C-H Activation and Sequential Addition to Dienes and Imines: Synthesis of Amines with -Quaternary Centers and Mechanistic Studies on the Complex Interplay Between the Catalyst and Three Reactants.

A Rh(III)-catalyzed sequential C-H bond addition to dienes and in situ formed aldimines was developed, allowing for the preparation of otherwise challenging to access amines with quaternary centers at the -position. A broad range of dienes were effective inputs and installed a variety of aryl and alkyl substituents at the quaternary carbon site. Aryl and alkyl sulfonamide and carbamate nitrogen substituents were incorporated by using different formaldimine precursors.

Synthesis of α-Quaternary Amides via Cp*Co(III)-Catalyzed Sequential C-H Bond Addition to 1,3-Dienes and Isocyanates.

The synthesis of sterically congested amides was accomplished via Cp*Co(III)-catalyzed sequential C-H bond addition to 1,3-dienes followed by aminocarbonylation with isocyanates, a coupling partner that had never been utilized in sequential C-H bond addition reactions. A variety of C-H bond reactants, internally substituted dienes, and aromatic isocyanates provided secondary amide products incorporating α-all-carbon quaternary centers. The conversion of the amide products to other useful compound classes was also demonstrated.

Nickel-Catalyzed O-Arylation of Primary or Secondary Aliphatic Alcohols with (Hetero)aryl Chlorides: A Comparison of Ni(I) and Ni(II) Precatalysts.

A comparative experimental and computational study examining the interplay of the ancillary ligand structure and Ni oxidation state in the Ni-catalyzed C(sp)-O cross-coupling of (hetero)aryl chlorides and primary or secondary aliphatic alcohols is presented, focusing on PAd-DalPhos ()-, CyPAd-DalPhos ()-, PAd2-DalPhos ()-, and DPPF ()-ligated [()NiCl] ( = 1 or 2) and ()Ni(-tol)Cl precatalysts. Both and were found to outperform the other ligands examined, with the latter proving to be superior overall. While Ni(II) precatalysts generally outperformed Ni(I) species, in some instances the catalytic abilities of Ni(I) precatalysts were competitive with those of Ni(II).

Three-component carboformylation: α-quaternary aldehyde synthesis Co(iii)-catalysed sequential C-H bond addition to dienes and acetic formic anhydride.

All carbon α-quaternary aldehydes are prepared Co(iii)-catalysed sequential C-H bond addition to dienes and acetic formic anhydride, representing a rare example of intermolecular carboformylation. A wide range of internally substituted dienes containing diverse functionality can be employed in this reaction, affording complex α-quaternary aldehydes that would not be accessible hydroformylation approaches. Mechanistic investigations, including control reactions and deuterium labeling studies, establish a catalytic cycle that accounts for formyl group introduction with an uncommon 1,3-addition selectivity to the conjugated diene.

Nickel-Catalyzed C-N Cross-Coupling of 4-Chloro-1,8-naphthalimides and Bulky, Primary Alkylamines at Room Temperature.

4-Amino-1,8-naphthalimides, potentially useful fluorescent probes in biological applications, are prepared via Ni(cod)/IPr-catalyzed cross-couplings between 4-chloro-1,8-naphthalimide electrophiles and α,α,α-trisubstituted, primary alkylamines at room temperature. This method represents the first synthesis of 4-amino-1,8-naphthalimides using Ni-catalyzed C-N cross-coupling and provides the first examples of 4-amino-1,8-naphthalimides incorporating such bulky primary alkylamines, thereby highlighting the utility of Ni-catalyzed processes in synthesizing naphthalimide scaffolds that were inaccessible using established methods (SAr; Pd or Cu catalysis).

Stereoselective Synthesis of Allenyl Alcohols by Cobalt(III)-Catalyzed Sequential C-H Bond Addition to 1,3-Enynes and Aldehydes.

An efficient and stereoselective Co -catalyzed sequential C-H bond addition to 1,3-enynes and aldehydes is disclosed. This transformation represents the first example of sequential C-H bond additions to 1,3-enynes and a second coupling partner and provides the first example of preparing allenes by C-H bond addition to 1,3-enynes. A wide range of aldehydes, C-H bond substrates and 1,3-enynes with large substituents on the alkynes are effective substrates.

Utilizing deep learning and graph mining to identify drug use on Twitter data.

Background: The collection and examination of social media has become a useful mechanism for studying the mental activity and behavior tendencies of users. Through the analysis of a collected set of Twitter data, a model will be developed for predicting positively referenced, drug-related tweets. From this, trends and correlations can be determined.

PhPAd-DalPhos: Ligand-Enabled, Nickel-Catalyzed Cross-Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines.

The base metal-catalyzed C-N cross-coupling of bulky α,α,α-trisubstituted primary alkylamines with (hetero)aryl electrophiles represents a challenging and under-developed class of transformations that is of significant potential utility, including in the synthesis of lipophilic active pharmaceutical ingredients. Herein, we report that a new, air-stable Ni(II) pre-catalyst incorporating the optimized ancillary ligand PhPAd-DalPhos enables such transformations of (hetero)aryl chloride, bromide, and tosylate electrophiles to be carried out for the first time with substrate scope rivalling that achieved using state-of-the-art Pd catalysts, including room temperature cross-couplings of (hetero)aryl chlorides that are unprecedented for any catalyst (Pd, Ni, or other).

Exploiting Ancillary Ligation To Enable Nickel-Catalyzed C-O Cross-Couplings of Aryl Electrophiles with Aliphatic Alcohols.

The use of (L)Ni( o-tolyl)Cl precatalysts (L = PAd-DalPhos or CyPAd-DalPhos) enables the C( sp)-O cross-coupling of primary, secondary, or tertiary aliphatic alcohols with (hetero)aryl electrophiles, including unprecedented examples of such nickel-catalyzed transformations employing (hetero)aryl chlorides, sulfonates, and pivalates. In addition to offering a competitive alternative to palladium catalysis, this work establishes the feasibility of utilizing ancillary ligation as a complementary means of promoting challenging nickel-catalyzed C( sp)-O cross-couplings, without recourse to precious-metal photoredox catalytic methods.

Interaction between uric acid and endothelial dysfunction predicts new onset of diabetes in hypertensive patients.

Background: Both uric acid and endothelial dysfunction are associated with new occurrence of type-2 diabetes but, at this moment, there is no evidence about a possible interaction between them. We tested, in untreated hypertensive patients, without clinical evidence of vascular damage, the hypothesis that serum uric acid and endothelial dysfunction may interact in predicting new diabetes.

Methods: In 500 uncomplicated hypertensive non diabetic (ADA criteria) patients we evaluated endothelial function, by strain-gauge plethysmography, and uric acid.

Angiotensin II type 1 receptor, but no type 2 receptor, interferes with the insulin-induced nitric oxide production in HUVECs.

Objective: Two subtypes of angiotensin II (ATII) receptor have been defined on the basis of their differential pharmacological and biochemical properties: ATII-type1 receptors (AT(1)-R) and ATII-type2 receptors (AT(2)-R). It has been hypothesized that part of the protective effects on the cardiovascular system of AT(1)-R blockers is mediated by an ATII-mediated overstimulation of AT(2)-R. We hypothesized that the inhibition of AT(1)-R has a stronger impact on insulin-induced nitric oxide (NO) production than ATII-mediated overstimulation of AT(2)-R.

Phenotypic characterization of normotolerant hypertensive patients.

Background: Normotolerant subjects (NGT) are considered at low risk, even if a plasma glucose value ≥ 155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify NGT at high-risk for type-2 diabetes and subclinical organ damage. Insulin resistance (IR) contributes to the pathogenesis of impaired glucose tolerance and participates to the development of subclinical organ damage. However, it is unknown whether NGT < 155 subjects are at low risk for the development of subclinical organ damage independently from other metabolic variables, such as IR/hyperinsulinemia.