Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

Abstract

The stereoselective synthesis of truxillic bis-amino esters from polyfunctional oxazolones is reported. The reaction of 4-((Z)-arylidene)-2-(E)-styryl-5(4H)-oxazolones 2 with Pd(OAc)2 resulted in ortho-palladation and the formation of a dinuclear open-book complexes 3 with carboxylate bridges, where the Pd atom is C^N bonded to the oxazolone. In 3 the two exocyclic C=C bonds of the oxazolone are in a face-to-face arrangement, which is optimal for their [2 + 2] photocycloaddition. Irradiation of dimers 3 in CH2Cl2 solution with blue light (465 nm) promoted the chemo- and stereoselective [2 + 2] photocycloaddition of the exocyclic C=C bonds and the formation of cyclobutane-containing ortho-palladated complexes 4. Treatment of 4 with CO in a MeOH/NCMe mixture promoted the methoxycarbonylation of the palladated carbon and the release of the corresponding ortho-functionalized 1,3-diaminotruxillic bis-amino esters 5 as single isomers.

Fluorescent Orthopalladated Complexes of 4-Aryliden-5(4H)-oxazolones from the Kaede Protein: Synthesis and Characterization

“…The orthopalladation was regioselective at the 6-position of the 4-arylidene ring, as inferred from the observation of an AB spin system (6.23 and 6.17 ppm, 4 J HH = 2 Hz) in the 1 H NMR spectrum of 2a , which corresponds to the C 6 H 2 palladated ring. This selectivity is the same as that observed previously in related systems [ 63 , 64 , 65 , 66 , 67 , 68 ]. Additional signals due to the presence of the styryl moiety and the vinyl proton were also evident.…”

“…In order to incorporate the Pd center into the oxazolone skeleton, the reactivity of 1a and 1b with Pd(OAc) 2 (1:1 molar ratio) in CF 3 CO 2 H was evaluated by previously published methods [ 63 , 64 , 65 , 66 , 67 , 68 ]. In the case of the electron-rich oxazolone 1a , the reaction took place at room temperature to afford dimer 2a in good yield (94%) (see Scheme 2 ).…”

“…The Pd1–N2 bond distance [2.110(3) Å] is longer than the Pd1–N1 bond distance [2.060(3) Å] and this is due to the higher trans influence of the C1 atom trans to N2 with respect to the N3 atom trans to N1, although all Pd–N bond distances fall in the usual range of values found in the literature for this type of bond [ 85 ]. The Pd1–C1 bond distance [2.013(3) Å] is also typical for this type of bond [ 64 , 65 , 66 , 67 , 68 ].…”

“…We recently described a contribution in this area in which palladium complexes were employed as an intramolecular lock, as shown in Figure 3 (left) [ 63 ]. The incorporation of the Pd(II) lock into the skeleton of ( Z )-4-arylidene-2-phenyl-5(4 H )-oxazolones and -imidazolones was achieved using C–H activation processes by methods developed by our group [ 64 , 65 , 66 , 67 , 68 ]. The acetylacetonate ligand was used as an ancillary group to complete the coordination sphere of the Pd center.…”

Pd-Oxazolone complexes conjugated to an engineered enzyme: improving fluorescence and catalytic properties

“…The incorporation of the Pd atom at the ortho-position of the 4-arylidene ring of the oxazolone skeleton was performed by C-H bond activation processes, following methods developed in our group. 10,11,[26][27][28][29] The treatment of 1a (or 1b) with Pd(OAc) 2 (1 : 1 molar ratio) in CF 3 CO 2 H at room temperature for 40 min afforded 2a (or 2b) as deep red solids in good isolated yields. Further treatment of 2a (2b) with excess of LiCl in MeOH at room temperature promoted the metathesis of the carboxylate bridges by chloride bridges and the formation of dinuclear 3a (3b) (Scheme 1) as very insoluble deep-red solids.…”