This Review compiles the evolution, mechanistic understanding, and more recent advances in enantioselective Pd-catalyzed allylic substitution and decarboxylative and oxidative allylic substitutions. For each reaction, the catalytic data, as well as examples of their application to the synthesis of more complex molecules, are collected. Sections in which we discuss key mechanistic aspects for high selectivity and a comparison with other metals (with advantages and disadvantages) are also included. For Pd-catalyzed asymmetric allylic substitution, the catalytic data are grouped according to the type of nucleophile employed. Because of the prominent position of the use of stabilized carbon nucleophiles and heteronucleophiles, many chiral ligands have been developed. To better compare the results, they are presented grouped by ligand types. Pd-catalyzed asymmetric decarboxylative reactions are mainly promoted by PHOX or Trost ligands, which justifies organizing this section in chronological order. For asymmetric oxidative allylic substitution the results are grouped according to the type of nucleophile used.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications.

The development of novel synthetic strategies to form new chemical entities in a stereoselective manner is an ongoing significant objective in organic and medicinal chemistry. This review analyses the development of new stereoselective approaches to spirocyclic oxindoles with spiro-3- to 8-membered rings. It highlights the importance of these structures for applications in medicinal chemistry, as intermediates or final products in total synthesis and as model compounds for the development of enantioselective catalytic methodologies.

Stereoselective synthesis and applications of spirocyclic oxindoles

Sustainability in chemical synthesis is a major aspect of the current synthetic endeavors and, therefore, mimicking the biological process in the laboratory nowadays has the highest priority. Towards achieving this goal, designing organic reactions in domino mode rather than the multistep synthetic pathways and using organocatalysis instead of metal catalysis have received a lot of attention due to the inherent advantages of these processes in terms of synthetic efficiency and sustainability. As a result, the field of asymmetric organocatalytic domino reactions has witnessed tremendous progress in recent years. This review attempts to summarize the latest developments in asymmetric organocatalyzed domino reactions since 2012, with the emphasis on the catalysts and reaction modes. Discussions on the reaction mechanisms and the applications of the developed domino reaction methods in the synthesis of biologically active molecules and natural products are also included when appropriate.

Recent progress in organocatalytic asymmetric domino transformations

This review aims to present the most recent contributions in the chemistry of nitrosoalkenes and azoalkenes, highlighting the chemical behavior that makes them important and versatile building blocks in organic synthesis. These are heterodienes used in the assembly of a variety of heterocyclic systems, spanning from five- to seven-membered heterocycles, as well as for the functionalization of heterocycles.

Recent Advances in the Chemistry of Conjugated Nitrosoalkenes and Azoalkenes.

https://pubs.rsc.org/en/content/articlepdf/2019/CC/C9CC02371B

Enantioselective synthesis of multi-nitrogen-containing heterocycles using azoalkenes as key intermediates

An atom-economic and highly efficient vinylogous umpolung strategy is developed for deconjugated carbonyl compounds, which generate electron-deficient π-allylpalladium complexes with Pd(OAc)2 under ligand-free conditions. In cooperation with a chiral-phosphonium-based phase-transfer catalyst, the asymmetric direct oxidative allylic alkylations of 3-substituted oxindoles are furnished under O2 atmosphere. The γ- or even remote ϵ-regioselective alkylation products, with substantial substituents, are delivered with excellent enantioselectivity, and can be further used to access diverse chiral spirocyclic architectures effectively. The Mukaiyama dienol silyl ether can be utilized similarly, indicating that the current active π-allylpalladium species results from tautomerization of the PdII -dienolate intermediate.

Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy.

Asymmetric Cascade Assembly of 1,2-Diaza-1,3-dienes and α,β-Unsaturated Aldehydes via Dienamine Activation

We disclose that the carbonates of 4-hydroxy-2-cyclopentenones can form π-allylpalladium-based 1,2-carbodipoles, which isomerize to interesting η2 -Pd0 -cyclopentadienone complexes. Compared with the labile parent cyclopentadienone, the HOMO energy of the related η2 -complex was significantly raised via the back-bonding of Pd0 as a π-Lewis base, rendering the uncoordinated C=C bond an electron-richer dienophile in inverse-electron-demand aza-Diels-Alder-type reactions with diverse 1-azadienes. The vinylogous (aza)Morita-Baylis-Hillman or cross Rauhut-Currier addition to (imine)carbonyls or activated alkenes, respectively, was also realized to afford chiral [4+2] or [2+2] cycloadducts, respectively, after trapping the re-generated π-allylpalladium species. New C1 -symmetric ligands from simple chiral sources were developed, exhibiting high stereoselectivity even with racemic substrates via an unusual dynamic kinetic resolution process. Besides, tropone could be similarly activated by a Pd0 complex.

π-Lewis-Base-Catalyzed Asymmetric Vinylogous Umpolung Reactions of Cyclopentadienones and Tropone.

A new type of 2,4-dienal with α-substitutions and featuring a benzofulvene skeleton has been designed and utilised in asymmetric Diels–Alder cycloaddition reactions with 3-olefinic oxindoles under the trienamine catalysis of a chiral secondary amine. An array of chiral polyhydrofluorene frameworks with complex molecular structures are constructed efficiently, generally in fair to high yields with good diastereoselectivity and excellent enantioselectivity.

Asymmetric Diels–Alder cycloadditions of benzofulvene-based 2,4-dienals via trienamine activation

The zwitterions bearing a π-allylmetal moiety, as highly reactive dipoles, have been employed for various asymmetric cycloadditions for the synthesis of diverse chiral carbo- and heterocycles. However, the reported all-carbon-based dipoles are generally limited to 1,3- or 1,4-type ones. Here, we disclose a new type of cyclic 1,5-carbodipoles, generated from the carbonates of 4-hydroxy-2-cyclopentenones under palladium catalysis via a deprotonation strategy, which can undergo highly asymmetric formal [5+4] cycloadditions with diverse 1-aza/oxadienes. New C1-symmetric bisphosphines containing two electronically and sterically different binding units or even hybrid phosphine/sulfonamide ligands from simple chiral sources are developed, which prove to be much superior to classical C2-symmetric ligands regarding the catalytic activity and stereoselectivity. Moreover, diastereodivergent catalysis could be realized for some substrate assemblies via ligand-control. Both 1,5-carbodipole species and chiral C1-symmetric ligands would find more application in asymmetric synthesis.

Jing-Fei Yue

Papers

Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy.

Asymmetric Cascade Assembly of 1,2-Diaza-1,3-dienes and α,β-Unsaturated Aldehydes via Dienamine Activation

π-Lewis-Base-Catalyzed Asymmetric Vinylogous Umpolung Reactions of Cyclopentadienones and Tropone.

Asymmetric Diels–Alder cycloadditions of benzofulvene-based 2,4-dienals via trienamine activation

C 1 -Symmetric Ligand-Enabled Stereoselective Formal [5+4] Cycloadditions of Palladium-Containing 1,5-Carbodipoles