A reagent based DOS strategy via Evans chiral auxiliary: highly stereoselective Michael reaction towards optically active quinolizidinones, piperidinones and pyrrolidinones

Abstract

A reagent based DOS strategy via Evans chiral auxiliary: highly stereoselective Michael reaction towards optically active quinolizidinones, piperidinones and pyrrolidinones3

One-Pot Multicomponent Coupling Reaction of Catechols, Benzyl Alcohols/Benzyl Methyl Ethers, and Ammonium Acetate toward Synthesis of Benzoxazoles

“…In an experiment, 2b was reacted with ammonium acetate first; then, 1a was added to the reaction media, and benzoxazole 4b was isolated in 87% yield, confirming the formation of imine and reaction with catechol according to the proposed reaction mechanism (Scheme C). The imine formation under this condition was strongly confirmed by previous studies. − In other experiments, 3,5-di- tert -butylcyclohexa-3,5-diene-1,2-dione ( 1aa ) was used instead of catechol, and surprisingly, benzimidazole ( 4ba ) was obtained (Scheme D). This result demonstrates that this process does not undergo the formation of the 1aa intermediate and a radical pathway is most likely.…”

Diversity-Oriented Asymmetric Synthesis

“…The popularity of chiral auxiliaries as templates for DOAS was further exemplified by Sen and co-workers in 2012, via an Evans' chiral oxazolidinone based strategy for the asymmetric synthesis of quinolizidinones, piperizidinones and pyrrolidinones. 35 These scaffolds adhere to the 'rule of three' as closely as possible (M ≥ 300, HBD ≥ 3 and HBA ≥ 3, ClogP = 3, number of rotatable bonds ≥ 3, polar surface area = 60 Å 2 ). 24,36 These parameters are generally accepted to be the most appropriate in creating fragment libraries.…”

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

“…In 2018, Ding reported the enantioselective hydrogenation of 3-ylidenephthalides (283) by using an Ir/SpinPHOX (248k) catalyst (Scheme 85). 98 This method provides a straightforward approach to a wide variety of 2-substituted chiral phthalides (284) in high yields with excellent enantioselectivities (up to >99% yield and 98% ee). The application of this methodology was demonstrated in the synthesis of chiral drugs and natural products such as (R)chuangxinol (284a), (R)-typhaphthalide (284b), and (S)-3-nbutylphthalide (NBP) (284c), a constituent of celery seed oil.…”

“…Ligand 600c was applied in the Cu-catalyzed asymmetric Michael reaction of a silyl keteneimide 766 and nitrostyrene 767 to generate valuable intermediates in high diastereomeric ratios and good yields ( Scheme 242 ). 284 …”

“…Ligand 600c was applied in the Cu-catalyzed asymmetric Michael reaction of a silyl keteneimide 766 and nitrostyrene 767 to generate valuable intermediates in high diastereomeric ratios and good yields (Scheme 242). 284 Ohkuma performed a kinetic resolution of sterically hindered racemic α-tert-alkyl-α-hydroxy esters 769 via an enantiomer-selective carbamoylation reaction (Scheme 243). Using ligand 600d and Cu(OTf) 2 as the catalyst and carrying out the reaction at 0 °C enantioselectivities up to >99.9% ee and selectivity factors of up to 261 were achieved.…”