New water soluble Pd-imidate complexes as highly efficient catalysts for the synthesis of C5-arylated pyrimidine nucleosides

Abstract

Recyclable water-soluble Pd complexes were revealed as excellent catalysts for Suzuki–Miyaura cross-coupling of challenging substrates like the antiviral nucleoside analogue 5-iodo-20-deoxyuridine.

Scale-Up of a Heck Alkenylation Reaction: Application to the Synthesis of an Amino-Modifier Nucleoside ‘Ruth Linker’

“…Our research group has over the years developed more efficient palladium-based catalytic systems involving caged phosphine ligands such as triazaphosphaadamantane (PTA) and its derivatives (PTABS and PTAPS). 30 These ligand systems either as complexes of palladium (e.g., PTA complexes such as [Pd(Sacc) 2 (PTA) 2 ] Cat 2 or [Pd(Mal) 2 (PTA) 2 ] Cat 3 shown in Figure 1) [31][32][33] or in situ activation with a palladium precursor [PTABS with Pd(OAc) 2 ] 34 have been effective in catalyzing the modification of nucleosides (Suzuki-Miyaura, Heck alkenylation, Sonogashira coupling, aminocarbonylation) 30,35 as well as the functionalization of chloroheteroarenes (amination, etherification, and thioetherification). [36][37][38] In 2015, utilization of [Pd(Sacc) 2 (PTA) 2 ] catalytic system in catalyzing the Heck alkenylation at 1.0 mol% concentration for 5′-O-DMTr-5-iodo-2′-deoxyuridine failed…”

“…The usefulness of PTABS as caged phosphine ligand in palladium-catalyzed cross-coupling reactions was first demonstrated by our group for a variety of applications. [32][33][34][35] Small-scale synthesis of zwitterionic ligand was accomplished by the reaction of 1,3,5-triaza-7-phosphaadamantane (PTA) with 1,4-butanesultone (Scheme 3). 34 Therefore to achieve the large-scale synthesis of PTABS, PTA would be required on a multigram scale.…”

C‐C Bond Formation: Synthesis of C5 Substituted Pyrimidine and C8 Substituted Purine Nucleosides Using Water Soluble Pd‐imidate Complex

“…This protocol describes the synthesis of the [Pd(Sacc) 2 (TPA) 2 ] IA complex from precursor [Pd(Sacc) 2 (Me 2 S) 2 ] I by treating with a neutral monodentate TPA ligand (molar ratio 1:2; Kapdi et al, 2014) as depicted in Figure 1.37.1. The intermediate complex [Pd(Sacc) 2 (Me 2 S) 2 ] I is synthesized by stirring palladium(II) acetate in dimethyl sulfide (as the solvent) at room temperature in the presence of a stoichiometric amount of saccharine (molar ratio of 1:2 for Pd:saccharin).…”

“…: (Kapdi et al, 2014) 162.4, 150.3, 138.3, 133.5, 128.4, 128.2, 127.5, 113.7, 87.8, 84.7, 70.5, 61.2, 40.1. 5, 150.2, 148.7, 148.5, 137.5, 126.1, 120.7, 113.7, 112.0, 111.9, 87.9, 84.9, 70.7, 61.4, 55.9, 55.8, 41.4.…”

“…Although, in most cases, water in combination with organic solvents has been employed in carrying out such transformations (Western et al, 2003;Capek and Hocek, 2005;Capek et al, 2006;Hocek and Silhar, 2007;Cho and Shaughnessy, 2012). We have recently reported on a series of water-soluble palladium complexes, with preliminary catalyst activity being displayed against simple aryl halides and 2 -deoxypyrimidine nucleosides in water as a solvent (Kapdi et al, 2014). In this unit, we describe the Suzuki-Miyaura arylation of unprotected 2 -deoxypyrimidine and 2 -deoxypurine nucleosides (5-iodo-2 -deoxyuridine [1], 5-iodo-2 -deoxycytidine [4], 8-bromo-2 -deoxyguanosine [7], and 8-bromo-2 -deoxyadenosine [10]) using the water soluble [Pd(Sacc) 2 (TPA) 2 ] complex IA.…”