O-Methylarenehydroxamates as ortho-lithiation directing groups. Titanium(III)-mediated conversion of O-methyl hydroxamates to primary amides

Fisher, Lawrence E.; Caroon, Joan M.; Jahangir, _; Stabler, S. Russell; Lundberg, Scott; Muchowski, Joseph M.

doi:10.1021/jo00066a014

Cited by 54 publications

(24 citation statements)

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“…Its 1 H NMR spectrum, with the accompanying mass ion (MH + ) of 176, are consistent with the formation of the 6-membered N-methoxy isoquinolinone 3 (Scheme 3). 12 The formation of this unexpected side product is attributed to the formation of the minor Z-isomer of 1aa, which undergoes 6-endo-trig cyclization in the subsequent aza-Wacker reaction (anti-addition). In the absence of an accessible -hydride, the putative intermediate (A) undergoes a syn-coplanar-phenyl elimination to afford compound 3.…”

Section: Resultsmentioning

confidence: 98%

Synthesis of Isoindolinones by Pd-Catalyzed Coupling between N-Methoxybenzamide and Styrene Derivatives

2016

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An atom-economical protocol for a tandem process involving Fujiwara-Moritani-aza-Wacker reactions has been developed for the Pd-catalyzed coupling between N-methoxy benzamide with styrene derivatives. The generality of the methodology was demonstrated by the synthesis of a library of twentyfive 3-benzylidene isoindolinones in moderate to good yields. A further twenty-two 3-benzyl derivatives were obtained by telescoping the process with a catalytic hydrogenation reaction.

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Section: Resultsmentioning

confidence: 98%

Synthesis of Isoindolinones by Pd-Catalyzed Coupling between N-Methoxybenzamide and Styrene Derivatives

2016

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“…Prior to undertaking further ligand screening, we needed to identify conditions under which the known decomposition of the N -methoxyamide to the unreactive ester via a radical process 10a–c was minimized (Table 1). The use of (2,2,6,6-tetramethylpiperidin-1-yl)oxy (TEMPO) to inhibit the radical process led to a slight drop in product yield (Table 1, entry 2).…”

Section: Resultsmentioning

confidence: 99%

“…This reasoning has led us to develop another acidic amide auxiliary (CONHAr F , Ar F = p -CF 3 C 6 F 4 ) that is compatible with aliphatic acid substrates containing α -hydrogen atoms (Figure 1). 9 Despite the broad utility of this new directing group, the simplicity of CONHOMe 10 in terms of installation and removal prompted us to develop new conditions that may overcome the limitation of this potentially broadly useful auxiliary. Our recent collaboration with Bristol-Myers Squibb to establish a robust and scalable method for the preparation of a wide range of unnatural amino acids through C–H functionalization of readily available amino acids such as alanine provided a further incentive for this endeavor.…”

Section: Introductionmentioning

confidence: 99%

Ligand-Enabled β-C–H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary

et al. 2015

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Pd-catalyzed β-C–H functionalizations of carboxylic acid derivatives using an auxiliary as a directing group have been extensively explored in the past decade. In comparison to the most widely used auxiliaries in asymmetric synthesis, the simplicity and practicality of the auxiliaries developed for C–H activation remains to be improved. We previously developed a simple N-methoxyamide auxiliary to direct β-C–H activation, albeit this system was not compatible with carboxylic acids containing α-hydrogen atoms. Herein we report the development of a pyridine-type ligand that overcomes this limitation of the N-methoxyamide auxiliary, leading to a significant improvement of β-arylation of carboxylic acid derivatives, especially α-amino acids. The arylation using this practical auxiliary is applied to the gram-scale syntheses of unnatural amino acids, bioactive molecules and chiral bis(oxazoline) ligands.

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“…From a brief search of the literature, we noticed that O-methyl hydroxamic acid had been used as a masked ester in synthesis. [13a,13b] Furthermore, a few examples of ortho -lithiation using this chelating group have also been reported [13c,13d] We reasoned that the well-balanced acidity would allow us to generate an imidate structure under mildly basic conditions. Such an imidate is anticipated to have a slightly improved coordinating ability to Pd(II) as compared to an alkali carboxylate.…”

Section: Palladium Catalysismentioning

confidence: 99%

A Simple and Versatile Amide Directing Group for C−H Functionalizations

et al. 2016

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Achieving selective C–H activation at a single and strategic site in the presence of multiple C–H bonds can provide a powerful and generally useful retrosynthetic disconnection. In this context, the directing group serves as a compass to guide the transition metal to C–H bonds using distance and geometry as powerful recognition parameters to distinguish between proximal and distal C–H bonds. However, the installation and removal of directing groups is a practical drawback. To improve the utility of this approach, one can seek solutions in three directions. First, simplifying the directing group; Second, use of common functional groups or protecting groups as directing groups; Third, attaching the directing group to substrates via a transient covalent bond to render directing groups catalytic. This review describes the rational development of an extremely simple and yet broadly applicable directing group for Pd(II), Rh(III) and Ru(II) catalysts, namely, the N-methoxy amide (CONHOMe). Through collective efforts in the community, a wide range of C–H activation transformations using this type of simple directing groups has been developed.

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O-Methylarenehydroxamates as ortho-lithiation directing groups. Titanium(III)-mediated conversion of O-methyl hydroxamates to primary amides

Cited by 54 publications

References 0 publications

Synthesis of Isoindolinones by Pd-Catalyzed Coupling between N-Methoxybenzamide and Styrene Derivatives

Synthesis of Isoindolinones by Pd-Catalyzed Coupling between N-Methoxybenzamide and Styrene Derivatives

Ligand-Enabled β-C–H Arylation of α-Amino Acids Using a Simple and Practical Auxiliary

A Simple and Versatile Amide Directing Group for C−H Functionalizations

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