Biaryl amides

Recent reports have emerged of several TRPV1 antagonists possessing a biaryl amide (14-16), urea (17), or urea isostere (18-20) scaffolds. Bicyclic derivatives 14-16 block capsaicin- or pH-stimulated calcium influx in FLIPR-based assays... 

Directed remote metalation (DreM) of biaryl amides and O-carbamates, conceptually based on the complex-induced proximity effect (CIPE) [15] provides, especially in view of their link to transition metal-catalyzed cross coupling regimens [16], general and versatile routes to fluorenones (16 —> 15, Scheme 4) [5,17] and biaryl amides (16 —> 17) [18] whose features are overriding Friedel-Crafts reactivity and yield enhancement in comparison to Suzuki-Miyaura coupling routes for highly hindered biaryls, respectively. Additional features of the O-carbamate DreM result is potential further DoM of 17 with appropriate phenol protection and cyclization to dibenzopyranones [18]. 

Beyond Do M The Directed Remote Metalation (DreM) of Biaryl Amides and O-Carbamates I 351... 

Scheme 36. Biaryl amide DreM. Versatile anionic Friedel-Crafts complements for assemblage of fluorenones and azafluorenones.

Biaryl Amide DreM. Versatile Anionic Friedel - Crafts Complements for Assemblege of Fluorenones and Azafluorenones... 

What of the feasibility of developing sequential DreM biaryl amide and O-carbamate reactions One attractive possibility (Scheme 25) involves remote anionic Fries rearrangement, 102 103 followed by remote methyl deprotonation and... 

The positive results observed in biaryl amide (Scheme 22) and O-carbamate (Scheme 23) DreM reactions, chemists Gilman, Truce, and Narasimhan, and the prince of serendipity all played roles in triggmng studies of caibanionic reactions of 2-amido 124 (DMG = CONEt2, X = SO2) and 2-O-carbamoyl 124 (DMG = OCONEt2, X = SO2) biaryl sulfones (Scheme 30). In fact, the mental insertion of any heteroatom X into biaryl 124 provokes questions regarding its anionic chanistry for DMG = CONEt2, by... 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

Fagnou and co-workers reported on the use of a palladium source in the presence of different phosphine ligands for the intramolecular direct arylation reaction of arenes with bromides [56]. Later, they discovered that new conditions employing palladium complex 27 promoted the direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls including different functionalities as ether, amine, amide and alkyl (Scheme 7.11) [57]. 

Electroreduction of the cobalt(II) salt in a mixture of either dimethylform-amide-pyridine or acetonitrile-pyridine as solvent, often in the presence of bipyridine, produces a catalytically active cobalt(I) complex which is believed to be cobalt(I) bromide with attached bipyridine ligands (or pyridine moieties in the absence of bipyridine). As quickly as it is electrogenerated, the active catalyst reduces an aryl halide, after which the resulting aryl radical can undergo coupling with an acrylate ester [141], a different aryl halide (to form a biaryl compound) [142], an activated olefin [143], an allylic carbonate [144], an allylic acetate [144, 145], or a... 

Other cases for amides Biaryl urea a laaaaal-[N H0]C(=O)[N H0]a... 

In a subsequent paper on the use of the Stille reaction to form biaryls,58 the reaction was carried out under ambient conditions to allow robotic automation of the process. Attachment of the tin species to resin was very straightforward, in that 4-tri-n-butylstannylphenyl acetic acid was linked to Rink amide resin simply using a DIC coupling. Loading of this species was determined by tin elemental analysis and correlated with a quantitative ninhydrin test of free amines remaining on the support (Scheme 24). 

Fluorous phase modifications of the Stille reaction were shown by Curran et al. to be accelerated by microwave irradiation.10 Similarly, Hallberg et al. demonstrated that such irradiation gives remarkably fast solid-phase Suzuki reactions, in the generation of biaryl units.9 Their reaction involved the coupling of a tethered (Rink amide TentaGel) aryl iodide or bromide with several boronic acids under 45 W of irradiation at 2450 MHz in sealed... 

Chiralcel CTA Cellulose triacetate, microcrystalline Amides, biaryl compounds ... 

Tri- and tetrazole aromatase inhibitors Mandelic amide Biaryl compounds Biaryl compounds Polycyclic aromatics Sulfur compounds Phosphorus compounds Nitrogen and cyano compounds... 

V. Remote aromatic metalation. An anionic Friedel-Crafts equivalent for the regioselective synthesis of condensed fluorenones from biaryl and m-teraryl 2-amides. /. Org. Chem. 1991, 56,1683-1685. 

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