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DOI: 10.1055/s-0028-1087560
1,6-Conjugate Addition of Boronic Acids to 2-Allylidenemalonates
Publication History
Publication Date:
16 February 2009 (online)
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
- See, for example:
-
1a
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1b
Tomioka K.Nagaoka Y. In Comprehensive Asymmetric Catalysis Vol. 3:Jacobsen EN.Pfaltz A.Yamamoto H. Springer; Berlin: 1999. Ch. 31.1. -
1c
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1d
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1f
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3f
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4a
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4e
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4f
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4g
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4h
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Okada S.Arayama K.Murayama R.Ishizuka T.Hara K.Hirone N.Hata T.Urabe H. Angew. Chem. Int. Ed. 2008, 47: 6860 ; and references cited therein - 5 For a recent example of the 1,6-addition
to related diunsaturated nitrodienes, see:
Belot S.Massaro A.Tenti A.Mordini A.Alexakis A. Org. Lett. 2008, 10: 4557 -
6a
Hayashi T.Yamamoto S.Tokunaga N. Angew. Chem. Int. Ed. 2005, 44: 4224 -
6b For an intramolecular
version using related pinacol boronate esters, see:
Tseng N.-W.Mancuso J.Lautens M. J. Am. Chem. Soc. 2006, 128: 5338 - 7
De la Herrán G.Murcia C.Csákÿ AG. Org. Lett. 2005, 7: 5629 - 8 For a related IrI-catalyzed
conjugate addition of boroxines to diunsaturated carbonyl compounds,
see:
Nishimura T.Yasuhara Y.Hayashi T. Angew. Chem. Int. Ed. 2006, 45: 5164 - 9 The synthesis of 1a was
carried out by reaction of diethyl malonate with acrolein (LiBr,
Ac2O) by a literature procedure:
Sylla M.Joseph D.Chevallier E.Camara C.Dumas F. Synthesis 2006, 1045 ; compound 1b was prepared similarly using cinnamaldehyde (80%). - Reviews:
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Yamamoto Y.Nishikata T.Miyaura N.
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References and Notes
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).
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).
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).
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).
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.