References and Notes
1
Blakeney JS.
Reid RC.
Le GT.
Fairlie DP.
Chem. Rev.
2007,
107:
2960
2a
Ogawa H.
Yamashita H.
Kondo K.
Yamamura Y.
Miyamoto H.
Kan K.
Kitano K.
Tanaka M.
Nagaya K.
Nakamura S.
Mori T.
Tominaga M.
Yabuuchi Y.
J. Med. Chem.
1996,
39:
3547
2b
Mayanoff BE.
Acc. Chem. Res.
2006,
39:
831
3a
Miyazaki T.
Fujiki H.
Yamamura Y.
Nakamura S.
Mori T.
Cardiovasc. Drug Rev.
2007,
25:
1
3b
Torisawa Y.
Furuta T.
Nishi T.
Aki S.
Minamikawa J.
Bioorg. Med.
Chem. Lett.
2007,
17:
6455
3c
Cordero-Vargas A.
Quiclet-Sire B.
Zard SZ.
Bioorg. Med. Chem.
2006,
14:
6165
4a
Caggiano TJ.
Drugs Future
2002,
27:
248
4b
Mayanoff BE.
Drug Discovery and Development
Vol. 1:
Chorghade MS.
Wiley;
New
Jersey:
2006.
p.313
5a
Proctor GR.
Azepines,
In Heterocyclic Compounds
Vol.
43:
Wiley;
New York:
1984.
p.637
5b
Smalley RK.
Azepines, In Comprehensive Heterocyclic Chemistry
Vol. N7:
Katritzky AR.
Rees CW.
Pergamon Press;
Oxford:
1984.
p.491
5c
Yet L.
Chem.
Rev.
2000,
100:
2963
6
Maruoka K.
Miyazaki T.
Ando M.
Matsumura Y.
Sakane S.
Hattori K.
Yamamoto H.
J.
Am. Chem. Soc.
1983,
105:
283
7
Grunwald GL.
Dahanukar VH.
Ching P.
Kriscione
KR.
J. Med.
Chem.
1996,
39:
3539
8a
Learmonth DA.
Proctor GR.
Scopes DIC.
J.
Chem. Soc., Perkin Trans. 1
1997,
2569
8b
Ikemoto T.
Ito T.
Nishiguchi A.
Miura S.
Tomimatsu K.
Org. Process
Res. Dev.
2005,
9:
168
9
Fujita K.
Yamamoto K.
Yamaguchi R.
Org.
Lett.
2002,
4:
2691
10a
Gibson SE.
Middleton RJ.
J. Chem. Soc., Chem. Commun.
1995,
1743
10b
Cropper EL.
White AJP.
Ford A.
Hii KK.
J.
Org. Chem.
2006,
71:
1732
11a
Omar-Amrani R.
Thomas A.
Brenner E.
Schneider R.
Fort Y.
Org. Lett.
2003,
5:
2311
11b
Margolis BJ.
Swidorski JJ.
Rogers BN.
J. Org. Chem.
2003,
68:
644
11c
Qadir M.
Priestley RE.
Rising TWDF.
Gelbrich T.
Coles SJ.
Hursthouse MB.
Sheldrake PW.
Whittall N.
Hii KK.
Tetrahedron
Lett.
2003,
44:
3675
12a
Kaim LE.
Grimaud L.
Oble J.
J. Org. Chem.
2007,
72:
5835
12b
Qadir M.
Cobb J.
Sheldrake PW.
Whittall N.
White AJP.
Hii (Mimi) KK.
Horton
PN.
Hursthouse MB.
J. Org. Chem.
2005,
70:
1545
12c
Dolman SJ.
Schrock RR.
Hoveyada AH.
Org. Lett.
2003,
5:
4899
12d
Kotha S.
Sha VR.
Eur. J. Org. Chem.
2008,
1054
13 For a recent review on medium-ring
heterocycle formation by RCM, see: Chattopadhyay SK.
Karmakar S.
Biswas T.
Majumdar KC.
Rahaman H.
Roy B.
Tetrahedron
2007,
63:
3919
14a
Chattopadhyay SK.
Maity S.
Panja S.
Tetrahedron Lett.
2002,
43:
7781
14b
Chattopadhyay SK.
Biswas T.
Neogi K.
Chem. Lett.
2006,
35:
376
14c
Chattopadhyay
SK.
Dey R.
Biswas S.
Synthesis
2005,
403
14d
Chattopadhyay SK.
Roy SP.
Ghosh D.
Biswas G.
Tetrahedron
Lett.
2006,
47:
6895
14e
Chattopadhyay SK.
Biswas T.
Maity S.
Synlett
2006,
2211
For some recent reviews on Claisen
rearrangement, see:
15a
Nubbemeyer U.
Synthesis
2003,
961
15b
Castro
AMM.
Chem. Rev.
2004,
104:
2939
16
Nubbemeyer U.
Top.
Curr. Chem.
2005,
244:
149
17
Krowichi K.
Paillous N.
Riviere M.
Lattes A.
J. Heterocycl. Chem.
1976,
13:
555
18
Rathore R.
Saxena N.
Chandrasekaran S.
Synth. Commun.
1986,
16:
1493
19
Representative
Procedure for the Sequence of Reactions in Scheme 1: N
,
N
-Diallyl-4-methylaniline (6b)
Allyl bromide (2.7 mL, 31.4
mmol) was added dropwise to a solution of 5b (1.7
g, 15.7 mmol) and Et3N (4.4 mL, 31.4 mmol) in dry MeCN
(25 mL), and the mixture was heated to reflux for 18 h. It was then
allowed to come to r.t., concentrated under reduced pressure, and
the residual mass was extracted with EtOAc (50 mL). The extract
was washed successively with H2O (25 mL), brine (25 mL),
and then dried (Na2SO4). It was filtered,
concentrated under reduced pressure, and the residue was purified
by chromatography over SiO2 using PE as eluent to afford 6b as a pale yellow viscous liquid (2.09
g, 71%). IR(neat): 1642, 1619, 1521, 1235, 1182 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.01
(d, 2 H, J = 8.2
Hz), 6.62 (d, 2 H, J = 7.8
Hz), 5.89-5.80 (m,
2 H), 5.20-5.12 (m,
4 H), 3.88 (d, 4 H, J = 4.8
Hz), 2.23 (s, 3 H). Anal. Calcd for C13H17N:
C, 83.37; H, 9.15; N, 7.48. Found: C, 83.34; H, 9.28; N, 7.39.
N
,2-Diallyl-4-methylaniline (7b)
Boron trifluoride etherate
(1.8 mL, 15 mmol) was slowly added to a solution of 6b (1.9
g, 10 mmol) in PhCl (15 mL) under nitrogen, and the mixture was
heated to reflux for 5 h. It was then allowed to come to r.t., quenched
with sat. aq NaHCO3 solution (20 mL), and the aqueous
layer was extracted with EtOAc (2 × 25
mL). The combined organic mixture was washed successively with H2O
(25 mL), brine (25 mL), and then dried (Na2SO4).
It was filtered, concentrated under reduced pressure, and the residue
was purified by chromatography over SiO2 using PE as
eluent to give starting 6b (0.17g, 9%)
followed by the product 7b (1.31g, 69%)
as a pale yellow viscous liquid. IR(neat): 3442, 3387, 1636, 1618,
1515, 1313 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 6.94
(d, 1 H, J = 8.1
Hz), 6.87 (s, 1 H), 6.55 (d, 1 H, J = 8.1
Hz), 5.98-5.92 (m, 2 H), 5.28-5.06 (m, 5 H), 3.76
(dt, 2 H, J = 5.4,
1.5 Hz), 3.28 (d, 2 H, J = 6.2
Hz), 2.24 (s, 3 H). Anal. Calcd for C13H17N:
C, 83.37; H, 9.15; N, 7.48. Found: C, 83.40; H, 9.26; N, 7.43.
N
-Allyl-
N
-(2-allyl-4-methylphenyl)-4-methylbenzene-sulfonamide (8b)
p-Toluenesulfonyl
chloride (1.71 g, 9 mmol) was added to a solution of 7b (1.1g,
5.9 mmol) and Et3N (1.7 mL, 12 mmol) in dry CH2Cl2 (20
mL), and the reaction mixture was stirred at r.t. for 12 h. It was
then diluted with CH2Cl2 (20 mL), and the
solution was washed successively with HCl (1 N, 2 × 25 mL),
H2O (25 mL), brine (25 mL), and then dried (Na2SO4). It
was filtered, concentrated under reduced pressure, and the residue
was purified by chromatography over SiO2 using EtOAc-PE
(1:19) as eluent to give the product as a colorless viscous liquid
(1.7 g, 85%). IR (CHCl3): 1638, 1598, 1497, 1349,
1219, 1164, 1062 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.58
(d, 2 H, J = 8.2
Hz), 7.26 (d, 2 H, J = 8.1
Hz), 7.09 (s, 1 H), 6.85 (d, 1 H, J = 7.9
Hz), 6.46 (d, 1 H, J = 8.0
Hz), 5.97-5.84 (m, 1 H), 5.80-5.68 (m, 1 H), 5.14-5.08
(m, 2 H), 5.01-4.93 (m, 2 H), 4.30 (dd, 1 H, J = 14.0,
5.6 Hz), 3.85 (dd, 1 H, J = 14.0,
7.6 Hz), 3.55 (dd, 1 H, J = 15.5,
6.5 Hz), 3.45 (dd, 1 H, J = 15.4,
6.5 Hz), 2.44 (s, 3 H), 2.30 (s, 3 H). Anal. Calcd for C20H23NO2S:
C, 70.35; H, 6.79; N, 4.10. Found: C, 70.48; H, 6.88; N, 4.29.
7-Methyl-1-tosyl-2,5-dihydro-1
H
-benzo[
b
]azepine (10b)
Catalyst 9 (14
mg, 5 mol%) was added to a solution of 8b (0.11g,
0.32 mmol) in dry, degassed CH2Cl2 (30 mL)
under nitrogen, and the reaction mixture was stirred at r.t. for
2 h. It was then concentrated under reduced pressure and the residue
was chromatographed over SiO2 using EtOAc-PE (1:13)
as eluent to give the product 10b (83 mg,
83%) as a colorless solid; mp 114 ˚C. IR (CHCl3):
1598, 1496, 1343, 1157 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.64
(d, 2 H, J = 8.2
Hz), 7.24 (d, 2 H, J = 8.5
Hz), 7.16 (d, 1 H, J = 8.0 Hz),
7.00 (d, 1 H, J = 7.9
Hz), 6.87 (s, 1 H), 5.66-5.60 (m,
1 H), 5.45-5.41
(m, 1 H), 4.35 (br s, 2 H), 2.92 (br s, 2 H), 2.42 (s, 3 H), 2.29
(s, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 143.1,
140.8, 138.7, 138.3, 136.0, 129.9, 129.7, 129.4, 128.0, 127.0, 125.8,
125.3, 49.1, 32.2, 21.5, 21.0. Anal. Calcd for C18H19NO2S:
C, 68.98; H, 6.11; N, 4.47. Found: C, 69.13; H, 6.18; N, 4.58. MS
(TOFMS ES+): m/z = 336 [M+ + Na].
Selected Data
Compound 10c: Mp 128 ˚C. IR (KBr): 1602,
1500, 1341, 1159 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.63
(d, 2 H, J = 8.2
Hz), 7.24 (d, 2 H, J = 8.1
Hz), 7.19 (d, 1 H, J = 8.8 Hz),
6.71 (dd, 1 H, J = 8.6,
2.9 Hz), 6.58 (d, 1 H, J = 2.7
Hz), 5.65-5.59 (m, 1 H), 5.45-5.41 (m, 1 H), 4.35
(br s, 2 H), 3.78 (s, 3 H), 2.88 (br s, 2 H), 2.42 (s, 3 H). ¹³C
NMR (75 MHz, CDCl3): δ = 159.2,
143.1, 142.5, 138.6, 131.2, 131.1, 129.4, 127.0, 125.9, 124.9, 114.6,
112.1, 55.3, 49.2, 32.4, 21.5. Anal. Calcd for C18H19NO3S:
C, 65.63; H, 5.81; N, 4.25. Found: C, 65.80; H, 5.98; N, 4.43. MS
(TOFMS ES+):
m/z = 352 [M+ + Na].
Compound 12b: Mp 135 ˚C. IR (KBr): 1715,
1596, 1491, 1352, 1168 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.91
(d, 2 H, J = 8.3
Hz), 7.41 (d, 1 H, J = 8.0
Hz), 7.32 (d, 2 H, J = 8.1
Hz), 7.18 (d, 1 H, J = 8.1
Hz), 7.03 (s, 1 H), 2.48-2.44 (m, 2 H), 2.38 (s, 3 H),
2.23 (s, 3 H), 2.10-2.04 (m,
3 H), 1.79-1.77
(m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 172.7,
144.8, 139.4, 136.6, 135.8, 133.4, 129.7, 129.3, 129.1, 128.8, 127.9,
34.4, 29.1, 27.3, 21.7, 21.1. Anal. Calcd for C18H19NO3S:
C, 65.63; H, 5.81; N, 4.25. Found: C, 65.78; H, 6.04; N, 4.48. MS
(TOFMS ES+): m/z = 352 [M+ + Na].
Compound 16: IR (CHCl3): 1735, 1597,
1342, 1160, 1109 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.91
(d, 1 H, J = 10.0 Hz),
7.68 (d, 2 H, J = 8.2
Hz), 7.35 (d, 1 H, J = 8.8
Hz), 7.30 (d, 2 H, J = 8.1
Hz), 7.17 (d, 1 H, J = 8.7
Hz), 6.43 (d, 1 H, J = 9.9
Hz), 5.79-5.71 (m, 1 H), 5.54-5.50 (m, 1 H), 4.37
(br s, 2 H), 3.34 (d, 2 H, J = 4.0
Hz), 2.45 (s, 3 H). ¹³C NMR (75 MHz,
CDCl3): δ = 159.7,
153.7, 143.6, 140.3, 139.6, 138.0, 135.2, 132.6, 129.7, 126.9, 126.7,
123.5, 116.5, 116.3, 115.5, 48.7, 24.6, 21.4. Anal. Calcd for C20H17NO4S:
C, 65.38; H, 4.66; N, 3.81. Found: C, 65.66; H, 4.83; N, 3.96. MS
(TOFMS ES+): m/z (%) = 390(100) [M + Na],
368(41) [M + H].
Compound 20: mp 224 ˚C IR (KBr): 1654,
1578, 1455, 1333, 1158, 1123 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.90
(d, 1 H, J = 10.0
Hz), 7.68 (d, 2 H, J = 8.2
Hz), 7.47 (d, 1 H, J = 9.0
Hz), 7.30-7.22 (m, 3 H), 6.72 (d, 1 H, J = 10.0
Hz), 5.80-5.73 (m, 1 H), 5.52-5.48 (m, 1 H), 4.13 (br
s, 2 H), 3.71 (s, 3 H), 3.35 (d, 2 H, J = 4.3
Hz), 2.44 (s,
3 H). ¹³C NMR
(75 MHz, CDCl3): δ = 161.6,
143.5, 140.2, 140.1, 138.4, 134.5, 133.4, 131.6, 129.7, 126.9, 124.1, 121.7,
118.1, 113.2, 49.0, 29.8, 24.6, 21.5. Anal. Calcd for C21H20N2O3S:
C, 66.29; H, 5.30; N, 7.36. Found: C, 66.36; H, 5.41; N, 7.24. MS
(TOFMS ES+): m/z = 403 [M + Na].
20a
O’Kennedy R.
Thornes RD.
Coumarins: Biology, Applications
and Mode of Action
Wiley and Sons;
Chichester:
1997.
20b
Fylaktakidou KC.
Hadjipavlou-Litina DJ.
Litinas KE.
Nicolaides DN.
Curr. Pharm. Des.
2004,
10:
3813
21a
Thorsett ED.
Latimer LH.
Curr. Opin. Chem. Biol.
2000,
4:
377
21b
Chevalier J.
Atifi S.
Eyraud A.
Mahamoud A.
Barbe J.
Pages J.-M.
J.
Med. Chem.
2001,
44:
4023
22a
Knölker H.-J.
Reddy KR.
Chem. Rev.
2002,
102:
4303
22b
Gallagher PT. In
Science of Synthesis
(Houben-Weyl)
Vol. 10:
Thomas EJ.
Thieme;
Stuttgart:
2001.
p.693
22c
Knölker H.-J.
Top. Curr. Chem.
2005,
244:
115