The Journal of Organic Chemistry
Article
1
1
1
6.5, 17.8, 21.5, 25.9, 44.5, 47.9, 59.2, 114.5, 121.2, 124.8, 127.2, 129.1,
yellow solid (77 mg, 72%): mp 82−84 °C; H NMR δ 1.17 (s, 6H),
2.12(s, 3H), 2.55 (s, 2H), 5.86 (s, 1H), 6.05 (s, 1H), 6.14 (q, J = 3.0
29.3, 129.6, 136.9, 137.1, 148.7, 165.6, 186.6; HRMS (ESI-TOF) m/
+
13
z: [M + H] calcd for C H N O 379.2380; found 379.2381.
Hz, 1H), 6.81 (d, J = 1.5 Hz, 1H), 10.8 (s, 1H); C NMR δ 15.8, 25.8,
24
31
2
2
8
-Carboethoxy-2,3-dihydro-1,2,2-trimethyl-7-phenyl-5-p-tolyldi-
44.3, 48.4, 106.5, 107.9, 108.4, 118.7, 131.3, 148.4, 186.1; HRMS (ESI-
+
pyrrin (5cc). Following the procedure for 5aa, 4cc (130 mg, 0.304
mmol) in DMF (10 mL) was treated with 1 M HCl (0.5 mL) and then
NH OAc (700 mg, 9.13 mmol) and Et N (1.2 mL, 9.2 mmol). The
TOF) m/z: [M + H] calcd for C H N 189.1386; found 189.1384.
12
17
2
2,3-Dihydro-1,2,2-trimethyl-5-p-tolyldipyrrin (5dc-DC). Following
the procedure for 5aa, 4dc-DC (unpurified, prepared from 608 mg of
3dc) in DMF (20 mL) was treated with 1 M HCl (1.0 mL) and then
NH OAc (1.47 g, 19.2 mmol) and Et N (2.6 mL, 19 mmol). The
4
3
standard reaction and workup including chromatography [silica,
hexanes/ethyl acetate (5:1)] afforded a light yellow solid (88 mg,
8%): mp 117−119 °C; H NMR δ 0.79 (s, 6H), 1.23 (t, J = 7.2 Hz,
H), 1.86 (s, 2H), 1.96 (s, 3H), 2.33 (s, 3H), 4.20 (q, J = 7.2 Hz, 2H),
.10−7.50 (m, 10H), 8.11 (s, 1H); C NMR δ 14.5, 15.9, 21.4, 25.5,
4.6, 48.4, 59.7, 114.4, 117.8, 124.7, 124.8, 126.5, 127.9, 128.8, 130.0,
30.3, 131.3, 135.2, 136.6, 136.8, 154.9, 165.1, 189.4; HRMS (ESI-
TOF) m/z: [M + H] calcd for C H N O 427.2380; found
4
3
1
6
3
7
4
1
standard reaction and workup including chromatography [silica,
hexanes/ethyl acetate (3:1)] afforded a white solid (57 mg, 12%
13
1
overall from 3dc): mp 103−105 °C; H NMR δ 1.11 (s, 6H), 2.15 (s,
3H), 2.35 (s, 2H), 2.38 (s, 3H), 5.61−5.64 (m, 1H), 6.06−6.09 (m,
1
3
1H), 6.86−6.88 (m, 1H), 7.16−7.22 (m, 4H), 11.4 (s, 1H); C NMR
δ 15.8, 21.5, 25.9, 44.2, 48.1, 108.1, 109.2, 118.9, 121.2, 129.1, 129.9,
134.1, 136.4, 137.1, 146.3, 185.5; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C H N 279.1856; found 279.1855.
+
28
31
2
2
4
27.2382.
-Carboethoxy-2,3-dihydro-1,2,2,5-tetramethyl-7-phenyldipyrrin
5cd). Following the procedure for 5aa, 4cd (120 mg, 0.342 mmol) in
DMF (10 mL) was treated with 1 M HCl (0.5 mL) and then NH OAc
8
19
23
2
(
8
-Carboethoxy-7-ethyl-2,3-dihydro-1-(1,1-dimethoxymethyl)-
17
4
2,2-dimethyldipyrrin (6aa). Following a general procedure,
a
(
524 mg, 6.85 mmol) and Et N (1.0 mL, 7.2 mmol). The standard
reaction and workup including chromatography [silica, hexanes/ethyl
acetate (4:1)] afforded a yellow solid (62 mg, 51%): mp 111−112 °C;
H NMR δ 1.06 (t, J = 7.2 Hz, 3H), 1.17 (s, 6H), 1.41 (s, 3H), 2.14 (s,
solution of 5aa (245 mg, 0.851 mmol) in 1,4-dioxane (15 mL) was
3
treated with SeO (284 mg, 2.55 mmol). The reaction mixture was
2
stirred at room temperature for 30 min. Ethyl acetate and water were
then added. The organic layer was washed (brine), dried, and
concentrated to dryness. The crude product was dissolved in
HC(OMe) (7.0 mL) and treated with TsOH·H O (48 mg, 0.25
1
3
(
4
1
H), 2.48 (s, 2H), 4.21 (q, J = 7.2 Hz, 2H), 7.28−7.29 (m, 5H), 7.48
d, J = 3.3 Hz, 1H), 12.18 (br, 1H); 13C NMR δ 14.3, 15.8, 18.1, 26.3,
3
2
3.8, 47.8, 59.2, 114.4, 115.6, 123.8, 123.9, 126.5, 127.2, 130.8, 131.1,
37.8, 148.0, 165.3, 185.1; HRMS (ESI-TOF) m/z: [M + H] calcd
for C H N O 351.2067; found 351.2073.
8
mmol). After 12 h with stirring at room temperature, the reaction
mixture was quenched by the addition of saturated aqueous NaHCO3
solution and then extracted with ethyl acetate. The organic layer was
dried (Na SO ) and concentrated. Column chromatography [silica,
+
22
27
2
2
-Carboethoxy-2,3-dihydro-1,2,2-trimethyl-5-(1-naphthyl)-
2
4
1
dipyrrin (5be). Following the procedure for 5aa, 4be (899 mg, 2.32
mmol) in DMF (50 mL) was treated with 1 M HCl (2.5 mL) and then
NH OAc (4.77 g, 46.4 mmol) and Et N (6.7 mL, 46 mmol). The
hexanes/ethyl acetate (4:1)] afforded a brown oil (74 mg, 25%): H
NMR δ 1.16 (t, J = 7.2 Hz, 3H), 1.27 (s, 6H), 1.33 (t, J = 6.9 Hz, 3H),
2.61 (s, 2H), 2.78 (q, J = 7.2 Hz, 2H), 3.44 (s, 6H), 4.28 (q, J = 6.9
Hz, 2H), 5.10 (s, 1H), 6.01 (s, 1H), 7.41 (d, J = 3.3 Hz, 1H), 10.96
4
3
standard reaction and workup including chromatography [silica,
hexanes/ethyl acetate (5:1)] afforded a yellow solid (678 mg, 75%):
(
br, 1H); 13C NMR δ 14.9, 16.2, 18.1, 26.2, 45.9, 48.1, 54.3, 59.7,
1
mp 133−135 °C; H NMR δ 1.07 (s, 3H), 1.11 (s, 3H), 1.22 (t, J = 7.2
102.2, 106.1, 125.7, 126.4, 128.3, 148.3, 165.7, 181.6; HRMS (ESI-
+
Hz, 3H), 2.00−2.26 (m, 5H), 4.18 (q, J = 7.2 Hz, 2H), 5.79 (t, J = 1.8
TOF) m/z: [M + H] calcd for C H N O 349.2122; found
19
29
2
4
13
Hz, 1H), 7.36−7.54 (m, 5H), 7.82−7.91 (m, 3H), 11.95 (s, 1H);
C
3
49.2116.
NMR δ 14.7, 16.0, 25.9, 26.0, 43.7, 48.3, 59.7, 109.6, 116.3, 118.1,
8
-Carboethoxy-2,3-dihydro-1-(1,1-dimethoxymethyl)-2,2-dime-
1
1
24.4, 125.7, 125.9, 126.0, 126.4, 127.8, 128.0, 128.6, 132.1, 134.1,
thyldipyrrin (6ba). Following the procedure for 5aa, 5ba (109 mg,
34.9, 136.4, 149.3, 165.5, 187.7; HRMS (ESI-TOF) m/z: [M + H]+
0.42 mmol) in 1,4-dioxane (10 mL) was oxidized with SeO (139 mg,
2
calcd for C H N O 387.2067; found 387.2081.
1.25 mmol) and then converted to the acetal by treatment with TsOH·
25
27
2
2
9
-(tert-Butoxycarbonyl)-2,3-dihydro-1,2,2-trimethyl-5-p-tolyldi-
H O (25 mg, 0.13 mmol) in HC(OMe) (5.0 mL). The standard
2
3
pyrrin (5dc). Following the procedure for 5aa, 4dc (228 mg, 0.602
reaction and workup including chromatography [silica, hexanes/ethyl
1
mmol) in DMF (20 mL) was treated with 1 M HCl (1.0 mL) and then
acetate (4:1)] afforded a yellow oil (41 mg, 30%): H NMR δ 1.27 (s,
NH OAc (1.62 g, 21.2 mmol) and Et N (2.9 mL, 21 mmol). The
4
3
6H), 1.33 (t, J = 7.2 Hz, 3H), 2.59 (d, J = 1.5 Hz, 2H), 3.44 (s, 6H),
standard reaction and workup including chromatography [silica,
4
7
5
.27 (q, J = 7.2 Hz, 2H), 5.10 (s, 1H), 5.95 (m, 1H), 6.47 (m, 1H),
.42 (m, 1H), 10.99 (br, 1H); 13C NMR δ 14.7, 26.1, 45.8, 48.4, 54.7,
hexanes/ethyl acetate (3:1)] afforded a white solid (150 mg, 66%):
1
mp 114−116 °C; H NMR δ 1.13 (s, 6H), 1.58 (s, 9H), 2.19 (s, 3H),
9.8, 102.3, 108.9, 109.4, 116.6, 124.9, 131.8, 149.4, 165.4, 182.1;
+
2
1
2
1
.38 (s, 5H), 5.63 (dd, J = 1.2, 2.4 Hz, 1H), 6.71 (dd, J = 1.2, 2.4 Hz,
HRMS (ESI-TOF) m/z: [M + H] calcd for C H N O 321.1809;
17
25
2
4
13
H), 7.14−7.21 (m, 4H), 12.0 (s, 1H); C NMR δ 16.1, 21.5, 25.9,
8.7, 44.3, 48.3, 80.3, 110.8, 114.8, 120.2, 124.5, 129.3, 129.8, 136.1,
37.0, 137.4, 149.9, 160.9, 188.0; HRMS (ESI-TOF) m/z: [M + H]+
found 321.1797.
-Carboethoxy-5-ethyl-2,3-dihydro-1-(1,1-dimethoxymethyl)-
8
2,2-dimethyldipyrrin (6bb). Following the procedure for 5aa, 5bb
(456 mg, 1.58 mmol) in 1,4-dioxane (20 mL) was oxidized with SeO2
(527 mg, 4.75 mmol) and then converted to the acetal by treatment
with TsOH·H O (90 mg, 0.475 mmol) in HC(OMe) (10 mL). The
calcd for C H N O 379.2380; found 379.2381.
24
31
2
2
9
-(tert-Butoxycarbonyl)-2,3-dihydro-1,2,2-trimethyldipyrrin
5da). Following the procedure for 5aa, 4da (181 mg, 0.626 mmol) in
DMF (20 mL) was treated with 1 M HCl (1.0 mL) and then NH OAc
(
2
3
4
standard reaction and workup including chromatography [silica,
(
0.957 g, 12.5 mmol) and Et N (1.7 mL, 13 mmol). The standard
3
hexanes/ethyl acetate (4:1)] afforded a brown solid (347 mg, 63%):
1
reaction and workup including chromatography [silica, hexanes/ethyl
mp 124−126 °C; H NMR δ 1.15 (t, J = 7.2 Hz, 3H), 1.29 (s, 6H),
acetate (3:1)] afforded a white solid (112 mg, 62%): mp 90−91 °C;
1
6
.35 (t, J = 7.2 Hz, 3H), 2.37 (q, J = 7.2 Hz, 2H), 2.60 (s, 2H), 3.44 (s,
1
H NMR δ 1.25 (s, 6H), 1.55 (s, 9H), 2.14 (s, 3H), 2.55 (s, 2H), 5.80
H), 4.28 (q, J = 7.2 Hz, 2H), 5.11 (s, 1H), 6.62 (s, 1H), 7.46 (dd, J =
13
13
(
s, 1H), 6.01−6.02 (m, 1H), 6.75−6.77 (m, 1H), 11.3 (s, 1H);
C
2.9, 1.5 Hz, 1H), 11.67 (s, 1H); C NMR δ 13.8, 14.8, 24.4, 26.5,
NMR δ 16.0, 23.8, 29.5, 44.7, 49.5, 80.2, 105.8, 109.7, 115.1, 124.3,
44.5, 47.9, 54.5, 59.8, 102.2, 107.8, 116.1, 123.1, 124.9, 133.5, 146.0,
+
+
1
35.0, 152.2, 160.4, 188.8; HRMS (ESI-TOF) m/z: [M + H] calcd
166.6, 179.7; HRMS (ESI-TOF) m/z: [M + H] calcd for
for C H N O 289.1910; found 289.1905.
C H N O 349.2122; found 349.2116.
17
25
2
2
19 29
2
4
2
,3-Dihydro-1,2,2-trimethyldipyrrin (5da-DC). Following the
8-Carboethoxy-2,3-dihydro-1-(1,1-dimethoxymethyl)-2,2-di-
methyl-5-p-tolyldipyrrin (6bc). Following the procedure for 5aa, 5bc
(247 mg, 0.706 mmol) in 1,4-dioxane (15 mL) was oxidized with SeO2
(235 mg, 2.12 mmol) and then converted to the acetal by treatment
with TsOH·H O (40 mg, 0.21 mmol) in HC(OMe) (10 mL). The
procedure for 5aa, 4da-DC (107 mg, 0.566 mmol) in DMF (20
mL) was treated with 1 M HCl (0.2 mL; the acid dose was reduced
due to substrate stability) and then NH OAc (0.87 g, 11.3 mmol) and
4
Et N (1.6 mL, 12 mmol). The standard reaction and workup including
3
2
3
chromatography [silica, hexanes/ethyl acetate (10:1)] afforded a
standard reaction and workup including chromatography [silica,
M
J. Org. Chem. XXXX, XXX, XXX−XXX