Notes
J . Org. Chem., Vol. 63, No. 13, 1998 4543
the first extraction. The combined organic extracts were dried
temperature for 27 h. The solution containing crystalline solid
over Na
2
SO
4
, filtered through glass wool, and concentrated in
was diluted with 150 mL of CH
mL of saturated aqueous NH
aqueous layer. Water (150 mL) was added, the layers were
separated, and the aqueous was layer back-extracted with CH
Cl
(3 × 200 mL). The combined organic extracts were washed
with 200 mL of saturated aqueous NaHCO . The aqueous layer
was back-extracted with CH Cl
(3 × 200 mL). The combined
organic extracts were dried over Na SO , filtered through cotton,
and concentrated in vacuo to give a yellow-white solid. The
resulting solid was triturated with hot pentane (1 × 150 mL, 1
× 50 mL, 2 × 40 mL), followed by hot gravity filtration. The
colorless extracts were concentrated in vacuo to give 16.3 g (91%
yield) of a white solid that was recrystallized from pentane to
give 14.6 g (82%) of a white crystalline solid. The mother liquors
2
Cl
2
, and upon washing with 250
vacuo to give 74.1 g of a white crystalline solid in a thick, slightly
4
Cl, a white solid formed in the
yellow oil. Distillation of (S)-tert-leucinol (3), bp 70-73 °C/2 mm
1
6
Hg (lit. 117-120 °C/57 mm) from a 30.0 g reduction reaction
performed in the above manner yielded 21.3 g of product (79%
yield) as a clear oil, which solidified upon cooling to room temper-
2
-
2
3
2
5
ature: [R]
D
+36.5° (c 1.22, EtOH); IR (CHCl
3
) 3420, 2970,
2
2
2
1
880, 1585, 1480, 1420, 1400, 1370, 1350, 1135, 1105, 1040,
2
4
020, 985, 940, 920 cm-1
;
1
H NMR (400 MHz, CDCl
) δ 3.73
3
(
1
(
dd, 1H, J ) 10.3, 3.8 Hz), 3.21 (t, 1H, J ) 10.3 Hz), 2.51 (dd,
H, J ) 10.3, 3.8 Hz), 1.86 (br s, 3H), 0.94 (s, 9H); 13C NMR
400 MHz, CDCl ) δ 62.4, 61.8, 33.2, 26.3. HRMS (CI, ammonia)
m/z 118.1232; exact mass calcd for C
3
+
6
H16NO [M + H] 118.1233.
For maximum overall yield, it is recommended that the
unpurified (S)-tert-leucinol be used in the acylation reaction
without distillation.
were purified by flash chromatography (20% EtOAc/CH
50% EtOAc/CH Cl ) to give an additional 1.2 g (6%) of 1: mp
88.9-89.8 °C; TLC R
(c 1.22, CH Cl ); IR (CCl
1395, 1385, 1365, 1350, 1335, 1300, 1250, 1210, 1190, 1145,
2 2
Cl to
2
2
Dim eth ylm a lon yl Dich lor id e (6).17 A dry 2-L round-
bottom flask equipped with a 150-mL addition funnel and
magnetic stir bar was charged with dimethylmalonic acid (5)
) 0.18 (3:7 EtOAc/hexanes); [R]
) 2960, 2930, 2870, 1665, 1480, 1465,
25
+113.2°
f
D
2
2
4
-
1 1
(57.0 g, 431 mmol, 1 equiv), dimethylformamide (4.2 g, 58.0
1115, 980, 920 cm ; H NMR (250 MHz, CDCl
3
) δ 4.15 (dd, 2H,
mmol, 4.0 mL, 0.13 equiv), and 650 mL of CH Cl . The solution
2
2
J ) 10.0, 8.7 Hz), 4.11 (dd, 2H, J ) 8.7, 7.0 Hz), 3.51 Hz (dd,
1
3
was cooled to 0 °C, and the addition funnel was charged with
oxalyl chloride (164.3 g, 1.30 mol, 113 mL, 3 equiv), which was
added dropwise with gas evolution over 1.5 h. The cloudy yellow
solution was stirred for 18 h at 25 °C. The solution cleared and
turned a deep yellow color as the reaction progressed. The
solution was concentrated in vacuo to give a yellow liquid with
denser orange oil droplets. The mixture was distilled im-
2H, J ) 10.1, 7.0 Hz), 1.51 (s, 6H), 0.87 (s, 18H); C NMR (100
MHz, CDCl ) δ 168.6, 68.9, 38.5, 33.8, 26.8, 25.6, 24.4. Anal.
Calcd for C17 : C, 69.35; H, 10.27; N, 9.51. Found: C,
3
30 2 2
H N O
69.39; H, 10.39; N, 9.57.
[Cu (S,S)-Bis(ter t-bu tyloxazolin e)](SbF ) (9). To an oven-
6 2
dried round-bottom flask containing a magnetic stirring bar was
added, in an inert atmosphere box, bis(oxazoline) 1 (1.472 g, 5.00
mediately (150-152 °C, 760 mmHg, N
2
) to afford 67.3 g (90%)
of a clear, colorless liquid: H NMR (250 MHz, CDCl ) δ 1.65
s, 6H).
S)-N,N′-Bis[1-(h yd r oxym eth yl)-2,2-d im eth ylp r op yl]-2,2-
mmol) and CuCl
a serum cap, removed from the inert atmosphere box and
charged with CH Cl (20 mL). After being stirred for 3.5 h, no
brown CuCl was observed, and the clear green solution was
transferred via cannula to a syringe fitted with a 0.45 µm PTFE
filter and filtered under nitrogen into a Schlenk flask. The
2
(0.672 g, 5.00 mmol). The flask was fitted with
1
3
(
2
2
(
2
1
d im eth yl-1,3-p r op a n ed ia m id e (7). A 5-L three-necked flask
fitted with a mechanical stirrer was charged with a solution of
unpurified (S)-tert-leucinol (3) (74.1 g, 610 mmol (based on a
solvent was removed in vacuo to deliver Cu(t-Bu-box)Cl
Cl (8) as a light green powder in 99% yield (2.52 g, 4.95 mmol):
mp > 180 °C; [R] -251° (c 1.06, CH Cl ); IR (CH Cl ) 2968,
1655, 1484, 1371, 1239, 1135, 947 cm . Anal. Calcd for C18
Cl CuN : C, 42.08; H, 6.28; N, 5.45. Found: C, 42.21; H, 6.24;
N, 5.51.
2
‚CH
2
-
1
00% yield of the previous reaction), 2 equiv) in 675 mL of CH
Cl . The solution was cooled in an ice bath, and triethylamine
153.0 g, 1.51 mol, 211 mL, 5 equiv) was added via syringe. A
solution of dimethylmalonyl dichloride (51.1 g, 302.5 mmol, 1
equiv) in 235 mL of CH Cl was slowly added via cannula to
2
-
2
2
D
2
2
2
2
-1
(
32
H -
4
2 2
O
2
2
the vigorously stirred reaction over 20 min. The ice bath was
removed, and the thick white suspension was stirred at room
To an oven-dried round-bottom flask containing a magnetic
stirring bar was added, in an inert atmosphere box, Cu(t-Bu-
temperature for 35 min. CH
most of the white solid. The reaction mixture was washed with
45 mL of 1 N HCl, and the aqueous layer was back-extracted
with 224 mL of CH Cl . The combined organic extracts were
washed with 445 mL of saturated aqueous NaHCO , and the
aqueous layer was back-extracted with 180 mL of CH Cl . The
combined organic extracts were washed with 445 mL of brine,
2
Cl
2
(1.78 L) was added, dissolving
box)Cl
0.20 mmol). The flask was fitted with a serum cap, removed
from the inert atmosphere box, and charged with CH Cl (2.0
mL). The mixture was stirred for 2-3 h in the absence of light
to produce a green solution with a white AgCl precipitate. The
mixture was filtered through a plug of oven-dried Celite to
provide a solution of 9 as a clear dark green solution. The
development of a blue color in room-temperature solutions of
this catalyst is indicative of the formation of the bis(aquo)
complex 10.
2
‚CH
2 2 6
Cl (8) (51.2 mg, 0.10 mmol) and AgSbF (68.7 mg,
4
2
2
2
2
3
2
2
and the aqueous layer was back-extracted with 180 mL of CH
Cl The combined organic extracts were dried over Na SO
2
-
,
2
.
2
4
filtered through glass wool, and concentrated in vacuo to give a
white solid, which was recrystallized from ethyl acetate to afford
[Cu (t-Bu -box)(H
9 obtained after the Celite filtration step in the preceding
experiment was washed through with 4 × 15 mL of CH Cl
(saturated with H O) into a flask. The blue solution containing
2 2 6 2 2 2
O) ](SbF ) (10). The CH Cl solution of
8
1
7.4 g (88%, two steps) of a white crystalline solid: mp 163.3-
25
63.7 °C; TLC R
f
) 0.22 (95:5 EtOAc/MeOH); [R]
D
+2.5° (c 0.75,
2
2
MeOH); IR (KBr) 3340, 2970, 2910, 2880, 1645, 1545, 1525, 1480,
400, 1380, 1370, 1340, 1270, 1240, 1190, 1100, 1050, 1020, 1000
2
1
the aquated complex 10 was concentrated slowly in vacuo to
afford 344 mg (99% yield) of 10 as an air-stable light blue solid
whose structure was established by X-ray crystallography.
[Cu (S,S)-bis(ter t-bu tyloxa zolin e)]OTf) (11). To an oven-
2
dried round-bottom flask containing a magnetic stirring bar were
-
1 1
cm ; H NMR (250 MHz, CDCl
.87 (m, 4H), 3.44 (m, 2H), 1.52 (s, 6H), 0.93 (s, 18H); C NMR
100 MHz, CDCl
3
) δ 6.39 (br d, 2H, J ) 9.6 Hz),
13
3
(
3
) δ 174.7, 62.2, 59.5, 50.3, 33.4, 26.8, 23.8. Anal.
: C, 61.79; H, 10.37. Found: C, 61.85; H,
Calcd for C17
H
34
N
2
O
4
1
0.27.
,2-Bis[2-[4(S)-ter t-bu tyl-1,3-oxa zolin yl]]p r op a n e [(S,S)-
added, in an inert atmosphere box, bis(oxazoline) 1 (14.7 mg,
2
0.050 mmol) and Cu(OTf)
was fitted with a serum cap, removed from the inert atmosphere
box, and charged with solvent (1.5-3.0 mL of THF or CH Cl ).
The resulting suspension was stirred rapidly for 4 h with CH
Cl to give a slightly cloudy bright green solution or for 1 h with
THF to give a clear dark green solution. When the CH Cl
2
(18.1 mg, 0.050 mmol). The flask
1
ter t-Bu tyl bis(oxa zolin e)] (1). A 1-L round-bottom flask with
a magnetic stir bar was charged with dihydroxymalonodiamide
2
2
7
(20.0 g, 60.6 mmol, 1 equiv), 4-(dimethylamino)pyridine (0.74
g, 6.06 mmol, 0.1 equiv), and 240 mL of CH Cl . Triethylamine
27.0 g, 267 mmol, 37.1 mL, 4.4 equiv) was added via syringe.
2
-
2
2
2
(
2
2
The flask was placed in a room temperature water bath, and a
solution of p-toluenesulfonyl chloride (23.1 g, 121 mmol, 2 equiv)
catalyst solution was cooled to -78 °C, a clear blue green solution
was obtained. Similarly, cooling the THF catalyst solution to
-78 °C yielded a clear blue-green solution. These catalyst
solutions must be kept rigorously anhydrous for optimal results
in reactions using this catalyst. The development of a blue color
in room-temperature solutions of this catalyst is indicative of
the formation of the bis(aquo) complex. The use of powdered 3
Å molecular sieves with hydrated catalyst solutions has been
in 50 mL of CH
2 2
Cl was added via cannula, followed by one 10
mL CH Cl rinse. The bright yellow solution was stirred at room
2
2
(
16) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.;
Kondo, M.; Itoh, K. Organometallics 1989, 8, 846-848.
17) Also available from Aldrich Chemical Co.
(