A Route to Carbasugar Analogues - Jonathan Clayden - The ...
A Route to Carbasugar Analogues - Jonathan Clayden - The ... A Route to Carbasugar Analogues - Jonathan Clayden - The ...
Experimental for chapter 4.1 Synthesis of (1R,2R,5S,6S)-5-((4R,5R)-4,5-diphenyloxazolin-2-yl)-1,2- bis(benzyloxy)-6-isopropyl-5-methylcyclohex-3-ene (289) Ph Ph Ph Ph O OH N OH BnBr, DMF, NaH n-Bu 4 NI 6 5 O 1 N 2 3 4 OBn OBn Adapted from the method of Provelenghi, 19 sodium hydride (25 mg, 0.62 mmol) was added slowly to a solution of benzyl bromide (0.1 cm 3 , 0.84 mmol), diol 213 (52 mg, 0.13 mmol) and tetrabutylammonium iodide (4 mg, 0.01 mmol) in DMF (1.5 cm 3 ) whilst the reaction mixture was maintained at ambient temperature. When the reaction was judged complete (c. 18 hr) aqueous ammonium chloride (saturated, 0.1 cm 3 ) was added to the reaction, the solvent removed under vacuum and the resulting residue partitioned between water (2 cm 3 ) and CH 2 Cl 2 (6 cm 3 ). The aqueous phase was washed with further CH 2 Cl 2 (2 x 5 cm 3 ) and the combined organic phases dried over sodium sulphate, before purification by flash chromatography (9:1 to 4:1 petrol:EtOAc) yielded benzyl ether 289 (54 mg, 72%) as a colourless oil. R f : 0.45 (4:1, petrol:EtOAc); [α] 20 D : +85 (c = 2.0, CH 2 Cl 2 ); MS m/z (ES+) 572 (100%, MH + ), 573 (40%, (M+1)H + ), 594 (7%, MNa + ), 465 (6%, [M-OBn]H + ); HRMS: found 572.3150, MH requires 572.3159; IR ν max (film)/cm⎯¹ 3030 (m, C-H), 1646 (C=N), 1453; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.47-7.24 (m, 20H, Ph), 5.85 (dd, 1H, J 10.0, 1.5, H5, H6), 5.82 (dd, 1H, J 10.0, 1.5, H5, H6), 5.23 (d, 1H, J 10.0, CHOPh), 5.13 (d, 1H, J 11.5, OBn), 5.10 (d, 1H, J 10.0, CHNPh), 4.72 (d, 1H, J 11.5, OBn'), 4.65 ("t", 2H, J 11.5, OBn, OBn'), 4.35 (d, 1H, J 6.5, H4), 4.16 (dd, 1H, J 10.0, 6.5, H3), 2.28 (p, 1H, J 7.0, CHMe 2 ), 1.88 (d, 1H, J 10.0, H2), 1.52 (s, 3H, Me), 1.16 (d, 3H, J 7.0, i-Pr), 1.01 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 170.1, 141.4, 139.2, 138.5, 134.0, 128.8, 128.7, 128.4, 128.3, 128.2, 127.8, 127.6, 127.5, 127.1, 126.7, 126.3, 126.0, 89.9, 82.8, 78.1, 77.8, 73.0, 70.4, 52.2, 43.9, 27.4, 26.4, 26.0, 18.2. 253
Experimental for chapter 4.1 Synthesis of (1S,2R,3S,4R,5R,6S)-5-((4R,5R)-4,5-diphenyloxazolin-2-yl)-3,4-epoxy- 6-isopropyl-5-methylcyclohexane-1,2-diol (216) Ph Ph Ph Ph O N O N OH OH mCPBA, CH 2 Cl 2 −40 °C - rt O 6 5 1 2 3 4 OH OH mCPBA (192 mg, 50%, 0.56 mmol) was added in a single portion to a vigorously stirred solution of allyl alcohol 213 (110 mg, 0.28 mmol) at 0 °C in CH 2 Cl 2 (3 cm 3 ). After 6 hr, aqueous sodium sulfite (1 cm 3 sat.) was added and the reaction warmed to ambient temperature. The reaction mixture was washed with aqueous sodium bicarbonate (2 cm 3 saturated) and the aqueous phase extracted with further CH 2 Cl 2 (3 x 10 cm 3 ). The combined organic layers dried over anhydrous sodium sulfate, and the solvent removed under vacuum to yield epoxide 216 (113 mg, 99%) as a colourless oil. R f : 0.14 (1:1, petrol:EtOAc); [α] 26 D : 109.3 (c = 1.8, CH 2 Cl 2 ); MS m/z (EI+) 408 (100%, MH + ), 409 (16%, (M+1)H + ), 430 (22%, MNa + ); HRMS: found 408.2179, MH requires 408.2169; IR ν max (film)/cm⎯¹ 3389 (br, OH), 2928 (m, C-H), 1637 (C=N), 1454 (m), 1056; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.41-7.33 (m, 7H, Ph), 7.32-7.28 (m, 1H, Ph), 7.26-7.23 (m, 1H, Ph), 5.26 (d, 1H, J 9.0, CHOPh), 5.14 (d, 1H, J 9.0, CHNPh), 4.06 (dd, 1H, J 11.0, 8.0, H3), 3.81 (dd, 1H, J 8.0, 1.5, H4), 3.46 (dd, 1H, J 4.0, 1.5, H5), 3.30 (d, 1H, J 4.0, H6), 2.24 (br s, 1H, OH), 2.00 (pd, 1H, J 7.0, 1.0, CHMe 2 ), 1.59 (s, 3H, Me), 1.39 (dd, 1H, J 11.0, 1.5, H2), 1.11 (d, 3H, J 7.0, CHMe A Me B ), 1.04 (d, 3H, J 7.0, CHMe A Me B ); ¹³C-NMR (CDCl 3 , 125 MHz) δ 168.9 (C=N), 141.5 (ipso-Ph), 139.1 (ipso-Ph), 128.8 (Ph), 128.7 (Ph), 128.6 (Ph), 127.7 (para-Ph), 126.9 (Ph), 126.8 (Ph), 89.7 (CHOPh), 77.6 (CHNPh), 75.9 (CHOH), 71.4 (CHOH), 61.0 (C6), 56.0 (C5), 53.7 (C2), 42.9 (C1), 28.9 (CHMe 2 ), 27.1 (CHMe A Me B ), 25.4 (Me), 19.0 (CHMe A Me B ). 254
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- Page 289 and 290: H13 H 0.8405 0.7136 -0.0889 0.026 U
- Page 291 and 292: C4 C5 1.454(2) . ? C5 C6 1.324(2) .
- Page 293 and 294: C24 C23 C22 120.0(2) . . ? C24 C23
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- Page 299 and 300: H11 H 0.8924 0.9592 0.6829 0.022 Ui
- Page 301 and 302: C2 H2 1.0000 . ? C3 C21 1.506(2) .
Experimental for chapter 4.1<br />
Synthesis of (1R,2R,5S,6S)-5-((4R,5R)-4,5-diphenyloxazolin-2-yl)-1,2-<br />
bis(benzyloxy)-6-isopropyl-5-methylcyclohex-3-ene (289)<br />
Ph Ph<br />
Ph Ph<br />
O<br />
OH<br />
N<br />
OH<br />
BnBr, DMF, NaH<br />
n-Bu 4 NI<br />
6<br />
5<br />
O<br />
1<br />
N<br />
2<br />
3<br />
4 OBn<br />
OBn<br />
Adapted from the method of Provelenghi, 19 sodium hydride (25 mg, 0.62 mmol) was<br />
added slowly <strong>to</strong> a solution of benzyl bromide (0.1 cm 3 , 0.84 mmol), diol 213 (52 mg,<br />
0.13 mmol) and tetrabutylammonium iodide (4 mg, 0.01 mmol) in DMF (1.5 cm 3 )<br />
whilst the reaction mixture was maintained at ambient temperature. When the reaction<br />
was judged complete (c. 18 hr) aqueous ammonium chloride (saturated, 0.1 cm 3 ) was<br />
added <strong>to</strong> the reaction, the solvent removed under vacuum and the resulting residue<br />
partitioned between water (2 cm 3 ) and CH 2 Cl 2 (6 cm 3 ). <strong>The</strong> aqueous phase was<br />
washed with further CH 2 Cl 2 (2 x 5 cm 3 ) and the combined organic phases dried over<br />
sodium sulphate, before purification by flash chroma<strong>to</strong>graphy (9:1 <strong>to</strong> 4:1<br />
petrol:EtOAc) yielded benzyl ether 289 (54 mg, 72%) as a colourless oil.<br />
R f : 0.45 (4:1, petrol:EtOAc); [α] 20 D : +85 (c = 2.0, CH 2 Cl 2 ); MS m/z (ES+) 572 (100%,<br />
MH + ), 573 (40%, (M+1)H + ), 594 (7%, MNa + ), 465 (6%, [M-OBn]H + ); HRMS: found<br />
572.3150, MH requires 572.3159; IR ν max (film)/cm⎯¹ 3030 (m, C-H), 1646 (C=N),<br />
1453; ¹H-NMR (CDCl 3 , 500 MHz) δ 7.47-7.24 (m, 20H, Ph), 5.85 (dd, 1H, J 10.0,<br />
1.5, H5, H6), 5.82 (dd, 1H, J 10.0, 1.5, H5, H6), 5.23 (d, 1H, J 10.0, CHOPh), 5.13 (d,<br />
1H, J 11.5, OBn), 5.10 (d, 1H, J 10.0, CHNPh), 4.72 (d, 1H, J 11.5, OBn'), 4.65 ("t",<br />
2H, J 11.5, OBn, OBn'), 4.35 (d, 1H, J 6.5, H4), 4.16 (dd, 1H, J 10.0, 6.5, H3), 2.28 (p,<br />
1H, J 7.0, CHMe 2 ), 1.88 (d, 1H, J 10.0, H2), 1.52 (s, 3H, Me), 1.16 (d, 3H, J 7.0, i-Pr),<br />
1.01 (d, 3H, J 7.0, i-Pr); ¹³C-NMR (CDCl 3 , 75.5 MHz) δ 170.1, 141.4, 139.2, 138.5,<br />
134.0, 128.8, 128.7, 128.4, 128.3, 128.2, 127.8, 127.6, 127.5, 127.1, 126.7, 126.3,<br />
126.0, 89.9, 82.8, 78.1, 77.8, 73.0, 70.4, 52.2, 43.9, 27.4, 26.4, 26.0, 18.2.<br />
253
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