<i>N</i>‑Cyanation of Secondary Amines Using Trichloroacetonitrile

A one-pot <i>N</i>-cyanation of secondary amines has been developed using trichloroacetonitrile as an inexpensive cyano source. A diverse range of cyclic and acyclic secondary amines can be readily transformed into the corresponding cyanamides in good isolated yields, with the method successfully utilized in the final synthetic step of a biologically active rolipram-derived cyanamide. This approach exhibits distinct selectivity when compared to the use of highly toxic cyanogen bromide

Accessing Highly Substituted Indoles via B(C₆F₅)₃‑Catalyzed Secondary Alkyl Group Transfer

Herein, we report a synthetic method to access a range of highly substituted indoles via the B(C6F5)3-catalyzed transfer of 2° alkyl groups from amines. The transition-metal-free catalytic approach has been demonstrated across a broad range of indoles and amine 2° alkyl donors, including various substituents on both reacting components, to access useful C(3)-alkylated indole products. The alkyl transfer process can be performed using Schlenk line techniques in combination with commercially available B(C6F5)3·nH2O and solvents, which obviates the requirement for specialized equipment (e.g., glovebox)

Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach

A general iron-catalyzed methylation has been developed using methanol as a C1 building block. This borrowing hydrogen approach employs a Knölker-type (cyclopentadienone)iron carbonyl complex as catalyst (2 mol %) and exhibits a broad reaction scope. A variety of ketones, indoles, oxindoles, amines, and sulfonamides undergo mono- or dimethylation in excellent isolated yields (>60 examples, 79% average yield)

Magnesiate Addition/Ring-Expansion Strategy To Access the 6–7–6 Tricyclic Core of Hetisine-Type C₂₀-Diterpenoid Alkaloids

A synthetic strategy to access the fused 6–7–6 tricyclic core of hetisine-type C₂₀-diterpenoid alkaloids is reported. This strategy employs a Diels–Alder cycloaddition to assemble a fused bicyclic anhydride intermediate, which is elaborated to a vinyl lactone-acetal bearing an aromatic ring in five steps. Aromatic iodination is followed by magnesium–halogen exchange with a trialkyl magnesiate species, which undergoes intramolecular cyclization. Subsequent oxidation provides the desired 6–7–6 tricyclic diketoaldehyde, with carbonyl groups at all three positions for eventual C–N bond formation and subsequent elaboration

Exploring Tandem Ruthenium-Catalyzed Hydrogen Transfer and S_NAr Chemistry

A hydrogen-transfer strategy for the catalytic functionalization of benzylic alcohols via electronic arene activation, accessing a diverse range of bespoke diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70% average yield), is reported. Taking advantage of the hydrogen-transfer approach, the oxidation level of the functionalized products can be selected by judicious choice of simple and inexpensive additives

Deoxycyanamidation of Alcohols with <i>N</i>‑Cyano‑<i>N</i>‑phenyl-<i>p</i>-methylbenzenesulfonamide (NCTS)

The first one-pot deoxycyanamidation of alcohols has been developed using <i>N</i>-cyano-<i>N</i>-phenyl-<i>p</i>-methyl­benzene­sulfonamide (NCTS) as both a sulfonyl transfer reagent and a cyanamide source, accessing a diverse range of tertiary cyanamides in excellent isolated yields. This approach exploits the underdeveloped desulfonylative (N–S bond cleavage) reactivity pathway of NCTS, which is more commonly employed for electrophilic <i>C</i>- and <i>N</i>-cyanation processes

A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine)

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C–N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type

Stereospecific Asymmetric N‑Heterocyclic Carbene (NHC)-Catalyzed Redox Synthesis of Trifluoromethyl Dihydropyranones and Mechanistic Insights

N-Heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels–Alder reactions of α-aroyloxyaldehydes with β-trifluoromethyl enones generates synthetically useful dihydropyranones containing a stereogenic trifluoromethyl substituent in good yields (up to 81%) and excellent diastereoselectivity and enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific, with use of either (<i>E</i>)- or (<i>Z</i>)-β-trifluoromethyl enones forming <i>syn</i>- or <i>anti</i>-dihydropyranone products, respectively. Mechanistic studies through in situ kinetic analysis of the reaction reveal key differences in reactivity between chiral NHC precursor <b>1</b> and an achiral NHC precursor

A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine)

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C–N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type

A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine)

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C–N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type