Using 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) as protecting groups and linker for oligodeoxynucleotide (ODN) synthesis, deprotection and cleavage are achieved under non-nucleophilic oxidative conditions. The nucleophile-sensitive thioester and α-chloroacetyl groups are conveniently incorporated into ODN sequences. The technology could be universally useful for electrophilic ODN synthesis.

Solid-phase synthesis of electrophilic oligodeoxynucleotides (ODNs) was achieved using dimethyl-Dmoc (dM-Dmoc) as amino protecting group. Due to the high steric hindrance of the 2-(propan-2-ylidene)-1,3-dithiane side product from deprotection, the use of excess nucleophilic scavengers such as aniline to prevent Michael addition of the side product to the deprotected ODN during ODN cleavage and deprotection was no longer needed. The improved technology was demonstrated by the synthesis and characterization of five ODNs including three modified ones. The modified ODNs contained the electrophilic groups ethyl ester, α-chloroamide, and thioester. Using the technology, the sensitive groups can be installed at any location within the ODN sequences without using any sequence- or functionality-specific conditions and procedures.

Rh(III) -catalyzed N-nitroso-directed CH addition to ethyl 2-oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N-nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful CH functionalization-based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic-fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.

In traditional oligodeoxynucleotide (ODN) synthesis, phosphate groups are protected with the 2-cyanoethyl group, and amino groups are protected with acyl groups. At the end of ODN synthesis, deprotection is achieved with strong bases and nucleophiles. Therefore, traditional technologies are not suitable for the synthesis of ODNs containing sensitive functionalities. To address the problem, we report the use of Dim and Dmoc groups, which are based on the 1,3-dithian-2-yl-methyl function, for phosphate and amine protection for the solid phase ODN synthesis. Using the new Dim–Dmoc protection, deprotection was achieved under mild oxidative conditions without using any strong bases and nucleophiles. As a result, the new technology is suitable for the synthesis of ODNs containing sensitive functions. To demonstrate feasibility, seven 20-mer ODNs including four that contain sensitive ester and alkyl chloride groups were synthesized, purified with RP HPLC, and characterized with MALDI-TOF MS and enzyme digestion essays. High purity ODNs were obtained.

This protocol provides details for the preparation of nucleoside phosphoramidites with 1,3-dithian-2-yl-methyl (Dim) and 1,3-dithian-2-ylmethoxycarbonyl (Dmoc) as protecting groups, and a linker with Dmoc as the cleavable function, then using them for solid phase synthesis of sensitive oligodeoxynucleotides (ODNs). Using these Dim-Dmoc phosphoramidites and Dmoc linker, ODN synthesis can be achieved under typical conditions using phosphoramidite chemistry with slight modifications, and ODN deprotection and cleavage can be achieved under mild conditions involving oxidation with sodium periodate at pH 4 followed by aniline at pH 8. Under the mild deprotection and cleavage conditions, many sensitive functional groups including but not limited to esters, thioesters, alkyl halides, N-aryl amides, and α-chloroamides-which cannot survive the basic and nucleophilic deprotection and cleavage conditions such as concentrated ammonium hydroxide and dilute potassium methoxide used in typical ODN synthesis technologies-can survive. Thus, it is expected that the Dim-Dmoc ODN synthesis technology will find applications in the synthesis of ODNs that contain a wide range of sensitive functional groups.

Secondary alcohols were conveniently tritylated under mild conditions within a short running time with tritylium trifluoroacetate generated in situ from trityl alcohols and trifluoroacetic anhydride. No expensive silver salts were needed for the reactions. Four secondary alcohols were tritylated with both mono- and dimethoxy trityl alcohols giving good to excellent isolated yields. The reaction was also tested on four nucleoside derivatives that have primary alcohols. Satisfactory results were also obtained.

No abstract

Ring-opening metathesis polymerization (ROMP) has emerged as an important tool for the preparation of architecturally unique macromolecules from cyclic olefins. A wide variety of catalytic systems, ranging from simple metal salts to highly sophisticated alkylidene metal complexes, have been used for the achievement of this synthetically useful transformation. Especially, tremendous efforts have been directed toward the ruthenium-based catalytic systems as well as the understanding of their reactivity patterns. And Grubbs catalysts represent the ultimate in terms of activity, but they are not cost effective due to the sophisticated ligand. Therefore, alternative catalyst precursors that are more readily accessible have been and are still being actively developed. Therefore, a hydride ligand containing mononuclear ruthenium complex Ru(p-cymene)HClPCy 3 reported here was designed to catalyze ring-opening metathesis polymerization of norbornene with high activity. The hydride ligand is critical based on its high trans effect (for ligand dissociation) and the ability to generate carbene species through plausible migratory insertion and α-elimination steps. This catalytic system bearing hydride ligand could be an alternative for the well-defined Ru-based initiators which rules out the need of installation of complex ancillary ligands like NHC or O-Ligand in the coordination sphere or the need of activation with diazo compounds in the search for novel active catalytic species. Further study on the catalytic polymerization activity of Ru(p-cymene)H 2 PCy 3 compared to the Ru(p-cymene)HClPCy 3 system revealed that chloride ligand was also crucial to the hydride containing mononuclear ruthenium system, which contains easily dissociated ligand p-cymene and large phosphine ligand that stabilizes the metal complex. And the possible mechanism for the reaction was proposed.