A General Catalytic Route to Enantioenriched Isoindolinones and Phthalides: Application in the Synthesis of (S)-PD 172938

Abstract

Chiral Brønsted acid catalyzed enantioselective syntheses of isoindolinones and phthalides have been accomplished via tandem Mannich-lactamization and aldol-lactonization reactions, respectively. A variety of enantioenriched isoindolinones (up to 99% ee) and phthalides (up to 85% ee) containing α-diazoesters were afforded in excellent yields. Furthermore, a concise synthesis of (S)-PD 172938 has been demonstrated by using this protocol.

Electrochemical Difunctionalization of Olefines: Access to Selenomethyl‐Substituted Cyclic Ethers or Lactones

“…[28] Many approaches have been explored to achieve this goal. [29] The primary disadvantages of these methods are long reaction time, low yield, and use of expensive metal catalysts. Thus, 2-vinylbenzoic acid (4 e) with different selenides were investigated via the current electrosynthesis.…”

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

“…This compound was further transformed to ( S )‐PD 172938 ( 489 ), which is a dopamine D 4 ligand, via a multistep sequence including removal of the diazo and the PMP groups, reduction the ester with LiBH 4 , and the final assembly with piperazine 488 (Scheme 52). Apparently, an organocatalytic reaction afforded the key intermediate 485 for this synthesis [99] …”

“…[98] In 2019, Singh and co-workers reported an enantioselective total synthesis of (S)-PD 172938 (489, Scheme 52). [99] The asymmetric tandem Mannich-lactamization of methyl 2-formylbenzoate (481) and p-anisidine (482) with ethyl diazoacetate (483) in the presence of the phosphoric acid 484 as the catalyst produced an optically active chiral isoindolinone containing αdiazo ester (485). This compound was further transformed to (S)-PD 172938 (489), which is a dopamine D 4 ligand, via a multistep sequence including removal of the diazo and the PMP groups, reduction the ester with LiBH 4 , and the final assembly with piperazine 488 (Scheme 52).…”

Metal‐Free Catalyzed Cyclization of N‐Methoxybenzamides to Construct Quaternary Carbon‐Containing Isoindolinones

“…[1] Therefore, the synthesis of this class of compounds caused a great interest of chemists, and various synthetic methods have been developed. [2] Remarkable progress has been made in the Rh(III)-, Pd(II)-, Cu(II)-, Co(II)-and Au(I)-catalyzed C-H bond functionalizations, which provides a step-and atom-economical route to isoindolinones from less functionalized substrates (Scheme 1a). [3] For instance, the group of Ma reported the Rh(III)-catalyzed synthetic route of isoindolinones via a sequential C-H activation/allene formation/cyclization pathway.…”