (CDCl3) δ
8.51 (s, 1H), 7.59 (d, 2H, J ) 8.1 Hz), 7.27 (d, 2H, J ) 8.1 Hz),
6.98 (s, 2H), 3.73 (s, 3H), 2.36 (s, 3H), 0.97 (s, 18H), 0.14 (s,
12H); 13C NMR (CDCl3) δ 160.7, 150.8, 147.8, 142.7, 142.2,
130.4, 129.8, 125.5, 116.5, 60.7, 26.3, 22.0, 18.9, -3.9. Anal.
Calcd for C27H43NO4SSi2: C, 60.76; H, 8.13; N, 2.63. Found:
C, 60.74; H, 8.15; N, 2.60.
Sta n d a r d P r oced u r e for th e Syn th esis of th e r-Am i-
n on itr iles. In a 25 mL two-neck round-bottom flask equipped
with a magnetic stir bar, rubber septa, and an argon balloon
was placed the appropriate sulfinimine 10 (1.2 mmol) in THF
(7 mL). The solution was cooled to -78 °C. In a separate 25
mL single-neck round-bottom flask equipped with a magnetic
stir bar, rubber septum, and argon balloon were placed THF
(6 mL), Et2AlCN (1.8 mL, 1.8 mmol, 1.0 M in toluene), and
anhydrous i-PrOH (0.1 mL). The solution was stirred for 15
min at room temperature and added via cannula to the
sulfinimine at -78 °C. After 15 min, the reaction mixture was
brought to room temperature, stirred, and monitoring by TLC
for the disappearance of the sulfinimine (4-24 h). The
reaction mixture was cooled to -78 °C and quenched by
addition of aqueous NaHCO3 (1.0 mL). The suspension was
diluted with EtOAc (20 mL), filtered through Celite, and
diluted with H2O (25 mL) and the aqueous phase extracted
with EtOAc (2 × 25 mL). The combined organic phases were
washed with brine (35 mL), dried (MgSO4), filtered, and
concentrated to give the crude amino nitriles 11 which were
purified by chromatography or crystallization.
(R )-(-)-[N -(R )-p -Tolylsu lfin yl]-2-a m in o-2-(3,4,5-t r i-
m et h oxy)p h en yla cet on it r ile (11a ): yield 77%, de 96%
(crystallization from ether); mp 166 °C; [R]25D-184.5 (c 0.7,
CHCl3); IR (KBr) 2217, 1596 cm-1; 1H NMR (CDCl3) δ 7.74 (d,
2H, J ) 8.5 Hz), 7.45 (d, 2H, J ) 8.5 Hz), 6.80 (s, 2H), 5.28 (s,
1H), 3.92 (s, 6H), 3.87 (s, 3H), 2.50 (s, 3H); 13C NMR δ 153.6,
142.5, 138.8, 138.1, 130.0, 129.0, 126.2, 117.5, 104.7, 60.7, 56.1,
43.8, 21.4. Anal. Calcd for C18H20N2O4S: C, 59.98; H, 5.60;
N, 7.76. Found: C, 60.01; H, 5.58; N, 7.69.
3,5-Diisop r op oxy-4-m et h oxyb en za ld eh yd e (8b ): yield
82% (flash chromatography 15% EtOAc/hexane); mp 72-73
1
°C (lit.19 mp 74 °C); IR (KBr) 1697 cm-1; H NMR (CDCl3) δ
9.73 (s, 1H), 7.02 (s, 2H), 4.53 (m, 2H), 3.82 (s, 3H), 1.29 (d,
12H, J ) 5.5 Hz); 13C NMR (CDCl3) δ 191.6, 152.7, 147.0,
132.2, 110.5, 72.1, 60.9, 22.5. Anal. Calcd for C14H20O4: C,
66.63; H, 8.00. Found: C, 66.62; H, 7.97.
3,5-Bis(ben zyloxy)-4-m eth oxyben za ld eh yd e (8c): yield
89%; mp 87 °C (lit.2c mp 85.5-87.5 °C).
3,5-Bis(ter t-bu tyld im eth ylsilyloxy)-4-m eth oxyben za l-
d eh yd e (8d ): yield 78%; mp 75-76 °C (lit.15 mp 74-75 °C).
Sta n d a r d P r oced u r e for th e Asym m etr ic Syn th esis of
Su lfin im in es.8 In a 250 mL single-neck round-bottom flask
equipped with a magnetic stir bar, rubber septum, and an
argon balloon was dissolved (1S,2R,5S)-(+)-menthyl-(R)-p-
toluenesulfinate (1.11 g, 3.78 mmol) in THF (35 mL) and cooled
to -78 °C. Via syringe, 1.0 M LiHMDS in THF (5.3 mL, 5.3
mmol) was added dropwise to the solution which was brought
to room temperature and stirred for 2 h. At this time the
reaction mixture was cooled to 0 °C, the appropriate aldehyde
8 (3.0 mmol) added, and the solution cooled to -78 °C and
monitored by TLC for the disappearance of the aldehyde (2-
24 h). At this time the solution was quenched with aqueous
NH4Cl (4 mL) and diluted with EtOAc (50 mL) and H2O (25
mL) and the aqueous phase extracted with EtOAc (3 × 50 mL).
The combined organic phases were washed with brine (50 mL),
dried (MgSO4), and concentrated to give the crude sulfinimines
10 which were purified by flash chromatography (EtOAc:n-
hexane, 2:8) or crystallization.
(R)-(-)-[N-(R)-p-Tolylsu lfin yl]-2-a m in o-2-(3,5-d iisop r o-
p oxy-4-m eth oxy)p h en yla ceton itr ile (11b): yield 77%, de
92% (flash chromatography 15% EtOAc/hexane); mp 154-156
1
°C; [R]25 -79.1 (c 1.6, CHCl3); IR (neat) 2198, 1571 cm-1; H
D
(R)-(-)-N-(3,4,5-Tr im eth oxyben zyliden e)-p-tolu en esu lfi-
n a m id e (10a ): yield 76% (crystallization from ether); mp 93
NMR (CDCl3) δ 7.60 (d, 2H, J ) 8.4 Hz), 7.30 (d, 2H, J ) 8.4
Hz), 6.49 (s, 2H), 5.05 (d, 1H, J ) 7.8 Hz), 4.76 (d, 1H, J ) 7.8
Hz), 4.43 (m, 2H), 3.74 (s, 3H), 2.38 (s, 3H), 1.30 (d, 12H, 6.3
Hz); 13C NMR (CDCl3) δ 152.9, 144.2, 130.5, 130.3, 128.8,
127.1, 126.4, 118.8, 108.8, 72.5, 61.1, 47.1, 22.8, 22.0. Anal.
Calcd for C22H28N2O4S: C, 63.44; H, 6.78; N, 6.73. Found: C,
63.41; H, 6.72; N, 6.62.
°C; [R]25 -24.3 (c 0.8, CHCl3); IR (KBr) 1575 cm-1; H NMR
1
D
(CDCl3) δ 8.64 (s, 1H), 7.62 (d, 2H, J ) 8.1 Hz), 7.31 (d, 2H, J
) 8.1 Hz), 7.09 (s, 2H), 3.89 (s, 9H), 2.40 (s,3H); 13C NMR
(CDCl3) δ 160.1, 153.4, 141.9, 141.8, 141.7, 129.8, 129.1, 124.7,
106.6, 60.9, 56.1, 21.4. Anal. Calcd for C17H19NO4S: C, 61.24;
H, 5.75; N, 4.19. Found: C, 61.19; H, 5.73; N, 4.14.
(R)-(-)-[N-(R)-p-Tolylsu lfin yl]-2-a m in o-2-[3,5-bis(ben -
zyloxy)-4-m eth oxy]p h en yla ceton itr ile (11c): yield 66%
(R)-(+)-N-[3,5-Diisop r op oxy-4-m eth oxyben zylid en e]-p-
tolu en esu lfin a m id e (10b): yield 80% (flash chromatography
(flash chromatography 40% CH2Cl2/hexane); mp 155 (dec) °C;
20% EtOAc/hexane); mp 123-125 °C; [R]25 +7.2 (c 0.8,
1
IR (KBr) 2282 cm-1; [R]25 -134.1 (c 1.1, CHCl3); H NMR δ
D
D
CHCl3); IR (KBr) 1570 cm-1; H NMR (CDCl3) δ 8.59 (s, 1H),
1
7.62 (d, 2H, J ) 8.1 HZ), 7.44-7.28 (m, 12H), 6.79 (s, 2H),
5.14 (d, 1H, J ) 6.0 Hz), 5.10 (s, 4H), 4.58 (d, 1H, J ) 6.0 Hz),
3.84 (s, 3H), 2.42 (s, 3H); 13C NMR δ 154.4, 144.0, 141.4, 140.4,
137.9, 131.5, 130.1, 129.5, 129.0, 128.5, 127.6, 118.9, 108.7,
72.5, 62.4, 45.3, 22.9. Anal. Calcd for C30H28N2O4S: C, 70.28;
H, 5.51; N, 5.46. Found: C, 70.21; H, 5.48; N,5.36.
7.60 (d, 2H, J ) 8.5 Hz), 7.28 (d, 2H, J ) 8.5 Hz), 7.05 (s, 2H),
4.54 (m, 2H), 3.84 (s, 3H), 2.36 (s, 3H), 1.33 (d, 12H, J ) 6.0
Hz); 13C NMR (CDCl3) δ 161.0, 152.7, 145.7, 142.6, 142.3,
130.4, 129.6, 125.5, 111.0, 72.4, 61.2, 22.7, 22.0; IR (KBr) 1570
(S)-(-)-[N-(R)-p-Tolylsu lfin yl]-2-a m in o-2-(3,5-bis(ben -
zyloxy)-4-m eth oxy)p h en yla ceton itr ile (11c): yield 7%; mp
(18) Williams, R. M.; Hendrix, J . A. J . Org. Chem. 1990, 55, 3723.
(19) Personal communication from Professor J ieping Zhu.