ortho-Lithium/Magnesium Carboxylate-Driven Aromatic Nucleophilic Substitution Reactions on Unprotected Naphthoic Acids

Abstract

Substitution of an ortho-fluoro or methoxy group in 1- and 2-naphthoic acids furnishing substituted naphthoic acids occurs in good to excellent yields upon reaction with alkyl/vinyl/aryl organolithium and Grignard reagents, in the absence of a metal catalyst without the need to protect the carboxyl (CO(2)H) group. This novel nucleophilic aromatic substitution is presumed to proceed via a precoordination of the organometallic with the substrate, followed by an addition/elimination.

Exploration of Biaryl Carboxylic Acids as Proton Shuttles for the Selective Functionalization of Indole C–H Bonds

“…The carboxylic acid was isolated by column chromatography, using petroleum ether/ethyl acetate (PE:EA = 5:1) as the eluent to get a white solid (931 mg 75%). Spectral data is consistent with previous reports …”

“…Spectral data is consistent with previous reports. 40 1 H NMR (400 MHz, CDCl 3 ) δ 8.01 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 9.2 Hz, 2H), 7.61−7.53 (m, 2H), 7.51−7.39 (m, 4H), 7.35−7.28 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 173.6, 142.9, 138.7, 135.3, 132.9, 129.7, 128.2, 128.0, 128.0, 128.0, 127.9, 127.6, 126.8, 126.7, 126.0.…”

Role of Organolithium Aggregates and Mixed Aggregates in Organolithium Mechanisms

“…In favorable situations additions of organolithium reagents to suitably activated aromatic rings can be observed, , including fullerenes and nanotubes…”

Axially Chiral 1,1'‐Binaphthyl‐2‐Carboxylic Acid (BINA‐Cox) as Ligands for Titanium‐Catalyzed Asymmetric Hydroalkoxylation

“…Syntheses of unsymmetrical 1,1'‐binaphthyl‐2‐carboxylic acids mostly proceed along a few key routes, exemplified by: (I) Coupling approaches, such as Ullmann coupling of 1‐halo‐2‐naphthoic acid derivatives to BINA‐DiCox derivatives, or cross‐coupling of 1‐metalated 2‐methylnaphthalene to 2‐methyl‐1,1‐binaphthyls, followed by oxidation (CH 3 →CO 2 H) . (II) S N Ar reactions of 1‐naphthyl Grignard reagents with 1‐alkoxy‐2‐naphthoates or 1‐alkoxy‐2‐naphthyl‐oxazolines, developed by Meyers, Cram, and Miyano, which afford enantiomerically or diastereomerically enriched BINA‐Cox derivatives if chiral alkoxy leaving groups are present . (III) Partial syntheses of BINA‐DiCox or BINA‐Cox derivatives from 2,2'‐BINOL by alkoxycarbonylation of sulfonates,, , reductive carboxylation of phosphates, or alternatively via Sandmeyer cyanation of the bis‐diazonium salt from 2,2‐diamino‐1,1'‐binaphthyl.…”

“…To learn about effects of specific variables on stereoselectivity and yield, data from published examples, was collected and supplemented with selected new experiments, in which we analyzed the composition of crude reaction mixtures by qNMR methods (Table S4; Scheme , c). The strategy of Miyano et al to work in a low‐polarity medium (Et 2 O–PhH; Table S4, entry I, II), at high dilution (0.05 m ), while seemingly optimal to support the chelated transition state of the stereoselective reaction,, [26b] is inconvenient for scale‐up considering the resulting large reaction volumes. Hoveyda et al had obtained equally good results in THF–PhH at 0.25 m (entry III), which implies that neither the low polarity of co‐solvent ether nor high dilution are necessary.…”