All-carbon quaternary centers in natural products and medicinal chemistry: recent advances

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…2, 3 This fact reflects unmet challenges posed by the de novo chemical synthesis of stereocenters bearing four different carbon substituents. 4–13 Orbital overlap is more difficult to achieve in the formation of such highly congested stereocenters, and, in the case of enantioselective processes, defining the approach of chiral reagents or catalysts is intrinsically more challenging. As illustrated by several historic milestones, significant progress has been made in the formation of quaternary carbon stereocenters in cyclic systems.…”

Enantioselective Construction of Acyclic Quaternary Carbon Stereocenters: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Amide Enolates

“…The Stoltz group has extensively contributed to the design of highly efficient catalysts for highly enantioselective allylic alkylation-type reactions, 13 especially those involving fully substituted cyclic allyl enol carbonates (Scheme 1D) 14 en route to the synthesis of complex natural products. 15 We envisaged developing a unified carbometalation–enantioselective catalysis approach to access de novo quaternary carbon stereocenters. Our approach would involve implementing achiral acyclic amide enolates in combination with enantioselective palladium-catalyzed decarboxylative allylic alkylation technology (Scheme 1E).…”

Palladium‐Catalyzed Asymmetric Construction of Vicinal Tertiary and All‐Carbon Quaternary Stereocenters by Allylation of β‐Ketocarbonyls with Morita–Baylis–Hillman Adducts

“…Although substantial progress has been made in the synthesis of singular all-carbon quaternary stereocenters, [1] catalytic construction of contiguous stereodyads proves far more difficult because of the increased steric demands and the stereochemical control in the CÀCbond formation. [2] Among the limited methods for building such am otif,s ome recent developments involve the use of transition-metal-catalyzed asymmetric allylic alkylations (AAA) [3] as aversatile tool for this challenging C À Cbond formation.…”

“…[b] 3aa/4aa [c] d.r. [a] Unless otherwise noted, the reactions were performed under conditionsB.The data within parentheses are the yields of isolated 3.In each case, the b/l and d.r.values were determined by 1 Considering the bifunctional role of SKPs in the allylic substitution of MBH acetates, [11] as well as the sense of asymmetric induction in the titled reaction, as chematic representation of the stereocontrol model is proposed in Figure 1. Except for 3ap,all the products (3aaao)w ere obtained in excellent enantioselectivities (93-> 99 % ee).…”