Ortho Acylation Research Articles

α-Keto Acids: Acylating Agents in Organic Synthesis.

A significant number of important acyl-transfer reactions, such as direct acylation, ortho acylation, heteroatom acylation, and a diversity of cyclization reactions using the title compound as a key starting material, have been described in recent years. Just like a sleeping beauty, α-oxocarboxylic acids were awakened from a 17-year sleep to become important reagents in classical and new acylation reactions. The greener characteristic of the coproduct formed in reactions using α-keto acid (only CO2), together with its versatility as a building block in catalytic organic synthesis, accredit it as a candidate to green acylating agent, an alternative to acyl chloride, and other acyl-transfer reagents. This review presents the impressive breakthroughs achieved mainly in the past decade in the development of new catalytic reactions for the formation of C-C, C-N, and C-S bonds using α-keto acids.

Palladium/Norbornene-Catalyzed Indenone Synthesis from Simple Aryl Iodides: Concise Syntheses of Pauciflorol F and Acredinone A.

To show the synthetic utility of palladium/norbornene (Pd/NBE) cooperative catalysis, here we report concise syntheses of indenone-based natural products, pauciflorol F and acredinone A, which are enabled by direct annulation between aryl iodides and unsaturated carboxylic acid anhydrides. Compared to the previous indenone-preparation approaches, this method allows simple aryl iodides to be used as substrates with complete control of the regioselectivity. The total synthesis of acredinone A features two different Pd/NBE-catalyzed ortho acylation reactions for constructing penta-substituted arene cores, including the development of a new ortho acylation/ipso borylation.

Palladium-catalyzed one-pot Catellani reaction: An efficient synthesis of α-alkynyl aromatic ketones via ortho acylation and ipso alkynylation

A palladium-catalyzed and norbornene-mediated Catellani reaction was developed through ortho-acylation and ipso-alkynylation for the aryl iodides. Acyl chlorides were used as acylation reagents and phenylpropiolic acids were used as termination reagents respectively in this transformation. As a result, the reactivity of these three different compounds matched well and this unreported combination could be used extensively.

Palladium/Norbornene-Catalyzed ortho Aliphatic Acylation with Mixed Anhydride: Selectivity and Reactivity.

A palladium/norbornene-catalyzed ortho acylation for the efficient synthesis of functionalized alkyl aryl ketones is reported. Studies on the electronic and steric properties of mixed aryl anhydrides indicated that the cross-coupling favored with the electron-enriched aryl acyl group. DFT calculation on the oxidative addition of Pd(II) with 2,4,6-(Cl)3C6H2CO2C(O)Ph suggested that 2,4,6-(Cl)3C6H2C(O)-O bond cleavage was more kinetically disfavored than that of the PhC(O)-O bond by 11.7 kJ/mol.

Palladium‐Catalyzed Pyridine‐Directed Regioselective Oxidative C–H Acylation of Carbazoles by Using Aldehydes as the Acyl Source

We herein report a highly regioselective reaction for the palladium‐catalyzed oxidative acylation of carbazole derivatives with various aromatic and aliphatic aldehydes as the acyl source. The carbazole derivatives are N‐protected with an easily removable pyridine moiety, which directs the Pd‐catalyzed ortho acylation to occur at the C‐1 and C‐8 positions. The reactions of dibromo‐ and diiodo‐substituted N‐pyridylcarbazole derivatives, however, provide only the 1‐acylated products. This method can be applied to a broad scope of substrates. A reaction mechanism has also been proposed.

Palladium-Catalyzed Environmentally Benign Acylation.

Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp(2) C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.

Acylperoxycoumarins asortho-CH Acylating Agentviaa Palladium(II)-Catalyzed Redox-Neutral Process

An unprecedented palladium(II)-catalyzed biomimetic aliphatic acyl (-COR) group transfer was observed from acyl-α-peroxycoumarins to the ortho CH sites of directing arenes. Here, the CH activation is associated with a concomitant acyl group transfer via a Pd(II)-catalyzed, redox-neutral process. While methods for ortho aroylation (-COAr) are well documented ortho acylation (-COR) processes are scarce, hence the present redox-neutral method is most ideal for o-acylation of directing substrates.

ChemInform Abstract: Palladium‐Catalyzed Decarboxylative ortho Acylation of Azobenzenes with α‐Oxocarboxylic Acids.

AbstractThis protocol is compatible to functional groups and can be used for para, ortho, and unsymmetrical substituted azobenzenes.

ChemInform Abstract: Palladium‐Catalyzed Chemoselective Decarboxylative ortho Acylation of Benzoic Acids with α‐Oxocarboxylic Acids.

AbstractThe title reaction is realized with silver carbonate as oxidant in the presence of a Pd(II)‐catalyst.

ChemInform Abstract: Rhodium‐Catalyzed ortho Acylation of Aromatic Carboxylic Acids.

AbstractThe catalyst [Rh(cod)Cl]2 is found to direct the acylation of benzoic acids with anhydrides into the ortho position.

Palladium-Catalyzed Decarboxylative Ortho Acylation of Azobenzenes with α-Oxocarboxylic Acids

A palladium-catalyzed decarboxylative ortho acylation of azobenzenes with α-oxocarboxylic acids via ligand-directed C-H activation has been explored. The reaction proceeded smoothly with potassium persulfate as the oxidant to afford acylated unsymmetrical azobenzenes in moderate to good yields and tolerated chloro, bromo, iodo, and methoxy groups. Para, ortho, and disubstituted as well as unsymmetrical azobenzenes could be used.

Palladium-Catalyzed Chemoselective Decarboxylative Ortho Acylation of Benzoic Acids with α-Oxocarboxylic Acids

Palladium-catalyzed chemoselective decarboxylative cross coupling of benzoic acids with α-oxocarboxylic acids was realized via an arene sp(2) C-H functionalization process. This work represents the first example of transition-metal-catalyzed cross-coupling reactions with two acids acting in different roles. The synthetic utility of this method was confirmed by the synthesis of pitofenone, an antispasmodic used in the combined drug Spasmalgon.

Rhodium‐Catalyzed ortho Acylation of Aromatic Carboxylic Acids

New directions: The carboxylic acid functional group directs the ortho acylation of benzoic acids with carboxylic anhydrides in the presence of a rhodium catalyst (see scheme; cod=cyclo-1,5-octadiene). The acylation at the ortho position is complementary to the meta selectivity of Friedel–Crafts reactions. The resulting products can undergo protodecarboxylation to deliver an aryl ketone. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Design of New Reaction Conditions for the Sugasawa Reaction Based on Mechanistic Insights

A process to prepare 2-propionyl-4-bromoaniline by ortho acylation of 4-bromoaniline under Sugasawa conditions was developed. Upon scale-up in a pilot plant, the process gave lower yields than in the laboratory in four out of five plant runs. Analysis of the pilot-plant data, in conjunction with reaction calorimetric experiments, showed that expulsion of HCl from the reaction medium was key for obtaining high product yields. New reaction conditions were subsequently developed for carrying out ortho acylation of 4-bromoaniline (1). The reaction mixture containing aniline/BCl3/AlCl3/C2H5CN was added to a refluxing solution of toluene to allow for substantial HCl expulsion and thus obtain the optimum yield of the desired product. Aniline hydrochlorides were also shown to be suitable starting materials under these conditions. Mechanistic implications of these findings are discussed. The new reaction conditions significantly increased the yield.

In situ NMR spectroscopic studies of aniline ortho acylation (“sugasawa reaction”): The nature of reaction intermediates and Lewis acid influence on yield

Ortho acylation of anilines by nitriles in the presence of BCl 3 and a second Lewis acid appear to proceed through an intermediate “supercomplex” including all four components. Yield improvements were obtained based on recognition that chloride affinity of the second Lewis acid governs supercomplex formation. Aniline protonation was found to be the cause of incomplete reaction.

ChemInform Abstract: Preparation of “Unnatural” Tellurium Analogues of Naturally Occurring Chromones and Flavones. The Control of Ipso vs Ortho Acylation, Selective Demethylation, and Olefin‐Forming Condensation Reactions in Benzo(b)tellurapyranones.

AbstractIntramolecular acylation approaches to the title tellurium compounds are complicated by ipso acylation of the tellurium‐bearing ring as shown by the reaction of the acid chloride (I).

Preparation of unnatural tellurium analogs of naturally occurring chromones and flavones. Control of ipso vs. ortho acylation, selective demethylation, and olefin-forming condensation reactions in benzo[b]tellurapyranones

Preparation of unnatural tellurium analogs of naturally occurring chromones and flavones. Control of ipso vs. ortho acylation, selective demethylation, and olefin-forming condensation reactions in benzo[b]tellurapyranones

Aminohaloborane in organic synthesis. IX. Exclusive ortho acylation reaction of N-monoaminoalkylanilines.

The exclusive ortho acylation reaction of aniline derivatives using boron trichloride made possible the one-step synthesis of 2-acyl-N-monoaminoalkylanilines (1) and the corresponding imines (2) from N-monoaminoalkylanilines, even in the case of compounds with a bulky substituent at the nitrogen atom. Conventional methods only give 1 via elaborate procedures.

Template catalysis via non-transition metal complexes. New highly selective syntheses on phenol systems

Abstract

アニリン類のオルト特異的Ｆｒｉｅｄｅｌ‐Ｃｒａｆｔｓ反応

A new general process has been developed for specific ortho hydroxybenzylation of secondary anilines and specific ortho acylation of anilines using anilinodichloroboranes. The distinctive exchange of the reaction site of anilines in the presence of boron trichloride instead of other electrophilic metal halide is very noteworthy. The mechanistic hypothesis, scope and limitations and application are described.