Palladium-Catalyzed Asymmetric Allylic Alkylation Strategies for the Synthesis of Acyclic Tetrasubstituted Stereocenters

Abstract

Over the past 20 years, the asymmetric synthesis of acyclic tetrasubstituted stereocenters by Pd-catalyzed asymmetric allylic alkylation (Pd-AAA) strategies has seen considerable growth. Despite the inherent difficulty in accessing acyclic tetrasubstituted stereocenters, creative approaches toward this problem have resulted in high stereoinduction on both electrophilic and nucleophilic reaction partners. Much of this chemistry has paved the way for unique solutions in Mo-, Ir-, and Rh-AAA, with many complimentary methods arising due to the unique regiochemical outcomes of AAA outside of Pd catalysis.1 Introduction2 Stereocontrol on Prochiral Electrophiles3 Stereocontrol on Prochiral Nucleophiles4 Temporary Cyclic Pronucleophiles5 Allylic Alkylation with Other Metals6 Conclusions and Outlook

Effective synthesis of bicyclodienes via palladium-catalyzed asymmetric allylic alkylation and ruthenium-catalyzed cycloisomerization

“…Only the steric effect of the ligands on the substrates is studied in detail. The reasons for the high ee in Table 2 have been previously calculated theoretically in detail for the Trost-ligand L std in the transition state of the Pd-catalyst [58][59][60][61]. The crystal structure, a 3D calculated model of the active catalyst of π-allyl palladium complex in situ, is shown in Figure 4 [58][59][60][61].…”

“…The reasons for the high ee in Table 2 have been previously calculated theoretically in detail for the Trost-ligand L std in the transition state of the Pd-catalyst [58][59][60][61]. The crystal structure, a 3D calculated model of the active catalyst of π-allyl palladium complex in situ, is shown in Figure 4 [58][59][60][61]. The ligand L consists mainly of three important parts: a linker (red), a chiral scaffold (black), and a binding post (green).…”

Development of Chemo‐ and Enantioselective Palladium‐Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α‐Nitroesters

“…For substrates without an ester for α‐stabilization, a single example of Pd‐AAA with a secondary di‐alkyl nitroalkane with modest enantioselectivity has been described by Shibasaki . Furthermore, setting fully‐substituted acyclic stereocenters by Pd‐AAA presents unique challenges . With this in mind, we were particularly intrigued with the prospect of developing a method for the chemoselective allylic alkylation of racemic secondary nitroalkanes to afford enantiopure acyclic tertiary nitroalkanes (Scheme c) using the diphenylphosphino benzamide ligands L1–L4 (Figure ).…”

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

“…[9][10][11][12][13][14] Despite their importance and noteworthy progress in synthetic methods, the assembly of quaternary stereocenters efficiently, especially in a catalytic asymmetric manner, is still highly desired yet challenging. [15][16][17] Figure 1 Bioactive compounds containing quaternary stereocenters and their general synthetic strategies.…”

“…[9][10][11][12][13][14] Despite their importance and notable progress in synthetic methods, the efficient assembly of quaternary stereocenters, especially in a catalytic asymmetric manner, remains highly desired, albeit challenging. [15][16][17] Generally, there are four strategies for the construction of quaternary stereocenters (Figure 1B): (i) C-C bond formation of prochiral olefins with carbon nucleophiles or electrophiles, such as asymmetric Diels-Alder reactions and intramolecular Heck reactions; 18,19 (ii) enantioselective desymmetrization of prochiral structures bearing four different substituents; 20 (iii) kinetic resolution of racemic molecules (with only 50% theoretical yields obtained); (iv) palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA), which was first reported by the groups of Tunge and Stoltz in 2004. 21,22 This powerful transformation in the construction of quaternary stereocenters has several potential advantages.…”