10.1002/ejoc.202000137
European Journal of Organic Chemistry
FULL PAPER
(E)-5-(iodomethylene)-1-methylpyrrolidin-2-one
(10b)
General
(Z)-4-(Bromomethylene)-3-phenyloxazolidin-2-one
(10i)
General
procedure A was followed starting from 9b. The crude product was purified
by flash chromatography (10% ethyl acetate in hexanes) on a silica gel
treated with 1% triethylamine to afford 10b as a white solid (45% NMR
yield); M.p. : degrades at room temperature; IR (neat), ν (cm-1): 3390 (w),
3319 (w), 3063 (m, CH alkene), 2968, 2940 and 2924 (m-w, CH aliphatic),
1695 (s, C=O), 1620 (s); 1H NMR, δ (ppm, Acetone-D6), J (Hz) : 2.46-2.54
(2H, m, O=C-CH2-CH2), 2.58-2.68 (2H, m, O=C-CH2-CH2), 2.93 (3H, s, N-
CH3), 5.25 (1H, t, J = 2.0, C=CH), 5.62 (CH2Cl2); 13C NMR, δ (ppm,
Acetone-D6) : 25.8 (O=C-CH2-CH2), 27.2 (O=C-CH2-CH2), 28.5 (N-CH3),
44.5 (C=CH), 149.3 (C=CH), 175.5 (C=O); HRMS (C6H8NOI) : calculated
mass = 236.9651 and experimental mass = 236.9647 (deviation = -1.62
ppm)
procedure A was followed starting from 9i. The crude product was purified
by flash chromatography using a gradient of eluent (5-20% ethyl acetate
in hexanes) on a silica gel treated with 1% triethylamine to afford 10i as a
white solid (18% NMR yield); M.p. : 100 °C (degradation); IR (neat), ν (cm-
1): 3087 (m, CH alkene and aromatic), 2952 and 2895 (w, CH aliphatic),
1771 (s, C=O), 1668 and 1595 (s-f, C=C aromatic); 1H NMR, δ (ppm,
Acetone-D6), J (Hz) : 2.82 (H2O), 5.09 (2H, d, J = 2.0, O-CH2), 5.37 (1H, t,
J = 2.0, C-CH), 7.37-7.51 (5H, m, ArH); 13C NMR, δ (ppm, Acetone-D6) :
69.0 (C=CH), 72.7 (O-CH2), 129.4-130.4 (Ar C2, C3, C4), 135.7 (Ar C1),
137.4 (C=CH), 157.2 (C=O); HRMS (C10H8NO2Br) : calculated mass
253.98112 and experimental mass = 253.98154 (deviation = -1.67 ppm)
=
(E)-1-(2-(iodomethylene)pyrrolidin-1-yl)ethanone
(13)
General
(E)-4-(iodomethylene)-3-phenyloxazolidin-2-one
(10d)
General
procedure A was followed starting from 12. The crude product was purified
by flash chromatography using a gradient of eluent (0-10% ethyl acetate
in hexanes) on a silica gel treated with 1% triethylamine to afford 33.0 mg
of 13 as a colorless oil (69%); IR (neat), ν (cm-1): 3124 (w, CH alkene),
2979, 2959 and 2880 (w, CH aliphatic), 1651 (s, C=O), 1597 (m); 1H NMR
δ (ppm, CDCl3), J (Hz): 6.95 (1h, s, C=CH), 3.95 (2H, t, J = 7.0 Hz, CH2-
CH2-CH2-N), 2.66 (2H, td, J = 7.6, 2.0 Hz, CH2-CH2-CH2-N), 2.10 (3H, s,
COCH3), 1.95 (2H, qt, J = 7.3 Hz, CH2-CH2-CH2-N); 13C NMR, δ (ppm,
CDCl3): 169.93 (C=O), 147.23 (C=CH), 59.04 (CH2-CH2-CH2-N), 52.99 (s,
C=CH), 37.38 (s, CH2-CH2-CH2-N), 24.26 (COCH3), 21.96 (CH2-CH2-CH2-
N); HRMS (C7H10NOI): calculated mass = 250.9807 and experimental
mass = 250.981 (deviation = 0.98 ppm)
procedures D and E were followed starting from 9d. The crude product
was purified by flash chromatography (10% ethyl acetate in hexanes) on
a silica gel treated with 1% triethylamine to afford 10d as a white solid.
Conditions D: 56% (237 mg). Conditions E: 85% (NMR yield). M.p. : 68 °C
(degradation); IR (neat), ν (cm-1): 3530 (w), 3091 (m, CH alkene and
aromatic), 2932 and 2875 (CH aliphatic), 1763 (s, C=O), 1652 and 1599
(s-m, C=C aromatic); 1H NMR, δ (ppm, Acetone-D6), J (Hz) : 4.98 (2H, d,
J = 2.6, O-CH2), 5.05 (1H, t, J = 2.6, C=CH), 7.40-7.60 (5H, m, ArH); 13
C
NMR, δ (ppm, Acetone-D6) : 44.4 (C=CH), 71.1 (O-CH2), 127.7 (Ar C2),
129.1 (Ar C4), 130.2 (Ar C3), 133.7 (Ar C1), 143.1 (C=CH), 156.2 (C=O);
HRMS (C10H8NO2I) : calculated mass = 300.9600 and experimental mass
= 300.9589 (deviation = -3.68 ppm)
(E)-1-(2-(iodomethylene)azetidin-1-yl)ethanone
(19a)
General
(E)-5-(Bromomethylene)-1-phenylpyrrolidin-2-one
(10e)
General
procedure A was followed starting from 18a. The crude product was
purified by flash chromatography (10% acetone in hexanes) on a silica gel
treated with 1% triethylamine to afford 19a as a white solid (9% NMR
yield); M.p. : 65.1-65.6 °C; IR (neat), ν (cm-1): 3092 (w, CH alkene), 2988,
2956, 2922 and 2890 (w, CH aliphatic), 1659 (s, C=O), 1631 (s); 1H NMR,
δ (ppm, Acetone-D6), J (Hz) : 1.87 (3H, s, O=C-CH3), 2.67 (2H, dd, J = 2.4
and J = 6.1, CH2-CH2-N), 2.82 (H2O), 4.08 (2H, t, J = 6.1, CH2-CH2-N),
6.03 (1H, t, J = 2.4, C=CH); 13C NMR, δ (ppm, Acetone-D6) : 19.1 (O=C-
CH3), 45.6 (CH2-CH2-N), 52.0 (C=CH), 148.2 (C=CH), 167.6 (C=O);
HRMS (C6H8NOI) : calculated mass = 237.97233 and experimental mass
= 237.97167 (deviation = 2.77 ppm)
procedure B was followed starting from 9e. The crude product was purified
by flash chromatography (10% ethyl acetate in hexanes) on a silica gel
treated with 1% triethylamine to afford 10e as a white solid (93% NMR
yield); M.p. : degrades at room temperature; IR (neat), ν (cm-1): 3094 (w,
CH alkene and aromatic), 2937 (w, CH aliphatic), 1726 (s, C=O), 1640 and
1597 (s-f, C=C aromatic); 1H NMR, δ (ppm, Acetone-D6), J (Hz) : 2.64-2.73
(2H, m, O=C-CH2-CH2), 2.82-2.93 (2H, m, O=C-CH2-CH2), 5.16 (1H, t, J =
2.2, C=CH), 7.23-7.30 (1H, m, ArH para), 7.37-7.57 (4H, m, ArH meta and
ortho); 13C NMR, δ (ppm, Acetone-D6) : 24.4 (O=C-CH2-CH2), 79.2 (C=CH),
127.7 (Ar C2), 128.3 (Ar C4), 129.5 (Ar C3), 135.3 (Ar C1), 147.0 (C=CH),
174.7 (C=O); HRMS (C11H10NOBr) : calculated mass = 252.00185 and
experimental mass = 252.00193 (deviation = -0.31 ppm)
(E)-8-(Bromomethylene)-1-azabicyclo[4.2.0]octan-2-one (19c) In an
ace pressure tube, dissolve 18c (1.00 eq.), cesium carbonate (2.00 eq.),
CuI (13 mol%) and N,N’-dimethylethylenediamine (20 mol%) in THF ([0.07
M]). Bubble nitrogen through the reaction mixture for 5 minutes. Heat at
55 °C in a oil bath until the reaction is complete (determined by TLC). Filter
on a Büchner funnel and rinse with DCM. Concentrate the filtrate under
reduced pressure. The crude product was purified by flash
chromatography using a gradient of eluent (10-50% ethyl acetate in
hexanes) to afford 96 mg of 19c as a white solid (72%); M.p. : 92.3°C -
92.7°C; IR (neat), μ (cm-1): 3110 (w, CH alkene), 2937 (w, CH aliphatics),
1678 (m, C=C alkene), 1635 (i, C=O lactam); 1H NMR, δ (ppm, CDCl3), J
(Hz): 1.35-2.55 (6H, m, COCH2CH2CH2CH), 2.72 (1H, ddd, J=2.8, J=5.1,
J=15.3, CHCH2C-Br), 2.97 (1H, ddd, J=2.3, J=6.6, J=15.3, CHCH2C-Br),
4.22-4.38 (1H, m, CH2CHN), 6.30 (1H, t, J=2.6, CCHBr); 13C NMR, δ (ppm,
CDCl3): 20.5 (CH2CH2CH2), 28.2, 30.2, 35.3 (CH2CH2CH2CHCH2), 60.1
(NCHCH2), 87.8 (NCHCBr), 143.9 (CH2CBrCH), 169.1 (NCOCH2); HRMS
(C8H10NOBr): calculated mass = 214.9946 and experimental mass =
214.9940 (deviation = 2.86).
(E)-5-(Bromomethylene)-1-methylpyrrolidin-2-one
(10f)
General
procedure A was followed starting from 9f. The crude product was purified
by flash chromatography using a gradient of eluent (0-10% ethyl acetate
in hexanes) on a silica gel treated with 1% triethylamine to afford 30.5 mg
of 10f as a colorless oil (43%); IR (neat), ν (cm-1): 3041 (w), 3338 (w), 3074
(s, CH alkene), 2972, 2943 and 2934 (w, CH aliphatic), 1702 (s, C=O),
1634 (s); 1H NMR, δ (ppm, Acetone-D6), J (Hz) : 2.45-2.53 (2H, m, O=C-
CH2-CH2), 2.64-2.74 (2H, m, O=C-CH2-CH2), 2.84 (H2O), 2.91 (3H, s, N-
CH3), 5.55 (1H, t, J = 2.1, C=CH); 13C NMR, δ (ppm, Acetone-D6) : 23.9
(O=C-CH2-CH2), 25.8 (O=C-CH2-CH2), 28.0 (N-CH3), 77.4 (C=CH), 146.3
(C=CH), 174.9 (C=O); This product is too unstable to be characterised by
HRMS.
(E)-4-(Bromomethylene)-3-phenyloxazolidin-2-one (10h) General
procedure B was followed starting from 9h. The crude product was purified
by flash chromatography using a gradient of eluent (0-10% ethyl acetate
in hexanes) on a silica gel treated with 1% triethylamine to afford 10h as a
white solid (58% NMR yield); M.p. : 85 °C (degradation); IR (neat), ν (cm -
1): 3097 and 3065 (w, CH alkene and aromatic), 2945 (w, CH aliphatic),
1774 (s, C=O), 1667 (s), 1596 (w); 1H NMR, δ (ppm, Acetone-D6), J (Hz) :
2.81 (H2O), 5.07 (1H, t, J = 2.4, C=CH), 5.35 (2H, d, J = 2.7, O-CH2), 7.40-
7.59 (5H, m, ArH); 13C NMR, δ (ppm, Acetone-D6) : 67.6 (C=CH), 75.8 (O-
CH2), 127.0 (Ar C2), 128.6 (Ar C4), 129.7 (Ar C3), 133.9 (Ar C1), 140.5
1-(4-Iodo-2,3-dihydro-1H-pyrrol-1-yl)ethanone
(20a)
General
procedure A was followed starting from 18a. The crude product was
purified by flash chromatography (10% acetone in hexanes) on a silica gel
treated with 1% triethylamine to afford 20a as a colorless liquid (63% NMR
yield). In solution, this compound exists as two rotamers, which produce
distinct signals in 1H and 13C NMR; IR (neat), ν (cm-1): 3094 (w, CH alkene),
2957, 2913 and 2859 (w, CH aliphatic), 1642 (s, C=O), 1605 (s); 1H NMR,
δ (ppm, Acetone-D6), J (Hz) : 1.98 (3H, s, O=C-CH3), 2.84 and 2.98 (2H,
dd, J = 2.1 and J = 9.1, CH2-CH2-N), 3.79 and 3.96 (2H, t, J =9.1 , CH2-
(C=CH), 155.5 (C=O); HRMS (C10H8NO2Br) : calculated mass
253.98112 and experimental mass = 253.98128 (deviation = -0.64 ppm)
=
10
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