One-pot Pd Research Articles

A one-pot Pd- and P450-catalyzed chemoenzymatic synthesis of a library of oxyfunctionalized biaryl alkanoic acids leveraging a substrate anchoring approach

A one-pot chemoenzymatic approach was developed by combining Palladium-catalysis with selective cytochrome P450 enzyme oxyfunctionalization. Various iodophenyl alkanoic acids could be coupled with alkylphenyl boronic acids to generate a series of alkyl substituted biarylalkanoic acids in overall high yield. The identity of the products could be confirmed by various analytical and chromatographic techniques. Addition of an engineered cytochrome P450 heme domain mutant with peroxygenase activity upon completion of the chemical reaction resulted in the selective oxyfunctionalization of those compounds, primarily at the benzylic position. Moreover, in order to increase the biocatalytic product conversion, a reversible substrate engineering approach was developed. This involves the coupling of a bulky amino acid such as L- phenylalanine or tryptophan, to the carboxylic acid moiety. The approach resulted in a 14 to 49% overall biocatalytic product conversion increase associated with a change in regioselectivity of hydroxylation towards less favored positions.

Palladium Catalyzed, Annulative Multiple C-H Bond Activations of BODIPYs to Access π-Extended Polycyclic Heteroaromatic Molecules with Deep Red Emissions and self-aggregation Behaviors.

Aromatic ring fusion on BODIPY core can effectively tune its electronic property, and red-shift the absorption and emission wavelength. In this work, we report that a one-pot Pd(II) catalyzed multiple C-H activation to access acenaphtho[b]-fused BODIPYs though the reaction of α,β-unsubstituted-BODIPYs and 1,8-dibromonaphthalenes. These newly synthesized acenaphtho[b]-fused BODIPYs revealed intensified deep red absorptions (639 - 669 nm) and emissions (643 - 683 nm), with high fluorescence quantum yields (0.53 - 0.84) in dichloromethane. Notably, these acenaphtho[b]-fused BODIPYs exhibited well-defined self-aggregation behavior in water/THF mixture, and for instance, the absorption of 3a was red-shifted by 53 to 693 nm after formingaggregates.

Multicomponent reaction comprising one-pot installation of bidentate directing group and Pd(II)-catalyzed direct β-arylation of C(sp3)[sbnd]H bond of aliphatic and alicyclic carboxamides

In this paper, we report a step-economical one-pot multicomponent reaction protocol comprising the installation of the bidentate directing group (auxiliary) followed by Pd(II)-catalyzed sp3 CH activation and β-arylation of various aliphatic/alicyclic carboxamides. Accordingly, the reaction of a mixture of an aliphatic/alicyclic acid chloride, bidentate directing auxiliary (e.g., 8-aminoquinoline) and an aryl iodide in the presence of the Pd(OAc)2 catalyst and Ag2CO3 additive directly afforded the corresponding β-CH-arylated N-(quinolin-8-yl)carboxamide derivative. To demonstrate the efficiency of the process, various bidentate directing auxiliaries were used and 8-Aminoquinoline was found to be the best directing group for accomplishing the one-pot Pd(II)-catalyzed, sp3 CH activation and β-arylation of aliphatic/alicyclic carboxamides. A variety of aliphatic/alicyclic acid chlorides and aryl iodides were used as the substrates and several β-CH arylated carboxamide derivatives were synthesized in moderate to high yields via the multicomponent reaction strategy.

Dehydrogenative Allylic Aminations of But-3-enoic Acid Derivatives

Two complementary Pd-catalyzed protocols enabling the γ-selective intermolecular allylic amination of but-3-enoic acid derivatives are reported. These transformations can be successfully achieved via either­ a direct Pd(II)-catalyzed protocol or by way of a one-pot Pd(II)/Pd(0)-catalyzed sequence, depending on the nature of the nitrogen nucleophile used.

A versatile approach to flavones via a one-pot Pd(II)-catalyzed dehydrogenation/oxidative boron-Heck coupling sequence of chromanones.

A variety of flavones were expediently synthesized from readily accessible chromanones via a one-pot sequence involving Pd(II)-catalyzed dehydrogenation and oxidative boron-Heck coupling with arylboronic acid pinacol esters. In particular, the use of arylboronic acid pinacol esters was found to significantly improve the yield of the reaction.

Efficient syntheses of [¹¹C]zidovudine and its analogs by convenient one-pot palladium(0)-copper(I) co-mediated rapid C-[¹¹C]methylation.

The nucleosides zidovudine (AZT), stavudine (d4T), and telbivudine (LdT) are approved for use in the treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. To promote positron emission tomography (PET) imaging studies on their pharmacokinetics, pharmacodynamics, and applications in cancer diagnosis, a convenient one-pot method for Pd(0)-Cu(I) co-mediated rapid C-C coupling of [(11)C]methyl iodide with stannyl precursor was successfully established and applied to synthesize the PET tracers [(11)C]zidovudine, [(11)C]stavudine, and [(11)C]telbivudine. After HPLC purification and radiopharmaceutical formulation, the desired PET tracers were obtained with high radioactivity (6.4-7.0 GBq) and specific radioactivity (74-147 GBq/µmol) and with high chemical (>99%) and radiochemical (>99.5%) purities. This one-pot Pd(0)-Cu(I) co-mediated rapid C-[(11)C]methylation also worked well for syntheses of [methyl-(11)C]thymidine and [methyl-(11)C]4'-thiothymidine, resulting twice the radioactivity of those prepared by a previous two-pot method. The mechanism of one-pot Pd(0)-Cu(I) co-mediated rapid C-[(11)C]methylation was also discussed.

Oxygen as single oxidant for two steps: base-free one-pot Pd(ii)-catalyzed alcohol oxidation & arylation to halogen-intact β-aryl α,β-enones

Using oxygen as the sole oxidant for two steps, we developed a new method to synthesize β-aryl α,β-enones by fine-tuning the Pd(ii)-catalyzed oxidation of allyl alcohol to subsequent arylation with arylboronic acids, arylboronic ester and aryltrifluoroborate salt.

Synthesis of new tetracyclic azaheteroaromatic cores via auto-tandem Pd-catalyzed and one-pot Pd- and Cu-catalyzed double C–N bond formation

Inter- and intramolecular transition metal-catalyzed amination of 2-chloro-3-iodopyridine and 2,3-dibromopyridine, respectively, with benzodiazinamines yielded six hitherto unknown tetracyclic azaheteroaromatic cores. C–N bond formation was achieved via auto-tandem (Pd-catalyst) as well as one-pot (sequential use of a Pd- and Cu-catalyst) catalysis.