Late-Stage C-H Nitration of Unactivated Arenes by Fe(NO)·9HO in Hexafluoroisopropanol.

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO)·9HO as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized.

Route to Functionalized Tetrahydrobenzo[]azepines via ReO-Mediated Intramolecular Friedel-Crafts Reaction.

We describe a ReO-mediated intramolecular dehydrative Friedel-Crafts reaction for the efficient synthesis of various benzo-fused heterocycles such as benzazepines and benzazocines. This process is characterized by a broad substrate scope, mild reaction conditions, high efficiency, and high atom economy. The potential application of this methodology was exemplified by the facile preparation of a NMDA antagonist as well as a key intermediate en route to SKF 38393.

Synthesis of 1-Aryltetralins via ReO/HReO Mediated Intramolecular Hydroarylations.

Here, we describe highly efficient intramolecular hydroarylations mediated by ReO/HReO. Styrene derivatives of different electronic properties have been activated to effect a challenging intramolecular hydroarylation for the facile access to various substituted 1-aryltetralin structures. This method is characterized by mild reaction conditions, broad substrate scope, high chemical yields, and 100% atom economy.

Ring-closing C-O/C-O metathesis of ethers with primary aliphatic alcohols.

In canonical organic chemistry textbooks, the widely adopted mechanism for the classic transetherifications between ethers and alcohols starts with the activation of the ether in order to weaken the C-O bond, followed by the nucleophilic attack by the alcohol hydroxy group, resulting in a net C-O/O-H σ-bond metathesis. In this manuscript, our experimental and computational investigation of a ReO mediated ring-closing transetherification challenges the fundamental tenets of the traditional transetherification mechanism. Instead of ether activation, the alternative activation of the hydroxy group followed by nucleophilic attack of ether is realized by commercially available ReO through the formation of perrhenate ester intermediate in hexafluoroisopropanol (HFIP), which results in an unusual C-O/C-O σ-bond metathesis.

Reactive Oxygen Species-Responsive Gel-Based Microneedle Patches for Prolonged and Intelligent Psoriasis Management.

Psoriasis is an inflammatory skin disease. Microneedle (MN) patches can improve psoriasis treatment outcomes by increasing local drug content in the skin. As psoriasis frequently relapses, developing intelligent MN-based drug delivery systems with prolonged therapeutic drug levels and improved treatment efficiency is of great significance.

ReO/HReO Mediated Intramolecular Hydroacyloxylation of Unactivated Alkenes: A Dual Hydrogen-Bonding Effect.

This publication describes the application of ReO in hexafluoroisopropanol (HFIP) for the activation of inert as well as electronically deactivated olefins to facilitate a challenging intramolecular hydroacyloxylation reaction. Both HFIP and an internal carboxy group have been proven to be crucial for the successful implementation of this transformation; these are proposed to assist the formation and stabilization of the key cationic intermediate via hydrogen-bonding interactions with perrhenate anion (ReO).

Fuzzy Sparse Deviation Regularized Robust Principal Component Analysis.

Robust principal component analysis (RPCA) is a technique that aims to make principal component analysis (PCA) robust to noise samples. The current modeling approaches of RPCA were proposed by analyzing the prior distribution of the reconstruction error terms. However, these methods ignore the influence of samples with large reconstruction errors, as well as the valid information of these samples in principal component space, which will degrade the ability of PCA to extract the principal component of data.

ReO-Catalyzed Approach to Spirocyclic Ether Formation from Acyclic Precursors: Observation of Remote Stereoinduction.

Ketones that are flanked by an allylic alcohol and an alkene isomerize to spirocyclic ethers in the presence of ReO through allylic alcohol transposition, oxocarbenium ion formation, and Prins cyclization. These processes provide significant increases in molecular complexity, with multiple stereocenters being set relative to a stereocenter in the substrate. Stereoselectivity arises from the initial reversible steps being more rapid than the final step, thereby allowing for thermodynamically controlled stereochemical equilibration prior to product formation.

Diarylmethane synthesis through ReO-catalyzed bimolecular dehydrative Friedel-Crafts reactions.

This manuscript describes the application of ReO to the syntheses of diarylmethanes from benzylic alcohols through solvolysis followed by Friedel-Crafts alkylation. The reactions are characterized by broad substrate scope, low catalyst loadings, high chemical yields, and minimal waste generation. The intermediate perrhenate esters are superior leaving groups to chlorides and bromides in these reactions.

Scalable and Highly Diastereo- and Enantioselective Catalytic Diels-Alder Reaction of α,β-Unsaturated Methyl Esters.

Despite tremendous advances in enantioselective catalysis of the Diels-Alder reaction, the use of simple α,β-unsaturated esters, one of the most abundant and useful class of dienophiles, is still severely limited in scope due to their low reactivity. We report here a catalytic asymmetric Diels-Alder methodology for a large variety of α,β-unsaturated methyl esters and different dienes based on extremely reactive silylium imidodiphosphorimidate (IDPi) Lewis acids. Mechanistic insights from accurate domain-based local pair natural orbital coupled-cluster (DLPNO-CCSD(T)) calculations rationalize the catalyst control and stereochemical outcome.

Catalytic Asymmetric [4+2]-Cycloaddition of Dienes with Aldehydes.

Despite its significant potential, a general catalytic asymmetric [4+2]-cycloaddition of simple and electronically unbiased dienes with any type of aldehyde has long been unknown. Previously developed methodologies invariably require activated, electronically engineered substrates. We now provide a general solution to this problem.

Catalytic Asymmetric Intramolecular [4+2] Cycloaddition of In Situ Generated ortho-Quinone Methides.

Herein, we describe the first catalytic asymmetric intramolecular [4+2] cycloaddition of in situ generated ortho-quinone methides. In the presence of a confined chiral imidodiphosphoric acid catalyst, various salicylaldehydes react with dienyl alcohols to give transient ortho-quinone methide intermediates, which undergo an intramolecular [4+2] cycloaddition to provide highly functionalized furanochromanes and pyranochromanes in excellent diastereoselectivity and enantioselectivity.

Catalytic Asymmetric Vinylogous Prins Cyclization: A Highly Diastereo- and Enantioselective Entry to Tetrahydrofurans.

We describe the design and development of the first catalytic asymmetric vinylogous Prins cyclization. This reaction constitutes an efficient approach for highly diastereo- and enantioselective synthesis of tetrahydrofurans (THFs) and is catalyzed by a confined chiral imidodiphosphoric acid (IDP). Aromatic and heteroaromatic aldehydes react with various 3,5-dien-1-ols to afford 2,3-disubstituted THFs in excellent selectivity (d.

Asymmetric Lewis acid organocatalysis of the Diels-Alder reaction by a silylated C-H acid.

Silylium ion equivalents have shown promise as Lewis acid catalysts for a range of important C-C bond-forming reactions. Here we describe chiral C-H acids that upon in situ silylation, generate silylium-carbanion pairs, which are extremely active Lewis acid catalysts for enantioselective Diels-Alder reactions of cinnamates with cyclopentadiene. Enantiomeric ratios of up to 97:3 and diastereomeric ratios of more than 20:1 are observed across a diverse set of substitution patterns with 1 mole percent (mol %) of C-H acid catalyst and 10 mol % of a silylating reagent.

Heterocycle synthesis based on allylic alcohol transposition using traceless trapping groups.

Allylic alcohols undergo transposition reactions in the presence of Re2 O7 whereby the equilibrium can be dictated by trapping one isomer with a pendent electrophile. Additional ionization can occur when the trapping group is an aldehyde or ketone, thus leading to cyclic oxocarbenium ion formation. Terminating the process through bimolecular nucleophilic addition into the intermediate provides a versatile method for the synthesis of diverse oxygen-containing heterocycles.

Cascade approach to stereoselective polycyclic ether formation: epoxides as trapping agents in the transposition of allylic alcohols.

Complexity from simplicity: polycyclic ethers are synthesized by cascade reactions involving the use of epoxides as electrophilic traps in the transposition of allylic alcohols. Stereogenic centers are created by functionalizing prochiral sites under thermodynamic control, and remote stereoinduction can be achieved through the use of ketones as conduits.

Isomer-dependent adsorption and release of cis- and trans-platin anticancer drugs by mesoporous silica nanoparticles.

We report on adsorption and release of the anticancer drugs cisplatin and transplatin from mesoporous silica nanomaterials, emphasizing the differences between cisplatin and its much less toxic isomer. Two types of particles, MCM-41 and SBA-15, were used, either as just synthesized or after calcination to remove the templates. The particles were characterized by TEM, nitrogen physisorption, and elemental analysis.