Chiral Brønsted acid-catalyzed intramolecular S_N2′ reaction for enantioselective construction of a quaternary stereogenic center

Abstract

Construction of a quaternary stereogenic center was accomplished through the enantioselective intramolecular allylic substitution reaction of bis-trichloroacetimidate catalyzed by a chiral phosphoramide derivative.

Enantioselective Intramolecular Allylic Substitution via Synergistic Palladium/Chiral Phosphoric Acid Catalysis: Insight into Stereoinduction through Statistical Modeling

“…Forc omparative purposes,w ea lso investigated the same reaction in the absence of Pd, according to work reported by the Takasu group in which aC PA catalyzes the allylic substitution when the alcohol is replaced by an activated trichloroacetimidate leaving group,s ubstrate 1a' '. [10] In the initial study,t he substitution of allylic alcohol 1a was carried out in the presence of 10 mol %o fb oth (R)-TCYP 3 and Pd(PPh 3 ) 4 ,r esulting in pyrrolidine product (S)-2a in full conversion with 84 % ee (entry 1). In contrast, the reaction of 1a' ' with (R)-TCYP 3 under metal-free conditions gave the opposite enantiomer of the product, (R)-2a,in78% ee (entry 2).…”

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

“…Based on the above preliminary results, a plausible catalytic cycle and transition states TS1 and TS2 were proposed (Figure ). First, the acid catalyst 4 promotes the elimination of the hydroxy group of propargyl alcohols 1 where X=AcNH or 6 (X=OH), and the generated cationic intermediate interacts with the catalyst through the hydrogen bonding as shown in either TS1 or TS2 . The Lewis basic oxygen atom on the phosphorus atom is close to the sterically hindered aryl substituent of the catalyst and might preferably interact with the sterically less hindered acetamido or hydroxy group as shown in TS1 .…”

“…The borane salt of the catalyst is readily hydrolyzed to regenerate the catalyst. In this reaction, interaction of two distant oxygen atoms of the catalyst with both nucleophile and electrophile may be crucial for obtaining high yields and selectivity . In this scenario, the two oxygen atoms of the phosphoric acid catalyst as Lewis bases might be too close to each other (Table , entry 3 vs. 7).…”

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

“…First, the acid catalyst 4 promotes the elimination of the hydroxy group of propargyl alcohols 1 where X = AcNH or 6 (X = OH), and the generated cationic intermediate interacts with the catalyst through the hydrogen bonding as shown in either TS1 or TS2. [11,12] The Lewis basic oxygen atom on the phosphorus atom is close to the sterically hindered aryl substituent of the catalyst and might preferably interact with the sterically less hindered acetamido or hydroxy group as shown in TS1.I nterconvertible cis and trans isomers of the cationic intermediate are generated during this process,a nd one geometric isomer might preferentially participate in the reaction. Theboroxine or the corresponding boronic acid, [13] which is generated in situ by hydrolysis of the boroxine,c an be activated as anucleophile through formation of the ate complex with the deprotonated catalyst, and carbon-carbon bond formation with the neighboring cationic intermediate might then occur to afford the product 3 or 7 stereoselectively.The borane salt of the catalyst is readily hydrolyzed to regenerate the catalyst.…”

“…In this reaction, interaction of two distant oxygen atoms of the catalyst with both nucleophile and electrophile may be crucial for obtaining high yields and selectivity. [11] In this scenario,the two oxygen atoms of the phosphoric acid catalyst as Lewis bases might be too close to each other (Table 1, entry 3vs. 7).…”