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Synlett 2009(4): 585-588  
DOI: 10.1055/s-0028-1087560
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

1,6-Conjugate Addition of Boronic Acids to 2-Allylidenemalonates

Gabriela de la Herrán, Aurelio G. Csákÿ*
Departamento de Química Orgánica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain
Fax: +34(91)3945030; e-Mail: csaky@quim.ucm.es;
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Publication History

Received 24 October 2008
Publication Date:
16 February 2009 (online)

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Abstract

The addition of boronic acids to 2-allylidenemalonates under RhI or Pd²+ catalysis shows an enhanced selectivity for the 1,6-addition reaction in comparison with diunsaturated monoesters. In the case of the RhI-catalyzed addition, the position of the new C=C double bond in the final product can be tuned with the choice of the base to give vinylmalonates of alkylidenemalonates.

Key words

addition reactions - catalysis - boron - rhodium - palladium

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10

General Procedure for the Rh I -Catalyzed Addition of Boronic Acids to 1a with NaHCO 3 as Base (Table 1, Entries 1-7)
To a mixture of boronic acid (2.0 equiv, 0.32 mmol) and [Rh(cod)Cl]2 (5% Rh, 2.0 mg, 0.004 mmol) under Ar was added a solution of 1a (1.0 equiv, 34 mg, 0.16 mmol) in dioxane-H2O (6:1, 0.5 mL) followed by NaHCO3 (0.1 equiv, 2.7 mg, 0.032 mmol). The mixture was stirred at
50 ˚C for 18 h. Evaporation under vacuum afforded the crude reaction products, which were purified by column chromatography (hexane-EtOAc, 85:15).

11

General Procedure for the Rh I -Catalyzed Addition of Boronic Acids to 1a and 2a with Et 3 N as Base (Table 1, Entries 8-15)
To a mixture of boronic acid (2.0 equiv, 0.32 mmol) and [Rh(cod)Cl]2 (5% Rh, 2.0 mg, 0.004 mmol) under Ar was added a solution of 1a or 2a (1.0 equiv, 0.16 mmol) in dioxane-H2O (10:1, 0.5 mL) followed by Et3N (1.0 equiv, 16.2 mg, 22 µL, 0.16 mmol). The mixture was stirred at
25 ˚C for 18 h. Evaporation under vacuum afforded the crude reaction products, which were purified by column chromatography (hexane-EtOAc, 85:15).

12

We have confirmed that isomerization of compounds 3 to 4 is a base-promoted process: treatment of compound (E)-3d in dioxane-H2O (10:1) with Et3N (1.0 equiv) at r.t. (18 h) afforded 4d (90% isolated yield).

13

General Procedure for the Rh I -Catalyzed Addition of Boronic Acids to 1b,c and 2b with Ba(OH) 2 as Base (Table 1, Entries 16-19)
To a mixture of boronic acid (2.0 equiv, 0.34 mmol) and [Rh(cod)2BF4] (5% Rh, 3.5 mg, 0.008 mmol) under Ar was added a solution of 1b or 2b (1.0 equiv, 0.17 mmol) in dioxane-H2O (10:1, 0.5 mL) followed by Ba(OH)2˙H2O (1.0 equiv, 32.2 mg, 0.17 mmol). The mixture was stirred at
25 ˚C for 18 h. Evaporation under vacuum afforded the crude reaction products, which were purified by column chromatography (hexane-EtOAc, 85:15).

14

Compound 1c was prepared by cross-metathesis reaction between 1a and 1-octene (5% Grubbs II catalyst, CH2Cl2, r.t., 18 h, 60% yield).

17

General Procedure for the Pd ²+ -Catalyzed Addition of Boronic Acids to 1a and 2a (Table 2)
To a mixture of Pd(acac)2 (5% Pd, 2,6 mg, 0.008 mmol), 1,2-diphenylphosphinobenzene (dppben, 3.8 mg, 0.008 mmol), Cu(BF4)2˙6H2O (12 mg, 0.034 mmol), and boronic acid (0.34 mmol) under Ar was added a solution of the starting material (0.17 mmol) in dioxane-H2O (10:1, 0.5 mL). The mixture was stirred at 25 ˚C for 18 h. Evaporation under vacuum afforded the crude reaction products, which were purified by column chromatography (hexane-EtOAc, 95:05).

18

Representative Data
( E )-2-(3-Phenylpropenyl)malonic Acid Diethyl Ester (3a) ¹H NMR (200 MHz, C6D6): δ = 7.08 (m, 5 H), 5.98 (dd, J = 7.7, 15.3 Hz, 1 H), 5.62 (dt, J = 7.1, 15.2 Hz, 1 H) 4.03 (d, J = 7.9 Hz, 1 H), 3.92 (q, J = 7.2 Hz, 4 H), 3.12 (d, J = 7.1 Hz, 2 H), 0.89 (t, J = 7.2 Hz, 6 H) ppm. ¹³C NMR (50.5 MHz, CDCl3): δ = 168.5, 139.7, 135.3, 128.8, 128.7, 126.4, 123.2, 61.8, 55.8, 39.0, 14.2 ppm.
( E )-2-(5-Phenylpenta-1,4-dienyl)malonic Acid Diethyl Ester (3d) ¹H NMR (300 MHz, C6D6): δ = 7.21 (m, 5 H), 6.35 (d, J = 15.9 Hz, 1 H), 6.18 (dd, J = 8.9, 15.5 Hz, 1 H), 6.09 (dt, J = 6.6, 15.9 Hz, 1 H), 5.68 (dt, J = 6.8, 15.5 Hz, 1 H), 4.22 (d, J = 8.9 Hz, 1 H), 4.05 (q, J = 7.0 Hz, 4 H), 2.79 (m, 2 H), 1.00 (t, J = 7.1 Hz, 6 H) ppm. ¹³C NMR (50.5 MHz, CDCl3): δ = 168.3, 137.4, 134.3, 131.2, 128.5, 127.5, 127.1, 126.1, 122.8, 61.6, 55.6, 35.7, 14.0 ppm.
( E )-2-(3,3-Diphenylpropenyl)malonic Acid Diethyl Ester (3h)
¹H NMR (200 MHz, CDCl3): δ = 7.20 (m, 5 H), 7.12 (m,
5 H), 6.08 (dd, J = 7.8, 15.7 Hz, 1 H), 5.64 (dd, J = 8.9, 15.7 Hz, 1 H), 4.70 (d, J = 7.7 Hz, 1 H), 4.12 (q, J = 7.3 Hz, 4), 4.02 (d, J = 8.9 Hz, 1 H), 1.18 (t, J = 7.1 Hz, 6 H) ppm. ¹³C NMR (75.5 MHz, CDCl3): δ = 168.7, 143.4, 139.1, 129.0, 128.9, 126.9, 124.0, 52.1, 55.9, 54.1, 14.5 ppm.
2-(3-Phenylpropylidene)malonic Acid Diethyl Ester (4a)
¹H NMR (200 MHz, CDCl3): δ = 7.21 (m, 5 H), 7.03 (t, J = 7.5 Hz, 1 H), 4.28 (q, J = 7.2 Hz, 2 H), 4.23 (q, J = 7.0 Hz, 2 H), 2.82 (m, 2 H), 2.62 (m, 2 H), 1.31 (t, J = 7.0 Hz,
3 H), 1.28 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR (50.5 MHz, CDCl3): δ = 165.4, 164.0, 148.1, 140.5, 132.5, 128.6, 128.3, 126.3, 61.2, 34.4, 31.4, 14.1, 14.07 ppm.
2-(5-Phenylpent-4-enylidene)malonic Acid Diethyl Ester (4d)
¹H NMR (200 MHz, CDCl3): δ = 7.28 (m, 5 H), 7.03 (t, J = 7.5 Hz, 1 H), 6.44 (d, J = 15.8 Hz, 1 H), 6.18 (dt, J = 6.6, 15.8 Hz, 1 H), 4.3 (q, J = 7.3 Hz, 2 H), 4.24 (q, J = 7.1 Hz,
2 H), 2.46 (m, 4 H), 1.31 (t, J = 7.2 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (50.5 MHz, CDCl3): δ = 165.6, 163.8, 148.2, 137.5, 131.3, 1292, 128.5, 128.4, 127.2, 126.1, 61.3, 31.6, 29.5, 14.1 ppm.