Bukeyan
Miao
a and
Shengming
Ma
*bc
aShanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University, 3663 North Zhongshan Lu, Shanghai 200062, P. R. China
bState Key Laboratory of Organometallic Chemistry and Shanghai Institute of Organic Chemistry and Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, P. R. China. E-mail: masm@sioc.ac.cn
cDepartment of Chemistry, Fudan University, 220 Handan Lu, Shanghai 200433, P. R. China
First published on 2nd December 2014
A direct carboxylation reaction of allylic bromides mediated by zinc powder has been developed. The reaction occurred smoothly at room temperature with 1 atm of CO2 provided by a balloon. The reaction was conducted in the presence of LiOAc giving excellent yields. An excellent branched regioselectivity was observed and the reaction was easily scaled-up to 10 gram-scale.
Entry | Metal powder (x equiv.) | Solvent | Additive | Yield of 2ab (%) | 1ab (%) |
---|---|---|---|---|---|
a The reaction was conducted with 1.0 mmol of allylic halide and metal powder in 5 mL of an anhydrous solvent with a CO2 balloon. b NMR yield. | |||||
1 | In (0.70) | DMF | — | Complicated | — |
2 | Al (0.70) | DMF | — | — | 76 |
3 | Fe (0.70) | DMF | — | — | 74 |
4 | Bi (0.70) | DMF | — | Complicated | — |
5 | Mn (1.05) | DMF | — | — | 68 |
6 | Zn (1.05) | DMF | — | 73 | — |
7 | Zn (1.05) | DMSO | — | 58 | — |
8 | Zn (1.05) | THF | — | 73 | — |
9 | Zn (1.05) | Dioxane | — | 25 | — |
10 | Zn (1.05) | Et2O | — | — | 87 |
11 | Zn (1.05) | THF | LiCl | 81 | 5 |
12 | Zn (1.05) | THF | LiBr | 74 | 6 |
13 | Zn (1.05) | THF | LiOCOCF3 | 34 | 1 |
14 | Zn (1.05) | THF | LiOAc | 84 | — |
In order to check whether any impurity in the zinc powder may have an impact on the yield of the reaction, zinc powders from different manufacturers with different purities were tested. The results in Table 2 show that different zinc powders gave the product in different yields.
However, we did consider that the difference was not caused by the purity but by the particle size of the zinc powder. The EDX (energy dispersive X-ray spectroscopy) results for the different zinc powders are shown in Fig. 1. It is obvious that the smaller the zinc powder size, the higher the yield.
In order to further confirm the above conclusion, the purity of the zinc powder purchased from Sinopharm Chemical Reagent Co., Ltd was measured by XRF (X-ray fluorescence) after washing and drying sequentially with 3 M HCl, acetone and Et2O (each 3 times). The purity was measured to be 99.94% and the confirmed impurities including Fe (0.03%) and Cr (0.03%) were caused by background information from the XRF studies. To further eliminate the possible catalytic effect of these impurities, 1 mol% each of these salts was added to the reactions with zinc powder purchased from J&K (purity: 98%) (Table 3). We didn't observe any obvious improvement in the yield.
Entry | Additive (1 mol%) | Yield of 2ab (%) |
---|---|---|
a The reaction was conducted with 0.01 mmol of additive, 1.0 mmol of 1a and 1.05 mmol of zinc powder in 5 mL of THF with a CO2 balloon. b NMR yield. | ||
1 | — | 68 |
2 | Fe powder | 61 |
3 | FeCl2 | 54 |
4 | FeCl3 | 53 |
5 | Fe2O3 | 70 |
6 | Cr powder | 65 |
7 | CrCl3 | 41 |
8 | Cr2O3 | 68 |
9 | CrCl3–FeCl3 = 1:1 | 40 |
The scope of the reaction was then investigated under the optimized conditions with zinc powder from Sinopharm. Reactions with 2-aryl, 2-benzyl- and 2-alkyl-substituted allylic bromides 1a–g were attempted and the corresponding acids were afforded in decent yields (Table 4, entries 1–5). Interestingly, substrates containing an enyne fragment 1f and 1g underwent the reaction smoothly with no CC bond isomerization observed although the yields were a little bit lower (Table 4, entries 6 and 7).
Entry | R | Yieldb (%) |
---|---|---|
a The reaction was conducted with 1.0 mmol of allylic halide and 1.05 mmol of zinc powder in 5 mL of anhydrous THF at room temperature with a CO2 balloon. b Isolated yield. c The reaction was conducted in the absence of LiOAc. | ||
1 | Ph (1a) | 82 (2a) |
2 | α-naphthyl (1b) | 79 (2b) |
3 | p-tol (1c) | 80 (61)c (2c) |
4 | Bn (1d) | 80 (2d) |
5 | n C6H13 (1e) | 83 (68)c (2e) |
6 | 49 (2f) | |
7 | 65 (2g) |
The reaction was then conducted on a 70 mmol scale successfully to afford 11.20 g of 2b, showing its practicality (Scheme 2).
To further investigate the generality of this reaction, the reaction of allylic bromides bearing halogen atoms at ortho-, meta- and para-positions of the 2-phenyl group was studied providing the corresponding carboxylic acids in good yields with an excellent chemoselectivity (Table 5, entries 1–5); a CF3- group did not affect the reaction (Table 5, entry 6); gratifyingly, ester and cyano functionalities, which are not compatible with organolithium or Grignard reagents, have been preserved under the standard reaction conditions (Table 5, entries 7–8); although a ketone carbonyl group is not directly applicable, the reaction proceeded successfully after a simple protection with glycol (Table 5, entry 9).
Entry | R | Yieldb (%) |
---|---|---|
a The reaction was conducted with 1.0 mmol of allylic halide and 1.05 mmol of zinc powder in 5 mL of anhydrous THF at room temperature with a CO2 balloon. b Isolated yield. c The reaction was conducted in the absence of LiOAc. d The reaction was conducted in 5 mL of DMF. | ||
1 | o-F (1h) | 78 (2h) |
2 | m-F (1i) | 74 (2i) |
3 | p-F (1j) | 83 (45)c (2j) |
4 | m-Cl (1k) | 73 (2k) |
5 | p-Cl (1l) | 73 (2l) |
6 | p-CF3 (1m) | 71 (2m) |
7 | p-COOEt (1n) | 55 (2n) |
8 | m-CN (1o) | 55 (2o)d |
9 | 71 (2p) |
The reaction was attempted with several commercially available differently substituted allylic bromides followed by esterification with benzyl alcohol. For the 3-substituted allylic bromides such as crotyl bromide, the branched product 3q was formed exclusively with no regioisomer detected as judged by 1H NMR analysis of the crude reaction mixture [Scheme 3, eqn (4)]; an all-carbon quaternary center could even be formed in a moderate yield when starting from 3-methyl-2-butenyl bromide [Scheme 3, eqn (5)]; 2-cyclohexenyl bromide also worked [Scheme 3, eqn (6)]. Replacing THF with DMF as the solvent gave a similar yield [Scheme 3, eqn (7)].
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4qo00300d |
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