Redox Reaction of the Pd⁰ Complex Bearing the Trost Ligand with meso‐Cycloalkene‐1,4‐biscarbonates Leading to a Diamidato Pd^II Complex and 1,3‐Cycloalkadienes: Enantioselective Desymmetrization Versus Catalyst Deactivation

Abstract

The Pd(0) complex 1 that bears the Trost ligand 2 undergoes a facile redox reaction with 1,4-biscarbonates 5b-d and rac-22 under formation of the diamidato-Pd(II) complex 7 and the corresponding 1,3-cycloalkadienes 8b-d. The redox deactivation of complex 1 was the dominating pathway in the reaction of 5b-d with HCO(3)(-) at room temperature. However, at 0 degrees C the six-membered biscarbonate 5b, catalytic amounts of complex 1, and HCO(3)(-) mainly reacted in an allylic alkylation, which led to a highly selective desymmetrization of the substrate and gave alcohol 6b with > or = 99% ee in 66% yield. An increase of the catalyst loading in the reaction of 5b with 1 and HCO(3)(-) afforded the bicyclic carbonate 12b (96% ee, 92%). Formation of carbonate 12b involves two consecutive inter- and intramolecular substitution reactions of the pi-allyl-Pd(II) complexes 16b and 18b, respectively, with O-nucleophiles and presumably proceeds through the hydrogen carbonate 17b as key intermediate. The intermediate formation of 17b is also indicated by the conversion of alcohol rac-6b to carbonate 12b upon treatment with HCO(3)(-) and 1. The Pd(0)-catalyzed desymmetrization of 5b with formation of 12b and its hydrolysis allow an efficient enantioselective synthesis of diol 13b. The reaction of the seven-membered biscarbonate 5c with ent-1 and HCO(3)(-) afforded carbonate ent-12c (99% ee, 39%). The Pd(0) complex 1 is stable in solution and suffers no intramolecular redox reaction with formation of complex 7 and dihydrogen as recently claimed for the similar Pd(0) complex 9. Instead, complex 1 is rapidly oxidized by dioxygen to give the stable Pd(II) complex 7. Thus, formation of the Pd(II) complex 10 from 9 was most likely due to an oxidation by dioxygen. Oxidative workup (air) of the reaction mixture stemming from the desymmetrization of 5c catalyzed by 1 gave the Pd(II) complex 7 in high yield besides carbonate 12c.

Improved Synthesis of MediPhos Ligands and Their Use in the Pd‐Catalyzed Enantioselective N‐Allylation of Glycine Esters

“…However, these impurities did not disturb the catalytic performance of the corresponding Pd complexes (see below), generated in situ by stirring the ligands (small excess) with [Pd(allyl)Cl] 2 in THF solution for 30 min at 25°C. While all ligands were characterized by NMR spectroscopy ( 1 H, 13 C, 31 P) and HRMS, the structure of ent-L3* was additionally confirmed by means of X-ray crystallography (Figure 2).…”

“…Therefore, it remains uncertain whether the coordination modes and geometries are similar to those of Trost-type ligands and whether the higher activity of our ligands [8a] relates to the lack of NH units in the chiral bridge, which promote the formation of catalytically inactive tetra-coordinate Pd(II) complexes. [13] Having successfully synthesized a set of different MediPhos ligands we continued with the investigation of their performance in the Pd-catalyzed N-allylation of tert-butyl glycinate (4 b) using the branched carbonate rac-5 a as a second reaction partner (Table 1). Initial experiments at lower temperatures (À 10°C or 0°C) resulted in the formation of the undesired carbamate 17 a as the main product, a type of by-product we had already observed in our previous study.…”

“…1 H NMR (600 MHz, CDCl 3 ): δ [ppm] = 7.29-7.13 (m, 22H), 7.01 (ψt, 3 J = 7.6 Hz, 2H), 6.49 (ddd, 3 J = 7.5 Hz, 3 J H,P = 4.0 Hz, 3 J = 1.6 Hz, 2H), 4.25 (d, 3 J = 10.3 Hz, 2H), 4.23-4.21 (m, 2H), 4.09 (d, 3 J = 9.1 Hz, 2H), 3.02 (tt, 3 J = 9.1 Hz, 3 J = 5.6 Hz, 2H), 1.75-1.63 (m, 4H), 1.58-1.40 (m, 4H), 1.18 (s, 6H), 0.82 (t, 3 J = 7.4 Hz, 6H), 0.76 (t, 3 J = 7.4 Hz, 6H). 13 C NMR (150 MHz, CDCl 3 ) δ [ppm] = 159.4, 159.3; 139.3, 139.2; 137.2, 137.1; 134.2, 134.0, 133.7, 133.5; 131.3, 131.2; 131.0; 128.5, 128.5, 128.4, 128.4, 128.3, 128.2; 125.0; 109.0; 75.5; 72.1, 72.1, 72.0; 39.7; 29.8, 28.7; 26.6; 12.4, 12. Typical procedure for the Pd-catalyzed allylic amination ( Outside the glovebox the Schlenk tube was connected to an argon line before dry THF (1.0 mL) was added, and the solution was stirred for 20 min at room temp. Then, carbonate rac-5 a (441 mg, 1.93 mmol) was added neat by means of a syringe and after 20 more min the amine 4 b (500 mg; 3.81 mmol) was added and stirring was continued for 18 h at room temperature.…”

“…= 7.8 Hz, 2H), 4.67-4.53 (m, 2H), 4.22-4.05 (m, 4H), 3.03 (tt, 3 J = 8.9 Hz, 3 J = 5.7 Hz, 2H), 1.68 (Ψtq, J = 13.5 Hz, 3 J = 7.3 Hz, 4H), 1.54 (s, 6H), 1.53-1.45 (m, 4H), 0.78 (t, 3 J = 7.4 Hz, 12H);13 C NMR (125 MHz, CDCl 3 ): δ [ppm] = 154.0; 141.7; 130.9; 126.7, 125.9. 125.9; 117.6; 110.2; 76.9; 73.1; 41.1; 29.4; 28.9; 27.3; 12.4; 12.2; HR-MS (ESI): Calcd.…”

The first multiplication atom-bond connectivity index of molecular structures in drugs

“…In this part, we discuss the structure on alkene and cycloalkenes which are widely used in medicine and pharmaceutical engineering. Some applications on alkene and cycloalkenes can refer to Dziechciejewski et al, 2015 , Babaee et al, 2012 , Sysoiev et al, 2012 , Tsarev et al, 2010 , and Wilson et al (2007) .…”