Sparse ordinal discriminant analysis.

Ordinal class labels are frequently observed in classification studies across various fields. In medical science, patients' responses to a drug can be arranged in the natural order, reflecting their recovery postdrug administration. The severity of the disease is often recorded using an ordinal scale, such as cancer grades or tumor stages. We propose a method based on the linear discriminant analysis (LDA) that generates a sparse, low-dimensional discriminant subspace reflecting the class orders. Unlike existing approaches that focus on predictors marginally associated with ordinal labels, our proposed method selects variables that collectively contribute to the ordinal labels. We employ the optimal scoring approach for LDA as a regularization framework, applying an ordinality penalty to the optimal scores and a sparsity penalty to the coefficients for the predictors. We demonstrate the effectiveness of our approach using a glioma dataset, where we predict cancer grades based on gene expression. A simulation study with various settings validates the competitiveness of our classification performance and demonstrates the advantages of our approach in terms of the interpretability of the estimated classifier with respect to the ordinal class labels.

Hydrotrifluoroacetylation of Alkenes via Designer Masked Acyl Reagents.

Because of its impressive ability to promote pharmaceutical activity, the introduction of trifluoromethylacyl (CF3CO) functionality into organic compounds has become an important and growing research area. Although various protocols have been developed to access trifluoroketones, the use of trifluoroacetyl radicals remains virtually undeveloped. Herein, we disclose a novel method for trifluoroacetylation through an umpolung reagent, thereby transforming an electrophilic radical into a nucleophilic radical. The applicability of this transformation is highlighted by large-scale, late-stage reactions of complex bioactive molecules sclareolide and loratadine. Furthermore, the direct transformation of trifluoromethyl ketones into various fluorinated analogues illustrates the potential synthetic application of our developed method.

C-H Methylation of Iminoamido Heterocycles with Sulfur Ylides*.

The direct methylation of N-heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp2 )-H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional-group tolerance were attained. Moreover, this method can be readily applied to the site-selective methylation of azauracil nucleosides. The feasibility of gram-scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium-labeling experiments aided the elucidation of a plausible reaction mechanism.

Deoxygenative Amination of Azine-N-oxides with Acyl Azides via [3 + 2] Cycloaddition.

A transition-metal-free deoxygenative C-H amination reaction of azine-N-oxides with acyl azides is described. The initial formation of an isocyanate from the starting acyl azide via a Curtius rearrangement can trigger a [3 + 2] dipolar cycloaddition of polar N-oxide fragments to generate the aminated azine derivative. The applicability of this method is highlighted by the late-stage and sequential amination reactions of complex bioactive compounds, including quinidine and fasudil. Moreover, the direct transformation of aminated azines into various bioactive N-heterocycles illustrates the significance of this newly developed protocol.

Ru(ii)-Catalyzed C-H addition and oxidative cyclization of 2-aryl quinazolinones with activated aldehydes.

The ruthenium(ii)-catalyzed cross-coupling reaction between 2-aryl quinazolinones and activated aldehydes is described. This method enables the site-selective hydroxyalkylation under redox-neutral conditions. Moreover, this protocol provides a facile access to various tetracyclic isoindoloquinazolinones by using Cu(OAc)2 as an external oxidant via C-H addition and subsequent intramolecular cyclization. A wide substrate scope and a high level of chemoselectivity as well as broad functional group tolerance are observed.

Synthesis of (2 H)-Indazoles through Rh(III)-Catalyzed Annulation Reaction of Azobenzenes with Sulfoxonium Ylides.

The rhodium(III)-catalyzed C-H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described. This protocol leads to the efficient formation of 3-acyl (2 H)-indazoles with a range of substrate scope. A high level of chemoselectivity and functional group tolerance of this transformation were also observed.

Ru(II)-Catalyzed C-H Aminocarbonylation of N-(Hetero)aryl-7-azaindoles with Isocyanates.

The ruthenium(II)-catalyzed C-H aminocarbonylation of N-(hetero)aryl-7-azaindoles with isocyanates is described. The excellent site selectivity at the ortho-position within the N-(hetero)aryl ring was observed to provide ortho-amidated N-(hetero)aryl-7-azaindoles under the mild reaction conditions. The resulting 7-azaindole derivatives can be readily transformed into 7-azaindoles containing carboxylic acid and alkyl amine functional groups.

Reductive C2-Alkylation of Pyridine and Quinoline N-Oxides Using Wittig Reagents.

The ability to alkylate pyridines and quinolines is important for their further development as pharmaceuticals and agrochemicals, and for other purposes. Herein we describe the unprecedented reductive alkylation of pyridine and quinoline N-oxides using Wittig reagents. A wide range of pyridine and quinoline N-oxides were converted into C2-alkylated pyridines and quinolines with excellent site selectivity and functional-group compatibility. Sequential C-H functionalization reactions of pyridine and quinoline N-oxides highlight the utility of the developed method. Detailed labeling experiments were performed to elucidate the mechanism of this process.

Synthesis and anti-inflammatory evaluation of N-sulfonyl anthranilic acids via Ir(III)-catalyzed C-H amidation of benzoic acids.

The iridium(III)-catalyzed ortho-C-H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of N-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vitro anti-inflammatory activity against interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compounds 4c and 4d, generated from p-OMe- and p-Br-sulfonyl azides, were found to display potent anti-inflammatory property stronger than that of well-known NSAIDs ibuprofen.

Synthesis of Succinimide-Containing Chromones, Naphthoquinones, and Xanthones under Rh(III) Catalysis: Evaluation of Anticancer Activity.

The weakly coordinating ketone group directed C-H functionalizations of chromones, 1,4-naphthoquinones, and xanthones with various maleimides under rhodium(III) catalysis are described. These protocols efficiently provide a range of succinimide-containing chromones, naphthoquinones, and xanthones with excellent site selectivity and functional group compatibility. All synthetic compounds were screened for in vitro anticancer activity against human breast adenocarcinoma cell lines (MCF-7). In particular, compounds 7aa and 7ca with a naphthoquinone scaffold were found to be highly cytotoxic, with an activity competitive with anticancer agent doxorubicin.

Mild and Site-Selective Allylation of Enol Carbamates with Allylic Carbonates under Rhodium Catalysis.

The rhodium(III)-catalyzed mild and site-selective C-H allylation of enol carbamates with 4-vinyl-1,3-dioxolan-2-one and allylic carbonates affords allylic alcohols and terminal allylated products, respectively. The assistance of the carbamoyl directing group provides a straightforward preparation of biologically and synthetically important allylated enol carbamates.

Trifluoromethylallylation of Heterocyclic C-H Bonds with Allylic Carbonates under Rhodium Catalysis.

The rhodium(III)-catalyzed γ-trifluoromethylallylation of various heterocyclic C-H bonds with CF3-substituted allylic carbonates is described. These reactions provide direct access to linear CF3-containing allyl frameworks with complete trans-selectivity via C-H bond activation followed by a formal SN-type reaction pathway.

Redox-Neutral Rh(III)-Catalyzed Olefination of Carboxamides with Trifluoromethyl Allylic Carbonate.

The rhodium(III)-catalyzed olefination of various carboxamides with α-CF3-substituted allylic carbonate is described. This reaction provides direct access to linear CF3-allyl frameworks with complete trans-selectivity. In particular, a rhodium catalyst provided Heck-type γ-CF3-allylation products via the ß-O-elimination of rhodacycle intermediate and subsequent olefin migration process.

Synthesis of N-Sulfonylamidated and Amidated Azobenzenes under Rhodium Catalysis.

The rhodium(III)-catalyzed ortho-C-H amidation of azobenzenes with arylsulfonyl and aryl and alkyl isocyanates is described. The N-sulfonyl amidation reaction using arylsulfonyl isocyanates is first reported in the C-H activation strategy. These transformations provide the facile and efficient construction of a range of amide moieties into azobenzenes.

Rh(III)-Catalyzed C-H Amidation of Indoles with Isocyanates.

The rhodium(III)-catalyzed direct amidation of indoles and pyrroles with aryl and alkyl isocyanates is described. These transformations provide a facile and efficient construction of C2-amidated N-heterocyclic scaffolds.

Mild Rh(III)-catalyzed C7-allylation of indolines with allylic carbonates.

The rhodium(III)-catalyzed direct allylation of indolines with allylic carbonates at room temperature is described. These transformations provide the facile and efficient construction of C7-allylated indolic scaffold.

Ru(II)-catalyzed selective C-H amination of xanthones and chromones with sulfonyl azides: synthesis and anticancer evaluation.

A ketone-assisted ruthenium-catalyzed selective amination of xanthones and chromones C-H bonds with sulfonyl azides is described. The reactions proceed efficiently with a broad range of substrates with excellent functional group compatibility. This protocol provides direct access to 1-aminoxanthones, 5-aminochromones, and 5-aminoflavonoid derivatives known to exhibit potent anticancer activity.

Pd-catalyzed oxidative coupling of arene C-H bonds with benzylic ethers as acyl equivalents.

A palladium-catalyzed oxidative coupling of arene C-H bonds with benzylic ethers via C-H bond activation is described. The reaction proceeds efficiently with a broad range of substrates bearing conventional directing groups with excellent functional group compatibility. This protocol potentially provides opportunities to use dibenzyl ethers as new acyl equivalents for catalytic acylation reactions.

Copper-catalyzed oxidative C-O bond formation of 2-acyl phenols and 1,3-dicarbonyl compounds with ethers: direct access to phenol esters and enol esters.

A copper-catalyzed oxidative coupling of 2-carbonyl-substituted phenols and 1,3-dicarbonyl compounds with a wide range of dibenzyl or dialkyl ethers is described. This protocol provides an efficient preparation of phenol esters and enol esters in good yields with high chemoselectivity. This method represents an alternative protocol for classical esterification reactions.

Rh-catalyzed oxidative C-C bond formation and C-N bond cleavage: direct access to C2-olefinated free (NH)-indoles and pyrroles.

The rhodium-catalyzed oxidative C2-olefination of indoles and pyrroles containing N-arylcarboxamide directing groups with a range of alkenes and subsequent cleavage of directing groups is described. This method provides direct and efficient access to C2-functionalized free (NH)-heterocycles.