Asymmetric synthesis of 3,3-disubstituted isoindolinones

Methyl 2-(1-methyl-3-oxoisoindolin-1-yl)acetate

“…The isoindolinone core is composed of a γ-lactam fused with the benzene ring and can be either unsubstituted, or monoor di-substituted in 3-position [1]. If, on one hand, the synthesis of 3-unsubstituted and 3-mono substituted isoindolinones is widely explored and many protocols are available [1,2] reports about the synthesis of 3,3-disubstituted derivatives are relatively few because the construction of a quaternary carbon is generally more challenging [3,4]. In our recent works, we have developed a convenient access to 3,3-disubstituted isoindolinones by cascade reactions of 2-acylbenzonitriles with several nucleophiles [5,6].…”

Catalytic Asymmetric Synthesis of Isoindolinones

“…[6] Chiral isoindolinones have attractedc onsiderable attention from organic synthetic chemists and great progress has been made to obtain such lactam compounds. Traditionalmethodologies [7][8][9][10][11][12] need ac hiral auxiliary,w hich may be tedious to cleave. These works will not be introduced in detail in this review.B eginning around 2010, particulare mphasis has been put on transition-metal catalyzed and organocatalyzed asymmetrics ynthesis of such phthalimidines.…”

Palladium/Brønsted-Acid-Catalyzed Diastereoselective Cyclization with Chiral Sulfinamides as Nucleophiles

“…To determine the origin of stereoinduction in chiral sulfinyl groups during the diastereoselective reaction, the cyclization of substrate ( R S )- 1a was examined using Pd(0)/Brønsted acid (Table ). The initial allylic substitution was performed with 10% Pd­(PPh 3 ) 4 and (PhO) 2 PO 2 H (diphenyl phosphate, DPP) in toluene at room temperature, yielding full conversion of the isoindoline ,,,,, product ( R , R S )- 3a′ at a diastereomeric ratio (dr) of 3:1 (entry 1). Control experiments revealed that Pd(0) and Brønsted acid catalysts are both required in the substitution reaction (entries 2 and 3).…”

“…Finally, the fully substituted cyclized product 4j was derivatized to the known compound 9j through a synthetic sequence of aldehyde reduction, protecting group replacement, and N -Boc reduction with a total yield of 41% (Scheme c). The absolute configuration of compound ( R )- 9j was determined by comparing its optical rotation with that described in a previous report …”