Allylpalladium(II) Histidylidene Complexes and Their Application in Z‐Selective Transfer Semihydrogenation of Alkynes

Abstract

We have studied the use of amino acid histidine as a precursor for N-heterocyclic carbene (NHC) ligands. This natural amino acid possesses an imidazole substituent, which makes it an interesting NHC precursor that contains both an acid and an amino functionality. These functionalities may be used for further tuning of NHC complexes. We have developed routes for the synthesis of symmetric and dissymmetric alkyl, benzyl, and aryl-substituted histidinium salts.[a] Molecular Scheme 3. Synthesis of symmetrically substituted benzylic histidinium bromides. The Cyclic Urea ApproachSubsequently, we employed the cyclic urea approach, which allows the synthesis of dissymmetrically substituted histidinium salts and further tuning of the properties of the NHC metal complex. This is not straightforward because histidine has two tautomeric forms, which means that the δ-and the ε-nitrogen of the imidazole possess both imine and amine character (compound 4, Scheme 5). [20] Therefore, mixtures of regioisomers are obtained when the imidazole is reacted with one equivalent of an electrophile. To obtain the desired dissymmetrically substituted histidinium salts, we applied a route based on the report by Hodges and Chivikas, [17] and was improved by Brégeon et al. [30] (Scheme 4). Scheme 4. The cyclic urea route toward dissymmetrically substituted histidinium salts.This cyclic urea route induces regioselectivity because only the six-membered cyclic urea 5 can be formed. The second nitrogen atom can then be functionalized selectively through nucleophilic substitution. Subsequently, the R 1functionalized urea compounds can be ring-opened by reaction with an alcohol, which liberates the δ-nitrogen atom of the imidazole, and provides a carbamate-protected amine. The use of tBuOH affords the Boc-protected histidine, Eur. J. Inorg. Chem. 2015, 982-996

The Golden Age of Transfer Hydrogenation

“…The substitution of NHC catalysts has a significant influence on the selectivity of the transfer semihydrogenation reaction. To this end, Elsevier’s group prepared a series of NHCs ligands containing both an acid and an amino functionality using the amino acid histidine as precursor. Subsequently, the corresponding palladium–NHCs complexes 189 were synthesized and utilized as precatalysts in the Z -selective transfer semihydrogenation of alkynes.…”

“…With this catalytic protocol involving robust palladium–NHC precatalysts containing additional donor functionalities, good selectivities were determined. Moreover, compound 189c that possesses two picolyl functional groups provided the best catalytic performance …”

“…Moreover, compound 189c that possesses two picolyl functional groups provided the best catalytic performance. 571 Hua's group 572 found that [Pd(OAc) 2 ] was extremely active in the catalytic transfer semihydrogenation of internal alkynes bearing various functional groups, delivering the desired Zalkenes in 86−99% yields and 86−99% selectivities, using DMF/KOH as hydrogen source (Scheme 70). With this procedure, the synthesis of the natural product Z-combretastatin A-4 (190) that is useful in organic and medicinal chemistry with important biological activities was achieved by performing the semihydrogenation of 1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl) acetylene in 94% isolated yield and >99% selectivity.…”

Reactivity Study of Unsymmetrical β-Diketiminato Copper(I) Complexes: Effect of the Chelating Ring

“…To address these issues, four unsymmetrical N -aryl- N ′-alkyl β-diketiminato ligands bearing pendant pyridyl groups (Chart ) and their corresponding copper­(I) complexes were prepared and characterized. The results suggest that pendant pyridyl arms on the N -aryl- N ′-alkyl β-diketiminato ligands may act as hemilabile Lewis bases protecting the copper­(I) center. − According to IR and NMR studies, the length of the pyridyl arm influences the binding mode interconversion and binding ability of carbon monoxide in solution of these copper­(I) complexes. The steric demands of the N -aryl substituent group play only a minor role in the CO binding (on/off rate) and solution binding behavior.…”

Antiproliferative Activity of Functionalized Histidine‐derived Au(I) bis‐NHC Complexes for Bioconjugation

“…proposed histidine as a NHC precursor and synthesized Pd complexes . Further Ru, Rh, Pd and Ir complexes were reported for catalytic applications and only one Au(I) histidinylidene complex, with moderate IC 50 values against various cancer cell lines, has been considered for medicinal applications . It is a neutral Au(I) complex bearing a Boc‐protected α‐amino‐group, methyl wingtips and a methyl ester group, but neither the amino acid backbone was modified, nor the stability discussed …”