Organocatalyzed Enantioselective Decarboxylative Stereoablation Reaction for the Construction of 3,3′-Disubstituted Oxindoles Using β-Ketoacids and 3-Halooxindoles

Abstract

An unprecedented method for the construction of optically active 3,3'-disubstituted oxindoles via an organocatalyzed decarboxylative stereoablation reaction has been developed. We describe the first asymmetric reaction between β-ketoacids and 3-halooxindoles utilizing an organocatalyst. This method allows for the formation of a variety of 3,3'-disubstituted oxindoles bearing a keto-carbonyl group, which are not easily accessible using other methodologies, in moderate to good yields with high enantioselectivities.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…85 Their system was later modified to allow for the use of ketone enolates as π-nucleophiles (product 70 ). 86 More recently, Jing and coworkers developed cinchona catalyst 74 that bears a squaramide hydrogen-bond donor for the O -alkylation of α-nitrophosphonates under similar conditions (product 71 ). 87 …”

Alcohols as Substrates and Solvents for the Construction of 3-Alkoxylated-2-Oxindoles by Direct Alkoxylation of 3-Halooxindoles

“…In our initial endeavor, the 3-chloroxindole 1a was prepared via a three-step approach (Knoevenagel condensation, reduction and chlorination) using benzaldehyde and 2-oxindole as the starting materials [ 17 ]. We then investigated 3-chloroxindole 1a as a starting substrate to substantiate the feasibility of the strategy under various reaction conditions, as shown in Table 1 .…”

“…Among them, the most important and efficient approaches involve the use of electrophilic isatins/isatinimines and nucleophilic 3-monosubstituted oxindoles for the synthesis of 3,3′-disubstituted oxindoles ( Figure 1 ) [ 2 , 3 , 4 , 5 , 12 , 13 ]. Despite these advances, however, the use of indol-2-ones (generated in situ from 3-halooxindoles) as electrophiles has been limited [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

β‐Keto Acids in Organic Synthesis

“…The Yuan group designed a decarboxylative substitution to give optically active 3,3'‐disubstituted oxindoles 29.2 (Equation 29–1). The stereo‐controlled synthesis was based on an organocatalyst 29.1 from Cinchona alkaloid derivatives.…”