Kinetic Resolution of Propargylic Ethers via [2,3]-Wittig Rearrangement to Synthesize Chiral α-Hydroxyallenes

Abstract

An efficient kinetic resolution of propargyloxy dicarbonyl compounds via asymmetric [2,3]-Wittig rearrangement was achieved by using a chiral N,N′-dioxide/NiII complex catalyst. Various chiral α-allenyl alcohols were obtained in high enantioselectivities under mild conditions. The utility of this method was readily demonstrated in the asymmetric synthesis of the chiral 2,5-dihydrofuran derivative.

Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes

“…28 Later in 2020, the same group further extended the strategy to demonstrate the kinetic resolution of propargyloxy dicarbonyl compounds 90 (Scheme 14B). 29 Chiral α-hydroxyallenes possessing various functional groups were afforded in high yields with good enantioselectivities.…”

Experimental and Theoretical DFT Investigations in the [2,3]-Wittig-Type Rearrangement of Propargyl/Allyl-Oxy-Pyrazolones

“…The base-promoted deprotonation of the intermediate I can occur at the α or α positions, leading to the formation of anion species II or II , respectively (Scheme 3). Intermediate II can theoretically undergo both [1,2]-or [2,3]-Wittig rearrangements, furnishing products III or IV, respectively, while intermediate II can give the [1,2]-or [1,4]-rearrangement, giving products III or III", respectively (Scheme 3) [40,47,49,[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81].…”

“…The base-promoted deprotonation of the intermediate I can occur at the α or α′ positions, leading to the formation of anion species II or II′, respectively (Scheme 3). Intermediate II can theoretically undergo both [1,2]-or [2,3]-Wittig rearrangements, furnishing products III or IV, respectively, while intermediate II′ can give the [1,2]-or [1,4]-rearrangement, giving products III′ or III″, respectively (Scheme 3) [40,47,49,[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81]. It is noteworthy that the process here described is highly regioselective, since the deprotonation occurs only in the α position of the intermediate I to produce II, as this proton is more acid than the one in the α position, being activated both from an amidic carboxylic group as well as from an imino function.…”

“…Among the several approaches that have been employed for their synthesis [37][38][39][40][41][42][43][44][45], the [2,3]-Wittig rearrangement of propargylic ethers represents an efficient way to assemble them [46,47]. The major limitation of this versatile bond reorganization process, which has many other applications in organic synthesis, is mainly correlated to the use of strong bases and very low temperatures together with the laborious, complicated, and expensive procedures required [48][49][50].…”

Cooperative Palladium/Brønsted Acid Catalysis toward the Highly Enantioselective Allenylation of β-Keto Esters

“…As a result, a series of diverse strategies have been established for its synthesis, among which 1,3-dicarbonyls have emerged as broadly applicable precursors. In this field, methods using acid or transition-metal catalysis for allenylation reactions have been predominant; however, asymmetric processes are still underdeveloped despite the impressive work of Kozlowski, Feng, and Sun (Scheme ). Whereas the former two processes are based on enantioselective propargyl vinyl ether rearrangements of indole- and indene-based substrates, respectively, only Sun’s approach pursues a direct, enantioselective allenylation of β-dicarbonyls.…”