Quaternary carbon stereocenters are present in a wide variety of organic compounds and drug molecules. Highly enantioselective construction of such quaternary carbon stereocenters has received considerable attention owing to the great challenges in their syntheses. With the development of asymmetric organocatalytic cascade reactions, several efficient methods for the construction of optically pure compounds with quaternary carbon centers have been developed. This focused review highlights the asymmetric synthesis of chiral compounds with quaternary centers through organocatalytic cascade reactions.

The enantioselective construction of a spirocyclic quaternary stereogenic carbon center at the C2 position of indole has long been an elusive problem in organic synthesis. Herein, by employing a rationally designed hydrogen-bonding network activation strategy, for the first time, 2,2′-pyrrolidinyl-spirooxindole, which is a valuable and prevalent indole alkaloid scaffold, was directly obtained through a catalytic asymmetric [3+2] cycloaddition reaction with high yields and excellent stereoselectivities.

A practical and efficient approach for the synthesis of various sulfonyl-substituted vinyl arenes is reported. In the process, hydrazones provide coupling partners for the Pd-catalyzed cross-coupling with aryl halides and sulfinate salts as nucleophiles, which realizes minimal waste and excellent atom economy.

o-Carboryne (1,2-dehydro-o-carborane) generated in situ from the precursor 1-iodo-2-lithio-o-carborane reacts with 6,6′-diarylfulvenes to give a series of carboranonorbornadienes in moderate yields with excellent regioselectivity. The resultant [4+2] cycloadducts can be further derivatized, thus leading to the formation of a variety of highly functionalized carboranes. This study shows that such Diels–Alder reaction serves as a convenient method for the preparation of a new class of multifunctionalized o-carborane derivatives that might find applications in medicine and materials science.

The development of a direct vinylogous Michael addition of linear nucleophilic substrates is a long-standing challenge because of the poor reactivity and the considerable difficulty in controlling regioselectivity. By employing a rationally designed multifunctional supramolecular iminium catalysis strategy, the first direct vinylogous Michael addition of unmodified linear substrates to α,β-unsaturated aldehydes, to afford chiral 1,7-dioxo compounds with good yields and excellent regio- as well as enantioselectivity, has been developed.

The development of a direct vinylogous Michael addition of linear nucleophilic substrates is a long-standing challenge because of the poor reactivity and the considerable difficulty in controlling regioselectivity. By employing a rationally designed multifunctional supramolecular iminium catalysis strategy, the first direct vinylogous Michael addition of unmodified linear substrates to α,β-unsaturated aldehydes, to afford chiral 1,7-dioxo compounds with good yields and excellent regio- as well as enantioselectivity, has been developed.

An intramolecular, quaternary carbon center forming hydroacylation of α-substituted acrylates has been discovered. This interesting transformation can be readily incorporated into a multicatalytic tandem process enabled by a combination of nucleophilic tertiary amine and N-heterocyclic carbene catalysis. With no additional stoichiometric base required, this transformation affords the quaternary pyrroloindolones with high levels of enantioselectivity.

A novel and direct synthesis of 1-aryl-5-arylvinyl-tetrazoles from easily prepared propargylic alcohols and TMSN₃ is developed in the presence of TMSCl under mild conditions (TMS=trimethylsilyl). The process involves an allenylazide intermediate, followed by a CC-bond cleavage and CN-bond formation to afford the desired products. Moreover, this method offers a good functional-group applicability and can be scaled-up to grams (yield up to 85 %).

An unusual Ph₃PO-catalyzed stereoselective 1,3-dicholorination of an unsaturated ketoester has been developed. The novel activation mode involved in this cascade reaction can promote consecutively elusive transformations. The products were obtained with good yields and excellent stereoselectivities. This reaction makes important complementation to the limitations associated with the field of dichlorination.

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium-catalyzed, norbornene-mediated CH activation/carbene migratory insertion is described. Extension to a one-pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani–Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd-catalyzed insertion of diazo compounds and Pd-catalyzed CH activation.

Without extra addition of sulfinate salt, allylic sulfones were synthesized by palladium-catalyzed cross-coupling of aryl iodide with N-tosylhydrazone. In this transformation, not only the diazo compound but also the sulfinate salt, which were both generated in situ from base-mediated decomposition of the N-tosylhydrazone, was used as nucleophilic partner.

The stereoselective syntheses of (−)-chloramphenicol, (+)-thiamphenicol and (+)-sphinganine are described. The two continuous chiral centers within three target molecules were constructed through aldol reaction of chiral tricyclic iminolactone and aldehyde.

An efficient , asymmetric, one-pot synthesis of a novel tetracyclic ring system incorporating both chroman and bicyclo[2.2.2]octane structural units was established through sequential reaction of nitroolefin enoates and α,β-unsaturated ketones. Six stereogenic centers including two quaternary stereocenters were formed with excellent diastereo- and enantioselectivity.

A simple and convenient synthetic approach to dihydrofurans has been developed from the cyclization of 2-propynyl-1,3-dicarbonyl compounds catalyzed by potassium tert-butoxide, copper(II) trifluoromethanesulfonate and triphenylphosphine using methanol/dichloromethane as the solvent under very mild conditions. Moreover, dihydrofurans could be easily transformed into the corresponding furans in the presence of trifluoroacetic acid.

An efficient synthetic method was developed for the construction of substituted 1,2-dihydropyridines by gold-catalyzed tandem reactions. The key intermediates 2,4-dienals were generated from propargyl vinyl ethers or allenic vinyl ethers with gold catalysts. These two reactions involved the process of gold-catalyzed [3,3]-sigmatropic rearrangement/isomerization/amine condensation/6π-aza-electrocyclization.

An alkylzinc-mediated simple and efficient procedure for the catalytic enantioselective synthesis of N-tosyl-(E)-(2-en-3-ynyl)-amines has been developed. The method works well with various N-tosylaldimines and alkynes.

A highly diastereo- and enantioselective synthesis of 2,3-disubstituted tetrahydropyridines was accomplished via a proline-mediated cascade Mannich-type/intramolecular cyclization reaction from preformed N-PMP (p-methoxyphenyl) aldimines and inexpensive aqueous tetrahydro-2H-pyran-2,6-diol.