Coupling of Diazoacetates
FULL PAPER
petrol); 1H NMR (400 MHz, CDCl3, 258C): d=6.27 (s, 2H; 2=CH),
3.88 (s, 4H; 2CH2), 0.95 ppm (s, 18H; 2CMe3); 13C NMR (100 MHz,
CDCl3, 258C): d=165.4 (2CO2), 129.7 (2=CH), 74.6 (2CH2), 31.3
(2CMe3), 26.4 ppm (2CMe3); IR (neat): n˜ =2962 (s), 1729 (C=O, s),
1646 (C=C, m), 1479 (s), 1410 (s), 1393 (s), 1368 (s), 1217 (s), 1165 cmꢀ1
(s); MS (CI): m/z (%): 187 (10), 257 [M+H]+ (10), 274 [M+NH4]+
(100); HRMS: m/z: calcd for C14H25O4: 257.1753 [M+H]+; found:
257.1751.
Ethyl cyclohexyl maleate (6c): This compound was prepared by the gen-
eral procedure, from ethyl diazoacetate (4a, 15.0 mg, 0.131 mmol)and
cyclohexyl diazoacetate (4h, 22.0 mg, 0.131 mmol)in CH Cl2 (5 mL). The
2
residue (Z/E>99:1, as determined by GCMS analysis)was purified by
flash chromatography (5!10% Et2O in petrol)to afford the maleate 6c
(17.0 mg, 57%)as a yellow liquid. Rf =0.46 (30% Et2O in petrol);
1H NMR (400 MHz, CDCl3, 258C): d=6.22 (s, 2H; 2=CH), 4.91–4.84
3
(m, 1H; OCH), 4.25 (q, J
A
CH2 cyclohexyl), 1.77–1.72 (m, 2H; CH2 cyclohexyl), 1.62–1.54 (m, 2H;
CH2 cyclohexyl), 1.32 (t, 3J
(H,H)=7.1 Hz, 3H; CH3), 1.50–1.21 ppm (m,
Diisopropyl maleate (5g): This compound was prepared by the general
procedure, from isopropyl diazoacetate (4g, 54.0 mg, 0.422 mmol)in
CH2Cl2 (5 mL). The residue (Z/E 97:3, as determeined by GCMS analy-
sis)was purified by flash chromatography (5% Et 2O in petrol)to afford
AHCTREUNG
4H; 2CH2 cyclohexyl); 13C NMR (100 MHz, CDCl3, 258C): d=165.3 +
164.8 (2CO2), 130.2 + 129.4 (2=CH), 73.9 (OCH), 61.2 (OCH2), 31.4,
25.3 + 23.7 (3CH2 cyclohexyl), 14.0 ppm (CH3); IR (neat): n˜ =2900 (s),
2846 (m), 1725 (C=O, s), 1640 (C=C, s), 1457 (m), 1403 (m), 1210 (s),
1164 cmꢀ1 (s); MS (CI): m/z (%): 145 (53), 162 (25), 227 [M+H]+ (100),
244 [M+NH4]+ (10); HRMS: m/z: calcd for C12H22NO4: 244.1549
[M+NH4]+; found: 244.1545.
[46]
the maleate 5g (40.0 mg, 95%)as a yellow liquid. Data as lit.
Dicyclohexyl maleate (5h): This compound was prepared by the general
procedure, from cyclohexyl diazoacetate (4h, 70.0 mg, 0.417 mmol)in
CH2Cl2 (3 mL). The residue (Z/E 95.5:4.5, as determined by GCMS anal-
ysis)was purified by flash chromatography (10% Et 2O in petrol)to
afford the maleate 5h (48.0 mg, 82%)as a colourless oil. Data as com-
mercial sample.
tert-Butyl ethyl maleate (6d): This compound was prepared by the gener-
al procedure, from ethyl diazoacetate (4a, 76.0 mL, 0.722 mmol)and tert-
butyl diazoacetate (4j, 100 mL, 0.722 mmol)in CH 2Cl2 (5 mL). The resi-
due (Z/E>99:1, as determined by GCMS analysis)was purified by flash
chromatography (5% Et2O in petrol)to afford the maleate 6d (61.0 mg,
42%)as a yellow liquid. Rf =0.35 (20% Et2O in petrol); 1H NMR
Diadamantan-2-yl maleate (5i): This compound was prepared by the gen-
eral procedure, starting from adamantan-2-yl diazoacetate (4i, 95.0 mg,
0.432 mmol)in CH 2Cl2 (3 mL). The residue (Z/E 95:5, as determined by
GCMS analysis)was purified by flash chromatography (5% Et 2O in
petrol)to afford the maleate 5i (62.0 mg, 75%)as a yellow liquid. Rf =
0.54 (30% Et2O in petrol); 1H NMR (400 MHz, CDCl3, 258C): d=6.26
(400 MHz, CDCl3, 258C): d=6.13 (d, 3J
4.25 (q, 3J
(H,H)=7.1 Hz, 2H; OCH2), 1.51 (s, 9H; CMe3), 1.31 ppm (t,
3J(H,H)=7.1 Hz, 3H; CH2CH3); 13C NMR (100 MHz, CDCl3, 258C): d=
165.3 164.4 (2CO2), 131.4 128.3 (2=CH), 82.2 (CMe3), 61.0
ACHTRE(UNG H,H)=3.6 Hz, 2H; 2=CH),
AHCTREUNG
AHCTREUNG
(s, 2H; 2=CH), 5.05 (t, 3J
ACHTRE(UNG H,H)=3.5 Hz, 2H; 2OCH), 2.06–1.99 (m,
+
+
8H; 4CH2), 1.87–1.74 (m, 16H; 6CH and 5CH2), 1.61–1.54 ppm (m,
(OCH2), 27.9 (CMe3), 14.1 ppm (CH2CH3); IR (neat): n˜ =2982 (s), 1728
(C=O, s), 1640 (C=C, s), 1458 (m), 1397 (s), 1369 (s), 1218 (s), 1151 cmꢀ1
(s); MS (CI): m/z (%): 104 (30), 162 (100), 164 (85), 201 [M+H]+ (35),
203 (15), 220 [M+NH4]+ (55); HRMS: m/z: calcd for C10H17O4: 201.1121
[M+H]+; found: 201.1122.
4H; 2CH and CH2); 13C NMR (100 MHz, CDCl3, 258C): d=164.8 (2
CO2), 129.9 (2=CH), 78.2 (2OCH), 37.3, 236.3
+ 231.6 (10
CH2), 231.7, 27.2 + 26.9 ppm (8CH); IR (neat): n˜ =2912 (s), 2858
(s), 1719 (C=O, s), 1642 (C=C, w), 1453 (s), 1402 (s), 1382 (m), 1365 (w),
1215 (s), 1169 (s), 1101 cmꢀ1 (s); MS (CI): m/z (%): 135 (40), 152 (38),
385 [M+H]+ (100), 402 [M+NH4]+ (10); HRMS: m/z: calcd for
C24H33O4: 385.2379 [M+H]+; found: 385.2384.
Adamantan-2-yl ethyl maleate (6e): This compound was prepared by the
general procedure, from ethyl diazoacetate (4a, 13.0 mL, 0.123 mmol)and
adamantan-2-yl diazoacetate (4i, 27.0 mg, 0.123 mmol)in CH Cl2 (5 mL).
2
Di-tert-butyl maleate (5j): This compound was prepared by the general
procedure, from tert-butyl diazoacetate (4j, 0.10 mL, 0.722 mmol)in
CH2Cl2 (5 mL). The residue (Z/E>99:1, as determined by GCMS analy-
The residue (Z/E>99:1, as determined by GC-MS analysis)was purified
by flash chromatography (5% Et2O in petrol)to afford the maleate 6e
(15.0 mg, 44%)as a yellow liquid. Rf =0.48 (30% Et2O in petrol);
sis)was purified by flash chromatography (10% Et O in petrol)to afford
2
3
1H NMR (400 MHz, CDCl3, 258C): d=6.25 (d, J
A
the maleate 5j (82.0 mg, quant.)as a yellow oil. Rf =0.44 (20% Et2O in
petrol); 1H NMR (400 MHz, CDCl3, 258C): d=6.06 (s, 2H; 2=CH),
1.54 ppm (s, 18H; 2CMe3); 13C NMR (100 MHz, CDCl3, 258C): d=
164.5 (2CO2), 130.1 (2=CH), 81.8 (2CMe3), 28.0 ppm (2CMe3);
IR (neat): n˜ =2935 (s), 1721 (C=O, s), 1642 (C=C, m), 1478 (m), 1395 (s),
1370 (s), 1217 (s), 1144 cmꢀ1 (s); MS (CI): m/z (%): 190 (100), 192 (70),
229 [M+H]+ (15); HRMS: m/z: calcd for C12H21O4: 229.1434 [M+H]+;
found: 229.1437.
=CH), 5.06 (t, 3J
2H; OCH2), 2.07–1.99 (m, 4H; 2CH2), 1.90–1.74 (m, 6H; 2CH and
2CH2), 1.60–1.56 (m, 4H; 2CH and CH2), 1.31 ppm (t, 3J
(H,H)=
(H,H)=3.2 Hz, 1H; OCH), 4.25 (q, 3J
ACHRTUNEG ACHTRE(UGN H,H)=7.1 Hz,
7.1 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3, 258C): d=165.4 + 164.7
(2CO2), 130.2 + 129.5 (2=CH), 78.3 (OCH), 61.2 (OCH2), 37.3, 2
36.3 + 231.7 (5CH2 adamantyl), 231.6, 27.1 + 26.9 (4CH ada-
mantyl), 14.0 ppm (CH3); IR (neat): n˜ =2908 (s), 2856 (m), 1728 (C=O,
s), 1642 (C=C, s), 1453 (m), 1403 (m), 1209 (s), 1164 (s), 1101 cmꢀ1 (w);
MS (CI): m/z (%): 148 (80), 152 (20), 279 [M+H]+ (100), 296 [M+NH4]+
(10); HRMS: m/z: calcd for C16H23O4: 279.1596 [M+H]+; found:
279.1592.
Heterocoupling of diazoacetates
General procedure: Grubbs second-generation catalyst 2 (0.005 equiv,
0.5 mol%)was added to a solution of mixture of diazoacetates (1.0 equiv
each)in CH 2Cl2. The reaction mixture was stirred at room temperature
for 12–16 h, concentrated under reduced pressure and purified by flash
chromatography.[45]
Benzyl cyclohexyl maleate (6 f): This compound was prepared by the
general procedure, from benzyl diazoacetate (4e, 29.4 mg, 0.167 mmol)
and cyclohexyl diazoacetate (4h, 28.0 mg, 0.167 mmol)in CH Cl2 (5 mL).
2
Ethyl isopropyl maleate (6b): This compound was prepared by the gener-
al procedure, from ethyl diazoacetate (4a, 36.5 mg, 0.320 mmol)and iso-
propyl diazoacetate (4g, 41.0 mg, 0.320 mmol)in CH 2Cl2 (4.5 mL). The
residue (Z/E 98:2, as determined by GCMS analysis)was purified by
flash chromatography (5% Et2O in petrol)to afford the maleate 6b
(25.0 mg, 42%)as a colourless liquid. Rf =0.44 (30% Et2O in petrol);
1H NMR (400 MHz, CDCl3, 258C): d=6.22 (s, 2H; 2=CH), 5.13
The residue (Z/E>99:1, as determined by GCMS analysis)was purified
by flash chromatography (10% Et2O in petrol)to afford the maleate 6 f
(24.0 mg, 50%)as a yellow liquid. Rf =0.47 (30% Et2O in petrol);
3
1H NMR (400 MHz, CDCl3, 258C): d=7.40–7.30 (m, 5H; Ar), 6.25 (d, J-
AHCTRE(NUG H,H)=6.0 Hz, 2H; 2=CH), 5.22 (s, 2H; CH2Ar), 4.89–4.77 (m, 1H;
CH cyclohexyl), 1.91–1.83 (m, 2H; CH2 cyclohexyl), 1.78–1.68 (m, 2H;
CH2 cyclohexyl), 1.59–1.49 (m, 2H; CH2 cyclohexyl), 1.44–1.18 ppm (m,
4H; 2CH2 cyclohexyl); 13C NMR (100 MHz, CDCl3, 258C): d=165.1 +
164.7 (2CO2), 135.2 (Ar, quart.), 131.0 (=CH), 128.7, 128.6, 128.5 +
128.4 (3Ar, =CH), 74.1 (OCH), 67.1 (OCH2), 31.4, 25.3 + 23.8 ppm
(3CH2 cyclohexyl); IR (neat): n˜ =2939 (s), 2869 (s), 1728 (C=O, s),
1643 (C=C, m), 1598 (s), 1454 (s), 1401 (m), 1365 (m), 1214 (s), 1164 (s),
1037 cmꢀ1 (m); MS (CI): m/z (%): 148 (75), 289 [M+H]+ (35), 306
[M+NH4]+ (100); HRMS: m/z: calcd for C17H24NO4: 306.1705
[M+NH4]+; found: 306.1703.
(heptet, 3J(H,H)=6.3 Hz, 1H; CHMe2), 4.25 (q, 3J
ACHTREUNG ACHTREU(GN H,H)=7.2 Hz, 2H;
OCH2), 1.36–1.26 ppm (m, 9H; 3CH3); 13C NMR (100 MHz, CDCl3,
258C): d=165.3 + 164.8 (2CO2), 130.2 + 129.4 (2=CH), 68.9 (CH),
61.2 (OCH2), 21.7 (CMe2), 14.0 ppm (CH2CH3); IR (neat): n˜ =2980 (s),
1708 (C=O, s), 1646 (C=C, s), 1450 (m), 1390 (s), 1210 (s), 1141 cmꢀ1 (s);
MS (CI): m/z (%): 70 (40), 87 (38), 131 (65), 187 [M+H]+ (100), 204
[M+NH4]+ (15); HRMS: m/z: calcd for C9H15O4: 187.0970 [M+H]+;
found: 187.0977.
Chem. Eur. J. 2007, 13, 3470 – 3479
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3477