Novel homoallylic alcohols incorporating sulfone moieties were synthesized by the treatment of different carbonyl compounds with allylic bromides in aqueous media
Ultrasonic assisted organic synthesis as a green synthetic approach is a powerful technique that is being used more and more to accelerate organic reactions [
The aryl sulfone moiety has been found in numerous biologically interesting compounds. These compounds include antifungal, antibacterial, or antitumor agents [
Nucleophilic additions to carbonyl groups are one of the cornerstones of organic chemistry. Carbonyl allylation forms homoallylic alcohols which are versatile subunits that can easily be converted to a number of other useful functions [
Herein, we report the results of the allylation reactions of aldehyde and ketone derivatives containing a sulfone moiety by indium in aqueous media under ultrasound irradiation compared to conventional methods. We also report that CuI/2,6-lutidine catalyzes the sulfonation of
The chemicals used in this work were obtained from Fluka and Merck and were used without purification. Indium powder was obtained from Sigma-Aldrich Company as 99.99% pure, but containing 1% Mg as anticaking agent. Melting points were determined on a Bibby Sterilin ltd electrothermal melting point apparatus and are uncorrected. Sonochemical reactions were carried out in a Branson B1510 DTH ultrasound cleaning bath (50 kHz, 245 W). The reactions were monitored by thin layer chromatography using Fluka GF254 silica gel plates with a fluorescent indicator; detection by means of UV light at 254 and 360 nm. The IR spectra were recorded on KBr disks on a Perkin Elmer 2000 FTIR spectrometer. The NMR spectra were recorded on a Varian Mercury VX-300 NMR spectrometer at 300.13 and 75.47 MHz. 1H NMR and 13C NMR spectra were recorded in deuterated chloroform (CDCl3) or dimethyl sulphoxide (DMSO-d6) using TMS as the internal standard. 13C chemical shifts were related to that of the solvent. Mass spectra were recorded on ESI-MS Thermo LTQ Orbitrap XL, infusion 5 uL/min, resolution: 100 000 at m/z 400, ca. 10 scans/sample averaged. The aryl sulfones
Following this procedure 2.0 mmol of other bases Et3N, K2CO3, piperidine, and no base, were used in place of 2,6-lutidine to screen the conditions. The yields are summarized in Table
Synthesis of homoallylic alcohols by allylation of
Compound | R | Ultrasonic irradiation | Conventional heating, 50°C | ||
---|---|---|---|---|---|
Time (h) | Yield (%) | Time (h) | Yield (%) | ||
|
H | 3 | 92 | 12 | 75 |
|
CH3 | 3 | 90 | 12 | 70 |
|
H | 5 | 93 | 24 | 73 |
|
CH3 | 5 | 89 | 24 | 70 |
Synthesis of 2-bromo-1-substituted ethanones
Compound | R | Ultrasonic irradiation | Stirred at room temperature | ||
---|---|---|---|---|---|
Time (min) | Yield (%) | Time (h) | Yield (%) | ||
|
Ph SO2 | 60 | 92 | 4 | 80 |
|
F | 30 | 95 | 3 | 82 |
|
PhSO2 | 60 | 93 | 8 | 79 |
|
F | 60 | 94 | 8 | 83 |
|
Br | 60 | 95 | 8 | 86 |
|
CH3 | 90 | 90 | 8 | 75 |
|
H | 60 | 92 | 8 | 78 |
|
PhSO2 | 12 h |
|
24 |
|
Sulfonation of
Base | Time (h) | Yield (%) |
---|---|---|
None | 6 | 11 |
Et3N | 6 | 25 |
K2CO3 | 6 | 50 |
Piperidine | 6 | 39 |
2,6-lutidine | 1 | 93 |
We first investigated the indium-mediated Barbier procedure for the allylation of the arylsulfonated 4-(phenylsulfonyl)benzaldehyde (
Synthesis of homoallylic alcohols
The homoallylic alcohols
In order to investigate the regio- and diastereoselectivities of the allylation reaction, cinnamyl bromide was used as an allylation reagent. Allylation reactions involving cinnamyl bromide can provide both an
The strong anti-selectivity obtained in the transformation of
As shown in Scheme
The facile reaction of the aromatic ketone
Synthesis of 2-bromo-1-substituted ethanones
Carbonyl compounds
The structure of 2-(phenylsulfonyl)-1-(4-(phenylsulfonyl)phenyl)ethanone
In the same manner as carried out for
Synthesis of homoallylic alcohols by allylation of
Compound | R | Ultrasonic irradiation | Conventional heating, 50°C | ||
---|---|---|---|---|---|
Time (h) | Yield (%) | Time (h) | Yield (%) | ||
|
PhSO2 | 1.5 | 95 | 12 | 83 |
|
F | 1.5 | 96 | 12 | 85 |
|
PhSO2 | 3 | 91 | 12 | 80 |
|
F | 3 | 89 | 12 | 75 |
Synthesis of homoallylic alcohols
Allylation of the brominated derivatives
In summary, we have demonstrated that ultrasound irradiation can markedly speed up the allylation of carbonyl compounds containing sulfone moieties
This work was supported by Yggdrasil research grant 2010/2011 from the Research Council of Norway (202902/V11). They are gratefully acknowledged for the financial support. Sources for equipment and materials are given for clarity in the experimental section, but the authors have no conflicting interests with these companies that could influence this work.