Organocatalyst Design for the Stereoselective Annulation towards Bicyclic Diketones and Analogues

Abstract

The Wieland–Miescher ketone, Hajos–Parrish–Eder–Sauer–Wiechert ketone, and their analogues are bicyclic diketones essential as building blocks for the synthesis of several natural and bioactive molecules. For this reason, since 1971, when Hajos and Parrish and Eder, Sauer, and Wiechert reported the stereoselective synthesis of these compounds promoted by L-proline, numerous methodologies and organocatalysts have been studied over the years with the aim of identifying increasingly efficient asymmetrical syntheses of these bicyclic ketones. This review will outline the methodological and stereochemical features of the organocatalytic stereoselective synthesis of these bicyclic scaffolds based on the different organocatalysts employed from 1971 until today. Particular emphasis will be given to the structural features of the catalysts and to the reaction conditions.

Electrochemical Bottom-Up Synthesis of Chiral Carbon Dots from L-Proline and Their Application as Nano-Organocatalysts in a Stereoselective Aldol Reaction

“…Afterwards, we decided to test the possibility of recycling these two catalysts. The recycling of CCD-16 resulted in an unsuccessful result, with a gradual decrease in both yield and stereoselectivity (Table 3, entries [21][22], probably due to the gradual desorption of L-Proline during the subsequent extraction workups. Remarkable results were obtained with CCD-17, where the catalyst could be recycled up to two times without catalytic activity loss (Table 3, entries [24][25].…”

“…In this context, since CDs have found efficient applications as catalytic materials in organic synthesis, CCDs could represent new recyclable heterogeneous organocatalysts to promote stereoselective reactions [13][14][15]. Organocatalysis is considered the third pillar of asymmetric synthesis and, due to the green aspects of organocatalytic procedures, has paved the way for the extension of organic stereoselective synthesis horizons toward efficient, practical and more sustainable methodologies [16][17][18][19][20][21][22][23][24]. Only in the last three years, the chirality of CDs has been preliminary investigated, in four articles, for the use of these nanoparticles as heterogeneous stereoselective catalysts, showing promising results [13,[25][26][27].…”

Stereoselective Synthesis of Spiro-Decalin Oxindole Derivatives via Sequential Organocatalytic Michael–Domino Michael/Aldol Reaction

“…HPLC: IA, hexane/iPrOH 95:5, 1.0 mL/min, dr >99:1, τ minor = 12.0 min τ major = 13.9 min; OR: [α] 20 D = +6.9 (c 0. 6.96 (d, J = 8.0, 1H), 5.47 (d, J = 11.9, 1H), 4.13 (t, J = 12.0, 1H), 3.88 (dt, J = 11.8, 7.1, 2H), 2.35 (td, J = 11.9, 2.9, 1H), 2.19 (d, J = 10.6, 1H), 2.03−1.75 (m, 2H), 1.67 (t, J = 15.7, 3H), 1.54 (d, J = 15.2, 1H), 1.33 (t, J = 7.2, 3H), 1.26 (s, 1H), 1.17 (d, J = 12.0, 2H). 13 (3S,3′R,4′R,4a′S,8a′S)-5-Chloro-1-ethyl-8a′-hydroxy-3′-nitro-2oxo-4′-phenyl-3′,4′,4a′,5′,6′,7′,8′,8a′-octahydro-1′H-spiro-[indoline-3,2′-naphthalene]-1′,1′-dicarbonitrile (5j).…”

“…The asymmetric synthesis of complex heterocyclic scaffolds with multiple stereocenters in a stereoselective fashion represents one of the major challenges in modern organic chemistry. In the past two decades, many research groups have devoted their efforts in the exponential development of asymmetric organocatalysis, as an environmentally friendly and robust approach to achieve this aim. − In fact, organocatalysts are usually stable in air and moisture and are characterized by a variety of possible activation modes of different functional groups.…”

Phosphonium Ion-Tethered Secondary Amines for Chemospecific 5-Enolexo Aldol Condensations of 6-Ketoaldehydes

“…They serve as fundamental building blocks in a large variety of natural products and pharmaceutical molecules. Intramolecular aldol reactions represent a promising approach for the synthesis of diverse carbocycles . An abnormal 5- enolexo aldol condensation technique involving aldehydes as donors and ketones as acceptors is a fascinating method to make cyclopentene derivatives .…”