Synthesis of 2- and 2,3-substituted pyrazolo[1,5-a]pyridines: scope and mechanistic considerations of a domino direct alkynylation and cyclization of N-iminopyridinium ylides using alkenyl bromides, alkenyl iodides, and alkynes.

Direct functionalization and tandem processes have both received considerable recent interest due to their cost and time efficiency. Herein we report the synthesis of difficult to obtain 2-substituted pyrazolo[1,5-a]pyridines through a tandem palladium-catalyzed/silver-mediated elimination/direct functionalization/cyclization reaction involving N-benzoyliminopyridinium ylides. As such, these biologically important molecules are prepared in an efficient, high-yielding manner, only requiring a two-step sequence from pyridine. Aryl-substituted alkenyl bromides and iodides are effective ylide coupling partners. Mechanistic studies led to the use of terminal alkynes, which extended the scope of the reaction to include alkyl substitution on the unsaturated reactive site. The optimization, scope, and mechanistic considerations of the process are discussed.

Ligand-controlled selectivity in the desymmetrization of meso cyclopenten-1,4-diols via rhodium(I)-catalyzed addition of arylboronic acids.

A highly enantioselective desymmetrization of meso cyclopent-2-ene-1,4-diethyl dicarbonates has been developed using a Rh-catalyzed asymmetric allylic substitution. Depending on the type of ligand used, each of two regioisomeric products can be obtained in good yield and excellent enantioselectivity. Under rhodium(I) catalysis, bisphosphine P-Phos ligands form trans-1,2-arylcyclopentenols as the major product, whereas Segphos ligands lead predominantly to trans-1,4-arylcyclopentenols.

Transition-Metal-Free Amination of Pyridine-2-sulfonyl Chloride and Related N-Heterocycles Using Magnesium Amides.

A new transition-metal-free amination of pyridine-2-sulfonyl chloride and related N-heterocycles using magnesium amides of type R2NMgCl·LiCl is reported. Additionally, the directed ortho-magnesiation of pyridine-2-sulfonamides using TMPMgCl·LiCl was investigated. Reaction of the magnesium intermediates with various electrophiles and subsequent amination using magnesium amides led to a range of 2,3-functionalized pyridines. Also, cyclization reactions providing an aza-indole and an aza-carbazole were carried out.

Directed Zincation with TMPZnCl·LiCl and Further Functionalization of the Tropolone Scaffold.

The directed zincation of tropolone derivatives was achieved using TMPZnCl·LiCl. Various functionalizations of the zincated intermediates by halogenation, acylation, allylation, and Negishi cross-coupling were successfully performed. Additionally, 1,8-conjugate addition-elimination reactions with a variety of arylmagnesium and secondary alkylzinc reagents were carried out to further elaborate the tropolone core.

Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: facile access to spiro 3,3'-cyclopropyl oxindoles.

The Pd-catalyzed, Ag(I)-mediated intramolecular direct arylation of cyclopropane C-H bonds is described. Various spiro 3,3'-cyclopropyl oxindoles can be obtained in good to excellent yields from easily accessible 2-bromoanilides. The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway.

Nickel(0)/NaHMDS adduct-mediated intramolecular alkylation of unactivated arenes via a homolytic aromatic substitution mechanism.

A variety of polycycles can be synthesized via an intramolecular alkylation cyclization promoted by Ni(PPh(3))(4) and NaHMDS. Mechanistic investigations support the catalytic nature of Ni(0) in the course of TEMPO scavenging experiments and its association with the substrate and NaHMDS to form an adduct by DOSY NMR.