Angelw: parallel kinetic resolution of allyl 1,3-dione

The new activation mode and the rapid development of atomic economic reaction have laid a solid foundation for the sustainable organic catalytic synthesis Recently, Professor Bernhard Breit of the University of Freiburg in Germany reported a series of asymmetric addition reactions between pronucleophiles and dienes or alkynes, which greatly expanded the scope of Tsuji Trost reaction Based on the asymmetric addition of 1,3-diketone to terminal malondiene previously reported by the author, Professor Bernhard Breit developed RH to catalyze the asymmetric addition of 1,3-diketone to 1,3-disubstituted malondiene, and realized the parallel kinetic resolution of allyl 1,3-diketone (scheme 1) Relevant research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201903365) (picture source: angel Chem Int ed.) firstly, racemic propanediene 1 and acetylacetone 2 were used as template substrates Under the co catalysis of RH and phosphide L1 ligands and Br? Nsted Acid, the E / Z mixed product 4 (scheme 2) could be obtained with medium yield and high enantioselectivity at room temperature When hydrogenation occurs, the enantioselectivity of (R) - 5 (scheme 3) is high (picture source: angelw Chem Int ed.) (picture source: angelw Chem Int ed.) the author speculated that the reason for the low E / Z selectivity of the reaction was that the product would undergo E / Z isomerization during the reaction process Therefore, the author monitored the E / Z ratio of different reaction processes (scheme 4) When the reaction time was 10 minutes, the E / Z ratio was 13:87; with the extension of the reaction time, the E / Z ratio decreased gradually This indicates that Z-configuration products will be transformed into e-configuration products gradually during the reaction The E / Z ratio of 4 was 15:85 Under the same conditions, the E / Z ratio remained unchanged Based on the above data, the author speculates that the reaction may undergo a parallel kinetic resolution process (scheme 5) (picture source: angelw Chem Int ed.) (picture source: angelw Chem Int ed.) in order to further understand the reaction mechanism, the author conducted a related control experiment (scheme 8) The results show that TFA ester 3 is the intermediate of the reaction, and TFA can be used as the leaving group to catalyze the reaction (image source: angel Chem Int ed.) in order to exclude the background reaction, the author prepared pure (R) - 1 reaction under standard conditions, and no racemization was found, thus eliminating the possibility of malodiene self racemization (scheme 9) (picture source: angelw Chem Int ed.) in order to further understand the reaction mechanism, the author monitored the reaction in the NMR tube by hydrogen spectrum (Figure 1) The results show that TFA ester rac-z-3 and rac-e-3 are intermediates in the reaction Rac-z-3 intermediate can be rapidly generated and converted into C-C coupling product (s) - Z-4, while e-tfa-ester intermediate is slightly slower, so the conversion to (s) - E-4 is much slower According to the results of the above control experiments, the author proposed a possible mechanism (scheme 10) Under the action of (R) - catalyst system, the (R) - 1 can be transformed into the intermediate of tfa-ester rac-e-3 rapidly, and then the coupling reaction takes place to produce the product (s) - E-4 At the same time, (s) - 1 will also form TFA ester rac-z-3 intermediate, and then produce the coupling reaction product (s) - Z-4, but the reaction process is relatively slow If the configuration of p-amide ligand is changed, the absolute configuration of the product will be changed accordingly It is worth mentioning that the E / Z configuration of the reaction depends on the formation of TFA ester 3 by RH catalyzed TFA and propylene, and the enantioselectivity of the reaction depends on the formation of coupling products by RH catalyzed TFA ester 3 and acetylacetone (image source: angelw Chem Int ed.) then, the author investigated the substrate range of 1,3-dione (Table 1) All kinds of aliphatic, aromatic and heterocyclic 1,3-diketones have good tolerance The yield of the product is greatly affected by E / Z ratio and steric hindrance The larger the steric hindrance is, the lower the yield is, and the single Z-configuration product can be obtained from the t-Bu substituted 1,3-dione with the largest steric hindrance Secondly, various diaryl substituted 1,3-diketones can adapt to the reaction conditions, and the corresponding products can be obtained in medium yield At the same time, all kinds of 1,3-disubstituted dienes have good tolerance (photo source: angelw Chem Int ed.) Summary: Professor Bernhard Breit, University of Freiburg, Germany, reported that RH catalyzes the asymmetric addition of 1,3-diketone and propadiene, realizing the parallel kinetic resolution of allyl 1,3-diketone Through the control experiment, the mechanism of the reaction was studied in detail.