Catalytic Epoxidation of Carbonyl Compounds via Carbonyl Ylides: from Racemic to Enantioselective.

Transition metal-catalyzed epoxidation of carbonyl compounds through carbonyl ylides represents a highly effective method for synthesizing a diverse range of valuable epoxides. This review offers an in-depth overview of the latest developments in inter- and intramolecular epoxidation reactions involving metal carbenes and carbonyl compounds, encompassing both racemic to enantioselective transformations. These catalytic epoxidations are reviewed by highlighting their product selectivity, diversity and applicability, and the related mechanistic rationale is showcased where possible.

Chiral Brønsted Acid-Catalyzed Asymmetric Reaction via Vinylidene Ortho-Quinone Methides.

Vinylidene ortho-quinone methides (VQMs) have been proven to be versatile and crucial intermediates in the catalytic asymmetric reaction in last decade, and thus have drawn considerable concentrations on account of the practical application in the construction of enantiomerically pure functional organic molecules. However, in comparison to the well established chiral Brønsted base-catalyzed asymmetric reaction via VQMs, chiral Brønsted acid-catalyzed reaction is rarely studied and there is no systematic summary to date. In this review, we summarize the recent advances in the chiral Brønsted acid-catalyzed asymmetric reaction via VQMs according to three types of reactions: a) intermolecular asymmetric nucleophilic addition to VQMs; b) intermolecular asymmetric cycloaddition of VQMs; c) intramolecular asymmetric cyclization of VQMs. Finally, we put forward the remained challenges and opportunities for potential breakthroughs in this area.

Copper-Catalyzed [2 + 2] Cyclization/Ring Expansion of Ene-Ynamides: Construction of Medium- and Large-Sized Rings.

Catalytic cyclization of enynes is an efficient approach for the preparation of cyclic compounds, and a large variety of four- to six-membered rings could be synthesized using this method. However, it has been rarely employed for the construction of medium- and large-sized rings. Herein, we describe a copper-catalyzed cycloisomerization of ene-ynamides through a [2 + 2] cyclization/electrocyclic ring opening cascade, leading to the atom-economical assembly of indole-fused medium- and large-sized rings in moderate to excellent yields under mild reaction conditions. Importantly, the synthetic utility of this reaction was demonstrated by the convenient synthesis of iprindole.

Gold Catalysis, Asymmetric Friedel-Crafts Alkylation Cascade for One-Pot Synthesis of Chiral Dihydrocarbazoles and Dihydrodibenzofurans.

A one-pot gold-catalyzed acyl migration followed by ytterbium-catalyzed asymmetric Friedel-Crafts alkylation is disclosed, leading to the rapid synthesis of chiral dihydrocarbazoles and dihydrodibenzofuran in generally moderate to good overall yields with good to excellent enantioselectivities. The gold-catalyzed acyl migration of propargyl acetates generates α-ylidene-ß-diketones with high E/Z ratios, which are then subjected to the ytterbium-catalyzed asymmetric Friedel-Crafts alkylation without any purification. Importantly, this protocol provides a new type of substrate for asymmetric Friedel-Crafts alkylation.

Nucleophile-Controlled Trapping of Gold Carbene by Nitriles and Water: Synthesis of 5H-Pyrimido[5,4-b]indoles and 2-Benzylidene-3-indolinones.

A gold-catalyzed, nucleophile-controlled cascade reaction of N-(2-azidophenyl-ynyl)methanesulfonamides with nitriles and water is described that provides structurally diverse 5H-pyrimido[5,4-b]indoles and 2-benzylidene-3-indolinones in good to excellent yields. Mechanistic studies indicate that the ß-sulfonamido-α-imino gold carbene is the key intermediate which is generated through the gold-catalyzed cyclization of N-(2-azidophenyl-ynyl)methanesulfonamides and undergoes formal [4 + 2] cascade annulation with nitriles and intramolecular SN2' type reaction with water, respectively.

Enantioselective functionalization of unactivated C(sp3)-H bonds through copper-catalyzed diyne cyclization by kinetic resolution.

Site- and stereoselective C-H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)-H functionalization reactions, the catalytic enantioselective C(sp3)-H functionalization based on vinyl cations, especially for an unactivated C(sp3)-H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)-H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)-H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)-H insertion reaction and elucidate the origin of enantioselectivity.

Brønsted-Acid-Catalyzed Enantioselective Desymmetrization of 1,3-Diols: Access to Chiral ß-Amino Alcohol Derivatives.

Herein, we describe a Brønsted-acid-catalyzed enantioselective desymmetrization of 1,3-diols with alkynes through a hydroalkoxylation/hydrolysis process. The reaction leads to the atom-economical synthesis of valuable chiral ß-amino alcohols under mild reaction conditions. Further synthetic transformations based on the ß-amino alcohol moiety provide divergent approaches toward chiral N-containing heterocycles.

Ir/Zn-cocatalyzed chemo- and atroposelective [2+2+2] cycloaddition for construction of C─N axially chiral indoles and pyrroles.

Here, an Ir/Zn-cocatalyzed atroposelective [2+2+2] cycloaddition of 1,6-diynes and ynamines was developed, forging various functionalized C─N axially chiral indoles and pyrroles in generally good to excellent yields (up to 99%), excellent chemoselectivities, and high enantioselectivities (up to 98% enantiomeric excess) with wide substrate scope. This cocatalyzed strategy not only provided an alternative promising and reliable way for asymmetric alkyne [2+2+2] cyclotrimerization in an easy handle but also settled the issues of previous [Rh(COD)2]BF4-catalyzed system on the construction of C─N axial chirality such as complex operations, limited substrate scope, and low efficiency. In addition, control experiments and theoretical calculations disclosed that Zn(OTf)2 markedly reduced the barrier of migration insertion to significantly increase reaction efficiency, which was distinctly different from previous work on the Lewis acid for improving reaction yield through accelerating oxidative addition and reductive elimination.