Amphiphilic Biaryl Monophosphine Ligands by Regioselective Sulfonation

Abstract

Amphiphilic ligands are valued for their ability to facilitate organometallic reactions in the presence of water. The regioselective sulfonation of a series of commercially available biaryl monophosphines to generate amphiphilic ligands is presented. In this one-step protocol, the temperature and addition of fuming sulfuric acid were carefully controlled to arrive at sulfonated biaryl monophosphine ligands in high yields with >95% regioselectivity without the need for chromatographic purification.

Oligonucleotide Bioconjugation with Bifunctional Palladium Reagents

“…[15] Despite their high reactivity,b oth 1 and 2 required the use of an organic co-solvent (typically 5-10 % dimethylformamide or dimethyl sulfoxide) to generate ah omogeneous solution at high micromolar concentrations.T o circumvent this limitation, we utilized ah ighly water-soluble dialkyl biarylphosphine ligand, which is ab is-sulfonated analog of SPhos L1 (bsSPhos (L3), Figure 2A). [16] Theu se of the ligand L3 enabled the synthesis of the new,fully watersoluble NHS OAC 3.R eagent 3 facilitated the acylation of a10-mer 5'-amino modified oligonucleotide (O1)inaqueous buffer at millimolar concentrations,w herein NHS ester hydrolysis is minimized.…”

“…Small-molecule probes commonly used for detection, stabilization, isolation, and crosslinking can be efficiently modified with O1-OAC 8.B iotin (P1), polyethylene glycol (P2), the fluorophore carboxytetramethylrhodamine (TAM-RA, P3), and adiazirine-based photoreactive crosslinker (P4) were individually coupled to as hort peptide linker (ARA-RARARAC) containing asingle cysteine to both enhance the water solubility of the small molecule and provide asingle site for conjugation (Figure 7). Incubation of P1-4 with O1-OAC 8 in PBS (pH 7.5) provided the conjugates (16)(17)(18)(19)in82-99 % conversion, as determined by LC-MS analysis of the crude reaction mixtures (SI Figure S18). Thee fficiency of these coupling reactions demonstrates that the isolated 8 can react with aw ide range of thiol-containing molecules despite the presence of potentially competing nucleophiles.…”

A mechanistic investigation of the Pd-catalyzed cross-coupling betweenN-tosylhydrazones and aryl halides

“…The use of a commercially available Buchwald-type ligand with an inherent negative charge, sulfonated SPhos (sSPhos), has since lead the Buchwald group to create alternative sulfonated ligands on a large scale, such as sulfonated BrettPhos. 315 Additionally, this mode of analysis can be applied to any reaction in which order of addition is important, or to investigate order of addition. It has since been used to study the Suzuki polycondensation reaction.…”

Oligonucleotide Bioconjugation with Bifunctional Palladium Reagents

“…To circumvent this limitation, we utilized a highly water‐soluble dialkyl biarylphosphine ligand, which is a bis‐sulfonated analog of SPhos L1 (bsSPhos ( L3 ), Figure 2 A). [16] The use of the ligand L3 enabled the synthesis of the new, fully water‐soluble NHS OAC 3 . Reagent 3 facilitated the acylation of a 10‐mer 5′‐amino modified oligonucleotide ( O1 ) in aqueous buffer at millimolar concentrations, wherein NHS ester hydrolysis is minimized.…”