Construction of all-carbon quaternary stereocenters by catalytic asymmetric conjugate addition to cyclic enones in natural product synthesis

Abstract

Asymmetric catalysis for chiral compound synthesis is a rapidly growing field in modern organic chemistry and provides enantioselective materials to meet the demands of various fields. However, the construction of...

Construction of vicinal 4°/3°-carbons via reductive Cope rearrangement

“…From our previous work, it is known that by adding either a 4-aromatic group 28 or a 4-methyl group 31 to a 3,3-dicyano-1,5-diene, low barrier (rt -80 °C) diastereoselective Cope rearrangements can occur. Notably, the 4-substituent was found to destabilize the starting material (weaken the C3-C4 bond, conformationally bias the substrate for [3,3]), and stabilize the product side of the equilibrium via resonance (phenyl group) or hyperconjugation (methyl group). In this study, we modeled substrates 1, 3, and 5 that have variable 4-substitution and would result in vicinal gem-dimethyland phenyl-containing 4°/3° carbons upon Cope rearrangement to 2, 4, or 6, respectively.…”

“…This stands in stark contrast to the plethora of other methods for establishing sterically congested vicinal carbons. [1][2][3][4][5] Central to the challenge are kinetic and thermodynamic issues associated with the transformation. In the simplest sense, Cope rearrangements proceed in the direction that results in highest alkene substitution (Figure 1).…”

“…In the simplest sense, Cope rearrangements proceed in the direction that results in highest alkene substitution (Figure 1). 6,7 To forge 4°/3° motifs by Cope rearrangement, additional driving forces must be introduced to reverse the [3,3] directionality and compensate for the energetic penalty associated with the steric and torsional strain of the targeted vicinal 4°/3° motif. With limited reports in all cases, oxy-Cope substrates (Scheme 1, equation 1), [8][9][10][11][12][13][14] divinylcyclopropanes (Scheme 1, equation 2), [15][16][17][18][19][20] and vinylidenecyclopropane-based 1,5-dienes 21…”

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

“…Generally, there are four strategies for the construction of quaternary stereocenters (Figure1, B): (i) C-C bond formation of prochiral olefins with carbon nucleophiles or electrophiles, such as the 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 Tunge group and Stoltz group in 2004, respectively. 21,22 This powerful transformation in the construction of quaternary stereocenters have several potential advantages.…”

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

“…Chiral complexes of Rh [17][18][19][20][21][22][23][24] and Pd usually catalyse the reaction, however, palladium holds a special place in this area. There are several review articles partially covering this topic [25][26][27][28][29][30][31]. However, a comprehensive review is missing.…”