Synthetic studies toward the citrinadins: enantioselective preparation of an advanced spirooxindole intermediate

Abstract

This manuscript describes the enantioselective preparation of a spirooxindole that is suited for advancedment to either Citrinadin A or B.

Recent Advances of Catalytic Enantioselective Heck Reactions and Reductive‐Heck Reactions

“…[ 56 ] Moreover, Wood and co‐workers realized an intramolecular Heck reaction to form spirooxindole 34 , which was a key intermediate for the synthesis of Citrinadin B. [ 57 ] In the presence of Pd 2 (dba) 3 and (–)‐BINAP, conversion of tetrasubstituted olefin 33 proceeded smoothly, achieving product 34 in 96% yield and 80% ee (Scheme 45).…”

Synthetic studies toward citrinadin A: construction of the pentacyclic core

“…We were pleased to learn that unlike the nitrone cycloaddition used en route to citrinadin B, which required 9 days, the reaction of 7 with 10 furnished the desired cycloadduct in just 24 h. 8 Although 15b was the minor diastereomer, we have demonstrated in preliminary studies that use of enantioenriched 7 , 5 gives a d.r. of 3:2, while use of enantioenriched 7 and enantioenriched 10 , derived from commercially available chiral ethyl-3-hydroxybutyrate, gives a d.r.…”

“…These efforts independently led to the conclusion that the structures assigned by Kobayashi were sound in terms of connectivity but required revision at the stereochemical level. 2,3,4,5 As illustrated in Figure 1 (bottom), the reassigned structures of citrinadins A and B differ at the stereogenic centers residing within the pentacyclic core. Herein, we report synthetic efforts toward citrinadin A ( 3 ) that have now resulted in the stereoselective preparation of its core structure.…”

Acetic acid catalysed solvent‐free synthesis of spiro‐isoxazolo[5,4‐b]pyridines/quinolines by mechano‐chemical grinding

“…Spirooxindoles fused with other heterocyclic moieties at C-3 of the oxindole core ( Figure 1) [5] are considered to be promising candidates for drug discovery as they form skeletal composition of some potential therapeutic agents. [6,7] Further, isoxazoles are a vital class of heterocyclic molecules that find applications not only as chiral ligands [8] and synthetic intermediates [9] but are also abundantly prevalent in a variety of natural products and biologically active compounds. [10][11][12] Additionally, isoxazole derivatives are also useful agrochemicals and are used as pesticides and insecticides.…”