The Journal of Organic Chemistry
Page 14 of 17
Following general procedure 2, N-chloroformylimidazolidinone 2n (150 mg, 0.65 mmol, 1.0 equiv.), KHMDS (0.77 mL, 0.77
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mmol, 1.2 equiv., 1.0 M in THF) and ethyl iodide (0.26 mL, 3.25 mmol, 5 equiv.) gave, after purification by automated FC
ퟐퟓ
(
SiO
2
, pet.ether/EtOAc, 4:1), the title compound (141 mg, 85%) as a colourless oil. R
f
= 0.36 (pet.ether/EtOAc = 4:1); [훂]퐃 =
1
–
116 (c = 1 in CHCl
3
); IR νmax = 2974 (C-H), 1737 (C=O), 1712 (C=O); H NMR (500 MHz, CDCl
3
) δ 5.18 (s, 0.51H), 5.16 (s,
0.49H), 3.02 (s, 1.47H), 3.01 (s, 1.53H), 2.49 (dq, J = 14.7, 7.4 Hz, 0.51H), 2.35 (dq, J = 14.7, 7.4 Hz, 0.49H), 1.94 (dq, J = 14.8,
.4 Hz, 0.51H), 1.77 (dq, J = 14.6, 7.3 Hz, 0.49H), 1.63 (s, 1.53H), 1.56 (s, 1.47H), 1.08 (s, 4.59H), 1.00 (s, 4.41H), 0.63 (t, J = 7.4
7
13
1
Hz, 1.53H), 0.59 (t, J = 7.3 Hz, 1.47H). C { H} NMR (125 MHz, CDCl
3
) δ 172.4, 172.2, 149.2, 145.7, 83.3, 82.9, 69.7, 67.7, 39.6,
0
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0
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0
+
3
9.2, 32.0, 31.7, 31.4, 28.9, 27.6, 26.9, 23.4, 22.7, 8.0. HRMS C12
H
22ClN
2
O
2
[M + H] calculated: 261.1364, found: 261.1372. The
relative stereochemistry was assigned by NOE experiments (See Supporting Information).
2S,5S)-2-(tert-Butyl)-3,5-dimethyl-4-oxo-5-(prop-2-yn-1-yl)imidazolidine-1-carbonyl chloride (3e)
Following general procedure 2, N-chloroformylimidazolidinone 2n (100 mg, 0.43 mmol), KHMDS (1M in THF, 0.47 mL,
.47 mmol) and propargyl bromide (80% in toluene, 53 µL, 0.47 mmol) gave, after purification by automated FC (SiO
(
0
2
;
pet. ether/Et
ether/Et
MHz, CDCl
dd, J = 16.9, 2.6 Hz, 0.5H), 3.07 (m, 3H), 2.87 (dd, J = 17.3, 2.7 Hz, 0.5H), 2.68 (dd, J = 16.9, 2.6 Hz, 0.5H), 2.03 (t, J = 2.6 Hz,
2
O 85:15 → pet. ether/Et
2
O 0:100), the title compound (72 mg, 62%) as a colourless oil. R
f
2
0.33 (SiO ; pet.
ퟐퟒ
-
1
1
O 50:50); [훂]퐃 = –40 (c = 0.5 in CHCl
); IR (neat, cm ): νmax 2968 (C–H), 1738 (C=O), 1716 (C=O); H NMR (400
2
3
3
) (mixture of rotamers in a 0.50:0.50 ratio) δ 5.23 (s, 0.5H), 5.21 (s, 0.5H), 3.38 (dd, J = 17.3, 2.7 Hz, 0.5H), 3.28
(
13
1
0.5H), 2.00 (t, J = 2.6 Hz, 0.5H), 1.65 (s, 1.5H), 1.58 (s, 1.5H), 1.10 (s, 4.5H), 1.02 (s, 4.5H); C { H} NMR (101 MHz, CDCl
3
) δ
1
71.7, 171.4, 148.6, 147.4, 84.0, 83.7, 78.2, 77.6, 72.8, 71.8, 68.6, 66.4, 39.5, 39.1, 32.2, 31.9, 30.2, 27.6, 27.3, 26.9, 22.6, 21.8;
+
2 2
HRMS C13H19ClN O Na [M+Na] calculated: 293.1027, found 293.1036.
(
2S,5S)-2-(tert-Butyl)-5-(4-chlorobenzyl)-3,5-dimethyl-4-oxoimidazolidine-1-carbonyl chloride (3f)
Following general procedure 2, N-chloroformylimidazolidinone 2n (150 mg, 0.65 mmol), KHMDS (1M in THF, 0.77 mL,
0
.77 mmol), and 4-chlorobenzyl bromide (146 mg, 0.72 mmol) gave, after purification by flash column chromatography,
ퟐퟓ
f 3
the title compound (170 mg, 74%) as a colourless foam. R ); IR νmax
= 0.23 (pet.ether/EtOAc 6:1). [훂]퐃 = -28 (c = 1 in CHCl
1
=
4
=
2983 (C-H), 1736 (C=O), 1709 (C=O); H NMR (500 MHz, CDCl
3
) δ 7.22 (dd, J = 8.6, 2.3 Hz, 2H), 7.08 (t, J = 8.5 Hz, 2H),
.59 (s, 0.57H), 4.52 (s, 0.43H), 3.72 (d, J = 14.2 Hz, 0.43H), 3.59 (d, J = 14.0 Hz, 0.57H), 3.11 (d, J = 14.2 Hz, 0.43H), 3.02 (d, J
13
1
14.0 Hz, 0.57H), 2.78 (s, 1.71H), 2.72 (s, 1.29H), 1.81 (s, 1.29H), 1.73 (s, 1.71H), 1.02 (s, 5.13H), 0.92 (s, 3.87H). C { H} NMR
(125 MHz, CDCl
3
) δ 171.5, 171.5, 148.3, 146.9, 133.7, 133.5, 133.4, 133.3, 131.6, 131.3, 128.6, 128.4, 82.8, 82.7, 70.5, 68.3, 42.8, 40.2,
+
3
9.9, 39.4, 31.8, 31.5, 27.7, 26.9, 23.7, 22.7. HRMS C17
H
23Cl
2
N
2
O
2
[M + H] calculated: 357.11311, found: 357.114325.
(
2S,5R)-5-Allyl-2-(tert-butyl)-3-methyl-4-oxo-5-phenylimidazolidine-1-carbonyl chloride (3g)
Following general procedure 2, N-chloroformylimidazolidinone 2m, KHMDS (0.61 mL, 0.61 mmol, 1.2 equiv., 1.0 M in
THF) and allyl bromide (0.13 mL, 1.53 mmol, 3 equiv.) gave, after purification by automated FC (SiO
2
, pet.ether/EtOAc,
:1), the title compound (140 mg, 82%) as a colourless solid. mp: 113-115 °C, [훂]퐃 = +124 (c = 1 in CHCl
); IR νmax = 2974 (C-
3
ퟐퟓ
6
1
H), 1737 (C=O), 1712 (C=O); H NMR (500 MHz, CDCl
3
) (mixture of rotamers in a 0.90:0.10 ratio) δ 7.74 – 7.62 (m, 2H), 7.33
–
5
2
7.22 (m, 2H), 7.21 – 7.16 (m, 1H), 5.49 – 5.45 (m, 0.1H), 5.44 – 5.35 (m, 0.9H), 5.28 – 5.25 (m, 0.1H), 5.23 (s, 0.9H), 5.20 –
.09 (m, 2H), 3.40 (dd, J = 14.5, 8.7 Hz, 0.1H), 3.31 (dd, J = 14.4, 8.8 Hz, 0.9H), 3.25 (ddt, J = 14.6, 5.9, 1.5 Hz, 0.1H), 3.00 (s,
13
1
3
.7H), 2.96 (s, 0.3H), 2.82 (ddt, J = 14.4, 5.7, 1.5 Hz, 0.9H), 0.88 (s, 0.9H), 0.79 (s, 8.1H). C { H} NMR (125 MHz, CDCl ) δ
170.2, 169.7, 150.8, 148.2, 139.4, 137.4, 131.1, 130.3, 128.5, 128.2, 128.1, 128.0, 128.0, 126.7, 126.1, 126.1, 122.1, 121.8, 84.2, 83.2, 74.6,
+
72.1, 44.8, 42.8, 39.3, 38.7, 31.9, 31.8, 27.2, 26.9. HRMS C18
H
24ClN
2
O
2
[M + H] calculated: 335.152082, found: 335.152680. The
relative stereochemistry was assigned by NOE experiments (See NOE section in Supporting Information).
14
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