portion. After the resulting biphasic mixture had been vigorously
stirred at the same temperature for 60 h, aq formaldehyde (37%
w/w, 74.5 µL, 1.0 mmol, 5.0 equiv) was added, followed by
1H), 5.68 (br s, 1H), 5.35 (br d, J ) 8.2 Hz, 1H), 4.63 (br q, J
) 7.8 Hz, 1H), 2.94 (br d, J ) 7.3 Hz, 2H), 2.31 (br s, 3H),
1.37 (br s, 9H); 13C NMR (100 MHz, CDCl3): δ 199.4, 155.0,
146.8, 129.2, 128.3, 127.9, 126.4, 79.3, 55.1, 40.8, 28.3, 26.6;
ESI-MS: 312 [M + Na+].
(-)-tert-Butyl 2-Methylene-3-oxo-1-phenylbutylcarbamate
(4g). Following the general procedure, the title compound was
obtained as white solid in 67% yield, after chromatography on
silica gel (petroleum ether/Et2O, 7:3). The ee of the product
was determined by HPLC (Chiralpak AD-H, n-hexane/i-PrOH
95:5, 0.75 mL/min, λ ) 215 nm: τmaj ) 18.6 min, τmin ) 15.2
min, 92% ee). [R]22D ) -19 (c 0.59, CH2Cl2); 1H NMR (600
MHz, CDCl3): δ 7.30-7.18 (m, 5H), 6.20 (s, 1H), 6.10 (s, 1H),
5.63 (d, J ) 8.2 Hz, 1H), 5.51 (br s, 1H), 2.28 (s, 3H), 1.43 (br
s, 9H); 13C NMR (150 MHz, CDCl3): δ 199.1, 155.2, 148.1,
140.4, 128.7, 127.6, 127.0, 126.7, 79.9, 56.4, 28.6, 26.8; ESI-
MS: 298 [M + Na+].
(-)-tert-Butyl 1-(4-methoxyphenyl)-2-methylene-3-oxobu-
tylcarbamate (4h). Following the general procedure, the title
compound was obtained as a thick oil in 69% yield, after
chromatography on silica gel (petroleum ether/Et2O, 65:35). The
ee of the product was determined by HPLC (Chiralpak AD-H,
n-hexane/i-PrOH 90:10, 0.75 mL/min, λ ) 215 nm: τmaj ) 16.1
min, τmin ) 14.5 min, 98% ee). [R]22D ) -47 (c 1.0, CH2Cl2);
1H NMR (600 MHz, CDCl3): δ 7.16 (br d, J ) 8.5 Hz, 2H),
6.82-6.79 (m, 2H), 6.17 (s, 1H), 6.06 (br s, 1H), 5.58 (br d, J
) 8.1 Hz, 1H), 5.41 (br s, 1H), 3.75 (s, 3H), 2.28 (s, 3H), 1.42
(s, 9H); 13C NMR (150 MHz, CDCl3): δ 199.1, 159.1, 155.1,
148.3, 132.6, 128.0, 126.3, 114.1, 79.9, 55.8, 55.5, 28.6, 26.9;
ESI-MS: 328 [M + Na+].
(-)-tert-Butyl 1-(4-Chlorophenyl)-2-methylene-3-oxobu-
tylcarbamate (4i). Following the general procedure, the title
compound was obtained as a white solid in 77% yield, after
chromatography on silica gel (petroleum ether/Et2O, 65:35). The
ee of the product was determined by HPLC (Chiralpak AD-H,
n-hexane/i-PrOH 90:10, 0.75 mL/min, λ ) 215 nm: τmaj ) 11.8
min, τmin ) 10.5 min, 86% ee). [R]22D ) -1 (c 1.2, CH2Cl2);
1H NMR (600 MHz, CDCl3): δ 7.26-7.23 (m, 2H), 7.19-7.16
(m, 2H), 6.21 (s, 1H), 6.11 (br s, 1H), 5.58 (br d, J ) 8.6 Hz,
1H), 5.54 (br s, 1H), 2.29 (s, 3H), 1.42 (br s, 9H); 13C NMR
(150 MHz, CDCl3): δ 199.1, 155.2, 147.7, 139.1, 133.3, 128.8,
128.0, 127.7, 80.1, 56.1, 28.6, 26.8; ESI-MS: 332 [M + Na+].
(-)-tert-Butyl 2-Methylene-3-oxo-1-(thiophen-2-yl)butyl-
carbamate (4j). Following the general procedure, the title
compound was obtained as white solid in 88% yield, after
chromatography on silica gel (petroleum ether/Et2O, 7:3). The
ee of the product was determined by HPLC (Chiralpak AD-H,
n-hexane/i-PrOH 95:5, 0.75 mL/min, λ ) 215 nm: τmaj ) 16.9
min, τmin ) 14.7 min, 93% ee). [R]22D ) -17 (c 0.71, CH2Cl2);
1H NMR (400 MHz, CDCl3): δ 7.16 (dd, J ) 5.3, 1.2 Hz, 1H),
6.90 (dd, J ) 5.1, 3.5 Hz, 1H), 6.85 (dt, Jd ) 3.4 Hz, Jt ) 1.1
Hz, 1H), 6.20 (s, 1H), 6.13 (br s, 1H), 5.84 (br d, J ) 9.0 Hz,
1H), 5.71 (br s, 1H), 2.34 (s, 3H), 1.44 (s, 9H); 13C NMR (100
MHz, CDCl3): δ 198.7, 154.7, 147.3, 144.5, 127.0, 126.9, 124.6,
124.5, 79.8, 52.6, 28.3, 26.5; ESI-MS: 304 [M + Na+].
(+)-Benzyl 4-Methylene-5-oxo-1-phenylhexan-3-ylcar-
bamate (4k). Following the general procedure, the title
compound was obtained as white solid in 89% yield, after
w
another portion of aq K3PO4 (50% /w, 1.08 mL, 4.0 mmol,
20.0 equiv). The mixture was then heated to 45 °C with stirring
for 4 h for compounds 4c, d, f-i, l or stirred at rt for 60 h, for
compounds 4e, j, k. The organic layer was then charged directly
on a silica gel chromatographic column, the aqueous phase was
extracted with toluene (2 × 0.5 mL), and the extracts were
charged as well. The aza-MBH adducts 4c-l were obtained,
eluting with petroleum ether/Et2O mixtures.
(+)-tert-Butyl 4-Methylene-5-oxo-1-phenylhexan-3-ylcar-
bamate (4c). Following the general procedure, the title com-
pound was obtained as white solid in 67% yield, after
chromatography on silica gel (petroleum ether/Et2O, 7:3). The
ee of the product was determined by HPLC (Chiralcel OJ-H,
n-hexane/i-PrOH 95:5, 0.75 mL/min, λ ) 215 nm: τmaj ) 16.1
min, τmin ) 14.3 min, 94% ee). [R]22D ) +10 (c 0.84, CH2Cl2);
1H NMR (400 MHz, CDCl3): δ 7.29-7.23 (m, 2H), 7.19-7.13
(m, 3H), 6.05 (s, 1H), 5.92 (br s, 1H), 5.30 (br d, J ) 8.8 Hz,
1H), 4.39 (br q, J ) 7.9 Hz, 1H), 2.73-2.51 (m, 2H), 2.31 (s,
3H), 2.02-1.85 (m, 2H), 1.42 (s, 9H); 13C NMR (100 MHz,
CDCl3): δ 199.8, 155.2, 147.9, 141.3, 128.3, 127.2, 125.9, 79.2,
53.9, 36.3, 32.9, 28.4, 26.6; ESI-MS: 326 [M + Na+].
(+)-tert-Butyl 3-Methylene-2-oxodecan-4-ylcarbamate (4d).
Following the general procedure, the title compound was
obtained as a colorless oil in 75% yield, after chromatography
on silica gel (petroleum ether/Et2O, 8:2). The ee of the product
was determined by HPLC (Chiralpak AD-H, n-hexane/i-PrOH
95:5, 0.75 mL/min, λ ) 215 nm: τmaj ) 6.6 min, τmin ) 7.2
min, 94% ee). [R]22D ) +12 (c 0.75, CH2Cl2); 1H NMR (600
MHz, CDCl3): δ 6.01 (br s, 1H), 5.82 (br s, 1H), 5.19 (br d, J
) 8.9 Hz, 1H), 4.29 (br q, J ) 7.6 Hz, 1H), 2.30 (s, 3H),
1.61-1.49 (m, 2H), 1.39 (s, 9H), 1.30-1.13 (m, 8H), 0.83 (t,
J ) 7.0 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 199.8, 155.2,
148.3, 126.7, 79.1, 53.9, 34.7, 31.7, 28.8, 28.4, 26.6, 26.5, 22.5,
14.0; ESI-MS: 306 [M + Na+].
(+)-tert-Butyl 3-Methylene-4-oxopentan-2-ylcarbamate
(4e). Following the general procedure, the title compound was
obtained as white solid in 63% yield, after chromatography on
silica gel (petroleum ether/Et2O, 7:3). The ee of the product
was determined by HPLC (Chiralcel OJ-H, n-hexane/i-PrOH
95:5, 0.75 mL/min, λ ) 215 nm: τmaj ) 8.8 min, τmin ) 7.9
min, 83% ee). [R]22D ) +12 (c 0.53, CH2Cl2); 1H NMR (400
MHz, CDCl3): δ 6.01 (s, 1H), 5.92 (s, 1H), 5.13 (br s, 1H),
4.51 (br q, J ) 8.0 Hz, 1H), 2.32 (s, 3H), 1.41 (s, 9H), 1.26 (d,
J ) 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 199.5, 154.9,
149.6, 125.5, 79.2, 48.7, 28.3, 26.6, 21.2; ESI-MS: 236 [M +
Na+].
(-)-tert-Butyl 3-Methylene-4-oxo-1-phenylpentan-2-ylcar-
bamate (4f). Following the general procedure but using 1.5
equiv of 1f, the title compound was obtained as white solid in
42% yield, after chromatography on silica gel (petroleum ether/
Et2O, 7:3). The ee of the product was determined by HPLC
(Chiralpak AD-H, n-hexane/i-PrOH 95:5, 0.75 mL/min, λ )
215 nm: τmaj ) 12.3 min, τmin ) 13.0 min, 80% ee). [R]22
)
D
-7 (c 0.42, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 7.28-7.22
(m, 2H), 7.21-7.15 (m, 1H), 7.13-7.08 (m, 2H), 5.94 (br s,
690
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Vol. 14, No. 3, 2010 / Organic Process Research & Development