IndirectorthoFunctionalization of Substituted Toluenes throughorthoOlefination ofN,N-Dimethylbenzylamines Tuned by the Acidity of Reaction Conditions

Abstract

Highly regioselective olefination of substituted N,N-dimethylbenzylamines was developed by tuning the acidity of reaction conditions based on analysis of their features. The ortho-functionalized N,N-dimethylbenzylamines were further transformed into 3-(2'-tolyl)propanoic acid and its derivatives under mild conditions. These two transformations could be combined into one pot, and 3-(2'-tolyl)propanoic acid and its derivatives were obtained in moderate to good yields. Mechanistic studies indicated that electrophilic attack on the phenyl ring by the Pd(II) ion assisted by the N,N-dimethylaminomethyl group was a key step during this catalytic transformation, which was controlled by the acidity of the reaction conditions.

Aerobic Palladium(II)‐Catalyzed 5‐endo‐trig Cyclization: An Entry into the Diastereoselective C‐2 Alkenylation of Indoles with Tri‐ and Tetrasubstituted Double Bonds

“…Intermolecular coupling reactions are, however, limited to unhindered alkenes. If not functionalized with a directing group, [3] di-or even trisubstituted alkenes are usually not sufficiently reactive, [4,5] and the few successful oxidative coupling reactions are associated with selectivity problems [5] (I)II and III, Scheme 1, upper). This situation changes in the intramolecular variant, in which those alkenes participate indeed in CÀC couplings.…”

“…[20] We therefore cannot rule out either mechanism, but alkene activation appears to be a reasonable explanation for this endo ring closure. [2a] Known methods for the palladium(II)-catalyzed C-2 alkenylation of indoles (or arenes) with disubstituted alkenes are often not completely diastereoselective [5,21] and alkene migration is likely to interfere. [5c,d] Our three-step sequence avoids these issues, thus allowing the CÀH bond alkenylation of indoles to occur with complete diastereocontrol of the tetrasubstituted double bonds.…”

Synthetic Chemistry with an Eye on Future Sustainability

“…Hence less waste and good atom economy are features of this new methodology. Great progress has also been made recently in arene-arene coupling via the reaction of sp 2 C-H/sp 2 C-H bonds by several other laboratories [27]. Nitrogen-containing compounds are of great importance as building blocks for pharmaceuticals, agrochemicals, dyes, and ligands [28].…”

2‐Pyridyl Sulfoxide: A Versatile and Removable Directing Group for the PdII‐Catalyzed Direct CH Olefination of Arenes

“…[2-8] Very efficient procedures for the Pd IIcatalyzed aryl C À H alkenylation of aniline derivatives, [2] pyridine N-oxides, [3] aromatic carboxylic acids, [4] alcohols, [5] and amines, [6] as well as heteroaromatic compounds, [7] have been recently reported. [9] Most of these protocols require a directing group that aids in the carbometallation of a proximal C À H bond, a common strategy in CÀH functionalization.…”