Stereochemical control on the Michael addition of chiral 1,3-oxazolidine-2-thiones to N-crotonyl 1,3-oxazolidin-2-ones

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

“…The use of a catalytic amount of base led to product 3a in a good yield (Table 1, entry 4) but with a loss of diastereoselectivity. Because the optically pure auxiliary and the conjugated ketone were not interacting well, a significant diastereoselectivity could not be obtained and we looked for improvements through the use of an appropriate chiral organocatalyst [63–65]. Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone ( S )- 3a with higher de (54%), (Table 1, entry 5).…”

“…Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone ( S )- 3a with higher de (54%), (Table 1, entry 5). We assumed such de increase resulted from a match effect [65–67] of the diastereomeric ion pair formed by the chiral nucleophile, the conjugated ketone and the cinchoninium salt. Hence, in our case, the chirality of the new stereochemical center was shown to be controlled by both Michael acceptor and donor interacting with the chiral ammonium.…”

Synthetic Applications of Sulfur-based Chiral Auxiliaries in Asymmetric Syntheses

“…A complex mixture is observed when a thiazolidinethione is added to N-crotonyl oxazolidinethione or oxazolidinethione is added to N-crotonyl thiazolidinethione because a concomitant trans-acylation occurs. [42] However, when the Michael acceptor is N-crotonyl oxazolidinone 25 and the nucleophiles are thiazolidinethione (X = S) or oxazolidinethione (X = O) 22, no trans-acylation is observed and Michael addition products 26 and 27 are cleanly obtained (Scheme 9).…”

<span>Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue.</span><span></span>

“…The use of a catalytic amount of base led to product 3a in a good yield (Table 1, entry 4) but with a loss of diastereoselectivity. Because the optically pure auxiliary and the conjugated ketone were not interacting well, a significant diastereoselectivity could not be obtained and we looked for improvements through the use of an appropriate chiral organocatalyst [63][64][65]. Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone (S)-3a with higher de (54%), (Table 1, entry 5).…”

“…Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone (S)-3a with higher de (54%), (Table 1, entry 5). We assumed such de increase resulted from a match effect [65][66][67] of the diastereomeric ion pair formed by the chiral nucleophile, the conjugated ketone and the cinchoninium salt. Hence, in our case, the chirality of the new stereochemical center was shown to be controlled by both Michael acceptor and donor interacting with the chiral ammonium.…”