Design and synthesis of novel and potent GPR119 agonists with a spirocyclic structure.

Exploration of alternative structures of the substituted piperidine or piperazine ring which are characteristic in most of the reported GPR119 agonists provided novel spirocyclic cyclohexane derivatives. The representative 17 with a high three-dimensionality exhibited potent agonistic activity (EC50 = 4 nM) with no CYP inhibitory activity (IC50 >10 µM). Compound 17 also displayed hypoglycemic activity with insulin secretion dependent on glucose concentration in an intraperitoneal glucose tolerance test in rats.

Gold-catalysed intramolecular trans-allylsilylation of alkynes forming 3-allyl-1-silaindenes.

3-Allyl-1-silaindenes are synthesised from alkynes having an allylsilane moiety by a gold-catalysed intramolecular trans-allylsilylation reaction.

Synthesis of silafluorenes by iridium-catalyzed [2 + 2 + 2] cycloaddition of silicon-bridged diynes with alkynes.

[reaction: see text] Silicon-bridged 1,6-diynes underwent [2 + 2 + 2] cycloaddition with alkynes in the presence of an iridium(I)-phosphine catalyst to afford densely substituted silafluorene derivatives. Extended silafluorene skeletons were constructed by the [2 + 2 + 2] cycloaddition of tetraynes.

Ruthenium-catalysed double trans-hydrosilylation of 1,4-diarylbuta-1,3-diynes leading to 2,5-diarylsiloles.

Dihydrosilanes undergo double trans-hydrosilylation with 1,4-diarylbuta-1,3-diynes in the presence of a cationic ruthenium catalyst to afford 2,5-diarylsiloles: in particular, 9-silafluorene is a good hydrosilylating agent to produce spiro-type siloles in good yield.

Molybdenum-catalyzed ring-closing metathesis of allenynes.

A ring-closing metathesis reaction of allenynes occurred at room temperature in the presence of a molybdenum alkylidene complex to give ring-closed vinylallenes. The vinylallene skeletons were constructed by a metathesis-type reaction between the alkyne moiety and the proximal carbon-carbon double bond of the allene moiety. [reaction: see text]

Acids direct 2-styrylcyclobutanone into two distinctly different reaction pathways.

Two structurally distinct carbocycles were selectively obtained by the reactions of 2-(o-styryl)cyclobutanones promoted by ytterbium salts. Treatment of the cyclobutanones with YbCl(3) in 1,4-dioxane at 100 degrees C afforded 2-(2-chloroethyl)naphthalenes. On the other hand, the reaction with Yb(OTf)(3) in chlorobenzene at 130 degrees C gave 9,10-dihydrobenzocycloocten-7(8H)-ones.

Ruthenium-catalyzed trans-hydrogermylation of alkynes: formation of 2,5-disubstituted germoles through double trans-hydrogermylation of 1,3-diynes.

Reaction of triethylgermane and alkynes in the presence of a ruthenium catalyst occurred in a trans fashion. The ruthenium-catalyzed trans-hydrogermylation of 1,3-diynes with dihydrogermanes afforded 2,5-disubstituted germoles in good yield through a two fold addition process. The hydrogermylation reaction was successfully applied to synthesis of 2,2'-bigermole.