J. R. Walker, R. W. Curley, Jr. / Tetrahedron 57 ꢀ2001) 6695±6701
6699
ꢀ
,
6
95%) was weighed and added to the reaction mixture in
1.2 g portions. The gray solution was heated to 508C for
h. After cooling the solution to 08C, 17.3 mL ꢀ10 equiv.)
of D O was carefully added dropwise and allowed to stir for
THF. The solution was chilled to 08C and 7.95 g
ꢀ45.7 mmol) of diethyl azodicarboxylate was added drop-
wise. The solution stirred at 08C for 4 h and then at rt for
18 h. The solvent was evaporated to give a yellow solid. The
resultant mixture was dissolved and passed through a silica
gel ®lter using 3:2 hexanes/ethyl acetate. The eluent was
subjected to silica gel chromatography using 4:1 hexanes/
2
3
0 min. Thionyl chloride was then added dropwise until the
mixture was slightly acidic ꢀpH,5). The entire solution was
poured onto ice and stirred until white solid precipitated.
The solid was dried via vacuum ®ltration to give 20.9 g
acetone and the product recrystallized using acetone/H O to
2
4
4
21
ꢀ
93% yield), mp 79±808C ꢀlit. mp 81±828C). IR ꢀcm )
give 6.71 g ꢀ60%) of white solid, mp 129±1318C ꢀlit. mp
133±1348C). IR ꢀcm ) 3045 ꢀw), 2967 ꢀw), 1705 ꢀs),
1
959 ꢀm), 1511 ꢀs), 1250 ꢀs), 1111 ꢀs), 839 ꢀm); H NMR
29
21
2
ꢀ
1
1515 ꢀm), 1243 ꢀm), 707 ꢀm); H NMR ꢀCDCl ) d 3.75 ꢀs,
CDCl ) d 2.54 ꢀbr, 4H), 3.67±3.71 ꢀm, 4H), 3.80 ꢀs, 3H,
3
3
1
3
CH O), 6.90 ꢀd, 2H, J8.8 Hz), 7.41 ꢀd, 2H, J8.8 Hz); C
3H, CH O), 4.74 ꢀbr m, 1H, a-H), 6.82 ꢀd, 2H, J8.7 Hz),
3
3
NMR ꢀCDCl ) d 49.80, 55.34, 61.50 ꢀt, J22.6 Hz), 66.63,
7.37 ꢀd, 2H, J6.7 Hz), 7.66±7.68 ꢀm, 2H), 7.80±7.82 ꢀm,
3
1
3
114.11, 115.38, 124.29, 129.29, 160.09; HRMS ꢀES) calcd
for C H DN O ꢀM1H) 234.1353, found 234.1354.
2H); C NMR ꢀCDCl ) d 40.75 ꢀdt, J8.8, 22.7 Hz), 55.21,
3
113.95, 123.23, 128.59, 130.12, 132.09, 132.16, 133.88,
1
3
15
2
2
1
59.18, 168.01 ꢀd, J12.7 Hz); HRMS ꢀES) calcd for
1
5
4
¯
ꢀ
.1.3. 4-Methoxybenzaldehyde-formyl-d ꢀ4). To a 1 L
ask equipped with a re¯ux condenser was added 62.5 g
0.27 mol) of 3 along with 600 mL of 2 M HCl. The suspen-
C H D NO ꢀM1Na) 292.0826, found 292.0830.
16 12 3
4.1.6. ꢀR)-2,2,2-Trichloroethyl ester [ꢀ4-methoxyphenyl)
1
5
sion was re¯uxed for 14 h. The mixture was allowed to cool
and extracted with CH Cl . The organic layers were
combined and washed with conc. NaHCO , water, and
methyl-d]-carbamic acid- N ꢀ7b). In a 500 mL ¯ask
equipped with a re¯ux condenser was added 3.45 g
ꢀ12.8 mmol) of 6 stirred in n-propanol ꢀ140 mL) and
water ꢀ22 mL). Sodium borohydride ꢀ2.43 g, 64.3 mmol)
was added in portions and left to stir at rt for 24 h. Carefully,
14 mL of glacial acetic acid was added dropwise and the
mixture heated to 80±908C for 5 h. After cooling to rt, the
solvent was removed by rotary evaporation and dissolved in
50 mL of dioxane/water ꢀ2:1). The solution was chilled to
08C and 5.66 g ꢀ53.4 mmol) of sodium carbonate was added
to give a basic solution ꢀpH,8). 2,2,2-Trichloroethyl
chloroformate ꢀ4.08 g, 19.3 mmol), dissolved in 50 mL of
dioxane/water ꢀ2:1), was added in portions to the reaction
which was left to stir on ice and warm to rt overnight. The
solvent was removed and the remaining aqueous suspension
acidi®ed with 1 M HCl to pH 2. The mixture was extracted
2
2
3
dried ꢀMgSO ). Evaporation of the solvent yielded 34.7 g
4
2
of an orange oil ꢀ95%). IR ꢀcm ) 3016 ꢀw), 2843 ꢀm), 1685
1
1
ꢀ
s), 1603 ꢀs), 1271 ꢀs), 1168 ꢀs); H NMR ꢀCDCl ) d 3.86 ꢀs,
3
3
H, CH O), 6.98 ꢀd, 2H, J8.3 Hz), 7.82 ꢀd, 2H, J8.7 Hz);
3
1
3
C NMR ꢀCDCl ) d 55.52, 114.27, 129.81, 131.92, 164.58,
3
1
90.49 ꢀt, J26.7 Hz); HRMS ꢀES) calcd for C H DO
8
7
2
ꢀ
M1H) 138.0665, found 138.0667.
4
.1.4. ꢀaS)-4-Methoxy-benzenemethan-d-ol ꢀ5). Under an
argon atmosphere, a dry 1 L ¯ask equipped with a re¯ux
condenser was charged with 500 mL ꢀ0.25 mol) of 0.5 M
THF solution of R-Alpine±Borane along with 20.5 g
w
ꢀ
0.15 mol) of aldehyde 4. The solution was stirred for
2
2
0 h followed by re¯ux for 1.5 h. After cooling to rt,
3 mL of acetaldehyde was added and the mixture stirred
with ether and dried ꢀMgSO ). The organic fraction was
4
concentrated and acetic acid removed by rotary evaporation
using toluene azeotrope. Silica gel chromatography using
3:2 hexanes/ethyl acetate gave an oil which was crystallized
with ether/hexanes yielding 3.55 g ꢀ88%), mp 63±648C
for 1 h. Rotary evaporation removed the solvent and pinene
is partially removed by vacuum pump at 508C for 3 h. The
resultant orange oil was dissolved in 250 mL of ether and
cooled to 08C. Then 15.25 g ꢀ0.25 mol) of aminoethanol was
added and left to stir at rt for 1 h. The white precipitate was
removed by vacuum ®ltration and washed with ether. The
organic fractions were combined, washed with water, and
4
5
21
ꢀunlabeled lit. mp 61±628C). IR ꢀcm ) 3328 ꢀbr), 3002
ꢀw), 2951 ꢀw), 1713 ꢀs), 1511 ꢀs), 1239 ꢀs), 816 ꢀm), 715
1
ꢀm); H NMR ꢀCDCl ) d 3.78 ꢀs, 3H, CH O), 4.31 ꢀbr m,
3
3
1H, a-H), 4.73 ꢀs, 2H, CH ), 5.18 ꢀdd, 1H, J5.8, 91.8 Hz,
2
1
1
5
3
dried ꢀMgSO ). Evaporation of the solvent yielded an
4
N±H), 6.86 ꢀd, 2H, J14.5 Hz), 7.21 ꢀd, 2H, J11.4 Hz);
orange oil which was further puri®ed by partitioning
between 10% aqueous methanol and octane. The alcohol
was isolated from the methanol layer by vacuum distillation
or silica gel chromatography ꢀ95:5 followed by 9:1 hexanes/
C NMR ꢀCDCl ) d 44.22±44.72 ꢀm), 55.28, 74.54, 95.58,
3
114.10, 128.96, 129.79, 154.54 ꢀd, J27.7 Hz), 159.16;
1
HRMS ꢀES) calcd for C H D NO Cl ꢀM1Na)
5
1
1
11
3
3
335.9814, found 335.9821.
2
1
ethyl acetate) to yield 18.8 g of yellowoil ꢀ90%). IR ꢀcm
)
348 ꢀbr), 2936 ꢀw), 1608 ꢀm), 1511 ꢀs), 1247 ꢀs), 1033 ꢀs),
3
8
4.1.7. ꢀR)-t-Butyl ester [ꢀ4-methoxyphenyl) methyl-d]-
carbamic acid- N ꢀ7a). This compound was obtained by
1
04 ꢀm); H NMR ꢀCDCl ) d 3.79 ꢀs, 3H, CH O), 4.58 ꢀbr
15
3
3
m, 1H, a-H), 6.87 ꢀd, 2H, J8.7 Hz), 7.27 ꢀd, 2H, J
the same procedure as that for the synthesis of 7b using di-
tert-butyl dicarbonate instead of 2,2,2-trichloroethyl
chloroformate to give 7a, a colorless oil, 88% yield. H
1
3
8
1
.4 Hz); C NMR ꢀCDCl ) d 55.26, 64.50 ꢀt, J22.0 Hz),
3
1
13.89, 128.63, 133.09, 159.12; HRMS ꢀES) calcd for
C H DO ꢀM1Na) 162.0641, found 162.0645.
8
NMR ꢀCDCl ) d 1.44 ꢀs, 9H), 3.77 ꢀs, 3H, CH O), 4.21
3
9
2
3
1
5
ꢀ
br, 1H, a-H), 4.76 ꢀdd, 1H, J5.4, 90.4 Hz, N±H), 6.84
4
.1.5. ꢀR)-2-[ꢀMethoxyphenyl) methyl-d]-1H-isoindole-
ꢀd, 2H, J8.67 Hz), 7.18 ꢀd, 2H, J8.5 Hz); HRMS ꢀEI)
1
,3ꢀ2H)-dione-2- N ꢀ6). Under an argon atmosphere, a
5
15
calcd for C H D NO 239.1398, found 239.1402.
1
dry three-neck 500 mL ¯ask equipped with a re¯ux con-
denser was charged with 5.78 g ꢀ41.6 mmol) of alcohol 5,
1
3
18
3
4.1.8. ꢀR)-N-[ꢀ2,2,2-Trichloroethyoxy) carbonyl]-glycine-
1
5
1
ꢀ
1.96 g ꢀ45.7 mmol) of triphenylphosphine, and 6.76 g
45.7 mmol) of N-phthalimide stirred in 300 mL of dry
d- N ꢀ8b). In a water bath, a rt 50 mL ¯ask was charged with
2.45 g ꢀ7.78 mmol) of 7b along with carbon tetrachloride
1
5