Chiral Amino-[D1]methyllithiums
FULL PAPER
under reduced pressure. The residue was purified by flash chromatogra-
phy (hexane/EtOAc 10:1; Rf =0.15) to give (2R)-[2-D1]-19·(R)-MTPA in
quantitative yield (9 mg). 1H NMR (400.13 MHz, 808C, [D8]toluene): d=
7.56–7.48 (m, 2Harom), 7.17–6.94 (m, 8Harom), 6.09 (d, J=4.3 Hz, 1H), 6.08
(d, J=8.3 Hz, 1H), 5.98 (d, J=8.1 Hz, 1H), 5.98 (d, J=4.7 Hz, 1H),
4.21–4.08 (brm, 1H), 3.41 and 3.34 (q, J=1.1 Hz, 3H), 3.42–3.29 (m,
1H), 3.23–3.16 (m, 0.5H), 3.12–3.06 (m, 0.5H), 1.38 and 1.37 ppm (s,
9H).
(100.61 MHz, CDCl3): d=29.2 (J(117/119Sn)=19.1 Hz, 3C), 27.4
(J(117/119Sn)=52.8 Hz, 3C), 25.3 (t, J=20.7 Hz), 13.7 (3C), 8.5 ppm
(J(117/119Sn)=317.4, 303.6 Hz, 3C); IR (Si): n˜ =2956, 2923, 2871, 1569,
1464 cmÀ1
.
1
Compound 23: H NMR (400.13 MHz, [D8]toluene): d=7.56 (s, 1H), 4.47
(brs, 1H), 2.332 and 2.330 (d, J=4.3 Hz, J(117/119Sn)=31.6 Hz, 2H), 1.65–
1.56 (m, 6H), 1.38 (sext, J=7.3 Hz, 6H), 1.02–0.97 (m, 6H), 0.97 ppm (t,
J=7.3 Hz, 9H); 13C NMR (100.61 MHz, [D8]toluene): d=161.7, 30.6
(J(117/119Sn)=20.7 Hz, 3C), 28.9 (J(117/119Sn)=54.3 Hz, 3C), 23.3, 15.0
(3C), 12.2 ppm (J(117/119Sn)=336.5, 321.1 Hz, 3C); IR (Si): n˜ =3255, 3044,
2956, 2922, 2853, 1651, 1376 cmÀ1; elemental analysis calcd (%) for
C14H31NOSn (348.1): C 48.30, H 8.98, N 4.02; found: C 49.15, H 9.00, N
4.07.
(R)-Mosher esters of N-(2-hydroxy-2-phenylethyl)-N-4-methoxybenzyl-
ammonium trifluoroacetate {20·(R)-MTPA and (1R)-[1-D1]-20·(R)-
MTPA} (Boc cleavage): A solution of 18·(R)-MTPA (30 mg, 0.052 mmol)
in TFA (1 mL) was stirred for 1.5 h at 08C. The solvent was then re-
moved in vacuo to give 20·(R)-MTPA as a colorless oil in quantitative
yield. Chemical shifts and coupling constants varied slightly due to differ-
ences in concentration/aggregation.
Compound 20·(R)-MTPA: 1H NMR (600.13 MHz, [D8]toluene): d=9.26
(vbrs, 2H), 7.49 (d, J=7.7 Hz, 1Harom), 7.41–7.37 (m, 1Harom), 7.21 (d,
J=6.8 Hz, 1Harom), 7.12–6.96 (m, 9Harom), 6.65 (dd, J=8.7, 2.9 Hz,
2Harom), 6.36 (X part of ABX system, J=8.7, 3.8 Hz, 1H) and 6.31 (X
part of ABX system, J=8.7, 3.8 Hz, 1H), 3.71 and 3.57 (AB system,
(S)-[D1]-23: The spectroscopic data were identical to those of 23, except
for the following signals: 1H NMR (400.13 MHz, [D8]toluene): d=
2.31 ppm
(t,
J=1.9 Hz,
J(117/119Sn)=31.1 Hz,
1H);
13C NMR
(100.61 MHz, [D8]toluene): d=23.02 ppm (t, J=21.0 Hz, 1C).
Tributyl(isocyanomethyl)stannane {24 and (S)-[D1]-24}: Et3N (101 mg,
138 mL, 1.0 mmol) was added to a solution of 23 (290 mg, 0.83 mmol) and
Ph3P (262 mg, 1.0 mmol) in dry MeCN (1.3 mL) and CCl4 (0.5 mL) under
argon at 58C. The mixture was stirred for 2.5 h, during which it was al-
lowed to warm to RT. A few drops of water were added and the solution
was directly subjected to flash chromatography (hexane/EtOAc 40:1;
Rf =0.28) to furnish 226 mg (82%) of 24 as a colorless oil. The slightly re-
duced yield is due to the instability of the isonitrile and its decomposition
on silica gel (probably through conversion to the formamide).
Compound 24: 1H NMR (400.13 MHz, CDCl3): d=2.96 (s, J(117/119Sn)=
28.6 Hz, 2H), 1.57–1.47 (m, 6H), 1.31 (sext, J=7.3 Hz, 6H), 1.08–1.02
(m, 6H), 0.89 ppm (t, J=7.3 Hz, 9H); 13C NMR (100.61 MHz, CDCl3):
d=28.7 (J(117/119Sn)=22.2 Hz, 3C), 27.2 (J(117/119Sn)=57.4 Hz, 3C), 21.5,
13.6 (3C), 9.8 ppm (J(117/119Sn)=338.0, 323.5 Hz, 3C); 1C not detected;
IR (Si): n˜ =2958, 2929, 2872, 2131, 1464 cmÀ1; elemental analysis calcd
(%) for C14H29NSn (330.1): C 50.94, H 8.86, N 4.24; found: C 51.79, H
9.17, N 4.16; HRMS: m/z: calcd for C14H29NSn+H+: 331.1324 [M+H+];
found: 331.1332.
JAB =13.1 Hz, 2H), 3.43 and 3.30 (s, 3H), 3.20 (s, 3H), 3.15 (dd [AB part
of ABX system], J=13.5, 8.7 Hz, 1H), 3.11 (dd [AB part of ABX
system], J=13.5, 8.7 Hz, 1H), 3.05 (dd [AB part of ABX system], J=
13.5, 3.8 Hz, 1H), 3.02 ppm (dd [AB part of ABX system], J=13.5,
3.8 Hz, 1H); two diastereomers.
(1R)-[1-D1]-20·(R)-MTPA: The spectroscopic data were identical to
those of 20·(R)-MTPA, except for the following signals: 1H NMR
(600.13 MHz, [D8]toluene): d=6.23 (d, J=4.0 Hz, 1H) and 6.15 (d, J=
8.4 Hz, 1H), 3.02 (d, J=8.4 Hz, 1H) and 2.95 ppm (d, J=4.0 Hz, 1H).
(1S)-[1-D1]-20·(R)-MTPA: The spectroscopic data were identical to
those of 20·(R)-MTPA, except for the following signals: 1H NMR
(600.13 MHz, [D8]toluene): d=6.23 (d, J=7.5 Hz, 1H) and 6.14 (d, J=
4.4 Hz, 1H), 3.04 (d, J=7.5 Hz, 1H) and 2.93 ppm (d, J=4.4 Hz, 1H).
N-Tributylstannylmethylphthalimide {21 and (S)-[D1]-21}: Tributylstan-
nylmethanol 6 (1.44 g, 4.50 mmol), Ph3P (1.42 g, 5.4 mmol), and phthali-
mide (792 mg, 5.40 mmol) were dissolved in dry THF (22.5 mL) under
argon. DEAD (940 mg, 850 mL, 5.40 mmol) was added at 08C, and then
the mixture was stirred at ambient temperature for 1 h. The reaction was
quenched by adding a few drops of water, the solvent was removed
under reduced pressure, and the residue was purified by flash chromatog-
raphy (hexane/EtOAc 15:1; Rf =0.33) to give 1.85 g (91%) of 21 as a
yellow oil. The spectroscopic data of the unlabeled compound were iden-
tical to those reported in the literature.[44]
(S)-[D1]-24: The spectroscopic data were identical to those of 24, except
for the following signals: 1H NMR (400.13 MHz, CDCl3): d=2.94 ppm
(brs, J(117/119Sn)=28.3 Hz, 1H) and 13C NMR (100.61 MHz, CDCl3): d=
21.2 ppm (t, J=22.2 Hz).
2-Isocyano-1-phenylethanol {26 and [2-D1]-26}: Macroscopic: nBuLi
(225 mL, 1.6m solution in hexane, 0.36 mmol) was added to a solution of
24 (99 mg, 0.30 mmol) in dry THF (3 mL) under argon at the requisite
temperature. The intermediate organolithium was trapped with benzalde-
hyde (390 mL, 1m solution in dry THF, 0.39 mmol) after the required
time. After a further 3 min, acetic acid (330 mL, 1m solution in dry THF,
0.33 mmol) was added, followed by a saturated aqueous solution of
NaHCO3 (5 mL). The organic phase was separated, the aqueous phase
was extracted with Et2O (3ꢃ5 mL), and the combined organic layers
were dried over MgSO4. The solvent was removed under reduced pres-
sure and the residue was purified by flash chromatography (hexane/
EtOAc 3:1; Rf =0.23) to give isocyano alcohol 26 as a colorless oil (for
details, see Table 5).[31b,37]
(S)-[D1]-21: 1H NMR (400.13 MHz, CDCl3): d=7.80–7.75 (m, 2Harom),
7.67–7.62 (m, 2Harom), 3.20 (brs, J(117/119Sn)=26.0 Hz, 1H), 1.52–1.43 (m,
6H), 1.25 (sext, J=7.3 Hz, 6H), 0.95–0.89 (m, 6H), 0.83 ppm (t, J=
7.3 Hz, 9H); 13C NMR (100.61 MHz, CDCl3): d=168.8 (2C), 133.6 (2C),
132.4 (2C), 122.8 (2C), 28.9 (J(117/119Sn)=20.7 Hz, 3C), 27.3 (J(117/119Sn)=
55.8 Hz, 3C), 21.0 (t, J=21.4 Hz), 13.6 (3C), 10.4 ppm (J(117/119Sn)=
335.0, 319.2 Hz, 3C); IR (Si): n˜ =2955, 2922, 2870, 2853, 1768, 1708, 1465,
1396 cmÀ1
.
N-(Tributylstannylmethyl)formamide {23 and (S)-[D1]-23}: N2H4·H2O
(6.0 mL) was added dropwise to a refluxing solution of 21 (1.35 g,
3.0 mmol) in ethanol (9 mL). The mixture was stirred for 1 h, cooled, and
diluted with freshly distilled Et2O (20 mL). The organic phase was sepa-
rated, washed with water (4ꢃ10 mL) and brine (2ꢃ10 mL), and concen-
trated under reduced pressure. The crude product (860 mg, 2.68 mmol)
was dissolved in tert-butyl methyl ether (6 mL), treated with 2,2,2-tri-
fluoroethyl formate (687 mg, 5.37 mmol, redistilled from P2O5),[33,34] and
the resulting mixture was stirred for 1.5 h. The solvent was then removed
under reduced pressure and the residue was purified by flash chromatog-
raphy (hexane/EtOAc 3:1; Rf =0.26) to give formamide 22 (760 mg,
73%) as a colorless oil. The spectroscopic data of 22 were identical to
those reported in the literature.[44]
Microscopic: nBuLi (0.75 mL, 1.6m solution in hexane, 1.2 mmol) was
slowly added to a solution of 24 (99 mg, 0.30 mmol) and benzaldehyde
(1.2 mL, 1m solution in dry THF, 1.2 mmol) in dry THF (2 mL) under
argon at À958C. After 3 min, acetic acid (1.32 mL, 1m solution in THF,
1.32 mmol) was added. The subsequent work-up was the same as de-
scribed for the macroscopic conditions. Compound 26 proved to be quite
unstable; if not stored as a dilute solution in toluene at À208C, it rapidly
cyclized to 5-phenyl-2-oxazoline.
1
Compound 26: H NMR (400.13 MHz, CDCl3): d=7.41–7.31 (m, 5Harom),
4.95 (t, J=5.9 Hz, 1H), 3.61 (d, J=5.9 Hz, 2H), 2.56 ppm (s, 1H);
13C NMR (100.61 MHz, CDCl3): d=157.9, 139.3, 128.9 (2C), 128.8, 125.9
(2C), 72.0, 49.2 ppm (t, J=6.9 Hz); IR (Si): n˜ =3392, 3033, 2919, 2850,
2153, 1454, 1065 cmÀ1; HRMS: m/z: calcd for C9H9NO: 147.0684; found:
147.0686 (also 147.1172).
(S)-[D1]-22: 1H NMR (400.13 MHz, CDCl3): d=2.60 (brs, J(117/119Sn)=
29.3 Hz, 1H), 2.09 (vbrs, 2H), 1.53–1.48 (m, 6H), 1.29 (sext, J=7.3 Hz,
6H), 0.93–0.86 (m, 6H), 0.88 ppm (t, J=7.3 Hz, 9H); 13C NMR
Chem. Eur. J. 2009, 15, 5729 – 5739
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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