Copper-catalysed chemoselective C-OH bond activation of N-benzoyl cytosine: facile access to 2-(dimethylamino)pyrimidine.

A novel method for the direct amination of N-benzoyl cytosine has been developed, giving access to 2-(dimethylamino)pyrimidine derivatives. A copper(II) catalyst and tert-butyl hydroperoxide easily promote the selective amination process that proceeds via C-OH bond activation. This practical approach can utilize different formamide molecules, N,N-dimethylformamide and N,N-diethylformamide, as efficient amino (-NMe2, -NEt2) sources. Moreover, the facile nature of the procedure, its broad tolerance of aliphatic and aromatic substrates, the high yields and ease of separation of the products, and the fact that it can be conducted under aerobic conditions are all notable advantages of the present protocol.

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2'-deoxyuridine (or cytidine).

Nucleosides modification via conventional cross-coupling has been performed using different catalytic systems and found to take place via long reaction times. However, since the pandemic, nucleoside-based antivirals and vaccines have received widespread attention and the requirement for rapid modification and synthesis of these moieties has become a major objective for researchers. To address this challenge, we describe the development of a rapid flow-based cross-coupling synthesis protocol for a variety of C5-pyrimidine substituted nucleosides. The protocol allows for facile access to multiple nucleoside analogues in very good yields in a few minutes compared to conventional batch chemistry. To highlight the utility of our approach, the synthesis of an anti-HSV drug, BVDU was also achieved in an efficient manner using our new protocol. Supplementary Information: The online version contains supplementary material available at 10.1007/s41981-023-00265-1.

Zinc-catalyzed transamidation and esterification of N-benzoyl cytosine via C-N bond cleavage.

We have utilized N-benzoyl cytosine for efficient transamidation and esterification via catalytic C-N bond cleavage. The one-pot strategy involves the reaction of secondary amide with various aliphatic or aromatic amines and alcohols in the presence of zinc triflate and DTBP, affording diverse amides and esters in excellent yields.

Quadrol-Pd(II) complexes: phosphine-free precatalysts for the room-temperature Suzuki-Miyaura synthesis of nucleoside analogues in aqueous media.

Commercially available Quadrol, N,N,N',N'-tetrakis(2-hydroxypropyl)ethylenediamine (THPEN), has been used for the first time as a N^N-donor neutral hydrophilic ligand in the synthesis and characterization of new water soluble palladium(II) complexes containing chloride, phthalimidate or saccharinate as co-ligands. [PdCl2(THPEN)] (1) [Pd(phthal)2(THPEN)] (2), [Pd(sacc)2(THPEN)] (3) and the analogous complex with the closely related N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine (THEEN) [Pd(sacc)2(THEEN)] (4) were efficiently prepared in a one-pot reaction from [PdCl2(CH3CN)2] or Pd(OAc)2. Structural characterization of 1 and 3 by single crystal X-ray diffraction produced the first structures reported to date of palladium complexes with Quadrol. The resultant palladium complexes are highly soluble in water and were found to be effective as phosphine-free catalysts for the synthesis of functionalized nucleoside analogues under room-temperature Suzuki-Miyaura cross-coupling conditions between 5-iodo-2'-deoxyuridine (& 5-iodo-2'-deoxycytidine) with different aryl boronic acids in neat water. This is the first report of the coupling process performed on nucleosides in water at room temperature.