Synthesis of α,β-Unsaturated Ketones by Rhodium-Catalyzed Carbonylative Arylation of Internal Alkynes with Arylboronic Acids

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

References and Notes

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• Other acylation reagents used:
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• 5c Kondo T. Tsuji Y. Watanabe Y. Tetrahedron Lett.  1987,  28:  6229 
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6

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 ˚C^7c). ^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 1640^7c) 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 ˚C^7c). ^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 1661^7c) 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 ˚C^7c). ^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.: 1640^7c) 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 ˚C^7c). ^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.: 1655^7c) 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.

8

See Figure  [¹] .

Figure 1