6934 J . Org. Chem., Vol. 64, No. 18, 1999
Notes
(1 mL). After 5 min the % de was determined by integration of
the Me proton in the 1H NMR spectra of the imine.
MHz) δ 17.3, 18.6, 21.4, 30.3 (d, J ) 19 Hz), 44.2 (d, J ) 20 Hz),
98.9 (d, J ) 183 Hz), 115.3, 126.1, 130.2, 139.0, 142.5; 19F NMR
(CFCl3 in CDCl3) δ -(193.14-193.34, m). Anal. Calcd for
Typ ica l P r oced u r e for th e P r ep a r a tion r-F lu or osu lfin -
im in es. (RS)-(-)-N-(2(S)-F lu or op h en yla cetylid en e)-p-tolu -
en esu lfin a m id e (9a ). In a 100 mL round-bottom flask, fitted
with a magnetic stir bar and calcium chloride tube, was placed
crude (S)-(+)-7a (0.276 g, 2 mmol) in CH2Cl2 (20 mL). Activated
(crushed) 4 Å molecular sieves (1.0 g) and (R)-(+)-p-toluene-
sulfinamide (8) (0.31 g, 2 mmol) in CH2Cl2 (5 mL) were added,
and the reaction mixture was stirred at room temperature for
6-8 h. The solution was filtered and concentrated. Chromatog-
raphy (EtOAc/hexane 10:90) afforded 0.380 g (69%) of (-)-9a :
C
13H17N2OSF: C, 58.18; H, 6.38; N, 10.43. Found: C, 57.99; H,
6. 27; N, 10.23.
(RS)-(-)-2-[N-(p-Tolu en esu lfin a m id o)]-3(R)-flu or o-3-p h e-
n ylp r op ion itr ile (14). Chromatography (EtOAc/hexane 15:85)
afforded 0.242 g (80%) of (-)-14: mp 121 °C; [R]23 -25.29 (c
D
0.85, CHCl3); IR (KBr) 3445-2874, 2249 cm-1; 1H NMR (CDCl3,
500 MHz) δ 2.43 (s, 3H), 4. 20-4.28 (m, 1H), 5.35 (d, J ) 9.73
Hz, 1H), 5.8 (dd, J ) 2.57, 45 8 Hz, 1H), 7.30-7.41 (m, 7H),
7.60 (d, J ) 8.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ 21.4, 48.5
(d, J ) 24.4 Hz), 94.3 (d, J ) 183.1 Hz), 114.5, 125.4, 126.2,
128.9, 129.8, 130.2, 133.5 (d, J ) 20.4 Hz), 139.0, 142.7. HRMS
calcd for C16H15N2OSF (M + H) 330.30967, found 303.0966 (M
+ H).
mp 91 °C; [R]23 -331.5 (c 0.38, CH2Cl2); IR (KBr) 1633 cm-1
;
D
1H NMR (CDCl3, 500 MHz) δ 1.68 (s, 3H), 5.50 (dd, J ) 4.0,
47.0 Hz, 1H), 6.56-6.67 (m, 7H), 6.78 (d, J ) 8.4 Hz, 2H), 7.60
(dd, J ) 4.0, 10.2 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 21.4,
92.8 (d, J ) 181 Hz), 124.6, 126.3, 126.4, 128.9, 129.5, 129.8,
134.3, 141.3, 162 (d, J ) 30.5 Hz); 19F NMR (CFCl3 in CDCl3) δ
-180.6 (dd, J ) 9, 45.7 Hz). Anal. Calcd for C15H14NOSF: C,
65.31; H, 5.11; N, 5.07. Found: C, 65.30; H, 4.94; N, 4.77.
(Rs)-(-)-N-(2(R)-F lu or op h en yla cet ylid en e)-p -t olu en e-
su lfin a m id e (13). Chromatography (EtOAc/hexane 10:90) af-
P r ep a r a tion of (2S,3S)-(+)-â-F lu or op h en ylp r op ion itr ile
(12). In a 50 mL round-bottom flask equipped with a magnetic
stir bar were placed 10a (0.150 g, 0.5 mmol) in CH2Cl2 (5 mL)
and 1 N HCl (5 mL). The solution was stirred at room temper-
ature for 2-3 h, the aqueous phase was separated and concen-
trated, and the resulting solid was treated with i-PrOH (2 mL)
and propylene oxide (0.058 g, 1 mmol). After being stirred for
5-6 h, the solution was concentrated to give 0.017 g (20%) of
forded 0.400 g (72%) of (-)-13: mp 64 °C; [R]23 -153.2 (c 2,
D
CHCl3); IR (KBr) 1628 cm-1; 1H NMR (CDCl3, 500 MHz) δ 2.39
(s, 3H), 6.11 (dd, J ) 4.0, 47.2 Hz, 1H), 7.26-7.39 (m, 7H), 7.48
(d, J ) 8 Hz, 2H), 8.31 (dd, J ) 4.0, 10.2 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) δ 22.1, 93.5 (d, J ) 179 Hz), 125.3, 127.0,
127.1, 129.6, 130.2, 130.5, 134.8 (d, J ) 20 Hz), 142.8, 162.6 (d,
J ) 28.5 Hz); 19F NMR (CFCl3 in CDCl3) δ -183.40 (dd, J )
9.2, 45.8 Hz). Anal. Calcd for C15H14NOSF: C, 65.31; H, 5.10;
N, 5.07. Found: C, 65.29; H, 4.69; N, 4.86.
(+)-12: mp 118 °C; [R]23 34.4 (c 1.2, CHCl3); IR (KBr) 3750-
D
3000, 2347 cm -1; H NMR (CDCl3, 500 MHz) δ 1.58-1.61 (bs,
1
2H), 4.17 (dd, J ) 5.0, 12.5 Hz, 1H), 5.54 (dd, J ) 5.0, 45 Hz,
1H), 7.45 (s, 5H); 13C NMR (CDCl3, 75 MHz) δ 48.6 (d, J ) 29
Hz), 93.8 (d, J ) 179 Hz), 126.2, 126.3, 128.7, 129.8, 133.8 (d, J
) 19 Hz); 19F NMR (CFCl3 in CDCl3) δ -184.5 (dd, J ) 12.2,
45.8 Hz).
(RS)-(+)-N-(2(S)-F lu or oisova ler ylid en e)-p-tolu en esu lfi-
n a m id e (9b). Chromatography (EtOAc/hexane 3:97) afforded
0.570 g (62%) of (+)-12: oil; [R]23D 209.8 (c 0.8, CHCl3); IR (NaCl)
1632 cm-1; 1H NMR (CDCl3, 500 MHz) δ 1.0 (2d, J ) 7 Hz, 6H),
2.2 (m, 1H), 2.42 (s, 3H), 5.0 (ddd, J ) 3.6, 4.8, 49.8 Hz, 1H), 7.3
(d, J ) 8.4 Hz, 2H), 7.5 (d, J ) 8.4 Hz, 2H), 8.25 (dd, J ) 3.7,
11.0 Hz, 1H); 19F NMR (CFCl3 in CDCl3) δ -(197.35-197.55, m).
The compound was found to be unstable and attempts to obtain
a satisfactory elemental analysis or HRMS failed.
Gen er a l P r oced u r e for th e Hyd r olysis of th e r-Am in o
Nit r iles. (2S,3S)-(+)-3-F lu or op h en yla la n in e (11a ). In
a
single-neck 25 mL round-bottom flask were placed 10a (0.302
g, 1 mmol) and 6 N HCl (20 mL), and the solution was refluxed
for 3-5 h. The aqueous phase was washed with ether (2 × 10
mL), and the aqueous solution was concentrated. The solid was
treated with i-PrOH (5 mL) and propylene oxide (0.232 g, 4
mmol), and the solution was stirred for 5-6 h. At this time, the
reaction mixture was concentrated and the product was crystal-
lized from 2-propanol to give 0.125 g (68%) of 11a : mp 170 °C
Typ ica l P r oced u r e for th e Ad d ition of EtAlCN/i-P r OH
to th e r-F lu or osu lfin im in es. (RS)-(+)-2-[N-(p-Tolu en esu lfi-
n a m id o)]-3-(S)-flu or o-3-p h en ylp r op ion itr ile (10a ). In an
oven-dried 100 mL round-bottom flask equipped with a magnetic
stir bar and an argon balloon was placed the (RS,S)-(-)-9a (0.275
g, 1.0 mmol) in THF (10 mL) and cooled to -78 °C. In a separate
two-neck round-bottom flask equipped with a magnetic stir bar,
an argon balloon, was placed diethylaluminum cyanide (1.5 mL,
1.5 mmol) and i-PrOH (0.1 mL). The reaction mixture was
stirred for 15 min at 10 °C and was cannulated to the solution
of 9a . After being stirred at -78 °C for 15 min, the solution was
warmed to room temperature and stirred for 12 h. The reaction
mixture was quenched with aqueous NaHCO3 (5 mL) and
extracted with EtOAc (2 × 10 mL), and the combined organic
phases were washed with brine, dried (Na2SO4), concentrated.
Chromatography (EtOAc/hexane 12:88) afford 0.235 g (78%) of
(lit.9a 168-169 °C); [R]23 8.4 (c 0.5, H2O); IR (KBr) 3570-2350
D
1
(bs), 1650-1540 cm-1; H NMR (D2O, 500 MHz) δ 5.1 (dd, J )
6.6, 14.3 Hz), 6.1 (dd, J ) 6.9, 45.5 Hz, 1H), 7.5 (s, 5H); 19F NMR
(CFCl3 in D2O) -179.5 (dd, J ) 13.7, 45.8 Hz).
(2S,3R)-(-)-3-Flu or oph en ylalan in e (15): yield 0.06 g (55%);
mp 149-150 °C (lit.9a mp 150-152 °C); [R]23 -14.5 (c 0.4,
D
MeOH); IR (KBr) 3570-2350 (bs), 1650-1540 (3s) cm-1
;
1H
NMR (CD3OD, 500 MHz) δ 5.1 (dd, J ) 3.0, 26.4 Hz, 1H), 6.0
(dd, J ) 2.6, 46 Hz, 1H), 7.5 (s, 5H); 19F NMR (CFCl3 in CD3-
OD) δ -184.5 (dd, J ) 27.4, 48.5 Hz).
(2S,3R)-(+)-3-F lu or oleu cin e (11b): yield 0.055 g (58%); mp
160-161 °C (dec) (lit.10b 162-163 °C (dec)); [R]23D 10.4 (c 1, H2O);
IR (KBr) 3650-2600, 1639, 1508 cm -1; 1H NMR (D2O, 500 MHz)
δ 0.9 (d, J ) 6.9 Hz, 3H), 1.1 (d, J ) 6.6 Hz, 3H), 2.28 (m, 1H),
4.55 (ddd, J ) 1.8, 9.5, 47.6 Hz, 1H), 4.93 (dd, J ) 2.2, 28.2 Hz,
1H); 19F NMR (CFCl3 in CDCl3) δ -(189.58-189.76, m).
(+)-10 as an oil: [R]23 14.0 (c 0.5, CH2Cl2); IR (NaCl) 3445-
D
2733, 2249 cm-1; 1H NMR (CDCl3, 500 MHz) δ 2.4 (s, 3H), 4.5-
4.7 (m, 2H), 5.7 (dd, J ) 5.5, 44.7 Hz, 1H), 7.3-7.6 (m, 9H); 13
C
Ack n ow led gm en t. This work was supported by
grants from the National Institutes of Health (GM
57870) and the National Science Foundation. We thank
Dr. G. Sundarababu for preliminary studies and Allied-
Signal Corp. for a generous supply of N-fluorobenzene-
sulfonimide (NFSi).
NMR (CDCl3, 125 MHz) δ 22.1, 47.9 (d, J ) 34.0 Hz), 92.5 (d, J
) 193.6 Hz), 116.2, 126.6, 126.8, 127.6, 129.6, 130.8, 133.6 (d, J
) 21.3 Hz), 139.6, 143.3; 19F NMR (CFCl3 in CDCl3) δ -177.7
(dd, J ) 10, 43 Hz). Anal. Calcd for C16H15FN2OS: C, 63.55; H,
5.00; N, 9.26. Found: C, 63.48; H, 4.94; N, 9.05.
(RS)-(+)-2-[N-(p-Tolu en esu lfin a m id o)]-3(S)-flu or oisoh ex-
Su p p or tin g In for m a tion Ava ila ble: IR and 1H and 13C
NMR spectra of 5b, 6b, 7a ,b, 12, and 14 and X-ray crystal
data for (+)-12. This material is available free of charge via
the Internet at http://pubs.acs.org.
a n on itr ile (10b). Chromatography (EtOAc/hexane 10:90) af-
forded 0.170 g (63%) of (+)-10b: mp 126 °C; [R]23 67.0 (c 0.45,
D
CH2Cl2); IR (KBr) 3588-2870, 2167 cm-1; 1H NMR (CDCl3, 500
MHz) δ 0.87 (d, J ) 7.0 Hz, 3H), 1.0 (d, J ) 7.0 Hz, 3H), 2.0 (m,
1H), 2.4 (s, 3H), 4.2-4.4 (m, 2H), 5.25 (d, J ) 8.8 Hz, 1H), 7.3
(d, J ) 8 Hz, 2H), 7.6 (d, J ) 8 Hz, 2H); 13C NMR (CDCl3, 75
J O990947N