Imidazolidinone based chiral auxiliary mediated acetate aldol reactions of isatin derivatives and stereoselective synthesis of 3-substituted-3-hydroxy-2-oxindoles

New Advances in the Synthetic Application of Enantiomeric 1-Phenylethylamine (α-PEA): Privileged Chiral Inducer and Auxiliary

“…3-Substituted-3-hydroxy-2-oxindoles are key intermediates for the synthesis of furoindolines and pyrroloindole-based natural products [ 59 ]. Their synthesis was based on the application of an α-PEA-containing chiral auxiliary.…”

“…Their synthesis was based on the application of an α-PEA-containing chiral auxiliary. The acetate aldol reaction, which was developed earlier by the same group [ 43 ], when run with N -substituted isatin, afforded the corresponding adducts with high yields and diastereoselectivity ( Scheme 36 ) [ 59 ].…”

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

“…The stereoselectivity estimated from the theoretical calculations matches the experimental dr very closely. It has been reported that the chiral α-phenylethyl auxiliary is readily removed by hydrogenolysis after acting as a valuable inductor for asymmetric synthesis [36][37][38][39][40][41][42][43]71 Hence, it is expected that such auxiliary can be removed in a like manner for most of the products obtained in the current study without affecting their functionalities. Experimental studies are being carried out to test this idea, and the results will be reported in due course.…”

“…34,35 Among the chiral auxiliaries used in asymmetric synthesis, those based on the 1-phenylethylamino group-containing scaffolds proved to be very efficient in many diastereoselective processes. [36][37][38][39][40][41][42][43] On the basis of the previously developed regioselective synthesis of N-substituted 4-oxazolin-2-ones 1 and 4-methylene-2-oxazolidinones 2, resulting from the condensation of α-ketol 3a and isocyanates 4 (Scheme 1), 44,45 in a preliminary report, we presented the one-pot synthesis of the optically pure version of heterocycles 1-2 by introducing the N-(S)-methylbenzyl moiety as the chiral auxiliary. 46 Although this methodology was also efficient for the preparation of the corresponding 3-substituted 4-oxazolin-2-thiones 6 and 4methylene-1,3-oxazolidin-2-thiones 7, 47 these heterocycles were not able to undergo further reactions when utilizing the thioenamide functionality as a nucleophile.…”

“…It is possible to carry out this synthetic approach via aldol, Mannich, Michael condensations, addition to metal π‐double and π‐triple activated C–C bonds, and Heck arylation, as well as in cascade vicinal difunctionalization or pericyclic reactions, leading to the formation of complex molecules with the generation of a number of stereogenic centers, including the total synthesis of natural products . Among the chiral auxiliaries used in asymmetric synthesis, those based on the 1‐phenylethylamino group‐containing scaffolds proved to be very efficient in many diastereoselective processes …”