A. Schweifer, F. Hammerschmidt / Tetrahedron 64 (2008) 7605–7610
7609
30–40% in Et2O according to the literature procedure12) as a color-
less liquid.
4.7.2. (Dimethylphenylsilyl)-[D2]methyl 2,2,6,6-
tetramethylpiperidine-1-carboxylate {[1,1-D2]11} from [1,1,1-D3]17
s-BuLi (4.24 mL, 5.93 mmol, 1.5 equiv, 1.4 M solution in cyclo-
hexane) was added dropwise to a stirred solution of methyl
carbamate [1,1,1-D3]17 (0.787 g, 3.95 mmol) and TMEDA (0.689 g,
0.89 mL, 5.93 mmol, 1.5 equiv) in dry Et2O (3.1 mL) at ꢀ78 ꢁC under
argon. After stirring for 72 h at ꢀ78 ꢁC, chlorodimethylphenylsilane
(1.012 g, 1.0 mL, 5.93 mmol, 1.5 equiv) was added, and the reaction
mixture was allowed to warm to room temperature for 18 h. Work
up and purification as for the unlabeled compound gave deuterated
silylmethyl carbamate [1,1-D2]11 (0.237 g, 18%).
1H NMR (400.1 MHz, CDCl3):
d 3.61 (s, 3H), 1.67–1.56 (m, 6H),
1.37 (s, 12H); 13C NMR (100.6 MHz, CDCl3): 157.9, 56.0 (2C), 50.9,
39.4 (2C), 29.8 (4C), 15.5.
4.6.2. [D3]Methyl 2,2,6,6-tetramethylpiperidine-1-carboxylate
{[1,1,1-D3]17}
A solution of 2,2,6,6-tetramethylpiperide-1-carbonyl chloride
was prepared from phosgene (4.85 mL, 9.37 mmol, approx. 20% so-
lution in toluene) according to General Procedure given in Ref.13 for
the ‘‘Synthesis of 2,2,6,6-Tetramethylpiperidine Urethanes’’ in the
literature, except that a two-necked round-bottomed flask fitted
with an argon balloon was used. Instead of filtering the mixture it
was cooled to ꢀ50 ꢁC and a solution of CD3OLi in THF was added. It
had been prepared by addition of n-BuLi (11.7 mL,18.72 mmol,1.6 M
in hexanes) to a stirred solution of CD3OD (0.675 g, 18.72 mmol,
0.68 mL) in dry THF (20 mL) under argon at ambient temperature.
Stirring was continued for 30 min at ꢀ50 ꢁC and 1 h at ambient
temperature. Water (25 mL) and HCl (5 mL, 2 M) were added. The
organic phase was separated and the aqueous one extracted twice
withCH2Cl2 (20 mL). Thecombinedorganiclayerswerewashed with
water (3ꢃ20 mL), dried (Na2SO4), and concentrated under reduced
pressure. The crude product was bulb-to-bulb distilled (100–105 ꢁC/
9 mbar) to give methyl carbamate [1,1,1-D3]17 (1.547 g, 82%).
The 1H and 13C NMR spectra were identical with that of the
unlabeled species, except for the missing signals for OCH3.
1H and 13C NMR spectra were identical with that of the un-
labeled species, except for the missing signals for OCH2Si.
4.7.3. (Dimethylphenylsilyl)-[D2]methyl 2,2,6,6-
tetramethylpiperidine-1-carboxylate {[1,1-D2]11} from [1,1-D2]17
s-BuLi (2.01 mL, 2.82 mmol, 1.3 equiv, 1.4 M solution in cyclo-
hexane) was added dropwise to a stirred solution of dideuterated
methyl carbamate [1,1-D2]17 (0.437 g, 2.17 mmol) and TMEDA
(0.328 g, 0.43 mL, 2.82 mmol, 1.3 equiv) in dry Et2O (2.17 mL) at
ꢀ78 ꢁC under argon. After stirring for 18 h at ꢀ78 ꢁC, chloro-
dimethylphenylsilane (0.47 mL, 2.82 mmol, 1.3 equiv) was added
and the reaction mixture was stirred while warming up to room
temperature within 3 h. Work up and purification as for the
unlabeled compound gave deuterated silylmethyl carbamate [1,1-
D2]11 (0.540 g, 74%).
IR (Si): nmax 2964, 1689, 1366, 1331, 1298, 1250, 1116, 1082 cmꢀ1
.
The 1H NMR spectrum was identical with that of the unlabeled
species, except for the missing signal for OCH2Si. It contained 3.3%
of mondeuterated species: 3.90 (t, J¼1.5 Hz, OCDHSi); 13C NMR
spectrum was identical with that of unlabeled species, except for
the signal for OCH2Si, which was replaced by the resonance for
OCDHSi: 55.5 (quint, J¼20.6 Hz).
4.6.3. [D2]Methyl 2,2,6,6-tetramethylpiperidine-1-carboxylate
{[1,1-D2]17}
It was prepared similarly to the trideuterated species, starting
from the same amount of phosgene in toluene, but using CD2HOH
(0.638 g, 18.72 mmol, 0.76 mL; 98% D2) instead of CD3OD, to yield
dideuterated carbamate [1,1-D2]17 (1.46 g, 78%).
1H NMR (400.1 MHz, CDCl3):
d
3.73 (t, J¼1.5 Hz, OCDH2, 1%), 3.58
(quint, J¼1.5 Hz, 1H, OCD2H, 99%), 1.68–1.55 (m, 6H), 1.37 (s, 12H);
13C NMR (100.6 MHz, CDCl3):
157.9, 56.0 (2C), 50.4 (quint,
4.8. (R,R)-1,2-Dicyclohexylethane-1,2-diol [(1S)- and (1R)-
(2,2,6,6-tetramethylpiperidine-1-carbonyloxy)-(dimethyl-
phenylsilyl)methyl]boronates {18 and 19, [1-D1]18
and [1-D1]19}
d
J¼22.2 Hz, OCD2H), 39.4 (2C), 29.8 (4C), 15.5.
4.8.1. Preparation of 18 and 19
4.7. Preparation of (dimethylphenylsilyl)methyl 2,2,6,6-
tetramethylpiperidine-1-carboxylates {11 and [1,1-D2]11}
A solution of silylmethyl carbamate 11 (1.004 g, 3.01 mmol) and
dry TMEDA (0.419 g, 0.54 mL, 3.61 mmol) in dry Et2O (9 mL) was
cooled to ꢀ78 ꢁC under argon. s-BuLi (2.58 mL, 3.61 mmol, 1.4 M
solution in cyclohexane) was added and after stirring for 1 h, the
freshly prepared5 boric acid ester 2 (3.61 mmol) dissolved in dry
Et2O (4.5 mL) was added. Stirring was continued for 1 h at ꢀ78 ꢁC.
The reaction was quenched with a mixture of saturated aqueous
solutions of NH4Cl and NaHCO3 (1:1, 40 mL). The organic phase was
separated and the aqueous layers were extracted with Et2O
(3ꢃ40 mL). The combined organic phase were dried (MgSO4),
concentrated, and purified by flash chromatography (hexanes/
EtOAc 10:1, Rf 0.45/0.33) to give a mixture of diastereomers 18 and
19 in a ratio of 1.8:1 (1H NMR), which were separated by pre-
parative HPLC (EtOAc/hexanes 1:19; 19: tR 5.5 min; 18: tR 8.8 min)
to give boronate 18 (0.527 g, 31%) and 19 (0.973 g, 57%) as colorless
oils.
4.7.1. (Dimethylphenylsilyl)methyl 2,2,6,6-tetramethylpiperidine-1-
carboxylate (11)
s-BuLi (4.28 mL, 6 mmol, 1.4 M solution in cyclohexane) was
added dropwise to a stirred solution of methyl carbamate 17
(0.996 g, 5 mmol) and dry TMEDA (0.697 g, 0.91 mL, 6 mmol) in dry
Et2O (10 mL) at ꢀ78 ꢁC under argon. After stirring for 4 h at ꢀ78 ꢁC,
chlorodimethylphenylsilane (1.024 g, 1.0 mL, 6 mmol) was added,
and the reaction mixture was stirred and allowed to warm to room
temperature in the cooling bath. After addition of a saturated
aqueous solution of sodium bicarbonate (20 mL), the organic phase
was separated and the aqueous layer was extracted with Et2O
(3ꢃ20 mL). The combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. The crude product was first
purified by flash chromatography (CH2Cl2/hexanes 15:1, Rf 0.35)
and finally bulb-to-bulb distilled (110–112 ꢁC/0.3 mbar) to give
silylmethyl carbamate 11 (1.118 g, 67%) as a colorless oil.
20
4.8.1.1. Compound 18. [
a
]
þ27.8 (c 1.3, acetone); IR (Si): nmax
D
2924, 2878, 1680, 1590, 1428, 1164 cmꢀ1
;
1H NMR (400.1 MHz,
IR (Si): nmax 2963, 2942, 1690, 1365, 1333, 1323, 1302, 1076 cmꢀ1
1H NMR (400.1 MHz, CDCl3):
7.53 (m, 2H), 7.32 (m, 3H), 3.92 (s,
2H), 1.59 (m, 6H), 1.32 (s, 12H), 0.36 (s, 6H); 13C NMR (100.6 MHz,
CDCl3): 158.4, 136.8, 133.8 (2C), 129.3, 127.8 (2C), 56.1, 56.0 (2C),
;
CDCl3): 7.63 (m, 2H), 7.29 (m, 3H), 3.80 (s, 1H), 3.50 (m, 2H), 1.86–
d
d
1.78 (m, 2H), 1.72–1.49 (m, 14H), 1.35 (s, 6H), 1.31 (s, 6H), 2.03–1.03
(m, 8H), 0.97–0.83 (m, 4H), 0.36 (s, 3H), 0.34 (s, 3H); 13C NMR
d
(100.6 MHz, CDCl3): d 163.8, 138.2, 134.4 (2C), 128.8, 127.4 (2C), 82.7
39.6 (2C), 29.7 (4C), 15.5, ꢀ4.0 (2C). Anal. Calcd for C19H31NO2Si
(2C), 58.2 (2C), 43.1 (2C), 40.7 (2C), 29.6 (2C), 29.5 (2C), 29.2 (2C),
28.6 (2C), 26.8 (2C), 26.3 (2C), 26.2 (2C), 15.6, ꢀ3.7, ꢀ3.9. Anal. Calcd
(333.55): C, 68.42; H, 9.37; N, 4.20. Found: C, 68.13; H, 9.21; N, 4.09.