RESUMO
We report a CO-free approach to indole-2-carboxylic esters: rhodium-catalysed C(2)-alkoxycarbonylation of indoles with 2,4,6-trimethylbenzoic acid-based carbonate anhydrides. Selective C-O bond cleavage of the anhydrides facilitates the introduction of various alkoxycarbonyl groups. Control experiments suggest that merging a rhodium catalyst and KI promotes the in situ formation of the RhI species.
RESUMO
We developed a rhodium-catalyzed chain-walking hydrothiolation process for internal alkenes, which offers a novel and efficient alternative for C(sp3)-H bond cleavage, while focusing on thiol incorporation. This method exclusively affords N,S-acetals at 36-90% yields. Regioconvergent hydrothiolation significantly improved the effectiveness of this transformation. Preliminary mechanistic investigations revealed that an amide-directing group is essential for regioselective synthesis, underlining its significance in this process.
RESUMO
Phthalimides are prevalent in numerous pharmaceuticals, prompting various phthalimide syntheses through C-H activation. Nevertheless, the necessity for stoichiometric additives limits their practicality and versatility. Herein, we introduced diethyl dicarbonate as a carbonyl source for an additive-free carbonylation of benzamides. This transformation signifies an operationally simple and CO-free phthalimide synthesis.
RESUMO
Stereoselective construction of unprotected ß-amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel copper-catalyzed diastereo- and enantioselective reductive Mannich-type reaction of α,ß-unsaturated carboxylic acids was developed, which provides a direct and scalable synthetic method for enantioenriched ß2,3,3 -amino acids with vicinal stereogenic centers. The protocol features inâ situ generation of transiently protected carboxylic acids by a hydrosilane and their diastereo- and enantioselective reductive coupling with ketimines. The synthetic utility of this process was demonstrated by a gram-scale reaction and the transformation of ß-amino acids.
RESUMO
We developed a rhodium-catalysed decarbonylative C(sp2)-H alkylation method for indolines. This reaction facilitates the use of alkyl carboxylic acids and their anhydrides as a cheap, abundant and non-toxic alkyl source under redox-neutral conditions, featuring the introduction of a primary alkyl chain, which cannot be addressed by previous radical-mediated decarboxylative reaction. Through a mechanistic investigation, we revealed that an initially formed C-7 acylated indoline was transformed into the corresponding alkylated indoline via a decarbonylation process.
Assuntos
Ródio , Alquilação , Anidridos , Ácidos Carboxílicos , Indóis , OxirreduçãoRESUMO
We developed rhodium-catalyzed alkoxylcarbonylation/acylation of indolines using anhydrides as a safe and easy-to-handle carbonyl source. This catalytic process represents an additive- and CO-free carbonylation, establishing a simple and straightforward protocol for synthesizing C7-carbonylated indolines. Notably, this reaction provides a successful example of C-H acylation of indolines that results in the formation of α-branched ketones, which were difficult to prepare by previously reported analogous catalytic reactions.
RESUMO
The first enantioselective reductive aldol reaction of unprotected α,ß-unsaturated carboxylic acids was developed by employing a copper/bisphosphine catalyst. The reaction features in situ protection and activation of an α,ß-unsaturated carboxylic acid by a hydrosilane. The copper enolate formed in situ reacts with an alkyl aryl ketone to afford the ß-hydroxy carboxylic acid with excellent enantioselectivity (up to 99 % ee). The corresponding gram-scale reaction with a low catalyst loading and the derivatization of the ß-hydroxy carboxylic acids highlight the practicality of this transformation.
Assuntos
Cobre , Cetonas , Aldeídos , Ácidos Carboxílicos , Catálise , Silanos , EstereoisomerismoRESUMO
Lewis acid-assisted palladium-catalysed dealkoxylation of N-alkoxyamides has been developed. This reaction proceeded smoothly with a range of N-alkoxyamides in the absence of an external reductant, thereby establishing a convenient and reductant-free protocol. In addition, a gram-scale reaction could be achieved. Preliminary mechanistic investigations indicated that ß-hydrogen elimination from a palladium alkoxide intermediate generated an intramolecular hydride source.
RESUMO
Catalytic alkylation reactions of weakly acidic carbonyl and related pronucleophiles such as amides, esters, and sulfonamides with substituted alkenes have been reported. In the presence of a strong Brønsted base catalyst system, potassium hexamethyldisilazide and 18-crown-6 ether, the desired reactions proceeded in high yields at ambient temperature with a wide substrate scope. These are atom-economical catalytic alkylation reactions of carbonyl and related compounds.
RESUMO
Catalytic addition reactions of very weakly acidic nonactivated alkylarenes such as toluene and its derivatives were developed by using a strongly basic mixed catalyst system under mild reaction conditions. The addition reactions with imines and alkenes proceeded smoothly under proton-transfer conditions to afford the desired products in good to high yields, and high levels of regio- and stereoselectivity were achieved. It was also revealed that the asymmetric addition reaction of an alkylarene was possible.
RESUMO
1,4-addition reactions of alkylazaarenes catalyzed by strong Brønsted bases have been developed for the first time. The desired reactions with α,ß-unsaturated amides proceeded under mild reaction conditions to give the 1,4-adducts in high yields. Both ortho- and para-substituted azaarenes afforded the desired adducts in high yields. Regioselective reactions of di- or trimethylpyridine were found to be possible depending on the acidity of the α-hydrogen atoms. Furthermore, a candidate of allosteric protein kinase modulators was synthesized in two steps. An asymmetric variant of this reaction was also found to be feasible.
RESUMO
The development of catalytic asymmetric carbon-carbon bond-forming reactions of alkylnitriles that do not have an activating group at the α-position, under proton-transfer conditions, is a challenging research topic. Here, we report catalytic asymmetric direct-type 1,4-addition reactions of alkylnitriles with α,ß-unsaturated amides by using a catalytic amount of potassium hexamethyldisilazide (KHMDS) with a chiral macro crown ether. The desired reactions proceeded in high yields with good diastereo- and enantioselectivities. To our knowledge, this is the first example of catalytic asymmetric direct-type 1,4-addition reaction of alkylnitriles without any activating group at the α-position.
Assuntos
Nitrilas/química , Catálise , Ligação de Hidrogênio , Estrutura MolecularRESUMO
The development of catalytic asymmetric direct-type reactions of less acidic carbonyl compounds such as amides and esters has been a challenging theme in organic chemistry for decades. Here we describe the asymmetric direct 1,4-addition reactions of simple amides with α,ß-unsaturated carbonyl compounds using a catalytic amount of a novel chiral catalyst consisting of a potassium base and a macrocyclic chiral crown ether. The desired 1,5-dicarbonyl compounds were obtained in high yields with excellent diastereo- and enantioselectivities. This is the first example of a highly enantioselective catalytic direct-type reaction of simple amides. In addition, the structure of the chiral potassium catalyst has been investigated by X-ray crystallographic, dynamic (1)H NMR, and MALDI-TOF MS analyses.
RESUMO
A catalytic Mannich reaction of a simple ester with no activating functionality at the α-position via a product-base mechanism was reported. The desired Mannich adducts were obtained in high yields using a catalytic amount of KH. This is a rare example of a Brønsted base-catalyzed Mannich reaction of unactivated esters as substrates.