cis-Selective Synthesis of 2-Ethynylaziridines
A R T I C L E S
flash chromatography over silica gel with n-hexane-EtOAc (10:1) gave,
in order of elution, 2,3-cis-aziridine 10b (44.4 mg, 76% yield) and its
2,3-trans-isomer 11b (9.5 mg, 16% yield). When the reaction was
conducted in THF (room temperature, 4 h), the cis-aziridine 10b was
obtained as the single isomer in 84% yield (Table 3, entry 2). All the
spectroscopic data for 10b and 11b and the other known aziridines
10f, 10g, 11f, and 11g listed in Tables 2 and 3 were in good agreement
with the literature.13b,8
General Procedure for the Ring-Opening Reaction of Ethynyl-
aziridines. Synthesis of (4S,aR)-1-Bromo-4-[N-(2,4,6-trimethylphen-
ylsulfonyl)amino]-5-phenylpenta-1,2-diene (9h). To a solution of the
aziridine 11h (51.0 mg, 0.15 mmol) in CH2Cl2 (1 mL) was added
dropwise methanesulfonic acid (20 µL, 0.30 mmol) at 0 °C with stirring,
and the mixture was stirred for 15 min. The mixture was made alkaline
with saturated NaHCO3 at 0 °C and extracted with Et2O. The extract
was washed with water and dried over MgSO4. Concentration under
reduced pressure gave a crude mesylate 12h. A mixture of CuBr‚Me2S
(61.6 mg, 0.30 mmol) and LiBr (26.1 mg, 0.30 mmol) was dissolved
in THF (1 mL) at room temperature under nitrogen. After this solution
was stirred for 2 min, a solution of the crude mesylate 12h in THF (1
mL) was added to this reagent at room temperature. The mixture was
stirred for 1 h with warming to 50 °C and quenched with saturated
NH4Cl (0.5 mL) and 28% NH4OH (0.5 mL). The whole was extracted
with Et2O. The extract was washed with water and dried over MgSO4.
The filtrate was concentrated under reduced pressure to give an oily
residue, which was purified by column chromatography over silica gel
with n-hexane-EtOAc (5:1) to give 9h (50.7 mg, 80% yield, 88% de).
Recrystallization from n-hexane-Et2O gave 9h (94% de) as colorless
(2R,3S)-2-Ethynyl-3-isopropyl-N-(4-methylphenylsulfonyl)aziri-
dine (10d) and Its (2S,3S)-Isomer (11d) (Table 2, Entry 4). By a
procedure identical to that described for the preparation of the aziridines
10b and 11b from 7b, the bromoallene 7d (68.9 mg, 0.20 mmol) was
converted into the cis-aziridine 10d (46.0 mg, 87% yield) and the trans-
isomer 11d (6.5 mg, 12% yield). When the reaction was conducted in
THF (room temperature, 17 h), the cis-aziridine 10d was obtained as
the single isomer in 99% yield (Table 3, entry 3). Compound 10d:
colorless crystals; mp 111 °C (from n-hexane-Et2O); [R]25D -64.1 (c
1.05, CHCl3); IR (KBr) cm-1 3273 (NSO2), 2129 (CtC), 1329 (NSO2);
1H NMR (270 MHz, CDCl3) δ 0.84 (d, J ) 6.8 Hz, 3H, CMe), 1.00
(d, J ) 6.8 Hz, 3H, CMe), 1.55-1.69 (m, 1H, Me2CH), 2.19 (d, J )
1.9 Hz, 1H, CtCH), 2.45 (s, 3H, PhMe), 2.55 (dd, J ) 9.7, 7.0 Hz,
1H, 3-H), 3.35 (dd, J ) 7.0, 1.9 Hz, 1H, 2-H), 7.34 (d, J ) 8.1 Hz,
2H, Ph), 7.84 (d, J ) 8.1 Hz, 2H, Ph); 13C NMR (67.8 MHz, CDCl3)
δ 18.7, 20.2, 21.8, 28.4, 33.2, 50.7, 72.4, 76.6, 128.0 (2C), 129.6 (2C),
134.4, 144.7. Anal. Calcd for C14H17NO2S: C, 63.85; H, 6.51; N, 5.32.
Found: C, 63.59; H, 6.48; N, 5.26. Compound 11d: colorless oil;
crystals: mp 73-75 °C; [R]25 -182 (c 0.92, CHCl3, 94% de); IR
D
(KBr) cm-1 3356 (NHSO2), 1957 (CdCdC), 1329 (NHSO2); 1H NMR
(500 MHz, CDCl3) δ 2.28 (s, 3H, PhMe), 2.51 (s, 6H, 2 × PhMe),
2.85 (dd, J ) 13.5, 7.0 Hz, 1H, PhCHH), 2.89 (dd, J ) 13.5, 7.0 Hz,
1H, PhCHH), 4.09-4.15 (m, 1H, 4-H), 4.66 (d, J ) 7.0 Hz, 1H, NH),
5.38 (dd, J ) 5.5, 5.5 Hz, 1H, 3-H), 5.88 (dd, J ) 5.5, 2.5 Hz, 1H,
1-H), 6.88 (s, 2H, Ph), 7.04-7.06 (m, 2H, Ph), 7.13-7.23 (m, 3H,
Ph); 13C NMR (75 MHz, CDCl3) δ 20.9, 23.0 (2C), 41.7, 52.4, 75.4,
101.7, 127.0, 128.7 (2C), 129.3 (2C), 131.9 (2C), 133.8, 135.8, 139.0
(2C), 142.2, 200.9; MS (FAB) m/z (%) 422 (MH+, 81Br, 8), 420 (MH+,
[R]23 +29.1 (c 1.14, CHCl3); IR (KBr) cm-1 3267 (NSO2), 2125
D
(CtC), 1329 (NSO2); 1H NMR (300 MHz, CDCl3) δ 0.79 (d, J ) 6.6
Hz, 3H, CMe), 0.94 (d, J ) 6.6 Hz, 3H, CMe), 1.41-1.53 (m, 1H,
Me2CH), 2.45 (s, 3H, PhMe), 2.51 (d, J ) 1.8 Hz, 1H, CtCH), 2.92
(dd, J ) 7.8, 4.5 Hz, 1H, 3-H), 2.99 (dd, J ) 4.5, 1.8 Hz, 1H, 2-H),
7.33 (d, J ) 8.1 Hz, 2H, Ph), 7.88 (d, J ) 8.1 Hz, 2H, Ph); 13C
NMR (75 MHz, CDCl3) δ 19.0, 19.3, 21.6, 30.0, 33.8, 53.7, 74.9, 76.6,
128.1 (2C), 129.4 (2C), 136.1, 144.4; MS (FAB) m/z (%) 264 (MH+,
100). HRMS (FAB) calcd for C14H18NO2S (MH+), 264.1058; found,
264.1059.
79Br, 9), 136 (100); HRMS (FAB) calcd for C20H23BrNO2S (MH+, 79
Br), 420.0633; found, 420.0623.
-
(4S,aS)-1-Bromo-5-methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)-
amino]-1-trimethylsilylhexa-1,2-diene (15). By a procedure identical
to that described for the synthesis of 7a from 6a, (3S,4S)-5-methyl-4-
[N-(2,4,6-trimethylphenylsulfonyl)amino]-1-trimethylsilylhex-1-yn-3-
ol13b (300 mg, 0.786 mmol) was converted into 15 (70 mg, 20% yield,
(2R,3S)-3-Benzyl-2-ethynyl-N-(4-methylphenylsulfonyl)aziri-
dine (10e) and Its (2S,3S)-Isomer (11e) (Table 2, Entry 5). By a
procedure identical to that described for the preparation of the aziri-
dines 10b and 11b from 7b, the bromoallene 7e (27.5 mg, 0.07
mmol) was converted into the cis-aziridine 10e (17.1 mg, 78% yield)
and the trans-isomer 11e (2.1 mg, 10% yield). When the reaction was
conducted in THF (room temperature, 22 h), the cis-aziridine 10e was
obtained as the single isomer in 71% yield (Table 3, entry 4). Com-
>99% de) as colorless crystals: mp 74-75 °C (n-hexane-Et2O); [R]27
D
+5.6 (c 0.51, CHCl3); IR (KBr) cm-1 3296 (NHSO2), 1940
1
(CdCdC), 1323 (NHSO2); H NMR (300 MHz, CDCl3) δ 0.18 (s,
9H, SiMe3), 0.83 (d, J ) 6.9 Hz, 3H, CMe), 0.88 (d, J ) 6.9 Hz, 3H,
CMe), 1.88-1.98 (m, 1H, 5-H), 2.30 (s, 3H, PhMe), 2.65 (s, 6H, 2 ×
PhMe), 3.70 (ddd, J ) 8.4, 5.7, 4.8 Hz, 1H, 4-H), 4.55 (d, J ) 8.4 Hz,
1H, NH), 5.01 (d, J ) 5.7 Hz, 1H, 3-H), 6.95 (s, 2H, Ph); 13C NMR
(75 MHz, CDCl3) δ -1.8 (3C), 17.9, 18.2, 20.9, 23.2 (2C), 32.9, 56.7,
90.6, 94.9, 132.1 (2C), 134.3, 138.8 (2C), 142.1, 202.6; MS (FAB)
m/z (%) 446 (MH+, 17, 81Br), 444 (MH+, 18, 79Br), 119 (100). HRMS
(FAB) calcd for C19H31BrNO2SSi (MH+, 79Br), 444.1028; found,
444.1028.
pound 10e: colorless needles; mp 115-116 °C (n-hexane-Et2O); [R]24
D
-48.1 (c 0.50, CHCl3); IR (KBr) cm-1 3288 (NSO2), 2127 (CtC),
1327 (NSO2); 1H NMR (500 MHz, CDCl3) δ 2.31 (d, J ) 1.5 Hz, 1H,
CtCH), 2.43 (s, 3H, PhMe), 2.85 (dd, J ) 14.5, 7.0 Hz, 1H, PhCHH),
2.95 (dd, J ) 14.5, 6.0 Hz, 1H, PhCHH), 3.07 (ddd, J ) 7.0, 6.5,
6.0 Hz, 1H, 3-H), 3.43 (dd, J ) 6.5, 1.5 Hz, 1H, 2-H), 7.10-7.18 (m,
5H, Ph), 7.22-7.23 (m, 2H, Ph), 7.68-7.70 (m, 2H, Ph); 13C
NMR (75 MHz, CDCl3) δ 21.6, 32.7, 34.5, 45.6, 73.3, 76.7, 126.6,
127.9 (2C), 128.5 (2C), 128.8 (2C), 129.7 (2C), 134.3, 136.7, 144.7;
MS (FAB) m/z (%) 312 (MH+, 68), 136 (100). HRMS (FAB) calcd
for C18H18NO2S (MH+), 312.1058; found, 312.1060. Compound
(4S,aR)-1-Bromo-5-methyl-4-[N-(2,4,6-trimethylphenylsulfonyl)-
amino]-1-trimethylsilylhexa-1,2-diene (16). By a procedure identical
to that described for the synthesis of 7a from 6a, (3R,4S)-5-methyl-
4-[N-(2,4,6-trimethylphenylsulfonyl)amino]-1-trimethylsilylhex-1-yn-
3-ol13b (840 mg, 2.2 mmol) was converted into 16 (296 mg, 30% yield,
>99% de) as colorless crystals: mp 97-99 °C (n-hexane-Et2O);
11e: colorless oil; [R]25 +34.6 (c 0.585, CHCl3); IR (KBr) cm-1
D
[R]24 -147 (c 1.00, CHCl3); IR (KBr) cm-1 3284 (NHSO2), 1940
1
D
3267 (NHSO2), 2127 (CtC), 1331 (NHSO2); H NMR (300 MHz,
1
(CdCdC), 1327 (NHSO2); H NMR (300 MHz, CDCl3) δ 0.21 (s,
CDCl3) δ 2.43 (s, 3H, PhMe), 2.47 (d, J ) 1.8 Hz, 1H, CtCH), 2.74
(dd, J ) 14.7, 6.9 Hz, 1H, PhCHH), 2.98 (dd, J ) 14.7, 5.7 Hz, 1H,
PhCHH), 3.08 (dd, J ) 4.2, 1.8 Hz, 1H, 2-H), 3.33 (ddd, J ) 6.9, 5.7,
4.2 Hz, 1H, 3-H), 6.99-7.03 (m, 2H, Ph), 7.13-7.23 (m, 5H, Ph),
7.68-7.71 (m, 2H, Ph); 13C NMR (75 MHz, CDCl3) δ 21.6, 34.2,
36.6, 48.9, 75.0, 76.5, 126.7, 127.8 (2C), 128.5 (2C), 128.7 (2C),
129.5 (2C), 136.2 (2C), 144.2; MS (FAB) m/z (%) 312 (MH+, 91), 91
(100). HRMS (FAB) calcd for C18H18NO2S (MH+), 312.1058; found,
312.1060.
9H, SiMe3), 0.75 (d, J ) 6.6 Hz, 3H, CMe), 0.84 (d, J ) 6.9 Hz, 3H,
CMe), 1.73-1.84 (m, 1H, 5-H), 2.23 (s, 3H, PhMe), 2.65 (s, 6H, 2 ×
PhMe), 3.75 (ddd, J ) 9.0, 5.4, 4.5 Hz, 1H, 4-H), 4.53 (d, J ) 9.0 Hz,
1H, NH), 5.05 (d, J ) 5.4 Hz, 1H, 3-H), 6.94 (s, 2H, Ph); 13C NMR
(75 MHz, CDCl3) δ -1.9 (3C), 17.7, 18.2, 20.9, 23.1 (2C), 33.0, 56.6,
91.0, 95.4, 132.0 (2C), 134.6, 138.8 (2C), 142.1, 202.8; MS (FAB)
m/z (%) 446 (MH+, 12, 81Br), 444 (MH+, 13, 79Br), 119 (100). HRMS
(FAB) calcd for C19H31BrNO2SSi (MH+, 79Br), 444.1028; found,
9
J. AM. CHEM. SOC. VOL. 124, NO. 51, 2002 15265