Rh(iii)-catalyzed sp3/sp2-C-H heteroarylations via cascade C-H activation and cyclization.

The development of an efficient strategy for facile access to quinoline-based bis-heterocycles holds paramount importance in medicinal chemistry. Herein, we describe a unified approach for accessing 8-(indol-3-yl)methyl-quinolines by integrating Cp*Rh(iii)-catalyzed C(sp3)-H bond activation of 8-methylquinolines followed by nucleophilic cyclization with o-ethynylaniline derivatives. Remarkably, methoxybiaryl ynones under similar catalytic conditions delivered quinoline tethered spiro[5.5]enone scaffolds via a dearomative 6-endo-dig C-cyclization. Moreover, leveraging this method for C8(sp2)-H bond activation of quinoline-N-oxide furnished biologically relevant oxindolyl-quinolines. This reaction proceeds via C(sp2)-H bond activation, regioselective alkyne insertion, oxygen-atom-transfer (OAT) and intramolecular nucleophilic cyclization in a cascade manner. One C-C, one C-N and one C[double bond, length as m-dash]O bond were created with concomitant formation of a quaternary center.

Access to Polysubstituted Furan Derivatives via Cascade Oxy-palladation and Hydrocarbofunctionalization of Unactivated Alkenes.

The development of an expedient strategy for the synthesis of biologically relevant multisubstituted furans is a much-desired yet challenging task. Herein, we report an efficient and versatile strategy involving two different pathways for the construction of diverse polysubstituted C3- and C2-substituted γ-furanyl carboxylic acid derivatives. The synthetic approach for C3-substituted furans involves intramolecular cascade oxy-palladation of alkyne-diols followed by the regioselective coordinative insertion of unactivated alkenes. In contrast, C2-substituted furans were obtained exclusively by performing the protocol in a tandem manner.

Pd(ii)-catalyzed ß- and γ-C-(sp3)-H dienylation with allenyl acetates.

Recent years have seen the emergence of transition metal catalyzed C-H activation as a powerful synthetic tool in organic chemistry. Allenes have fascinated synthetic chemists due to their unique reactivity. While directing group assisted functionalization of C(sp2)-H bonds with allenes is well documented in the literature, their coupling with more challenging aliphatic C(sp3)-H bonds remains elusive. In this regard, we hereby report a Pd(ii) catalyzed 8-aminoquinoline directed aliphatic C(sp3)-H dienylation protocol using allenyl acetates. A variety of carboxylic acids including fatty acids and amino acids were efficiently functionalized at ß and γ-positions to afford diversely functionalized 1,3-dienes. Preliminary mechanistic studies revealed the crucial role of the base in the success of the transformation. The reaction proceeds via regioselective 2,3-migratory insertion of the allene with the alkylpalladium(ii) species followed by ß-acetoxy elimination.

Ru(II)-Catalyzed Regioselective Annulation of 2-Hydroxystyrenes with Allenyl Acetates via Vinylic C-H Activation.

Herein, we disclose an unprecedented and robust Ru(II)-catalyzed non-oxidative [5+1] annulation of 2-hydroxystyrenes with allenyl acetates to access biologically relevant chromene skeletons. The heteroatom on allene plays a pivotal role in controlling the regioselectivity of migratory insertion, and the reaction proceeds through a Ru-σ-allyl pathway, which has been elusive so far in C-H activation reactions with allenes. The protocol is sustainable in nature as it proceeds at room temperature and avoids the use of any toxic metal oxidants. In addition, the synthetic utility of the protocol was also demonstrated by late stage functionalization and modular synthesis of various natural product conjugates.

Rh(iii)-Catalyzed [5 + 1] annulation of 2-alkenylanilides and 2-alkenylphenols with allenyl acetates.

Herein, we report a mild and highly regioselective Rh(iii)-catalyzed non-oxidative [5 + 1] vinylic C-H annulation of 2-alkenylanilides with allenyl acetates, which has been elusive so far. The reaction proceeds via vinylic C-H activation, regioselective 2,3-migratory insertion, ß-oxy elimination followed by nucleophilic cyclization to get direct access to 1,2-dihydroquinoline derivatives. The strategy was also successfully extended to C-H activation of 2-alkenylphenols for constructing chromene derivatives. In the overall [5 + 1] annulation, the allene serves as a one carbon unit. The acetate group on the allene is found to be crucial both for controlling the regio- and chemoselectivity of the reaction and also for facilitating ß-oxy elimination. The methodology was scalable and also further extended towards late stage functionalization of various natural products.

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines.

A metal- and additive-free, highly efficient, step-economical deoxygenative C2-heteroarylation of quinolines and isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products.

Catalytic, Regioselective Hydrocarbofunctionalization of Unactivated Alkenes Triggered by trans-Acetoxypalladation of Alkynes.

Herein we demonstrate a Pd(II)-catalyzed regioselective hydrocarbofunctionalization of unactivated alkenes. The σ-vinyl-palladium(II) intermediate generated by the trans-acetoxypalladation of alkynes was added across carbon-carbon double bond to realize an efficient hydroalkenylation protocol. Bidentate auxiliary 8-aminoquinoline controls the regioselectivity of the carbopalladation step and thereby controls the regioselectivity of the hydroalkenylation. Additionally, when alkynes containing a hydroxy group at the three- or four-position were employed, the cascade sequence led to 1,6-dicarbonyl compounds via hydroalkenylation followed by intramolecular acyl migration.

Hypopituitarism: A Rare but Often Neglected Condition.

Pituitary insufficiency is an uncommon disorder. The most common cause is compression due to a pituitary mass. Other causes include inflammatory damage and vascular injury like postpartum pituitary apoplexy. Postpartum pituitary apoplexy, also known as Sheehan's syndrome, leads to hormonal deficiencies and causes postpartum amenorrhea, lactational failure, chronic hyponatremia, hypoglycemia, and loss of secondary sexual characters. Here we are discussing the clinical course of 15 female patients of panhypopituitarism. Most of them had a history of postpartum hemorrhage. Knowledge about this entity is essential as it is a treatable condition and ignorance could prove to be fatal. HOW TO CITE THIS ARTICLE: Bhushan D, Agarwal M, Shukla RK. Hypopituitarism: A Rare but Often Neglected Condition. Indian J Crit Care Med 2020;24(5):350-352.

Cobalt-Catalyzed C8-Dienylation of Quinoline-N-Oxides.

An efficient Cp*CoIII -catalyzed C8-dienylation of quinoline-N-oxides was achieved by employing allenes bearing leaving groups at the α-position as the dienylating agents. The reaction proceeds by CoIII -catalyzed C-H activation of quinoline-N-oxides and regioselective migratory insertion of the allene followed by a ß-oxy elimination, leading to overall dienylation. Site-selective C-H activation was achieved with excellent selectivity under mild reaction conditions, and 30 mol % of a NaF additive was found to be crucial for the efficient dienylation. The methodology features high stereoselectivity, mild reaction conditions, and good functional-group tolerance. C8-alkenylation of quinoline-N-oxides was achieved in the case of allenes devoid of leaving groups as coupling partners. Furthermore, gram-scale preparation and preliminary mechanistic experiments were carried out to gain insights into the reaction mechanism.

Palladium-catalyzed highly diastereoselective cascade dihalogenation of alkyne-tethered cyclohexadienones via Umpolung of palladium enolate.

Herein, we report a highly diastereo- and regioselective dihalogenation of alkyne-tethered cyclohexadienones for the synthesis of cis-hydrobenzofurans. One carbon-carbon and two carbon-halogen bonds were formed in an efficient manner and three contiguous stereocenters were generated. The reaction proceeds through cis-halopalladation, migratory insertion followed by a nucleophilic attack of a halide anion on a palladium enolate.

PdII -Catalyzed Cascade Synthesis of Chromane Derivatives Initiated by cis-Chloropalladation or trans-Acetoxypalladation.

A highly regio- and stereoselective PdII -catalyzed cascade synthesis of biologically relevant chromane derivatives from easily available enynes was developed under operationally simple conditions. The cascade reaction consists of nucleopalladation of alkynes, insertion of the alkene and protonation. When CuCl2 was employed as nucleophile, a cis-chloropalladation initiates the cascade. Whereas in the case of AcOH, a trans-acetoxypalladation takes place.

Rh(II)-Catalyzed Denitrogenative Reaction of N-Sulfonyl-1,2,3-triazoles with Isatins for the Construction of Indigoids.

A convenient, Rh(II)-catalyzed, denitrogenative reaction of N-sulfonyl-1,2,3-triazoles and isatins to access (E)-2-(1-amino-2-oxo-2-phenylethylidene)indolin-3-ones, the core structure of indigo dyes, was achieved under operationally simple conditions with high levels of diastereoselectivity. Moreover, photophysical and electrochemical studies were conducted to understand their applicability in optoelectronic applications.