Notes
J . Org. Chem., Vol. 63, No. 22, 1998 8079
2-Meth yl-5-isopr open yl-2-cycloh exen on e (car von e)oxim e:
Water (25 mL) was then added, and the solution was extracted
with ether (3 × 25 mL). The combined organic solutions were
washed with water and brine and dried. Evaporation and flash
chromatography (1:1 hexanes/ethyl acetate) afforded the prod-
ucts.
Dia ster eoselective Red u ction Resu lts of Cyclic N-Di-
p h en ylp h osp h in yl Cycloh exen yl Im in es. Experimental pro-
cedures are as given above. Ratios of diastereomeric products
were determined by 31P NMR measurements on the crude
product mixtures. Identification and characterization of the
saturated cyclohexyl N-diphenylphosphinyl amine products (4a -
c,d ) was accomplished by comparison with authentic samples.1a
Characterization of the major cyclohexenyl phosphinylamine
diastereomers of 5 are presented below.
yield, 89%; mp 70-71 °C (lit.8b mp 73.1-73.5 °C).
4-Ch olesten -3-on e oxim e: yield, 90%; mp 145-148 °C (1:3
E:Z mixture) [lit.8c mp 152-153 °C (2:3 E:Z mixture)].
3,5-Dim eth yl-2-cycloh exen on e oxim e: yield, 92%; mp 69-
70 °C (lit.8d mp 70.5-73.5 °C).
2-Isop r op ylid en e-5-m et h ylcycloh exa n on e (p u legon e)
oxim e: yield, 78%; viscous oil. Anal. Calcd for C10H17NO: C,
71.85; H, 10.17; N, 8.38. Found: C, 71.47; H, 9.91; N, 8.05.
4,4-Dim eth yl-2-cycloh exen on e oxim e: yield, 90%; mp 48-
48.5 °C (lit.8e “low melting”).
3,5,5-Tr im eth yl-2-cycloh exen on e oxim e: yield: 93%; mp
73-74 °C (lit.8b mp 73.1-73.7 °C).
Gen er al P r ocedu r e for th e Syn th esis of N-Diph en ylph os-
p h in yl Im in es. The appropriate oxime (2.4 mmol) was added
to an oven-dried 100-mL three-neck flask kept under argon. Dry
methylene chloride (25 mL), dry petroleum ether (25 mL), and
triethylamine (2.4 mmol) were added, and the resulting solution
was cooled to -40 °C. To this solution was added chlorodiphen-
ylphosphine (2.4 mmol) via syringe, and the mixture was allowed
to stir at -40 °C for 1.5-2 h (white precipitate of triethylamine
hydrochloride was observed). The mixture was then cooled to
-78 °C and transferred via cannulla (positive argon or nitrogen
pressure) to a filter under the inert atmosphere. The resulting
clear colorless solution was carefully evaporated (high vacuum
bled through a CaSO4 drying tube) at 0 °C. The crude phos-
phinyl imines were immediately subjected to the appropriate
reducing agent as described below.
Gen er a l P r oced u r e for th e Red u ction of N-Dip h en -
ylp h osp h in yl Im in es w ith Lith iu m Tr i-sec-bu tylbor oh y-
d r id e (L-Selectr id e). To a solution of crude phosphinyl imine
(1.5 mmol) in dry tetrahydrofuran (20 mL) was added L-
Selectride (3.2 mmol, 3.2 mL of 1.0 M solution in THF). The
resulting yellow solution was stirred for 3 h at room temperature
under argon and then quenched with water (2 mL). The
organoboranes were decomposed via one of two methods: In
method A, the solution was cooled to 0 °C and 15% sodium
hydroxide (0.5 mL) was added followed by the slow addition of
30% hydrogen peroxide (0.5 mL). The cooling bath was removed,
and the solution was stirred for 30 min. Water (15 mL) and
ether (25 mL) were then added. The layers were separated, and
the aqueous layer was extracted with ether (2 × 15 mL). The
combined organics were washed with 30% sodium bisulfite (2 ×
20 mL) and brine and then dried. In method B, sodium
perborate tetrahydrate, NaBO3‚4H2O, (1.48 g, 9.6 mmol) was
added, and the mixture was stirred at room temperature for 2
h. Water (15 mL) and ether (30 mL) were added and the layers
were separated. The aqueous layer was extracted with ether
(2 × 25 mL). The combined organic phase was washed with
brine and dried. Evaporation and flash column chromatography
yielded the products.
Gen er a l P r oced u r e for th e Red u ction of N-Dip h en -
ylp h osp h in yl Im in es w ith Diisobu tyl Alu m in u m Hyd r id e
(DIBAH). To the appropriate phosphinyl imine (1.8 mmol)
under argon in dry tetrahydrofuran (20 mL) at room tempera-
ture was added DIBAH (3.9 mmol, 1.0 M in THF). The re-
sulting solution was stirred overnight at room temperature. The
reaction was quenched with water (2 mL) and 15% sodium
hydroxide (2 mL) and allowed to stir for 30 min. Water (30 mL)
was then added, and the solution was extracted with ether (3 ×
25 mL). The combined organic solutions were washed with
water and brine and dried. Evaporation and flash chromatog-
raphy (1:1 hexanes/ethyl acetate) afforded the products.
Gen er a l P r oced u r e for th e Red u ction of N-Dip h en -
ylp h osp h in yl Im in es w ith 9-Bor obicyclo[3.3.1]n on a n e (9-
BBN). To the appropriate phosphinyl imine (1.8 mmol) under
argon in dry tetrahydrofuran (20 mL) at room temperature was
added 9-BBN (4.0 mmol, 0.5 M in THF). The resulting solution
was stirred for 40 h at room temperature. The reaction was
quenched with water (2 mL) and allowed to stir for 30 min.
tr a n s-N-(Dip h en ylp h osp h in yl)-4-ter t-bu tyl-2-cycloh ex-
en yla m in e (5a ): mp 144-146 °C (from 9:1 hexane/ethyl ac-
etate); 31P NMR (CDCl3) 23.75. Anal. Calcd for C22H28NOP:
C, 74.78; H, 7.93; N, 3.96. Found: C, 74.49; H, 7.28; N, 3.83.
tr a n s-N-(Dip h en ylp h osp h in yl)-4-isop r op yl-2-cycloh ex-
en yla m in e (5b): mp 148-149 °C (from 9:1 hexane/ethyl ac-
etate); 31P NMR (CDCl3) 23.95. Anal. Calcd for C21H26NOP:
C, 74.31; H, 7.72. Found: C, 73.97; H, 7.71.
cis-N-(Dip h en ylp h osp h in yl)-2-m et h yl-5-isop r op en yl-2-
cycloh exen yla m in e (5c): mp 143-145 °C (from 9:1 hexane/
ethyl acetate); 31P NMR (CDCl3) 22.97. Anal. Calcd for C22H26
-
NOP: C, 75.21; H, 7.40; N, 3.98. Found: C, 75.31; H, 8.20; N,
3.64.
N-(Dip h en ylp h osp h in yl)-4-ch olesten -3â-a m in e (5d ): mp
217 °C (dec, from 9:1 hexane/ethyl acetate); 13P NMR (CDCL3)
23.56. Anal. Calcd for C39H56NOP: C, 79.96; H, 9.63; N, 2.39.
Found: C, 79.71; H, 9.80; N, 2.16.
cis-N-(Dip h en ylp h osp h in yl)-3,5-d im et h yl-2-cycloh exe-
n yla m in e (5e): mp 140-142 °C (from 9:1 hexane/ethyl acetate);
31P NMR (CDCl3) 23.88. Anal. Calcd for C20H24NOP: C, 73.84;
H, 7.38; N, 4.30. Found: C, 73.65; H, 7.46; N, 3.59.
cis-N-(Dip h en ylp h osp h in yl)-2-isop r op en yl-5-m et h yl-2-
cycloh exen yla m in e (5f): mp 108-110 °C (from 9:1 hexane/
ethyl acetate); 31P NMR (CDCl3) 22.68. Anal. Calcd for C22H28
-
NOP: C, 73.94; H, 7.84; N, 3.92. Found: C, 73.81; H, 7.70; N,
3.82.
N -(D ip h e n y lp h o s p h in y l)-4,4-d im e t h y l-2-c y c lo h e x e -
n yla m in e (5 g): mp 142-144 °C (from 9:1 hexane/ethyl acetate);
31P NMR (CDCl3) 23.42. Anal. Calcd for C20H24NOP: C, 73.84;
H, 7.38; N, 4.30. Found: C, 73.67; H, 7.71; N, 3.62.
N-(Dip h en ylp h osp h in yl)-3,3,5-t r im et h yl-2-cycloh exe-
n yla m in e (5h ): mp 140-142 °C (from 9:1 hexane/ethyl acetate);
31P NMR (CDCl3) 23.75. Anal. Calcd for C21H26NOP: C, 74.31;
H, 7.72; Found: C, 73.94; H, 7.84.
N-(Dip h en ylp h osp h in yl)-N-(4-ter t-bu tylcycloh ex-1-en e)-
a m in e (9). To a solution of 4-tert-butylcyclohexyl oxime1a (0.80
g, 4.7 mmol) and triethylamine (0.72 mL, 5.2 mmol) in 1:1
methylene chloride/hexanes (mL) at -40 °C was added chlo-
rodiphenylphosphine (0.95 mL, 5.2 mmol) via syringe. The
temperature immediately rose to -30 °C. After addition was
complete, the reaction mixture was stirred at -40 °C for 2 h
and then filtered under nitrogen to remove triethylamine
hydrochloride. The solvent was removed under vacuum, dry
THF (30 mL) was added, and the solution of 8 was cooled to
-40 °C. To this was added n-BuLi (1 M, 5.2 mL, 5.2 mmol)
dropwise, and the solution was stirred for 2 h. The reaction was
then quenched with water at 0 °C and extracted with ether. The
organic phase was washed with brine and dried over anhydrous
Na2SO4. Evaporation and recrystallization from 9:1 hexanes/
1
ethyl acetate afforded 9 as white crystals: mp 134-135 °C; H
NMR (CDCl3) 7.3-7.9 (m, 10H), 5.0-5.2 (br s, 1H), 4.3-4.5 (d,
1H), 2.0-2.2 (m, 2H), 1.6-1.9 (m, 2H), 1.6-1.9 (m, 3H), 0.8 (s,
9H); 31P NMR (CDCl3) 18.27; 13C NMR (CDCl3) 131.7, 131.6,
131.5, 128.4, 128.2, 107.3, 43.4, 31.9, 30.5, 27.0, 25.2, 23.8. Anal.
Calcd for C22H28NOP: C, 74.78; H, 7.93; N, 3.96. Found: 74.49;
H, 7.28; N, 3.86.
ci s-N -(D ip h e n y lp h o s p h in y l)-4-t er t -b u t y c y c lo h e x y l-
a m in e (4a ). To a solution of 9 (0.40 g, 1.1 mmol) in dry THF
was added L-Selectride (1 M, 2.8 mL, 2.2 mmol) dropwise at
room temperature. The reaction mixture was stirred for 2.5 h,
quenched with 3 equiv of sodium perborate, and extracted with
ether. The organic phase was dried (Na2SO4), and the solvent
was removed at reduced pressure. The crude product obtained
(8) (a) Adams, J . Ph.D. Thesis, Drexel University, 1994. (b) Mont-
gomery, R. S.; Doughery, C. J . Org. Chem. 1952, 17, 823. (c) Suginome,
H.; Kaji, M.; Yamada, S. J . Chem. Soc., Perkin Trans. 1 1988, 321. (d)
Horning, E. C.; Stromberg, V. I.; Llyod, H. A. J . Am. Chem. Soc. 1952,
74, 5153. (e) Wolkowski, Z. W.; Thoai, N.; Weimann, J . Tetrahedron
Lett. 1970, 93.