On the Triple Role of Fluoride Ions in Palladium-Catalyzed Stille Reactions.

The mechanism of Stille reactions (cross-coupling of ArX with Ar'SnnBu3 ) performed in the presence of fluoride ions is established. A triple role for fluoride ions is identified from kinetic data on the rate of the reactions of trans-[ArPdBr(PPh3 )2 ] (Ar=Ph, p-(CN)C6 H4 ) with Ar'SnBu3 (Ar'=2-thiophenyl) in the presence of fluoride ions. Fluoride ions promote the rate-determining transmetallation by formation of trans-[ArPdF(PPh3 )2 ], which reacts with Ar'SnBu3 (Ar'=Ph, 2-thiophenyl) at room temperature, in contrast to trans-[ArPdBr(PPh3 )2 ], which is unreactive. However, the concentration ratio [F(-) ]/[Ar'SnBu3 ] must not be too high, because of the formation of unreactive anionic stannate [Ar'Sn(F)Bu3 ](-) . This rationalises the two kinetically antagonistic roles exerted by the fluoride ions that are observed experimentally, and is found to be in agreement with the kinetic law. In addition, fluoride ions promote reductive elimination from trans-[ArPdAr'(PPh3 )2 ] generated in the transmetallation step.

Oxidative Addition of Haloheteroarenes to Palladium(0): Concerted versus SN Ar-Type Mechanism.

The kinetics of the oxidative additions of haloheteroarenes HetX (X=I, Br, Cl) to [Pd(0) (PPh3 )2 ] (generated from [Pd(0) (PPh3 )4 ]) have been investigated in THF and DMF and the rate constants have been determined. In contrast to the generally accepted concerted mechanism, Hammett plots obtained for substituted 2-halopyridines and solvent effects reveal a reaction mechanism dependent on the halide X of HetX: an unprecedented SN Ar-type mechanism for X=Br or Cl and a classical concerted mechanism for X=I. These results are supported by DFT studies.

Removal of the pyridine directing group from α-substituted N-(pyridin-2-yl)piperidines obtained via directed Ru-catalyzed sp3 C-H functionalization.

Two strategies, "hydrogenation-hydride reduction" and "quaternization-hydride reduction", are reported that make use of mild reaction conditions (room temperature) to efficiently remove the N-pyridin-2-yl directing group from a diverse set of C-2-substituted piperidines that were synthesized through directed Ru-catalyzed sp(3) C-H functionalization. The deprotected products are obtained in moderate to good overall yields irrespective of the strategy followed, indicating that both methods are generally equally effective. Only in the case of 2,6-disubstituted piperidines, could the "quaternization-hydride reduction" strategy not be used. The "hydrogenation-hydride reduction" protocol was successfully applied to trans- and cis-2-methyl-N-(pyridin-2-yl)-6-undecylpiperidine in a short synthetic route toward (±)-solenopsin A (trans diastereoisomer) and (±)-isosolenopsin A (cis diastereoisomer). The absolute configuration of the enantiomers of these fire ant alkaloids could be determined via VCD spectroscopy.

Ruthenium-catalyzed α-(hetero)arylation of saturated cyclic amines: reaction scope and mechanism.

Transition-metal-catalyzed sp(3) C-H activation has emerged as a powerful approach to functionalize saturated cyclic amines. Our group recently disclosed a direct catalytic arylation reaction of piperidines at the α position to the nitrogen atom. 1-(Pyridin-2-yl)piperidine could be smoothly α-arylated if treated with an arylboronic ester in the presence of a catalytic amount of [Ru3(CO)12] and one equivalent of 3-ethyl-3-pentanol. A systematic study on the substrate and reagent scope of this transformation is disclosed in this paper. The effect of substitution on both the piperidine ring and the arylboronic ester has been investigated. Smaller (pyrrolidine) and larger (azepane) saturated ring systems, as well as benzoannulated derivatives, were found to be compatible substrates with the α-arylation protocol. The successful use of a variety of heteroarylboronic esters as coupling partners further proved the power of this direct functionalization method. Mechanistic studies have allowed for a better understanding of the catalytic cycle of this remarkable transformation featuring an unprecedented direct transmetalation on a Ru(II)-H species.

Direct α-functionalization of saturated cyclic amines.

Recent advances in synthetic methods for the direct α-functionalization of saturated cyclic amines are described. Methods are categorized according to the in situ formed reactive intermediate (α-amino cation, α-amino anion, and α-amino radical). Transition-metal-catalyzed reactions involving other intermediates have been treated as a separate and fourth class.

Pedometer accuracy in slow walking older adults.

The purpose of this study was to determine pedometer accuracy during slow overground walking in older adults (Mean age = 63.6 years). A total of 18 participants (6 males, 12 females) wore 5 different brands of pedometers over 3 pre-set cadences that elicited walking speeds between 0.3 and 0.9 m/s and one self-selected cadence over 80 meters of indoor track. Pedometer accuracy decreased with slower walking speeds with mean percent errors across all devices combined of 56%, 40%, 19% and 9% at cadences of 50, 66, and 80 steps/min, and self selected cadence, respectively. Percent error ranged from 45.3% for Omron HJ105 to 66.9% for Yamax Digiwalker 200. Due to the high level of error across the slowest cadences of all 5 devices, the use of pedometers to monitor step counts in healthy older adults with slower gait speeds is problematic. Further research is required to develop pedometer mechanisms that accurately measure steps at slower walking speeds.

A superior precursor for palladium(0)-based cross-coupling and other catalytic reactions.

The easily synthesized, easily handled compound Pd(eta(3)-1-PhC(3)H(4))(eta(5)-C(5)H(5)) (II) reacts readily with mono- and bidentate tertiary phosphines to produce the corresponding bis-phosphine palladium(0) complexes in good yields; II is thus an excellent precursor, perhaps the most efficacious and reliable available, for the synthesis of palladium(0) cross-coupling catalysts.