Directing groups benzamide

In addition to the perfluoroalkylation of arenes Pd(dba)2 competently facilities the ortho-C-H amination of A-aryl benzamides with electrophilic 0-benzoyl hydroxylamines. Pd(dba)2 showed equal reactivity to other precatalysts, such as Pd(OAc)2. Although mechanistically unclear, the addition of AgOAc signiflcantly improved conversion, while the addition of external phosphine ligands was detrimental. Finally, the 4-CF3(C6p4) directing group was optimal because acidic N-H bonds are essential for this transformation (eq 36). ... 

The use of A, A/ -bidentate directing group in the carbonylation of C-H bonds has been achieved by the use of carbon monoxide (CO) as the carbonyl source in conjunction with Ru3(CO)i2 [40] or Co(acac)2 as the catalysts [41]. Ge recently reported on the Ni(ll)/Cu(ll)-catalyzed carbonylation of benzamides containing an 8-aminoquinoline as the directing group with DMF as the carbonyl source (Scheme 15) [42]. The presence of both a Ni and a Cu catalyst was required for the reaction to proceed. The product yield was improved by the addition of a... 

The use of benzamides as the directing group has been successfully implemented in Yu s group, wherein Pd-catalyzed ortho C—H activation and selective... 

By using 8-aminoquinoline benzamide substrates and picolinic acid auxiliaries as the directing groups, the Daugulis group reported a novel method for selective mono- or di-fluorination of arene and heteroarene C—H bonds. AgF was used as fluoride source and DMF, pyridine, or DMPU as solvent. This Cu-promoted C—H activation method shows excellent functional group tolerance and provides a straightforward way for the preparation of ortto-fluorinated benzoic acids (Scheme 9.14). ... 

By modification of the directing groups, [Cp RhCl2]2 is capable of catalyzing the oxidative olefination of benzamides (eq 8) and iV-(l-napthyl)sulfonamides (eq 9) with acrylates followed... 

The Glorius group independently reported a Rh(III)-catalyzed intramolecular C-H cyclization of tethered olefin-containing benzamides (Scheme 6.12) [22]. Noteworthy, a redox-neutral CONHPiv directing group was used. 

One example by Glorius and co-workers showed that a Rh(m) catalyst in the presence of a AgSbFg co-catalyst, could successfully couple two arenes with the use of a tertiary benzamide directing group (Scheme 6.12). ... 

Scheme 6.12 Rh-Catalyzed biaiyl CDC with a tertiaiy benzamide directing group. ...

Hydroxylation of 711 at C-2 can be achieved by an intramolecular conjugate addition of the benzamide to the enone system. The reaction takes place in high yield in the presence of a Lewis acid and affords direct hydroxylation with a syn relationship to the amide group via an intermediate 1,3-oxazoline (Scheme 7.223). " ... 

The reversed sense of diastereoselectivity is also observed in the direct Birch reduction alkylation of a number of ort/w-alkylated benzamides of 2-(methoxymethyl)pyrrolidine [i.e., l-(2-alkylbenzoyl)-2-(methoxymethyl)pyrrolidines, 8] which also give high diastereoselectivities of a-methylated products (see Table 6)33. Diastereomeric ratios (TR/TS) for the different R groups range from 5 95 for R = ethyl to 2 98 for R = 2-(tm-butyldimethylsilyloxy)ethyl33. 

Mills, Taylor and Snieckus103 describe a methodology based on the preferre o metallation of benzamides (equation 40). In this case the trimethylsilyl group is use to block one of the ortho positions, directing the electrophile to the other. 

Generally, the direct metallation of unactivated alkyl groups is not a synthetically useful reaction. However, under certain circumstances unactivated a-silylcarbanion formation has been reported. Treatment of orf/zo-silylated benzamides 149 with LDA gave an a-silyl carbanion 150, stabilized by a complex-induced proximity effect, which then underwent... 

The first application of the AA process was the short and efficient synthesis of the paclitaxel (Taxol) side chain 32 (Scheme 4) [58]. The hydroxysulfonamide 31 crystallized directly from the reaction mixture (69% yield, 82% ee) and was transformed to 32 in two steps. The procedure was further improved when the acetamide-AA was discovered [22]. The hydroxyactamide 33 was easily obtained in good yield (71%) and excellent ee (99% ee) and removal of the N-protecting group was nearly quantitative. A direct benzamide-AA gave 34, the isopropyl ester of 32, in a single step, though with lower yield (46%) than the acetamide-AA [24]. 

Direct synthesis of atropisomeric benzamides and anilides from prochiral precursors has been reported using chiral-amide-mediated deprotonation of 2,6-dimethyl-substituted ben-zamide and anilide chromium complexes. A screening of amides revealed that (R,R) 3 was the most selective in the deprotonation of the benzylic methyl groups (Scheme 51)92 94. 

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