3.99–4.03 (1H, m, OCH(CH3)2), 4.18 (1H, dd, J 9.1, 7.5,
OCH2), 4.26–4.32 (2H, m, OCH2 and CHCH3), 4.40 (1H, dd,
J 7.4, 1.2, NCH), 4.71 (1H, d, J 8.0, CH((OCH(CH3)2)2); dC
(50 MHz, CDCl3) 14.5, 22.1, 23.7, 23.8, 24.1, 26.1, 36.1, 41.8,
61.6, 65.5, 67.7, 68.9, 101.2, 155.0, 174.7; m/z (ESI+) 388 ([M +
MeCN + NH4]+, 100%); HRMS (ESI+) C17H31NO5Na ([M +
Na]+) requires 352.2100; found 352.2101. Spectral data of the
minor fraction (4S,2ꢀR)-oxazolidinone is reported in the ESI. The
diastereoisomeric excess was determined by integration of the
resonance at d 4.71 (4S,2ꢀS)-73 (CH(OCH(CH3)2)2) and d 5.02
(4S,2ꢀR)-oxazolidinone (CH(OCH(CH3)2)2).
82.7, 104.0, 153.4, 174.9; m/z (ESI+) 402 ([M + MeCN + NH4]+,
100%); HRMS (ESI+) C18H34NO5 ([M + H]+) requires 344.2437;
found 344.2445. Spectral data of the minor fraction (4S,2ꢀR)-
oxazolidinone is reported in the ESI. The diastereoisomeric excess
was determined by integration of the resonance at d 4.68 (4S,2ꢀS)-
75 (CH(OCH2CH2CH3)2) and d 4.79 (4S,2ꢀR)-oxazolidinone
(CH(OCH2CH2CH3)2).
(4S,2ꢀS)-3-(3ꢀ,3ꢀ-Di-iso-propoxy-2ꢀ-methylacryloyl)-4-iso-propyl-
5,5-dimethyloxazolidin-2-one 76
Following general procedure 5, oxazolidinone 63 (113 mg,
0.50 mmol), PdCl2 (9 mg, 0.05 mmol), CuCl (50 mg, 0.50 mol)
and i-PrOH (0.96 mL, 12.5 mmol) in DME (1.00 mL) at room
temperature for 4 d to afforded the title compound 76 (55 mg,
32%) as a yellow oil after purification via column chromatography
on silica (EtOAc–petroleum ether [30–40], 1 : 7); [a]2D2 +74.3
(4S,2ꢀS)-3-(3ꢀ,3ꢀ-Diethoxymethylacryloyl)-4-iso-propyl-5,5-
dimethyloxazolidin-2-one 74
Following general procedure 5, oxazolidinone 63 (113 mg,
0.50 mmol), PdCl2 (9 mg, 0.05 mmol), CuCl (50 mg, 0.50 mol)
and EtOH (0.74 mL, 12.5 mmol) in DME (1.00 mL) at room
temperature for 4 d afforded the title compound 74 (113 mg,
72%) as a yellow oil after purification via column chromatography
on silica (EtOAc–petroleum ether [30–40], 1 : 7); [a]2D3 +73.6
=
=
(c 1.0 in CHCl3); mmax (film) 1779 (C Oexo), 1700 (C Oendo); dH
(400 MHz, CDCl3) 0.95 (3H, d, J 6.9, CH(CH3)2), 1.02 (3H, d,
J 6.9, CH(CH3)2), 1.05 (3H, d, J 6.1, OCH(CH3)2), 1.12 (3H,
d, J 6.2, OCH(CH3)2), 1.17 (3H, d, J 6.1, OCH(CH3)2), 1.21
(3H, d, J 6.2, OCH(CH3)2), 1.27 (3H, d, J 6.9, CHCH3), 1.42
(3H, s, C(CH3)2), 1.51 (3H, s, C(CH3)2), 2.14 (1H, septd, J 6.9,
3.5, CH(CH3)2), 3.87–3.93 (1H, m, OCH(CH3)2), 3.98–4.05 (1H,
m, OCH(CH3)2), 4.13 (1H, d, J 3.5, NCH), 4.25–4.32 (1H, m,
CHCH3), 4.80 (1H, d, J 8.1, CH(OCH(CH3)2)2); dC (100 MHz,
CDCl3) 14.3, 17.0, 21.3, 21.5, 23.4, 23.4, 23.7, 25.3, 28.5, 29.5,
41.7, 66.3, 67.5, 68.2, 82.6, 101.2, 153.4, 174.9; m/z (ESI+) 402
([M + MeCN + NH4]+, 100%); HRMS (ESI+) C18H33NO5Na
([M + Na]+) requires 366.2256; found 366.2247. Spectral data
of the minor fraction (4S,2ꢀR)-oxazolidinone is reported in the
ESI. The diastereoisomeric excess was determined by integration
of the resonance at d 4.78 (4S,2ꢀS)-75 (CH(OCH(CH3)2)2) and d
4.98 (4S,2ꢀR)-oxazolidinone (CH(OCH(CH3)2)2).
=
=
(c 0.5 in CHCl3); mmax (film) 1778 (C Oexo), 1699 (C Oendo); dH
(400 MHz, CDCl3) 0.94 (3H, d, J 6.9, CH(CH3)2), 1.02 (3H, d, J
6.9, CH(CH3)2), 1.11 (3H, t, J 7.1, OCH2CH3), 1.20 (3H, t, J 7.1,
OCH2CH3), 1.24 (3H, d, J 6.9, CHCH3), 1.39 (3H, s, C(CH3)2),
1.50 (3H, s, C(CH3)2), 2.13 (1H, septd, J 6.9, 3.5, CH(CH3)2),
3.43–3.50 (1H, m, OCH2CH3), 3.55–3.72 (3H, m, OCH2CH3),
4.13 (1H, d, J 3.5, NCH), 4.30–4.37 (1H, m, CHCH3), 4.68 (1H,
d, J 8.4, CH(OCH2CH3)2); dC (100 MHz, CDCl3) 14.0, 15.1, 15.3,
17.0, 21.3, 21.5, 28.4, 29.5, 40.3, 59.6, 63.4, 66.4, 82.7, 104.0,
153.5, 174.9; m/z (ESI+) 374 ([M + MeCN + NH4]+, 100%);
HRMS (ESI+) C16H33N2O5 ([M + NH4]+) requires 333.2389;
found 333.2400. Spectral data of the minor fraction (4S,2ꢀR)-
oxazolidinone is reported in the ESI. The diastereoisomeric
excess was determined by integration of the resonance at d 4.64
(4S,2ꢀS)-74 (CH(OCH2CH3)2) and d 4.77 (4S,2ꢀR)-oxazolidinone
(CH(OCH2CH3)2).
References and notes
1 D. A. Evans, Aldrichimica Acta, 1982, 15, 2.
2 D. A. Evans, J. M. Takacs, L. R. McGee, M. D. Ennis, D. J. Mathre
and J. Bartroli, Pure Appl. Chem., 1981, 53, 1109.
3 D. J. Ager, D. R. Allen and D. R. Schaad, Synthesis, 1996, 1283; W. R.
Roush and B. B. Brown, J. Org. Chem., 1993, 58, 2162; M. A. Blanchette,
W. Choy, J. T. Davies, A. P. Essenfeild, S. Masamune, W. K. Roush and
T. Sakai, Tetrahedron Lett., 1984, 25, 2183.
4 D. A. Evans, J. Bartroli and T. L. Shih, J. Am. Chem. Soc., 1981, 103,
2127.
5 D. A. Evans, J. A. Ellman and R. L. Dorow, Tetrahedron Lett., 1987,
28, 1123.
(4S,2ꢀS)-3-(3ꢀ,3ꢀ-Dipropoxy-2ꢀ-methylacryloyl)-4-iso-propyl-5,5-
dimethyloxazolidin-2-one 75
Following general procedure 5, oxazolidinone 63 (113 mg,
0.50 mmol), PdCl2 (9 mg, 0.05 mmol), CuCl (50 mg, 0.50 mol)
and n-PrOH (0.94 mL, 12.5 mmol) in DME (1.00 mL) at room
temperature for 4 d afforded the title compound 75 (103 mg, 60%)
as a yellow oil after purification via column chromatography on
silica (EtOAc–petroleum ether [30–40], 1 : 7); [a]2D3 +77.8 (c 1.0 in
6 D. A. Evans, M. D. Ennis and D. J. Mathre, J. Am. Chem. Soc., 1982,
104, 1737.
7 L-tert-Leucine, £22.20 per gram; D-tert-leucine, £161.20 per gram;
Aldrich Chemical Company 2005–2006.
=
=
CHCl3); mmax (film) 1779 (C Oexo), 1699 (C Oendo); dH (400 MHz,
CDCl3) 0.85 (3H, t, J 7.4, OCH2CH2CH3), 0.92-.096 (6H, m,
CH(CH3)2 and OCH2CH2CH3), 1.02 (3H, d, J 7.0, CH(CH3)2),
1.25 (3H, d, J 6.8, CHCH3), 1.39 (3H, s, C(CH3)2), 1.43–1.65
(4H, m, OCH2CH2CH3), 1.50 (3H, s, C(CH3)2), 2.13 (1H, septd,
J 7.0, 3.5, CH(CH3)2), 3.34–3.40 (1H, m, OCH2CH2CH3), 3.44–
3.52 (2H, m, OCH2CH2CH3), 3.54–3.60 (1H, m, OCH2CH2CH3),
4.13 (1H, d, J 3.5, NCH), 4.29–4.36 (1H, m, CHCH3), 4.70 (1H,
d, J 8.4, CH(OCH2CH2CH3)2); dC (100 MHz, CDCl3) 10.6, 10.8,
14.1, 17.0, 21.3, 21.5, 22.8, 23.1, 28.4, 29.5, 40.4, 65.6, 66.3, 69.6,
8 S. G. Davies and H. J. Sanganee, Tetrahedron: Asymmetry, 1995, 6, 671;
S. D. Bull, S. G. Davies, S. Jones, M. E. C. Polywka, R. S. Prasad and
H. J. Sanganee, SYNLETT, 1998, 519.
9 For selected recent applications of enantiomerically pure 5,5-
dimethyloxazolidin-2-ones in synthesis from this laboratory, see: S. G.
Davies, R. L. Nicholson and A. D. Smith, SYNLETT, 2002, 1637;
S. D. Bull, S. G. Davies, R. L. Nicholson, H. J. Sanganee and A. D.
Smith, Org. Biomol. Chem., 2003, 1, 2886; S. G. Davies, M.-S. Key,
H. Rodriguez-Solla, H. J. Sanganee, E. D. Savory and A. D. Smith,
SYNLETT, 2003, 1659; S. G. Davies, I. A. Hunter, R. L. Nicholson,
2962 | Org. Biomol. Chem., 2006, 4, 2945–2964
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