Organocatalytic synthesis of spiro compounds via a cascade Michael–Michael-aldol reaction

Abstract

The synthesis of spiro compounds via a Michael-Michael-aldol reaction is reported. The reaction affords spirooxindole derivatives in good yields and in almost diastereo- and enantiopure form. Moreover, the reaction works with several heterocycles such as oxindoles, benzofuranones, pyrazolones or azlactones rendering the final spiro compounds in good yields and excellent stereoselectivities.

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…[137] In this work, two equivalents of a,b-unsaturated aldehydes reacted with oxindoles 292a-e to afford the corresponding almost enantiopure spirooxindoles 293a-e in good yields and excellent diastereoselectivities of > 92% de in almost all cases of substrates studied, as shown in Scheme 76. Remarkably, the scope of this reaction was extended to a range of other heterocycles, such as benzofuran-A C H T U N G T R E N N U N G ones, pyrazolones or azlactones, rendering the corresponding spiro compounds in comparable yields and stereoselectivities.…”

Catalytic Asymmetric Synthesis of Chiral Benzofuranones

“…In 2010, Rios and Melchiorre independently reported the trimethylsilyl (TMS) protected diphenylprolinol 6 catalyzed cascade Michael-Michael-aldol reaction of benzofuran-2(3H)-one 4 and a,b-unsaturated aldehydes 5 through an iminium-iminium-enamine activation sequence. [15] In Melchiorres work, only 5 mol% catalyst and 5 mol% benzoic acid were used, by which the desired product could be obtained in moderate to high yield (38-80% yield) with excellent diastereoselectivities (> 19:1 dr) and enantioselectivities (up to > 99 % ee) (Scheme 1). Different substituents at the aromatic moiety, regardless of their electronic properties, and a heteroaromatic substituent were well-tolerated (Scheme 1, selected examples).…”

Highly Enantioselective Synthesis of Spiro[cyclohexanone‐oxindoles] and Spiro[cyclohexanone‐pyrazolones] by Asymmetric Cascade [5+1] Double Michael Reactions

“…[20] During this period, more asymmetric organocatalytic methodologies for the construction of the intriguing spirocyclic oxindole skeletons in the presence of primary amines, secondary amines, or Brønsted acid/Lewis base bifunctional organocatalysts were successfully developed. They include a cascade Michael/Michael/aldol reaction [21] or a domino Michael/Michael/Michael/aldol reaction for spiro[cyclohexenecarbaldehyde-oxindoles], [22] a Michael/ ketone aldol/dehydration domino reaction for spiro[cyclohexenone-oxindoles], [17] a formal [2+2+2] annulation for spiro [cyclohexanol-oxindoles] and spiro[cyclopiperidineoxindoles], [23] a Knoevenagel/Michael cyclization for spiro[4H-pyran-oxindoles], [24] and direct asymmetric intermolecular aldol reaction for spiro [cyclooxazolidinethioneoxindoles]. [25] On the other hand, there are only a few literature reports for the organocatalytically asymmetric synthesis of spiropyrazolone derivatives.…”