Synthesis of Chiral Spiro-Aziridine Oxindoles via Aza-Corey–Chaykovsky Reaction of Isatin Derived N-tert-Butanesulfinyl Ketimines

Abstract

A general and direct strategy for the synthesis of chiral spiro-aziridine oxindoles has been developed via an aza-Corey-Chaykovsky reaction of isatin-derived N-tert-butanesulfinyl ketimines with excellent selectivity (dr = 98:2 to >99:1). The method is explored for the synthesis of chiral 3-substituted spiro-aziridine oxindoles with high (2S,3S)-selectivity over (2S,3R).

Asymmetric transformations from sulfoxonium ylides

“…This intermediate was then taken to (−)-Brevipolide H (65) after 8 steps. The contributions depicted in Schemes 8 and 9, as well as others 18,51,98,104,105 , illustrate the importance and versatility of sulfoxonium ylides in asymmetric synthesis, but there are also challenges to be addressed. For example, all reactions described in this section followed usual Corey-Chaykovsky reactivity, but the exploration of different reactivities is highly desirable.…”

3-Arylaziridine-2-carboxylic Acid Derivatives and (3-Arylaziridin-2-yl)ketones: The Aziridination Approaches

“…Other ylides can work in a similar way. Thus, aziridinations via ammonium [ 78 , 79 , 80 ] and sulfonium [ 81 , 82 , 83 , 84 ] ylides are known. A simple protocol for the reaction of phenacyl bromides 15g with imines 2a2 promoted by tertiary amine (DABCO) via in situ generated ylide ( Scheme 19 ) has been reported [ 78 ].…”

“…A series of 3-arylated N-diphenylphospinoyl aziridine-2 carboxamides trans - 1b7 are synthesized in similar route from amide sulfonium salts via type 25 stabilized ylides [ 83 ] as well as series of chiral 3-aryl spiro-aziridine oxindoles 1b8 (11 examples, 60–76%, dr > 99:1) from corresponding imines using ylides generated from sulfonium salts in presence of NaH ( Scheme 24 ) [ 84 ]. Therefore, sulfonium ylides as well as the above mentioned guanidinium and ammonium ylides are useful tools in target aziridine synthesis.…”

“…Five different 3-arylated aziridine-2-carboxylates trans-1a1 were obtained in moderate to good yields (40-80%) and good trans-selectivity > 98:2 dr. Scheme 24. Sulfur ylide aziridination products [83,84].…”

Recent applications of isatin in the synthesis of organic compounds

“…Hajra et al carried out the asymmetric synthesis of spiroaziridine oxindoles 67a, 67b via the aza Corey-Chaykovsky reaction of isatin-derived tert-butanesulfinyl ketimines 64 with in situ generated sulfur ylide from trimethylsulfonium iodide 65 (or the reaction of benzyl sulfur ylides generated from S-benzyl tetrahydrothiophenium bromide 66 with chiral tertbutanesulfinyl ketimines 64) and NaH (Scheme 23). 61 …”