The Journal of Organic Chemistry
Note
addition, the reaction temperature was increased to 23 °C and stirred
for 2 h when LC/MS showed complete conversion to the desired
unprotected tetramine. The mixture was concentrated under reduced
pressure and partitioned between 20 mL of CHCl3 and 20 mL of 2 M
NaOH. The organic layer was separated, and the aqueous layer was
extracted twice with 20 mL of CHCl3. The organic layers were
combined, dried over Na2SO4, filtered, and concentrated under
reduced pressure. The tetramine 16 (0.602 g, 92% yield) was isolated
tetraazamacrocycle 2 (0.083 g, 79% yield) as a colorless oil: 1H NMR
(500 MHz, CDCl3) δ 2.94−2.85 (m, 4H), 2.76 (t, J = 5.9 Hz, 4H),
2.70−2.55 (m, 8H), 2.22 (d, J = 13.0 Hz, 2H), 2.09 (d, J = 14.8 Hz,
2H), 2.04 (t, J = 4.4 Hz, 2H), 1.84 (p, J = 5.4, 4.9 Hz, 2H), 1.79−1.71
(m, 2H), 1.60−1.52 (m, 2H), 1.26 (tdd, J = 13.5, 5.6, 2.6 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 60.0, 52.1, 50.9, 48.3, 47.9, 38.8,
32.9, 26.7; IR 2930, 2799, 1466, 1120 cm−1; HRMS (ESI) m/z [M +
25
H]+ calcd for [C16H33N4]+ 281.2705, obs 281.2705 [α]D −0.81 (c
1
as a yellow oil and used without further purification: H NMR (500
0.27 CHCl3).
(1S,5S,14S,18S)-5,8,11,14-Tetraazatricyclo[12.5.0.05,18]-nonade-
cane (21). The bis-lactam 20 (0.020 g, 0.068 mmol, 1 equiv) was
dissolved in anhydrous CH2Cl2 (0.225 mL, 0.3 M) and cooled to −78
°C. DIBAL-H (1.2 M in PhMe) (0.452 mL, 0.543 mmol, 8 equiv) was
added dropwise at −78 °C. Upon completion of addition, the reaction
mixture was warmed to 23 °C and stirred for 2 h. The reaction was
cooled to 0 °C and quenched with 0.350 mL of deionized H2O, 0.230
mL of 2 M NaOH, and 0.570 g of Rochelle’s salt. The mixture was
stirred vigorously for 3 h when two clear layers were apparent. This
mixture was added to 5 mL of CH2Cl2 and 5 mL of 2 M NaOH. The
layers were separated, and the aqueous layer was extracted three times
with 5 mL of CH2Cl2. The organic layers were combined, dried over
Na2SO4, filtered, and concentrated under reduced pressure to get the
tetraazamacrocycle 21 (0.022 g, quantitative yield) as a colorless oil:
1H NMR (500 MHz, CDCl3) δ 2.99 (d, J = 7.0 Hz, 4H), 2.90−2.74
MHz, CDCl3) δ 3.25 (dd, J = 6.5, 3.2 Hz, 2H), 3.10 (dd, J = 14.1, 3.6
Hz, 2H), 2.91−2.84 (m, 2H), 2.75−2.59 (m, 4H), 2.59−2.49 (m,
4H), 2.37 (td, J = 10.3, 9.9, 4.0 Hz, 2H), 2.11 (dd, J = 14.7, 4.2 Hz,
2H), 2.04−1.92 (m, 4H), 1.86 (dd, J = 13.5, 3.9 Hz, 2H), 1.67 (ddt, J
= 15.0, 7.3, 3.6 Hz, 8H), 1.47−1.37 (m, 2H), 1.37−1.29 (m, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 59.6, 55.7, 53.0, 52.6, 46.7, 38.3,
34.7, 34.6, 28.6, 27.5; IR 2918, 1458, 1135 cm−1; HRMS (ESI) m/z
25
[M + H]+ calcd for [C20H39N4]+ 335.3175, obs 335.3161 [α]D
−12.43 (c 0.14 CHCl3).
(1S,5S,15S,19S)-5,8,12,15-Tetraazatricyclo[13.5.0.05,19]-icosane-
7,13-dione (19). The chiral secondary diamine (−)-617 (0.100 g,
0.648 mmol, 1 equiv) was dissolved in anhydrous CH3CN (65 mL,
0.01 M). To this mixture was added Na2CO3 (0.250 g, 2.37 mmol,
3.65 equiv) and the bis-chloroacetamide 1727 (0.147 g, 0.648 mmol, 1
equiv). The reaction mixture was heated to reflux in an oil bath for 16
h. The reaction mixture was cooled to 23 °C, filtered over a pad a
Celite, and concentrated under reduced pressure. The residue was
purified via flash chromatography on SiO2 using 5% MeOH/CH2Cl2
as eluent to give the bis-lactam 19 (0.138 g, 69% yield) as a colorless
oil: 1H NMR (500 MHz, CDCl3) δ 8.11 (s, 2H), 3.73 (ddd, J = 13.8,
11.4, 6.5 Hz, 2H), 3.38−3.28 (m, 4H), 3.10 (dd, J = 5.1, 3.1 Hz, 2H),
3.00 (ddd, J = 14.1, 12.3, 1.6 Hz, 2H), 2.92 (d, J = 17.4 Hz, 2H), 2.55
(dt, J = 14.4, 3.9 Hz, 2H), 2.13−2.08 (m, 2H), 2.02 (d, J = 15.2 Hz,
2H), 1.89−1.83 (m, 2H), 1.80 (dt, J = 12.9, 3.8 Hz, 2H), 1.68 (dp, J =
7.3, 2.6 Hz, 2H), 1.38 (dddd, J = 15.4, 13.3, 5.5, 2.5 Hz, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 170.8, 59.0, 58.4, 54.7, 39.1,
(m, 5H), 2.70 (t, J = 9.3 Hz, 3H), 2.58 (dt, J = 14.4, 3.8 Hz, 2H), 2.44
(td, J = 11.6, 2.7 Hz, 2H), 2.30 (dt, J = 12.5, 2.7 Hz, 2H), 2.14−1.98
(m, 4H), 1.94−1.81 (m, 2H), 1.61−1.48 (m, 2H), 1.35−1.23 (m,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 60.5, 53.3, 53.2, 49.5, 48.9,
39.8, 33.5, 27.6; IR 3378, 2928, 1466, 1333 cm−1; HRMS (ESI) m/z
25
[M + H]+ calcd for [C15H31N4]+ 267.2549, obs 267.2567 [α]D
+4.20 (c 0.37 CHCl3).
(1S,5S,15S,19S)-5,8,12,15-Tetraazatricyclo[13.5.0.05,19]-icosane
Ni(NO3)2 Complex (22). The tetraazamacrocycle 2 (0.036 g, 0.128
mmol, 1 equiv) was added to anhydrous CH3CN (1.28 mL, 0.2 M).
Ni(NO3)2·6H2O (0.037 g, 0.128 mmol, 1 equiv) was added to the
tetraazamacrocycle solution, and the mixture was then degassed by
bubbling Ar through for 15 min. The reaction mixture was heated
under reflux in an oil bath for 3 h. It was cooled to 23 °C and diluted
with 5 mL of CH3CN and then triturated with 20 mL of Et2O,
resulting in a yellow precipitate. The suspension was centrifuged, and
the solvent was decanted. Trituration with 20 mL of Et2O,
centrifugation, and decantation were repeated two times more. The
yellow film was then dried under a high vacuum to get the Ni complex
(0.040 g, 67% yield) as a yellow solid. A single crystal suitable for X-
ray analysis was grown from the vapor diffusion of ether into a
solution of 22 in methanol: HRMS (ESI) m/z [M + H]+ calcd for
[C16H31N4Ni]+ 337.1902, obs 337.1937; mp 264 °C.
36.9, 33.4, 27.1, 27.0; IR 3312, 2933, 1662, 1536 cm−1; HRMS (ESI)
m/z [M + H]+ calcd for [C16H29N4O2]+ 309.2291, obs 309.2291
25
[α]D −22.37 (c 0.23 CHCl3).
(1S,5S,14S,18S)-5,8,11,14-Tetraazatricyclo[12.5.0.05,18]-nonade-
cane-7,12-dione (20). The enantioenriched secondary diamine 6
(0.020 g, 0.129 mmol, 1 equiv) was dissolved in anhydrous CH3CN
(12.9 mL, 0.01 M). To this mixture were added Na2CO3 (0.050 g,
0.470 mmol, 3.65 equiv) and the bis-chloroacetamide 1827 (0.028 g,
0.129 mmol, 1 equiv). The reaction mixture was heated to reflux in an
oil bath for 16 h. The reaction mixture was cooled to 23 °C, filtered
over a pad a Celite, and concentrated under reduced pressure. The
residue was purified via flash chromatography on SiO2 using 5%
MeOH/CH2Cl2 as eluent to give the bis-lactam 20 (0.019 g, 50%
yield) as a white foam: 1H NMR (500 MHz, DMSO-d6) δ 8.16 (d, J =
84.3 Hz, 2H), 4.04 (s, 1H), 3.30 (tt, J = 4.6, 2.7 Hz, 4H), 3.20−3.10
(m, 3H), 3.04−2.89 (m, 3H), 2.79−2.62 (m, 3H), 2.53−2.46 (m,
1H), 2.00 (dt, J = 9.0, 4.8 Hz, 3H), 1.68 (tdt, J = 13.1, 8.5, 4.3 Hz,
2H), 1.48−1.16 (m, 4H); 13C{1H} NMR (125 MHz, DMSO-d6) δ
172.5, 166.2, 59.9, 59.5, 55.8, 42.6, 38.5, 38.4, 37.4, 33.7, 27.3; IR
2938, 1650, 1529, 1462, 726 cm−1; HRMS (ESI) m/z [M + H]+ calcd
(1S,5S,14S,18S)-5,8,11,14-Tetraazatricyclo[12.5.0.05,18]-nonade-
cane Ni(NO3)2 Complex (23). The tetraazamacrocycle 21 (0.100 g,
0.375 mmol, 1 equiv) was added to anhydrous CH3CN (1.90 mL, 0.2
M). Separately, Ni(NO3)2·6H2O (0.109 g, 0.375 mmol, 1 equiv) was
suspended in anhydrous CH3CN (1.90 mL, 0.2 M). The Ni(NO3)2
suspension was added to the tetraazamacrocycle solution, and the
mixture was then degassed by bubbling Ar through for 15 min. The
reaction mixture was heated under reflux in an oil bath for 16 h. It was
cooled to 23 °C and diluted with 5 mL of CH3CN and then triturated
with 20 mL of Et2O, resulting in a tan precipitate. The suspension was
centrifuged, and the solvent was decanted. Trituration with 20 mL of
Et2O, centrifugation, and decantation were repeated two times more.
The tan solid was then dried under high-vacuum to get the Ni
complex 23 (0.126 g, 75% yield) as a light brown powder. A single
crystal suitable for X-ray analysis was grown from the slow
evaporation of a methanol solution: HRMS (ESI) m/z [M + H]+
calcd for [C15H29N4Ni]+ 323.1746, obs 323.1750; mp 272 °C.
Methods for the Epoxidation of trans-β-Methylstyrene. (1) trans-
β-Methylstyrene (1.2 mg, 0.01 mmol, 1 equiv) was dissolved in
CH2Cl2 (0.05 mL), CH3CN (0.05 mL), DMA (0.05 mL), or toluene
(0.05 mL). Nickel complex 22 (0.5 mg, 0.001 mmol, 0.1 equiv) was
added to the reaction mixture. NaOCl solution (reagent grade,
available chlorine 10−15%, 0.05 mL) and benzyltrimethylammonium
25
for [C15H27N4O2]+ 295.2134, obs 295.2140 [α]D −7.11 (c 0.17
CHCl3).
(1S,5S,15S,19S)-5,8,12,15-Tetraazatricyclo[13.5.0.05,19]-icosane
(2). The bis-lactam 19 (0.115 g, 0.373 mmol, 1 equiv) was dissolved
in anhydrous CH2Cl2 (1.25 mL, 0.3 M) and cooled to −78 °C.
DIBAL-H (1.2 M in PhMe) (2.50 mL, 2.98 mmol, 8 equiv) was
added dropwise at −78 °C. Upon completion of addition, the reaction
mixture was warmed to 23 °C and stirred for 4 h. The reaction was
cooled to 0 °C and quenched with 2 mL of deionized H2O, 1.25 mL
of 2 M NaOH, and 3.1 g of Rochelle’s salt. The mixture was stirred
vigorously for 3 h when two clear layers were apparent. This mixture
was added to 5 mL of CH2Cl2 and 5 mL of 2 M NaOH. The layers
were separated, and the aqueous layer was extracted three times with
5 mL of CH2Cl2. The organic layers were combined, dried over
Na2SO4, filtered, and concentrated under reduced pressure to get the
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J. Org. Chem. 2021, 86, 5417−5422