Successive C-C coupling of dienes to vicinally dioxygenated hydrocarbons: ruthenium catalyzed [4 + 2] cycloaddition across the diol, hydroxycarbonyl, or dione oxidation levels.

The ruthenium(0) catalyst generated from Ru3(CO)12 and tricyclohexylphosphine or BIPHEP promotes successive C-C coupling of dienes to vicinally dioxygenated hydrocarbons across the diol, hydroxyketone, and dione oxidation levels to form products of [4 + 2] cycloaddition. A mechanism involving diene-carbonyl oxidative coupling followed by intramolecular carbonyl addition from the resulting allylruthenium intermediate is postulated.

Expedient synthesis of 3-alkoxymethyl- and 3-aminomethyl-pyrazolo[3,4-b]pyridines.

An effective strategy has been developed for the preparation of 3-alkoxymethyl-pyrazolo[3,4-b]pyridines, compounds that are currently not readily accessible by existing synthetic methods. Further manipulation of these compounds allows for access to 3-alkoxymethyl-pyrazolo[3,4-b]pyridines with a variety of substitution patterns as well as 3-aminomethyl-pyrazolo[3,4-b]pyridines.

A highly efficient asymmetric synthesis of vernakalant.

A novel synthesis of vernakalant is described. Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral centers in the cyclohexane ring, and (3) a pyrrolidine ring formation via alkyl-B(OH)2-catalyzed amidation and subsequent imide reduction.