Arylacetic Acids in Organic Synthesis

Abstract

Arylacetic acids are widely used in organic reactions and their recent advances are summarized in six categories according to their triggered pathways: (1) the acid as directing group in ortho-or meta-CÀ H activation; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Reactions with alkenes, alkynes, aldehydes, amines, water, Grignard reagents, silanes and so forth are discussed. We hope this Minireview will promote future research in this area. Recently, the Zeng group [3g] reported a weakly coordinationassisted alkynylation of arylacetic acids with iridium catalysis under air atmosphere (Eq. 2-2). It was supported the sixmembered ring cycloiridiated 2.5 acted as the key intermediate. The alkynylation of indole, thiophene, pyrrole, and benzo[b] thiophene afforded better yields than phenylacetic acids. The acid moiety could also participated in the intramolecular ortho-CÀ H activation, which was developed by the Shi group to obtain lactonization 2.6 (Eq. 2-3) (Scheme 2). Meta-CÀ H ArylationThe study of Yu group [3e] in 2017 revealed a successful control of meta selectivity 3.1 of arylation from aryl iodides (Eq. 3-1). The use of mono-protected 3-amino-2-hydroxypyridine (as ligand) and 2-carbomethoxynorbornene (NBE-CO 2 Me) were crucial. In the absence of NBE-CO 2 Me, only ortho-arylated product was obtained. This method was still efficient in a gramsale (Scheme 3). Decarboxylation Decarboxylative CouplingAs shown in Scheme 4, the decarboxylation could generate benzyl radicals 4.1. Then, direct couplings of 4.1 with diverse [ + ] These authors contributed equally. Scheme 1. Six categories based on triggered mechanism. 2 3 4 5 6 7 8 . Passerini Three-Component ReactionThe Passerini reaction was the oldest multicomponent reaction (MCR) [37d] in which isocyanides, carboxylic acids and aldehydes were used. It was powerful for the rapid construction of complex molecules. The tactic to expand the scope of Passerini reaction was to use surrogates of the carbonyl partners. As described in Scheme 51, syn-chlorooximes, [37b] diazoketones, [37c] alcohols, [37d,e] azirines [37f] and isatins [37g] could be employed instead of aryl or alkyl aldehydes [37a] (Scheme 51). Besides, in 2018, Zhang and co-workers [37] have firstly reported asymmetric phosphoric acid-catalyzed four-component Ugi reaction, which Scheme 45. BTM-catalyzed cycloaddition. Scheme 46. HBTM-catalyzed cycloaddition. Scheme 47. TFA-catalyzed reaction. Scheme 48. Friedel-Crafts triggered tandem reactions. Scheme 49. C-acylation of 1,3-diones. Scheme 50. C-acylation of 1,3-indandiones.

Continuous Flow Photochemical and Thermal Multi-Step Synthesis of Bioactive 3-Arylmethylene-2,3-Dihydro-1H-Isoindolin-1-Ones

“…The developed reaction protocols may be transferred to more advanced and custom-designed continuous flow tandem reactors such as the Vapourtec UV-150 module [8,34]. The process furthermore demonstrates the synthesis potential of arylacetic acids [35] as well as photodecarboxylations [36][37][38].…”

Water-Mediated ortho-Carboxymethylation of Aryl Ketones under Ir(III)-Catalytic Conditions: Step Economy Total Synthesis of Cytosporones A–C

“…Aryl ketone having an ortho -carboxymethyl group represents an important structural motif found in many bioactive natural products and drug molecules (Figure ). , Additionally, aryl acetic acid and keto functionality make them a versatile intermediate for synthetic chemists . As a result, significant efforts have been made by the research community for the efficient synthesis of these molecules. − Apart from the Friedel Crafts acylation of the fully functionalized arenes (Scheme a), Rh-catalyzed hydroacylation of functionalized benzaldehyde with olefines emerged as an alternative strategy (Scheme b) .…”

Lithiated Oppolzer Enolates: Solution Structures, Mechanism of Alkylation, and Origin of Stereoselectivity

“…The bulk of the study focuses on the structures of aryl acetamide-derived enolates and their alkylation . Although this is logical given the prevalence of pharmaceutical agents with aryl propionate substructures and considerable room for further development of their syntheses using the Oppolzer enolates, the aryl acetamide-derived enolates are more structurally tractable than their alkyl counterparts.…”