Kinetic Measurements of the Light-Initiated Cu(I)-Catalyzed

The reaction mixture of 7, 11 (each 0.4 mmol), 1 (4 mol%), NEt3 (1 eq) and CuCl2

(8 mol%) in MeCN was irradiated under identical conditions (see GP 4) for various lengths of time (from 0 to 180 sec) and the reaction rate of the initiated Cu(I)-catalyzed cycloaddition in the dark was monitored (diagram 3). The quenching of the fluorescence of 7 can even be followed with bare eyes (fig. 9).

0 (initial irradiation time: 180 s). Values were derived from 3 repititions.

Figure 9: Emission fading during the photoinitiated cycloaddition; initial irradiation time was 90 s;

from left to right: emission of the solution after 1 min, 10 min and 20 min reaction time in the dark.

A slow background reaction was observed without irradiation due to the spontaneous reduction of Cu²⁺ to Cu⁺ by NEt3. Experimental results showed that after addition of 1 eq NEt3, enough Cu⁺ was generated from CuCl2 to start the cycloaddition reaction.

However, within irradiation times of 30 to 180 s, a significant increase of the reaction rate was observed (diagram 4).

0 10 20 30 40 50 60 70 80 90 100

0 10 20 30 40 50 60

reaction time [min]

conversion [%]

0 sec 30 sec 90 sec 180 sec

Diagram 4: Conversion vs. reaction time depending on time of initial irradiation.

Of course, this background reaction is not desired. In order to slow this reaction down or even stop it completely, the dependence of this “dark reaction” on the concentration of NEt was investigated. Diagram 5 shows the reaction process

exemplary for two reactions with 1 eq and 0.1 eq NEt3. There is a significant drop of the reaction rate if catalytic amounts of sacrificial electron donor are used.

0 100 200 300 400 500

0 20 40 60 80 100

time [min]

intensity [a.u.]

0.1 eq NEt3 1 eq NEt3

Diagram 5: Decrease of fluorescence of reaction batch with 1 eq and 0.1 eq NEt3.

Considering that an equimolar relation between NEt3 and 1 is sufficient to enable formation from 1-H2, and the following reduction of Cu(II), the use of 0.1 eq NEt3

should not slow down the light initiated reaction. Experimental results showed otherwise: the use of lower amounts of NEt3 slowed the light-initiated reaction more than the “dark reaction”. When 0.15 eq NEt3 or less was used, the light initiated reaction stopped completely (diagram 6).

0 50 100 150 200 250 300 350

0 20 40 60 80 100 120

time [min]

intensity [a.u.]

Diagram 6: Fluorescence vs. reaction time after initial irradiation of 180 s with 0.1 eq NEt3. The arrow marks the addition of further 0.9 eq NEt3 after 72 min.

However, after the addition of further 0.9 eq NEt3, the reaction started immediately, without any further irradiation. The reaction proceeded only insignificantly lower than the corresponding one with 1 eq NEt3. This means that upon irradiation, almost all sacrificial electron donor is used up, and formation of 1-H2 takes place. 1-H2 is stable

+ 0.9 eq NEt3

in the reaction mixture for at least 70 min, but the dihydroflavine itself is not able to reduce Cu²⁺ to Cu⁺. Thus, the presence of NEt3 is essential, as it forms a Cu(II)-amine complex. Exceptionally [Cu(NEt3)4]²⁺ can be reduced by 1-H2. This confirms the prior assumption in chapter [1.2.2.]. Thus, for all subsequent experiments 1 eq of NEt3 was used.

To estimate the efficiency of the light to catalyst conversion of the reaction, the dependence of the reaction rate of formation of 12 on the Cu(I) concentration under the experimental conditions, was determined (GP 5).

0 10 20 30 40 50

0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9

[CuI] in mmol / L

reaction rate in µmol / s L

Diagram 7: Dependence of the cycloaddition reaction rate on the Cu(I)-concentration.

Diagram 7 shows the reaction rate with respect to the concentration of copper iodide.

Reaction rates were calculated from linear region in conversion vs. time diagram (up to 40 % conversion). Results clearly show a linear dependence for the experimental conditions employed (MeCN as solvent; NEt3 as additive; low CuI-concentration of 10^-4 to 10^-3 mol/L). Thus, the reaction rate is first order in Cu(I). For catalytic reactions in aqueous solution and concentrations > 10^-2 mol/L, a binuclear Cu(I)-complex was previously proposed.³⁷

Now with information from diagram 4 and diagram 7, the dependence of the rate enhancement, as well as the dependence of the surplus Cu(I) formation on the amount of photons, can be determined (diagram 8).

0,0 5,0 10,0 15,0 20,0 25,0

0 10 20 30 40 50 60 70

photons [µmol]

delta reaction rate [µmol/Ls]

22 28 33 39 44 50

conversion Cu(II) [%]

Diagram 8: Acceleration of the initial reaction rate and conversion of Cu(II) to Cu(I) depending on the amount of light (data points are for irradiation-times of 0, 15, 30, 60, 90, 135 and 180 s).

Results show that even without irradiation, already 22 % of Cu(II) is converted.

Further, with short irradiation times (< 30 s), the background reaction becomes important, while longer irradiation (> 100 s) leads to a non-linear response of the photoreceptor due to bleaching of 1-H2,^17b the formation of side-products instead of 1-H2,21 and decreasing concentrations of the sacrificial electron donor and CuCl2

(related flavin photoreactions showed a similar behaviour).^22,24

In order to improve the performance of the photoreceptor, concentrations of 1 and CuCl2 were varied. Under better reaction conditions, the course of the graph in diagram 8 should become steeper. In particular, the efficiency of the Cu(II)-conversion is rather low – between 20 % and 60 %. Theoretically, larger concentrations of 1 (up to 15 mol%) should not only lead to more Cu(II)-conversion (and therefore a wider linear range), but also to shorter irradiation times. In contrast, experimental results showed that larger concentrations of 1 lead primarily to an acceleration of the background reaction. The reason for this is unknown. Use of lower amounts of 1 or varying the concentration of Cu(II) also showed no improvement in performance. Thus, reaction conditions with 1 eq NEt3, 4 mol% 1 and 8 mol% of CuCl2 were found to be optimal.

Results from diagram 8 give a quantum yield of the Cu(I) generation of 0.2 and an overall quantum yield of triazole-formation (which can also be called the overall

amplification factor of the reaction cascade) of up to 15 after 20 min reaction time.

This corresponds to a turnover number of 70 for Cu⁺ after that time.