Functionalized 1,3‐Diaminotruxillic Acids by Pd‐Mediated C–H Activation and [2+2]‐Photocycloaddition of 5(4H)‐Oxazolones

Abstract

The orthopalladation of (Z)-4-arylidene-5(4H)-oxazolones (1a-1o), with electron-withdrawing substituents (Cl, F, CF 3 ) in the 4-arylidene ring has been carried out by C-H bond activation. The process is regioselective and only the ortho C-H bond of the 4-arylidene ring is activated. The orthopalladated complexes (2a-2o) have different structures (mono-, di-and trinuclear), although the dinuclear open-book scaffold, in which the C=C bonds of the arylidene group are in a face-to-face tran- [a] Scheme 4. Different reaction pathways observed in the oxidation of 3d: synthesis of functionalized halogenated cyclobutanes 5d and 6d.

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

“…The same conclusions can be drawn from the analysis of the 13 C NMR spectra, where the presence of the PdC 6 H 3 R-C(H)= group is clear. Therefore, the orientation of the C-H activation in these 4-aryliden-2-styryloxazolones is exactly the same as that observed for the 4-aryliden-2-aryloxazolones [28][29][30]56]. Signals corresponding to the activation of other C-H bonds present in oxazolones 2 (styryl, aryl) were not observed, so the reaction shows full selectivity towards the ortho-arylidene positions despite the presence of different C-H bonds that could be activated.…”

“…However, irradiation of solutions of 2 in CD 2 Cl 2 with blue LED light (465 nm), under the same conditions as reported previously by us for similar oxazolones [27], did not produce the expected cyclobutanes or gave only very low conversions (<5%) after long reaction times (96 h). As this reactivity was poor, it was decided to attempt the reaction using Pd complexes as templates [28][29][30]. The first step in this process was to study the C-H bond activation in oxazolones 2 promoted by Pd(OAc) 2 , which shows multiple possibilities ( Figure 2b).…”

“…Our group is interested in the synthesis of 1,3-diaminotruxillic derivatives and we have made some contributions to this area of research [27][28][29][30]. Firstly, we demonstrated that (Z)-4-arylidene-2-aryl-5(4H)-oxazolones ( Figure 2a) are excellent precursors for the synthesis of this type of derivative, both by irradiation of the free species [27] and on using Pd complexes as templates [28][29][30]. The latter approach has shown good potential as a synthetic tool because it allows 1,3-diaminotruxillic derivatives to be obtained in a fully regio-and stereoselective way (only the ε-isomer is obtained).…”

“…The process requires very mild reaction conditions in only three steps, with moderate to high yields in short reaction times under flow conditions [29], and it is compatible with substituents with different electronic properties (electron-releasing or electron-withdrawing) in the 4-arylidene ring. In addition, the ortho-position of the 2,4-aryl rings in the resulting bis-amino acids can be functionalized [30].…”

Protein-Pd Complexes Conjugates as Artificial Enzymes

“…Palladium complexes have shown a great relevance in different areas, especially in catalytic application in different process such as C-C bond formation, C-H activation, reduction, multicomponent processes, [1,2] but also in biomedical applications [3] and as GFP-like fluorophores. [4,5] Metalloenzymes are natural biological catalysts. They contain a metal nucleus involved in their catalytic activity in many important biological processes.…”