Rhodium(I)-Catalyzed Cycloisomerization of 1,6-Enynes

This manuscript is dedicated to Peter Vollhardt, who launched SYNLETT 25 years ago and since that time has continuously served in a number of important editorial capacities.

Abstract

A new and unexpected rhodium(I)-catalyzed cycloisomerization of 1,6-enynes is reported. Several different alkyne substitution patterns were evaluated under the reaction conditions, including a deuterated derivative that provides some insight into the reaction mechanism.

Key words

rhodium - homogeneous catalysis - ring closure - isomerization - enones

• References and Notes

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• 9 Experimental Procedures for the Generation of Imines and Rhodium-Catalyzed Cycloisomerization(Z)-2-(2-Methylcyclohex-2-en-1-ylidene)acetaldehyde (10a)In an inert atmosphere box, to the solution of 7a (86 mg, 0.63 mmol) in toluene (3 mL) was added benzylamine (68 mg, 0.63 mmol) and 3 Å MS (800 mg). The flask was removed from the box, and the mixture was stirred at r.t. for 3 h. The 3 Å MS were removed via filtration over Celite, which was washed with toluene (8 mL). The filtrate was degassed and brought into an inert atmosphere box. To the solution was added a solution of [RhCl(coe)₂]₂ (23 mg, 0.031 mmol) and Me₂NPhPEt₂ (13 mg, 0.62 mmol) in toluene (2 mL), and the mixture was stirred at 75 °C for 1 h. After removal of the solvent, the residual oil was purified by column chromatography on grade III Al₂O₃ (hexanes–EtOAc, 100:0 to 99:1,) to afford 10a (Z/E = 6.7:1) as colorless oil (41 mg, 0.30 mmol, 48% yield). R_f = 0.70 (hexanes–EtOAc. 4:1). ¹H NMR (400 MHz, CDCl₃): δ = 10.23 (d, J = 8.4 Hz, 1 H), 6.11 (ddd, J = 5.4, 2.7, 1.3 Hz, 1 H), 5.81 (d, J = 8.4 Hz, 1 H), 2.44 (ddd, J = 6.5, 4.3, 1.2 Hz, 2 H), 2.30–2.20 (m, 2 H), 2.17 (dd, J = 3.3, 1.8 Hz, 3 H), 1.84–1.74 (m, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 192.28, 156.42, 138.87, 131.95, 127.42, 35.59, 26.55, 26.04, 22.34. IR (thin film): 2927, 2867, 2834, 1653, 1615, 1580, 1448, 1406, 1223, 1178, 1149, 1130, 1101, 1025, 948 cm^–1. MS (EI): m/z [M]⁺ calcd for C₉H₁₂O⁺: 136.09; found: 136.10.(Z)-2-[2-(Methyl-d ₃)cyclohex-2-en-1-ylidene]acetaldehyde (10b)Compound 10b was synthesized according to the procedure used for compound 10a. From 80 mg (0.57 mmol) of 7b was obtained 39 mg (0.28 mmol, 49% yield) of 10b (Z/E = 6.7:1) as colorless oil after purification by column chromatography on grade III Al₂O₃ eluting with hexanes–EtOAc (100:0 to 99:1). R_f = 0.70 (hexanes–EtOAc. 4:1). ¹H NMR (400 MHz, CDCl₃): δ = 10.21 (d, J = 8.5 Hz, 1 H), 6.11 (td, J = 4.2, 1.3 Hz, 1 H), 5.81 (d, J = 8.5 Hz, 1 H), 2.48–2.40 (m, 2 H), 2.29–2.21 (m, 2 H), 1.83–1.74 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 192.28, 156.44, 138.87, 131.89, 127.46, 35.60, 26.57, 22.38. IR (thin film): 3009, 2926, 1651, 1611, 1580, 1406, 1230, 1156, 1137, 1096, 1051, 974 cm^–1. MS (EI): m/z [M]⁺ calcd for C₉H₉D₃O⁺: 139.11; found: 139.15.(Z)-2-(2-Ethylcyclohex-2-en-1-ylidene)acetaldehyde (10c)Compound 10c was synthesized according to the procedure used for compound 10a. From 40 mg (0.27 mmol) of 7c was obtained 18 mg (0.12 mmol, 45% yield) of 10c (Z/E = 20:1) as colorless oil after purification by column chromatography on grade III Al₂O₃ eluting with hexanes–EtOAc (100:0 to 99:1). R_f = 0.70 (hexanes–EtOAc. 4:1). ¹H NMR (400 MHz, CDCl₃): δ = 10.11 (d, J = 8.5 Hz, 1 H), 6.08 (ddd, J = 5.4, 2.8, 1.3 Hz, 1 H), 5.76 (d, J = 8.5 Hz, 1 H), 2.53–2.44 (m, 2 H), 2.44–2.37 (m, 2 H), 2.30–2.22 (m, 2 H), 1.84–1.75 (m, 2 H), 1.11 (t, J = 7.4 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 192.40, 156.54, 138.12, 135.90, 126.41, 36.28, 30.99, 26.52, 22.88, 13.16. IR (thin film): 2966, 2928, 2876, 1660, 1617, 1583, 1453, 1409, 1222, 1174, 1150, 1127, 1107, 1081cm^–1. MS (EI): m/z [M]⁺ calcd for C₁₀H₁₄O⁺: 150.10; found: 150.10.(Z)-2-(2-Benzylcyclohex-2-en-1-ylidene)acetaldehyde (10d)Compound 10d was synthesized according to the procedure used for compound 10a. From 63 mg (0.30 mmol) of 7d was obtained 32 mg (0.15 mmol, 51% yield) of 10d (Z/E = 15.5:1) as colorless oil after purification by column chromatography on grade III Al₂O₃ eluting with hexanes–EtOAc (100:0 to 99:1). R_f = 0.70 (hexanes–EtOAc. 4:1). ¹H NMR (500 MHz, CDCl₃): δ = 10.04 (d, J = 8.4 Hz, 1 H), 7.29 (t, J = 7.5 Hz, 2 H), 7.21 (t, J = 7.4 Hz, 1 H), 7.13 (d, J = 7.3 Hz, 2 H), 6.01 (td, J = 4.0, 1.0 Hz, 1 H), 5.73 (d, J = 8.4 Hz, 1 H), 3.83 (s, 2 H), 2.50–2.43 (m, 2 H), 2.32 (ddd, J = 6.0, 5.1, 2.0 Hz, 2 H), 1.90–1.82 (m, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 192.10, 155.61, 140.14, 138.71, 135.05, 128.58, 128.55, 126.66, 126.41, 44.05, 36.22, 26.72, 22.65. IR (thin film): 3025, 2925, 2862, 1688, 1653, 1616, 1582, 1495, 1453, 1405, 1223, 1147, 1124, 978 cm^–1. MS (EI): m/z [M]⁺ calcd for C₁₅H₁₆O⁺: 212.12; found: 212.10.(E)-2-(2-Methylcyclohex-2-en-1-ylidene)acetaldehyde (11a)To a solution of 10a (40 mg, 0.29 mmol) in THF (2 mL) was added a 1 M aqueous solution of HCl (1 mL, 1 mmol), and the mixture was stirred at r.t. for 18 h. After being neutralized with aq Na₂CO₃, the aqueous layer was extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with H₂O and brine and dried over with MgSO₄. After filtration, the solvent was removed under reduced pressure. The residual oil was purified by column chromatography on silica gel (33:1, pentane–Et₂O) to afford 11a as a colorless oil (36 mg, 0.26 mmol, 89% yield). R_f = 0.70 (hexanes–EtOAc. 4:1). ¹H NMR (400 MHz, CDCl₃): δ = 10.15 (d, J = 8.1 Hz, 1 H), 6.18 (t, J = 4.3 Hz, 1 H), 5.93 (d, J = 8.1 Hz, 1 H), 2.95–2.86 (m, 2 H), 2.26 (dtd, J = 7.8, 4.1, 1.9 Hz, 2 H), 1.85 (dd, J = 3.1, 1.7 Hz, 3 H), 1.80 (dt, J = 12.5, 6.2 Hz, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 191.49, 157.28, 138.03, 132.99, 122.62, 26.32, 25.82, 22.26, 19.65. IR (thin film): 2924, 2860, 1663, 1622, 1591, 1455, 1435, 1401, 1386, 1370, 1177, 1145, 1087, 1048 cm^–1. MS (EI): m/z [M]⁺ calcd for C₉H₁₂O⁺: 136.09; found: 136.00.
• 10 For an unusual rhodium-catalyzed intramolecular trans hydroacylation of an alkyne, see: Tanaka K, Fu GC. J. Am. Chem. Soc. 2001; 123: 11492
• 11 In previous studies on rhodium-catalyzed β-alkylation of α,β-unsaturated imines with alkenes, we observed >95:5 Z/E selectivity for rhodium-catalyzed alkylation, but this Z/E ratio degraded by as much as 5–15% during alumina-mediated imine hydrolysis. This loss in stereochemical purity was dependent upon the structure of the imine. Colby DA, Bergman RG, Ellman JA. J. Am. Chem. Soc. 2006; 128: 5604
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For leading references on rhodium-catalyzed cycloisomerizations that proceed by ene-type pathways, see:
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