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DOI: 10.1055/s-2008-1078047
Synthesis of α,β-Unsaturated Ketones by Rhodium-Catalyzed Carbonylative Arylation of Internal Alkynes with Arylboronic Acids
Publikationsverlauf
Publikationsdatum:
10. September 2008 (online)
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Abstract
The Rh-catalyzed reaction of arylboronic acids with internal alkynes under a CO atmosphere in the presence of an acid additive afforded α,β-unsaturated ketones as the major products. Hydroacylation of internal alkynes, except in the case of diaryl acetylenes, proceeded in syn fashion, yielding the E-configured isomer. A mixture of E- and Z-isomers was obtained with diphenyl acetylene. Reactions were also highly regioselective for various nonsymmetric alkynes.
Key words
carbonylation - boron - rhodium - enones - alkynes
- 1
Aksin Ö.Dege N.Artok L.Türkmen H.Çetinkaya B. Chem. Commun. 2006, 3187 -
2a
Sauthier M.Castanet Y.Mortreux A. Chem. Commun. 2004, 1520 -
2b
Chochois H.Sauthier M.Maerten E.Castanet Y.Mortreux A. Tetrahedron 2006, 62: 11740 -
2c
Menard F.Weise CF.Lautens M. Org. Lett. 2007, 9: 5335 -
2d
Dheur J.Sauthier M.Castanet Y.Mortreux A. Adv. Synth. Catal. 2007, 349: 2499 -
3a
Willis MC.Randell-Sly HE.Woodward RL.Steven J.McNally SJ.Currie GS. J. Org. Chem. 2006, 71: 5291 -
3b
Tanaka K.Shibata Y.Suda T.Hagiwara Y.Hirano M. Org. Lett. 2007, 9: 1215 -
3c
Imai M.Tanaka M.Tanaka K.Yamamoto Y.Imai-Ogata N.Shimowatari M.Nagumo S.Kawahara N.Suemune H. J. Org. Chem. 2004, 69: 1144 -
3d
Jun C.-H.Lee H.Hong J.-B.Kwon BI. Angew. Chem. Int. Ed. 2002, 41: 2146 -
3e
Moxham GL.Randell-Sly HE.Brayshaw SK.Woodward RL.Weller AS.Willis MC. Angew. Chem. Int. Ed. 2006, 45: 7618 -
3f
Tanaka K.Tanaka M.Suemune H. Tetrahedron Lett. 2005, 46: 6053 -
3g
Willis MC.Sapmaz S. Chem. Commun. 2001, 2558 -
3h
Jun C.-H.Jo E.-A.Park J.-W. Eur. J. Org. Chem. 2007, 1869 -
3i
Stemmlera RT.Bolma C. Adv. Synth. Catal. 2007, 349: 1185 -
3j
Imai M.Tanaka M.Nagumo S.Kawahara N.Suemune H. J. Org. Chem. 2007, 72: 2543 -
3k
Rueda XY.Castillón S. J. Organomet. Chem. 2007, 692: 1628 -
3l
Lochow CF.Miller RG. J. Am. Chem. Soc. 1976, 98: 1281 -
3m
Kokubo K.Matsumasa K.Miura M.Nomura M. J. Org. Chem. 1997, 62: 4564 -
3n
Miura M.Nomura M. J. Synth. Org. Chem. Jpn. 2000, 58: 578 -
3o
Kokubo K.Matsumasa K.Nishinaka Y.Miura M.Nomura M. Bull. Chem. Soc. Jpn. 1999, 72: 303 -
3p
Marder TD.Roe DC.Milstein D. Organometallics 1988, 7: 1451 - Other acylation reagents used:
-
4a Hydrogenative aroylation
with an anhydride:
Hong Y.-T.Barchuk A.Krische MJ. Angew. Chem. Int. Ed. 2006, 45: 6885 -
4b Hydroacylation of ethylene
with acyl halides:
Schwartz J.Cannon JB. J. Am. Chem. Soc. 1974, 96: 4721 - Other metal catalysis - Ir catalyzed:
-
5a
Nishinaka Y.Satoh T.Miura M.Morisaka H.Nomura M.Matsui H.Yamaguchi C. Bull. Chem. Soc. Jpn. 2001, 74: 1727 - Ni catalyzed:
-
5b
Tsuda T.Kiyoi T.Saegusa T. J. Org. Chem. 1990, 55: 2555 - Ru catalyzed:
-
5c
Kondo T.Tsuji Y.Watanabe Y. Tetrahedron Lett. 1987, 28: 6229 -
5d
Kondo T.Akazome M.Tsuji Y.Watanabe Y. J. Org. Chem. 1990, 55: 1286 - Co catalyzed:
-
5e
Lenges CP.Brookhart M. J. Am. Chem. Soc. 1997, 119: 3165 -
7a
Duke PJ.Boykin DW. J. Org. Chem. 1972, 37: 1436 -
7b
Black WB.Lutz RE. J. Am. Chem. Soc. 1953, 75: 5990 -
7c
Mittal S.Durani S.Kapil RS. J. Med. Chem. 1985, 28: 492 - 9
Hayashi T.Inoue K.Taniguchi N.Ogasawara M. J. Am. Chem. Soc. 2001, 123: 9918 - 10 Rhodium(I)-catalyzed reaction of
2-bromo-substituted phenylboronic acids with alkynes under CO atmosphere leading
to indenone structures was reported. See:
Harada Y.Nakanishi J.Fujihara H.Tobisu M.Fukumoto Y.Chatani N. J. Am. Chem. Soc. 2007, 29: 5766
References and Notes
Typical Conditions
for the Synthesis of 3
A mixture of alkyne (1.5 mmol),
arylboronic acid (3 mmol), [Rh(C2H4)2Cl]2 (3
mol% Rh), TFA (2 mmol), H2O (0.1 mL) in MeOH
(9.9 mL, predried) was added into a 50 mL stainless steel autoclave
with a glass insert tube. Then, the sealed autoclave was evacuated,
and purged with 10 atm CO twice, successively. Subsequently, the
reactor was pressurized to 5 atm with CO and the mixture was stirred magnetically
in a preheated oil bath. After cooling, the reaction mixture was
recovered with EtOAc. The products were analyzed by GC and GC-MS
and isolated by column chromatography. Purity of the products were >96% as determined
by ¹H NMR analyses.
(
E
,
Z
)-1,2,3-Triphenylprop-2-en-1-one
(3aa)
Hexane-EtOAc.
Isomer (E)-3aa: white
solid; mp 98.7-99.2 ˚C (lit.: 99-101 ˚C,7a 103-103.5 ˚C,7b 96.5-97.5 ˚C7c). ¹H
NMR (400 MHz, CDCl3): δ = 7.07-7.56
(m, 14 H), 7.86 (d, J = 7.2
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 126.4,
128.0, 128.2, 128.4, 128.7, 128.8, 128.9, 129.7, 130.1, 133.6, 135.4,
136.3, 138.0, 140.8, 199.4. MS (EI): m/z (%) = 284(93) [M+], 256(5),
206(9), 178(31), 105(100), 77(20). FTIR (ATR): ν = 1649
(CO) (lit.: 1661,7a 16407c) cm-¹.
HRMS: m/z calcd [M+]:
284.1196; found: 284.1189.
Isomer (Z)-3aa: yellow solid; mp 78.0-84.1 ˚C
(lit.: 85-87 ˚C,7a 88-89 ˚C,7b 82.5-83.5 ˚C7c). ¹H
NMR (400 MHz, CDCl3): δ = 7.10-7.50
(m, 14 H), 7.99 (d, J = 6.8
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 127.9,
128.2, 128.3, 128.8, 128.9, 129.7, 129.8, 130.3, 132.2, 134.8, 136.5,
138.2, 140.1, 140.8, 197.6. MS (EI): m/z (%) = 284
(87) [M+], 256 (7), 206 (20),
178 (47), 105 (100), 77 (83). FTIR (ATR):
ν = 1660
(CO) (lit.: 1671,7a 16617c) cm-¹.
HRMS: m/z calcd [M+]:
284.1196; found: 284.1197.
(
E
,
Z
)-1-(4-Methoxyphenyl)-2,3-diphenylprop-2-en-1-one
(3ab)
Hexane-benzene; hexane-CH2Cl2.
Isomer
(E)-3ab: white
solid; mp 81.1-84.3 (lit.: 84-84.3 ˚C7c). ¹H
NMR (400 MHz, CDCl3): δ = 3.85 (s,
3 H), 6.92 (d, J = 8.8
Hz, 2 H), 7.09-7.36 (m, 11 H), 7.90 (d, J = 8.8 Hz,
2 H). ¹³C NMR (100 MHz, CDCl3: δ = 55.5,
113.6, 127.9, 128.2, 128.6, 128.8, 129.6, 130.2, 130.4, 132.3, 135.0,
136.8, 137.8, 141.0, 163.1, 196.3. MS (EI): m/z (%) = 314
(47) [M+], 197 (14), 178 (14),
135 (100), 107 (9), 92 (10), 77 (19). FTIR (ATR): ν = 1633
(CO) (lit.: 16407c) cm-¹.
HRMS: m/z calcd [M+]:
314.1301; found: 314.1294.
Isomer (Z)-3ab: pale yellow solid; mp 88.7-89.2 ˚C
(lit.: 78-79 ˚C7c). ¹H
NMR (400 MHz, CDCl3): δ = 3.79 (s,
3 H), 6.83 (d, J = 8.8
Hz, 2 H), 7.12-7.48 (m, 11 H), 7.97 (d, J = 8.8
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 55.4, 114.0,
126.3, 127.9, 128.1, 128.4, 128.8, 129.4, 129.5, 132.1, 135.5, 138.2,
140.9, 164.0, 197.9. MS (EI): m/z (%) = 314
(58) [M+], 197 (18), 178 (19),
135 (100), 107 (12), 92 (13), 77 (23). FTIR (ATR): ν = 1657
(CO) (lit.: 16557c) cm-¹. HRMS: m/z calcd [M+]:
314.1301; found: 314.1301.
(
E
,
Z
)-2,3-Diphenyl-1-
p
-tolylprop-2-en-1-one
(3ac)
Hexane-benzene.
Isomer (E)-3ac: white
solid; mp 90.8-91.8 ˚C. ¹H
NMR (400 MHz, CDCl3): δ = 2.41 (s,
3 H), 7.08-7.39 (m, 13 H), 7.79 (d, J = 8.0
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 21.6,
126.3, 127.9, 128.2, 128.8, 128.8, 129.0, 129.6, 130.1, 130.3, 134.9,
135.3, 136.7, 139.1, 140.9, 143.0, 197.5. MS (EI): m/z (%) = 298
(75) [M+], 283 (15), 205 (6),
181 (23), 178 (25), 119 (100), 91 (48). FTIR (ATR): ν = 1643
(CO) cm-¹. HRMS: m/z calcd [M+]:
298.1352; 298.1346.
Isomer (Z)-3ac: pale yellow solid; mp 59.8-61.8 ˚C. ¹H NMR
(400 MHz, CDCl3): δ = 2.32 (s, 3 H),
7.10-7.47 (m, 13 H), 7.89 (d, J = 8.4
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 21.7,
126.3, 128.0, 128.1, 128.5, 128.8, 129.5, 129.7, 129.9, 134.0, 135.5,
138.1, 141.0, 144.7, 199.0. MS (EI): m/z (%) = 298
(100) [M+], 283 (12), 182
(20), 119 (55), 91 (11). FTIR (ATR): ν = 1654
(CO) cm-¹. HRMS: m/z calcd [M+]:
298.1352; found: 298.1341.
(
E
,
Z
)-2,3-Diphenyl-1-
m
-tolylprop-2-en-1-one
(3ad)
Hexane-benzene.
Isomer (E)-3ad: further
column chromatographed with hexane-EtOAc; white solid;
mp 66.3-68.7 ˚C. ¹H NMR (400
MHz, CDCl3): δ = 2.40 (s, 3 H), 7.06-7.38
(m, 13 H), 7.64 (d, J = 7.6
Hz, 1 H), 7.68 (s, 1 H). ¹³C NMR (100
MHz, CDCl3): δ = 21.4, 127.06, 127.9,
128.08, 128.2, 128.8, 128.9, 129.7, 130.2, 130.3, 132.9 134.9, 136.6,
138.2, 138.2, 140.0, 140.9, 197.9. MS (EI): m/z (%) = 298
(75) [M+], 283 (10), 181 (23),
178 (25), 119 (100), 91 (48). FTIR (ATR):
ν = 1635
(CO) cm-¹. HRMS: m/z calcd [M+]:
298.1352; 298.1351.
Isomer (Z)-3ad: yellow oil. ¹H
NMR (400 MHz, CDCl3):
δ = 2.32
(s, 3 H), 7.10-7.48 (m, 13 H), 7.65 (d, J = 8.0
Hz, 1 H), 7.83 (s, 1 H). ¹³C NMR (100
MHz, CDCl3): δ = 21.3, 126.3, 127.3,
128.0, 128.1, 128.4, 128.6, 128.8, 129.9, 129.9, 134.5, 135.5, 136.3,
138.1, 138.5, 141.0, 199.5. MS (EI): m/z (%) = 298
(92) [M+], 283 (11), 181 (25),
178 (30), 119 (100), 91 (33). FTIR (ATR): ν = 1660
(CO) cm-¹. HRMS: m/z calcd [M+]:
298.1352; found: 298.1359.
(
E
)-1-Phenyl-2-propylhex-2-en-1-one
(3ba)
Hexane-EtOAc; pale yellow oil. ¹H
NMR (400 MHz, CDCl3): δ = 0.94 (t, J = 7.4 Hz,
3 H), 0.96 (t, J = 7.4
Hz, 3 H), 1.41-1.52 (m, 4 H), 2.27 (q, J = 7.2
Hz, 2 H), 2.47 (t, J = 7.2
Hz, 2 H), 6.20 (t, J = 7.6
Hz, 1 H), 7.38-7.43 (m, 2 H), 7.47-7.52 (m, 1
H), 7.63-7.67 (m, 2 H). ¹³C
NMR (100 MHz, CDCl3): δ = 14.0, 14.1,
22.2, 28.7, 30.9, 128.0, 129.3, 131.4, 139.1, 141.2, 145.7, 199.0.
MS (EI): m/z (%) = 216 (100) [M+],
173 (7), 145 (9), 105 (27), 77 (5). FTIR (ATR): ν = 1647
(CO) cm-¹. HRMS: m/z calcd [M+]:
216.1509; found: 216.1507.
(
E
)-1-(4-Methoxyphenyl)-2-propylhex-2-en-1-one
(3bb)
Hexane-EtOAc; pale yellow oil. ¹H
NMR (400 MHz, CDCl3): δ = 0.91-0.98
(m, 6 H), 1.41-1.51 (m, 4 H), 2.26 (q, J = 7.2
Hz, 2 H), 2.46 (t, J = 7.6
Hz, 2 H), 3.86 (s, 3 H), 6.11 (t, J = 7.6
Hz, 1 H), 6.91 (d, J = 8.8
Hz, 2 H), 7.71 (d, J = 8.8 Hz,
2 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.0,
14.1, 22.2, 22.3, 29.2, 30.7, 55.4, 113.3, 131.4, 131.8, 141.1,
143.1, 162.6, 198.0. MS (EI): m/z (%) = 246
(14) [M+], 203 (22), 175 (18),
135 (100), 107 (10), 92 (14), 77 (21). FTIR (ATR): ν = 1641
(CO) cm-¹. HRMS: m/z calcd [M+]:
246.1614; found: 246.1603.
(
E
)-2-Propyl-1-
p
-tolylhex-2-en-1-one
(3bc)
Hexane-EtOAc; pale yellow oil. ¹H
NMR (400 MHz, CDCl3): δ = 0.94 (t, J = 7.6 Hz,
6 H), 1.46 (sext, J = 7.6
Hz, 4 H), 2.26 (q, J = 7.6
Hz, 2 H), 2.40 (s, 3 H), 2.46 (t, J = 8.0 Hz,
2 H), 6.16 (t, J = 7.4
Hz, 1 H), 7.21 (d, J = 8.0
Hz, 2 H), 7.59 (d, J = 8.0
Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.0,
14.1, 21.5, 22.2, 22.3, 28.9, 30.8, 128.7, 129.6, 136.2, 141.2,
142.1, 144.6, 198.8. MS (EI): m/z (%) = 230
(36) [M+], 215 (92), 201 (20),
187 (38), 173 (29), 159 (39), 145 (22), 119 (100), 91 (71). FTIR
(ATR): ν = 1645 (CO)
cm-¹.
HRMS: m/z calcd [M+]:
230.1665; found: 230.1662.
(
E
)-Methyl 4-(4-Methoxyphenyl)-3-butyl-4-oxobut-2-enoate
(3cb)
Hexane-EtOAc; pale yellow oil. ¹H
NMR (400 MHz, CDCl3): δ = 0.89 (t, J = 7.2 Hz,
3 H), 1.40-1.50 (m, 4 H), 2.98 (t, J = 7.6
Hz, 2 H), 3.76 (s, 3 H), 3.88 (s, 3 H), 5.99 (s, 1 H), 6.95 (d, J = 9.2 Hz,
2 H), 7.84 (d, J = 9.2
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.8,
22.9, 29.2, 30.5, 51.5, 55.5, 113.8, 122.0, 128.8, 132.2, 157.9,
163.9, 166.1, 196.5. MS (EI): m/z (%) = 276
(28) [M+], 245 (20), 217 (22),
135 (100). FTIR (ATR): ν = 1654 (CO), 1722 (COOMe)
cm-¹. HRMS: m/z calcd [M+]:
276.1356; found: 276.1355.
(
E
)-Methyl 4-(4-Methoxyphenyl)-3-methyl-4-oxobut-2-enoate
(3db)
Hexane-EtOAc; pale yellow oil. ¹H
NMR (400 MHz, CDCl3): δ = 2.42 (d, J = 1.6 Hz,
3 H), 3.77 (s, 3 H), 3.88 (s, 3 H), 6.09 (q, J = 1.6
Hz, 1 H), 6.95 (d, J = 9.2
Hz, 2 H), 7.83 (d, J = 8.8
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 16.0, 51.6,
55.5, 113.9, 123.0, 128.1, 132.2, 153.1, 163.9, 166.3, 196.5. MS
(EI): m/z (%) = 234
(16) [M+], 203 (20), 135 (100),
107 (10), 92 (10), 77 (10), 62 (9). FTIR (ATR):
ν = 1651
(CO), 1720 (-COOCH3) cm-¹.
HRMS: m/z calcd [M+]:
234.0887; found: 234.0884.
(
E
)-2-Methyl-1,3-diphenylprop-2-en-1-one
(3ea)
Hexane-EtOAc; yellow oil. ¹H
NMR (400 MHz, CDCl3):
δ = 2.27
(d, J = 1.6
Hz, 3 H), 7.18 (d, J = 1.6
Hz, 1 H), 7.30-7.56 (m, 8 H), 7.71-7.77 (m, 2
H). ¹³C NMR (100 MHz, CDCl3): δ = 14.4,
128.2, 128.5, 128.6, 129.5, 129.7, 131.7, 135.8, 136.9, 138.5, 142.2,
199.5. MS (EI): m/z (%) = 222 (100) [M+],
207 (33), 115 (32), 77 (48). FTIR (ATR): ν = 1642
(CO) cm-¹. HRMS: m/z calcd [M+]:
222.1039; found: 222.1032.
(
E
)-1-(4-Methoxyphenyl)-2-methyl-3-phenylprop-2-en-1-one
(3eb)
Hexane-EtOAc; yellow oil. ¹H
NMR (400 MHz, CDCl3):
δ = 2.25
(d, J = 1.6
Hz, 3 H), 3.87 (s, 3 H), 6.95 (d, J = 9.2 Hz,
2 H), 7.10 (d, J = 1.6
Hz, 1 H), 7.30-7.43 (m, 5 H), 7.81 (d, J = 9.2
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.9, 55.5,
113.5, 128.3, 128.4, 129.6, 130.7, 132.0, 137.0, 140.0, 162.8, 198.3.
MS (EI): m/z (%) = 252
(38) [M+], 135 (100), 145
(15), 115 (26). FTIR (ATR): ν = 1638 (CO) cm-¹. HRMS: m/z calcd [M+]:
252.1145; found: 252.1138.
Compounds
3fb and 3fb′Hexane-EtOAc.
(
E
)-2-Benzylidene-1-(4-methoxyphenyl)pentan-1-one (3fb)
Pale
yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 0.98
(t, J = 7.2
Hz, 3 H), 1.57 (sext, J = 7.6
Hz, 2 H), 2.71 (t, J = 7.8 Hz,
2 H), 3.89 (s, 3 H), 6.95 (d, J = 9.2
Hz, 2 H), 6.98 (s, 1 H), 7.30-7.42 (m, 5 H), 7.85 (d, J = 9.2 Hz,
2 H). ¹³C NMR (100 MHz, CDCl3): δ = 14.3,
22.0, 30.2, 55.5, 113.5, 128.1, 128.4, 129.1, 130.9, 132.1, 135.9,
138.5, 142.4, 163.0, 198.2. MS: (EI): m/z (%) = 280
(56) [M+], 251 (15), 173 (16),
135 (100). FTIR (ATR): ν = 1636 (CO) cm-¹.
HRMS: m/z calcd [M+]:
280.1458; found: 280.1460.
(
E
)-1-(4-Methoxyphenyl)-2-phenylhex-2-en-1-one
(3fb′)
Pale yellow oil. ¹H
NMR (400 MHz, CDCl3): δ = 0.92 (t, J = 7.2 Hz,
3 H), 1.49 (sext, J = 7.6
Hz, 2 H), 2.24 (q, J = 7.2 Hz,
2 H), 3.85 (s, 3 H), 6.35 (t, J = 7.4
Hz, 1 H), 6.89 (d, J = 9.2
Hz, 2 H), 7.23-7.38 (m, 5 H), 7.81 (d, J = 9.2
Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.9,
22.5, 31.4, 55.4, 113.4, 127.3, 128.2, 129.4, 130.8, 132.2, 136.5,
141.6, 142.2, 162.9, 196.1. MS (EI): m/z (%) = 280
(12) [M+], 251 (39), 135 (100).
FTIR (ATR): ν = 1638 (CO) cm-¹.
HRMS: m/z calcd [M+]:
280.1458; found: 280.1460.
See Figure [¹] .
![](https://www.thieme-connect.de/media/synlett/200817/d207_f1.gif)
Figure 1