Carbonyl Activation by Selenium‐ and Tellurium‐Based Chalcogen Bonding in a Michael Addition Reaction

Abstract In the last years the use of chalcogen bonding—the noncovalent interaction involving electrophilic chalcogen centers—in noncovalent organocatalysis has received increased interest, particularly regarding the use of intermolecular Lewis acids. Herein, we present the first use of tellurium‐based catalysts for the activation of a carbonyl compound (and only the second such activation by chalcogen bonding in general). As benchmark reaction, the Michael‐type addition between trans‐crotonophenone and 1‐methylindole (and its derivatives) was investigated in the presence of various catalyst candidates. Whereas non‐chalcogen‐bonding reference compounds were inactive, strong rate accelerations of up to 1000 could be achieved by bidentate triazolium‐based chalcogen bond donors, with product yields of >90 % within 2 h of reaction time. Organotellurium derivatives were markedly more active than their selenium and sulphur analogues and non‐coordinating counterions like BArF 4 provide the strongest dicationic catalysts.


Experimental Conditions
All experiments were carried out in flame dried Schlenk flasks under argon atmosphere and with dry solvents. Solvents used for chromatography were previously distilled. All used chemicals are commercially available and were used without further purification.

ATR-IR Measurements
IR spectra were recorded with a Shimadzu IR Affinity -1S spectrometer and are reported in  = cm -1 and are indicted with w (weak), m (middle), s (strong) or vs (very strong).

Elemental Analysis
CHNS Elemental Analysis was performed with a vario Micro cube from Elementar Analysentechnik.

Balance for Stock Solutions
Starting materials for stock solutions were weight in on a Mettler Toledo XSR 105 Dual Range balance.

Synthesis of 5 S
Compound 5 S was synthesized according to literature. [3] 1.5.5.

Synthesis of 5 Te
Compound 5 Te was synthesized according to literature. [3]

Synthesis of compound 4 S-BArF4
Compound 4 S-BArF4 was synthesized after the following procedure [3] :300 mg (0.35 mmol, 1 eq.) of compound 4 S-BF4 were dissolved in 35 ml dry chloroform (0.01 M) and 820 mg TMABAr F 4 (0.88 mmol, 2.5 eq.) were added to the solution, which was then stirred for 18 h at room temperature. Subsequently, the solvent was removed and the solid was taken up in ether and the solution was cooled to -78°C until a precipitate (TMABF4) was formed, which was filtered off and was washed two times with -78 °C cold ether. Then, the solvent of the organic solution was removed, and the solid residue was diluted with a little amount of chloroform and cooled to -55 °C until a solid precipitated (excess of TMABAr F 4). The mixture was filtered, and the solid residue was washed three times with -55 °C cold chloroform. After the solvent of the organic phase was removed, 4 S-BArF4 was obtained with 600 mg (0.25 mmol, 71%)yield as yellowish sticky resin.

Synthesis of compound 4 Se-BArF4
Compound 4 Se-BArF4 was synthesized after the following procedure [3] :300 mg (0.32 mmol, 1 eq.) of compound 4 Se-BF4 were dissolved in 32 ml dry chloroform (0.01 M) and 650 mg TMABAr F 4 (0.69 mmol, 2.2 eq.) were added to the solution, which was then stirred for 18 h at room temperature. Subsequently, the solvent was removed and the solid was taken up in ether and the solution was cooled to -78°C until a precipitate (TMABF4) was formed which was filtered off and was washed two times with -78 °C cold ether. Then, the solvent of the organic solution was removed, and the solid residue was diluted with a little amount of chloroform and cooled to -55 °C until a solid precipitated (excess of TMABAr F 4). The mixture was filtered, and the solid residue was washed three times with -55 °C cold chloroform. After the solvent of the organic phase was removed, 4 Se-BArF4 was obtained with 540 mg (0.21 mmol, 68%) yield as yellowish sticky resin.

Synthesis of compound 4 Se-OTf
Compound 4 Se-OTf was synthesized from 5 Se . 508 mg of Compound 5 Se (0.68 mmol, 1 eq.) were added to a flame dried Schlenk flask and were dissolved in 68 ml dry DCM (0.01 M).
Subsequently, 0.22 ml methyl triflate (0.21 mmol, 3 eq.) were added and the mixture was stirred for 24 h. Removal of the solvent yielded a crude residue which was dissolved in a little amount of DCM and precipitated through addition of ether as sticky resin. Finally, the sticky resin was washed with pentane to yield 351 mg 4 Se-OTf (0.33 mmol, 48%) as solid. [3] 1 H NMR (300 MHz, Chloroform-d):  ppm]

1 H NMR Reaction Setup
Scheme 1: Chalcogen bond catalysed Michael addition reaction of 5-methoxyindole and trans-βnitrostyrene in presence of 7 TeBArF .

Determination of k rel values
krel was determined by a linear fit from the kinetic plot of the reaction (see Figure 3). To this end, the gradient between zero hours and 2-2.6 h and the corresponding yield of 3 was determined for selected experiments. All used values for the slope determination are rounded to 2 h and the next highest number ( Table 1). The reaction with halogen bond donor 4 I-BArF4 was chosen as reference slope with a value of krel = 1. All other krel values were referred to this value ( Table 1).     1  1  2  1  3  1  4  1  5  1  10  5  15  5  20  5  25  5  30  5  40  10  60  20  80  20  100  20  150  50  200 50 For the determination of the binding constants the shift of the N-Me protons or the ChPh protons from the respective catalyst were observed relative to the signal of the solvent. The measured shifts were plotted against the guest-equivalents and the resulting curve was fitted using http://supramolecular.org/. [9] For the calculations of the binding constants (K) a 1:1 binding was assumed.

Equivalents Added amount (μl) of the guest solution
In the following, titration plots for all tested compounds are given as well as a table with the binding constants.