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Synlett 2005(19): 2923-2926  
DOI: 10.1055/s-2005-921890
LETTER
© Georg Thieme Verlag Stuttgart · New York

Evaluating the Baylis-Hillman Reaction of Cyclic Enones Using Surfactants in Water

Achim Porzelle, Craig M. Williams*, Brett D. Schwartz, Ian R. Gentle
School of Molecular and Microbial Sciences, University of Queensland, Brisbane, 4072, Queensland, Australia
Fax: +61(7)33654299; e-Mail: c.williams3@uq.edu.au;
Further Information

Publication History

Received 24 August 2005
Publication Date:
27 October 2005 (online)

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Abstract

Conjugated cyclic enones react smoothly in water with a variety of aldehydes (Baylis-Hillman reaction) in the presence of surfactants above their critical micelle concentrations (CMC).

Key words

Baylis-Hillman reaction - cyclic enones - surfactant - green chemistry - aldehydes - aqueous media

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10

Isolated yield 32%. Yield based on starting material recovery, 43%.

11

Tilly, D. P.; Williams, C. M.; Bernhardt, P. V. Org. Lett., accepted.

15

A) Representative Procedure for Reactions with Formalin and DMAP.
To a mixture of H2O (200 µL) and 1 (40 mg, 0.208 mmol) were added SDS (6 mg, 0.02 mmol) and DMAP (25 mg, 0.2 mmol). After stirring for 15 min formalin (200 µL) was added and stirred for 16 h at r.t. The mixture was then quenched with brine (1 mL) and extracted with EtOAc (2 × 3 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Then the residue was purified by column chromatography (PE-EtOAc 2:1, R f = 0.33) to give 2 (39 mg, 85%) as a colorless liquid.
B) Representative Procedure for Reactions with Formalin and Imidazole.
To a mixture of 1 M NaHCO3 (200 µL) and 1 (40 mg, 0.208 mmol) were added CTAB (8 mg, 0.02 mmol) and imidazole (14 mg, 0.2 mmol). After stirring for 15 min formalin (200 µL) was added and stirred for 16 h at r.t. The mixture was then quenched with brine (1 mL) and extracted with EtOAc (2 × 3 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (PE-EtOAc 2:1, R f = 0.33) to give 2 (30 mg, 65%) as a colorless liquid.

16

Representative Procedure for Reactions with Formalin and DMAP.
To a mixture of H2O (3 mL) and of dimethylcyclohexenone (372 mg, 3 mmol) were added SDS (80 mg, 0.3 mmol) and DMAP (366 mg, 3 mmol). After stirring for 15 min formalin (3 mL) was added and stirred for 45 min at r.t. The mixture was then quenched with brine (5 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (PE-EtOAc 2:1, R f = 0.36) to give 2-(hydroxymethyl)-4,4-dimethylcyclo-hex-2-enone (4c, 305 mg, 67%) as a colorless liquid.

17

We were unable to obtain the reported yield (99%, ref. 8).

18

Representative Procedure for Reactions with Various Aldehydes in Water.
To a mixture of H2O (6 mL) and cyclohexenone (300 mg, 3 mmol) were added SDS (80 mg, 0.3 mmol) and DMAP (366 mg, 3 mmol). After stirring for 15 min, p-nitrobenzaldehyde (538 mg, 3.6 mmol) was added and stirring continued for 16 h at r.t. The mixture was then quenched with brine (5 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (PE-EtOAc 2:1, R f = 0.36) to give 2-[(4-nitrophenyl)(hy-droxy)methyl]cyclohex-2-enone (6d, 500 mg, 68%) as a yellow syrup.

19

Spectroscopic Data for New Compounds.
Compound 4c: 1H NMR (400 MHz, CDCl3): δ = 1.17 (s, 6 H), 1.86 (t, 2 H, J = 6.7 Hz), 2.48 (t, 2 H, J = 6.7 Hz), 3.00 (br s, 1 H), 4.21 (s, 2 H), 6.63 (s, 1 H). 13C NMR: δ = 27.7, 32.7, 34.5, 35.8, 61.5, 135.0, 155.8, 200.3. MS (EI):
m/z (%) = 154 (25) [M+ ], 139 (26), 136 (8), 125 (37), 121 (17), 111 (22), 97 (24), 79 (29), 69 (30), 57 (20), 55 (41), 43 (100). HRMS: m/z calcd for C9H14O2: 154.0994; found: 154.0993.
Compound 6c: 1H NMR (400 MHz, CDCl3): δ = 1.93-1.96 (m, 2 H), 2.33-2.41 (m, 4 H), 3.58 (br s, 1 H), 5.45 (s, 1 H), 6.72-6.74 (m, 1 H), 7.18-7.20 (m, 2 H), 7.40-7.42 (m, 2 H). 13C NMR: δ = 22.4, 25.7, 38.4, 71.7, 121.2, 128.2, 131.3, 140.7, 140.9, 147.5, 200.2. MS (EI): m/z (%) = 282 (38) [M+ ], 281 (58), 280 (42) [M+ ], 279 (51), 264 (2), 262 (2), 236 (2), 219 (2), 208 (13), 206 (12), 202 (15), 201 (100), 195 (3), 185 (25), 183 (23), 169 (1), 157 (12), 155 (28), 145 (15), 131 (10), 129 (10), 128 (14), 125 (13), 123 (19), 116 (16), 97 (17), 96 (40), 95 (19), 79 (11), 78 (19), 77 (61). HRMS: m/z calcd for C13H13BrO2: 280.0099; found: 280.0104 for (79Br).
Compound 6f: 1H NMR (400 MHz, CDCl3): δ = 1.95-2.01 (m, 2 H), 2.37-2.47 (m, 4 H), 3.40 (br s, 1 H), 5.06 (d, 1 H, J = 5.9 Hz), 6.29 (dd, 1 H, J = 6.3, 15.9 Hz), 6.62 (d, 1 H, J = 15.9 Hz), 6.97 (t, 1 H, J = 4.2 Hz), 7.19-7.37 (m, 5 H). 13C NMR: δ = 22.5, 25.7, 38.5, 71.6, 126.5, 127.6, 128.6, 129.6, 130.6, 136.6, 140.2, 147.0, 200.3. MS (EI): m/z (%) = 228 [M+ ] (43), 210 (12), 200 (10), 182 (5), 172 (11), 167 (5), 153 (5), 137 (17), 131 (12), 128 (15), 124 (19), 123 (18), 115 (23), 105 (18), 104 (17), 103 (18), 96 (100), 95 (21), 91 (37), 77 (37). HRMS: m/z calcd for C15H16O2: 228.1150; found: 228.1151.
Compound 6g: 1H NMR (400 MHz, CDCl3): δ = 1.17 (s, 6 H), 1.84 (t, 2 H, J = 6.7 Hz), 2.47 (t, 2 H, J = 6.7 Hz), 3.30 (br s, 1 H), 5.00 (d, 1 H, J = 5.9 Hz), 6.26 (dd, 1 H, J = 6.3, 15.9 Hz), 6.60 (m, 2 H), 7.38-7.19 (m, 5 H). 13C NMR: δ = 27.6, 27.8, 32.9, 34.9, 35.6, 71.7, 126.5, 127.6, 128.5, 129.6, 130.8, 136.6, 136.8, 155.8, 200.2. MS (EI): m/z (%) = 256 [M+ ] (29), 223 (5), 201 (16), 200(100), 181 (5), 172 (28), 165 (5), 158 (5), 151 (14), 137 (11), 131 (22), 124 (29), 115 (18), 109 (35), 104 (20), 91 (33), 77 (30). HRMS: m/z calcd for C17H20O2: 256.1463; found: 256.1458.