Muhammad Usman

This review mainly focuses on the recent advances in Co-catalyzed [2 + 2 + 2] cycloaddition reaction of alkynes with nitriles to access multi-substituted pyridines. Meanwhile, brief mechanistic insights are also discussed to explain the observed regioselectivity.

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5–7-membered α-cyano cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.

Tetrahydrocarbazol‐4‐one represents a prevalent framework of numerous natural products and pharmaceuticals. This review summaries the recent synthetic progresses of this core structure, including Fischer indolization, oxidative and reductive coupling, α‐arylative cyclization by means of transition‐ metal catalysis or under metal‐free conditions, and other methods. The recently emerged enantioselective catalytic methods of tetrahydrocarbazol‐4‐ ones are also described. The mechanistic insights and applications of these strategies as a key step in the total (formal) synthesis of complex alkaloids are highlighted as well.

An iron-catalyzed asymmetric oxidative homo-coupling of 2-naphthols for the synthesis of 1,1′-Bi-2-naphthol (BINOL) derivatives is reported. The coupling reaction provides enantioenriched BINOLs in good yields (up to 99%) and moderate enantioselectivities (up to 81:19 er) using an iron-complex generated in situ from Fe(ClO₄)₂ and a bisquinolyldiamine ligand [(1R,2R)-N¹,N²-di(quinolin-8-yl)cyclohexane-1,2-diamine, L1]. A number of ligands (L2–L8) and the analogs of L1, with various substituents and chiral backbones, were synthesized and examined in the oxidative coupling reactions.

A copper-catalyzed annulation of alkyne-tethered enaminones for the synthesis of 2,3-ring fused pyrroles is reported. The 5-exo-dig cyclization/olefin migration reaction delivers the multi-substituted pyrroles in 59–99% yields with 16 examples. This strategy features easily available starting materials, mild reaction conditions, and cheap ligand-free copper catalyst. The atom-economic transformation provides a simple access to a variety of synthetic useful pyrroles and their derivatives.

A copper-catalyzed efficient enantioselective construction of chiral quaternary carbon-containing chromanes and 3,4-dihydropyrans is reported. The desymmetric C–O coupling is enabled by a chiral dimethylcyclohexane-1,2-diamine ligand and provides the desired products in good yields with high enantioselectivities. This method presents a broad substrate scope and is applicable to diversely substituted aryl bromides and alkenyl bromides. The application is demonstrated by a gram-scale synthesis and derivatization of the products toward valuable building blocks.

An efficient strategy for N/O-(deutero)alkylation of indoles and phenols with alkoxides/alcohols as the alkylation reagents is described. The consecutive detosylation/alkylation transformations feature mild reaction conditions, high ipso-selectivity, and good functional group tolerance (>50 examples). A one-pot selective N-alkylation of unprotected indoles with alcohols and TsCl is also realized. The application of this method is demonstrated by the introduction of isotope-labeled (CD₃ and ¹³CH₃) groups using the readily accessible labeled alcohols and the synthesis of pharmaceuticals.

Cyclic sulfonamides (sultams) play a unique role in drug discovery and synthetic chemistry. A direct synthesis of sultams by an intramolecular C(sp³)–H amidation reaction using an iron complex in situ derived from Fe(ClO₄)₂ and aminopyridine ligand is reported. This strategy features a readily available catalyst and tolerates a broad variety of substrates as demonstrated by 22 examples (up to 89% yield). A one-pot iron-catalyzed amidation/oxidation procedure for the synthesis of cyclic N-sulfonyl ketimines is also realized with up to 92% yield (eight examples). The synthetic utility of the method is validated by a gram-scale reaction and derivatization of the products to ring-fused sultams.

An efficient synthesis of N-fused polycyclic and 2,3-disubstituted indoles by copper-catalyzed direct annulation/acyl migration reaction of enaminones is reported. This strategy features cheap and low loading of the catalyst/ligand, readily available starting materials, and good functional group compatibilities. Notably, allyl-containing substrates are also tolerated, which allows the downstream derivatization toward indole alkaloids.

The application of dialkyl azodicarboxylates as versatile reagents in Mitsunobu, oxidation, electrophilic, amination and carbonylation reactions is reviewed.