mp 117–119 ЊC; νmax (solid)/cmϪ1 1732s (C᎐O), 1684s (C᎐O,
ammonium chloride (14 mg, 62.1 µmol) followed by p-toluene-
᎐
᎐
NHCO), 1608w (C᎐C, Ar), 1507s and 1339s (N᎐O), 1157s
sulfonyl (3,3-diphenyl-2-propenylidene)hydrazide sodium salt
17 (185 mg, 466 µmol). The clear orange mixture was stirred at
40 ЊC for 15 h, by which time it had become cloudy and yellow
in appearance, it was then allowed to return to RT. TLC (25 : 75
ethyl acetate/petrol) showed trans-19 (Rf 0.32) and cis-19 (Rf
0.22), both compounds were UV and potassium permanganate
active. The reaction was quenched by the addition of water (10
mL) and ethyl acetate (10 mL). The layers were separated and
the aqueous further extracted with ethyl acetate (4 × 10 mL).
The combined organic extracts were dried over anhydrous
Na2SO4 and evaporated under reduced pressure (85 mm Hg,
40 ЊC) and this crude mixture was purified by column chroma-
tography on silica using 25 : 75 ethyl acetate/petrol as eluent to
give trans-(N-tert-butoxycarbonyl)-1-amino-1-(p-nitrobenzyl-
oxycarbonyl)-2-(2,2-diphenylethenyl)cyclopropane E-19 (93 mg,
58%) as a yellow solid; mp 146–148 ЊC; νmax (solid)/cmϪ1 1731m
᎐
᎐
(C–O, CO2), 913m (C–H, alkene) and 846m (C–H, Ar); δH(300
MHz at 55 ЊC; CDCl3) 1.27 (1H, dd, J 8.4 and 5.1, CHH
(cyclopropane)), 1.41 (9H, s, C(Me)3), 1.92 (1H, dd, J 8.4 and
5.1, CHH (cyclopropane)), 2.43 (1H, q, J 8.4, CH2CHCH ),
4.91 (1H, br s, NH), 5.21 (1H, d, J 13.7, CHHAr), 5.24 (1H, d,
J 9.7, CHHCH), 5.27 (1H, d, J 13.7, CHHAr), 5.28 (1H, d,
J 17.2, CHHCH), 5.57 (1H, ddd, J 17.2, 9.7 and 8.4, CH2CH ),
7.44–7.54 (2H, m, C(3)H and C(5)H (Ar)) and 8.15–8.23 (2H,
m, C(2)H and C(6)H (Ar)); δC(75.4 MHz; CDCl3) 23.6 (CH2
(cyclopropane)), 28.3 (C(Me)3), 31.9 (CH2CHCH), 39.4
(CCO2), 65.7 (CH2Ar), 80.4 (C(Me)3), 118.9 (CH2CH), 123.9
(C(2) and C(6) (Ar)), 128.1 (C(3) and C(5) (Ar)), 133.4
(CH2CH), 143.1 (C(4) (Ar)), 147.8 (C(1) (Ar)), 156.0 (NCO2)
and 172.2 (CO2); HRMS (ES, [M–C(Me)3 ϩ H]Hϩ) Found:
307.0922. Calc. for C14H15N2O6 307.0930; m/z (ES) 363 (MHϩ,
35%), 348 (17), 307 (89), 263 (100), 241 (6) and 136 (15).
(CO ), 1686s (C᎐O, NHCO), 1607w (C᎐C, Ar), 1508s (N᎐O),
᎐
᎐
᎐
2
1160s (C–O, CO2), 845s (C–H, PNB), 768m, 739m, 705s and
699s (C–H, Ph); δH(300 MHz at 55 ЊC; CDCl3) 1.41 (9H, s,
C(Me)3), 1.55 (1H, dd, J 9.3 and 5.4, CHH (cyclopropane)),
1.97 (1H, dd, J 8.1 and 5.4, CHH (cyclopropane)), 2.14 (1H, dd,
J 9.3 and 8.1, Ph2CCHCH ), 5.00 (1H, br s, NH), 5.19 (1H, d,
J 13.3, CHHAr (PNB)), 5.35 (1H, d, J 13.3, CHHAr (PNB)),
5.94 (1H, d, J 9.3, Ph2CCHCH), 7.00–7.42 (10H, m, PhH),
7.41–7.49 (2H, m, C(3)H and C(5)H (Ar, PNB)) and 8.00–8.08
(2H, m, C(2)H and C(6)H (Ar, PNB)); δC(75.5 MHz; CDCl3)
25.3 (CH2 (cyclopropane)), 28.2 (C(Me)3), 32.5 (Ph2CCHCH),
41.7 (CCO2), 65.6 (CH2Ar), 80.4 (C(Me)3), 123.7 (C(2) and C(6)
(Ar, PNB)), 124.1 (Ph2CCHCH), 127.2 (2C, PhCH), 127.5,
127.5, 127.7 and 127.9 (4C, PhCH), 128.1 (C(3) and C(5) (Ar,
PNB)), 128.4 (2C, PhCH), 130.1 and 130.1 (2C, PhCH), 139.6
and 141.6 (2C(1) (Ph)), 142.9 (C(4) (Ar, PNB)), 145.2 (Ph2-
CCHCH) and 147.5 (C(1) (Ar, PNB)), 155.5 (NCO2) and 170.8
(CO2); HRMS (CI, [M–Boc ϩ H]Hϩ) Found: 415.1657. Calc.
for C25H23N2O4 415.1658; m/z (CI) 469 ([M–NO2]Hϩ, 1%), 441
(3), 415 (64), 398 (12), 335 (34), 234 (100), 167 (80), 122 (42) and
57 (66); LCMS 18.5 min, m/z (ES) 515 (MHϩ, 100%), 459 (27)
and 415 (6), and cis-(N-tert-butoxycarbonyl)-1-amino-1-(p-
nitrobenzyloxycarbonyl)-2-(2,2-diphenylethenyl)cyclopropane
Z-19 (46 mg, 29%) as a yellow solid; mp 112–113 ЊC; νmax
(solid)/cmϪ1 1727m (C᎐O, CO ), 1693s (C᎐O, NHCO), 1607w
p-Toluenesulfonyl (3,3-diphenyl-2-propenylidene) hydrazide 1620
The procedure outlined by Aggarwal et al.,20 was followed:
dropwise addition of β-phenyl-cinnamaldehyde (5 g, 24.0
mmol) in methanol (20 mL) to a mixture of p-toluenesulfonyl
hydrazide (4.92 g, 26.4 mmol) in methanol (10 mL) resulted in
the formation of a thick colourless precipitate. The mixture was
stirred at RT for 1 h, cooled to 0 ЊC and the precipitate was
collected by filtration and washed with methanol (5 mL). The
solid was recrystallised from methanol to give the hydrazone 16
(8.56 g, 95%) as colourless crystals; mp 171 ЊC (from methanol)
(lit.,20 172–174 ЊC); δH(300 MHz; CDCl3) 2.43 (3H, s, Me), 6.80
(1H, d, J 9.7, CHCHN), 7.10–7.18 (2H, m, ArH ), 7.21–7.42
(11H, m, ArH and CHCHN), 7.50 (1H, br s, NH) and 7.79–
7.85 (2H, m, ArH ); LCMS 17.1 min, m/z (ES) 377 (MHϩ,
100%).
p-Toluenesulfonyl (3,3-diphenyl-2-propenylidene)hydrazide
sodium salt 17
Following the procedure of Aggarwal et al.,20 for the synthesis
of tosylhydrazone sodium salts: a 1 M solution of sodium
methoxide was prepared by adding sodium (1 g, 43.5 mmol) to
anhydrous methanol (43 mL) at 0 ЊC. 25 mL of this 1 M sodium
methoxide solution was then added to p-toluenesulfonyl
(3,3-diphenyl-2-propenylidene)hydrazide 16 (8.47 g, 22.5 mmol)
under a nitrogen atmosphere. The resultant clear yellow
solution was stirred for 15 min at RT and the solvent was
removed under reduced pressure (85 mm Hg, 40 ЊC). Residual
methanol was removed by azeotroping with toluene, then ethyl
acetate, then chloroform under reduced pressure (5 mm Hg,
25 ЊC) to give p-toluenesulfonyl (3,3-diphenyl-2-propenylidene)-
hydrazide sodium salt 17 (10.1 g, 113%) as a pale orange solid,
which was kept away from direct sunlight, ground into a fine
powder and stored at Ϫ20 ЊC prior to use; νmax (solid)/cmϪ1
1062s, 811m (C–H, Ts), 764m and 695s (C–H, Ph); δH(300
MHz; CD3OD) 2.30 (3H, s, Me), 6.80 (1H, d, J 10.0, CHCHN),
7.05–7.34 (10H, m, ArH ), 7.43–7.51 (2H, m, ArH ), 7.54 (1H,
d, J 10.0, CHCHN) and 7.63–7.74 (2H, m, ArH ); δC(75.4 MHz;
CD3OD) 20.0 (Me), 123.9 (Ph2CCH), 126.8 and 126.9 (4C, CH
(Ar)), 127.1 and 127.2 (2C, CH (Ar)), 127.9, 128.0, 128.5 and
130.2 (8C, CH (Ar)), 139.6, 140.7, 141.8, 142.0 and 143.4 (5C,
2C(1) (Ph), Ph2CCH, C(1) and C(4) (Ar, Ts)) and 144.1 (CHN);
HRMS (CI, [M–Ph ϩ H]Hϩ) Found: 323.0834. Calc. for
C16H16N2O2SNa 323.0830; m/z (CI) 384 ([M–Me]Hϩ, 1%), 323
(1), 307 (3), 221 (41), 206 (17), 193 (100) and 91 (22).
᎐
᎐
2
(C᎐C, Ar), 1510s and 1338s (N᎐O), 1156s (C–O, CO ), 844s
᎐
᎐
2
(C–H, PNB), 762s, 737s and 696s (C–H, Ph); δH(300 MHz at
55 ЊC; CDCl3) 1.42 (10H, s, C(Me)3 and CHH (cyclopropane)),
1.98 (1H, dd, J 9.2 and 5.1, CHH (cyclopropane)), 2.46 (1H, q,
J 9.2, Ph2CCHCH ), 5.06 (1H, br s, NH), 5.10 (1H, d, J 13.6,
CHHAr (PNB)), 5.26 (1H, d, J 13.6, CHHAr (PNB)), 5.69 (1H,
d, J 9.2, Ph2CCHCH), 7.15–7.35 (10H, m, PhH), 7.35–7.43
(2H, m, C(3)H and C(5)H (Ar, PNB)) and 8.11–8.19 (2H, m,
C(2)H and C(6)H (Ar, PNB)); δC(101 MHz; CDCl3) 25.3 (CH2
(cyclopropane)), 28.1 (CCO2), 28.3 (C(Me)3), 30.1 (Ph2C-
CHCH), 65.5 (CH2Ar), 80.5 (C(Me)3), 123.8 (C(2) and C(6)
(Ar, PNB)), 124.4 (Ph2CCHCH), 127.6 (PhCH), 127.6 (2C,
PhCH), 127.6 (2C, PhCH), 128.1 (PhCH), 128.4, 128.5 and
130.0 (6C, 4PhCH, C(3) and C(5) (Ar, PNB)), 139.5 (2C, C(1)
(Ph)), 142.1 (C(4) (Ar, PNB)), 143.1 (Ph2CCHCH) and 147.7
(C(1) (Ar, PNB)), 156.1 (NCO2) and 171.7 (CO2); HRMS (CI,
[M–Boc ϩ H]Hϩ) Found: 415.1657. Calc. for C25H23N2O4
415.1658; m/z (CI) 469 ([M–NO2]Hϩ, 1%), 441 (3), 415 (64), 398
(10), 335 (28), 234 (100), 167 (84), 122 (52) and 57 (84); LCMS
17.9 min, m/z (ES) 515 (MHϩ, 68%), 459 (100), 415 (45) and
398 (9).
cis- and trans-(N-tert-Butoxycarbonyl)-1-amino-1-(p-nitro-
benzyloxycarbonyl)-2-(2,2-diphenylethenyl)cyclopropane 19
N,N-Di-(tert-butoxycarbonyl)-dehydroalanine p-nitrobenzyl
ester 21
To a solution of N-(tert-butoxycarbonyl)-dehydroalanine p-
nitrobenzyl ester 6 (100 mg, 311 µmol) in anhydrous dioxane
(5 mL) under a nitrogen atmosphere, was added benzyltriethyl-
To a solution of N-(tert-butoxycarbonyl)-dehydroalanine p-
nitrobenzyl ester 6 (500 mg, 1.55 mmol) in anhydrous
acetonitrile (5 mL) was added 4-(dimethylamino)pyridine (19
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 5 4 2 – 5 5 3
547