Organocatalytic Asymmetric Michael Addition of Pyrazolin‐5‐ones to Nitroolefins with Bifunctional Thiourea: Stereocontrolled Construction of Contiguous Quaternary and Tertiary Stereocenters

Abstract

The first organocatalytic diastereo-and enantioselective Michael addition reaction of 4-substituted-pyrazolin-5-ones to nitroolefins has been developed with a chiral bifunctional thiourea as organocatalyst. A wide variety of desired multi-substituted pyrazolin-5-one derivatives with contiguous quaternary and tertiary stereocenters are smoothly obtained in very good yields (up to 98%) with excellent enantioselectivities (up to > 99% ee) and acceptable diastereoselectivities (up to 80:20). This experimentally simple process facilitates the access to various enantioenriched, multiply substituted pyrazolin-5-one derivatives, potential biologically active molecules, starting from readily available starting materials.

Highly enantioselective Michael addition of pyrazolin‐5‐ones to nitroolefins catalyzed by cinchona alkaloid derived 4‐methylbenzoylthioureas

“…4‐Methyl benzoylthioureas I , III , and V could all gave the excellent yields and better ee values (entries 1, 3, and 5, Table ). In the postulated dual H‐bonding enhanced catalytic cycle, the first step is the formation of the complex of nitrostyrene and dual H‐donor through hydrogen bonding . Then the hydrogen bond energies of complexes the formed with catalysts and nitrostyrene were preliminarily calculated and analyzed by Hartree‐Fock method.…”

“…6 Therefore, the broad spectrum of biological activities of pyrazolone derivatives have resulted in considerable interest in investigation on the chemistry of pyrazolones especially the development of asymmetric methods for building of pyrazolone-based chiral compounds. [7][8][9][10][11][12][13][14] Pyrazolin-5-ones are widely used pyrazolone derivatives and have active property, especially at the C-4 location, where nucleophilic reactions can easily occur. 7 It has been used as Michael donors in the asymmetric additions to react with 1,4-dicarbonyl but-2-enes, 8 azodicarboxylates, 9 alkynones, 10 α,β-unsaturated aldehydes, 11 nitroolefins, 7,[12][13][14] etc.…”

Mild Nitration of Pyrazolin‐5‐ones by a Combination of Fe(NO3)3 and NaNO2: Discovery of a New Readily Available Class of Fungicides, 4‐Nitropyrazolin‐5‐ones

“…[45] In addition, the oxidative destruction of the pyrazolin-5-one ring is also known. [46,47] Among the recent work devoted to the functionalization of pyrazolin-5-ones by the attack of electrophiles [48][49][50][51][52][53][54][55] or radicals [56][57][58] at the 4-position of the heterocycle, only one involved the creation of the CÀN bond, in which azodicarboxylates were used as the nitrogen electrophiles. [52] In this work we proposed aF e(NO 3 ) 3 /NaNO 2 nitrating system that has allowed the synthesis of 4-nitropyrazolin-5-ones bearing as ubstituent at C-4 under ambient conditions (Scheme 1d).…”

Organocatalyzed Cascade Aza‐Michael/Michael Addition for the Asymmetric Construction of Highly Functionalized Spiropyrazolone Tetrahydroquinolines

“…[1] In particular, pyrazol-3ones, which have approved anti-inflammatory, antiviral, antitumor, and antibacterial properties, [2] have been widely used in organic synthesis and pharmaceutical chemistry ( Figure 1). [4] Later, the groups of Feng, [5] Rios, [6] Du, [7] Ma, [8] and Zhou [9] also used pyrazolones as nucleophiles for the synthesis of chiral pyrazolone derivatives, and highly enantioselectivities were achieved. In 2010 Yuan and co-workers employed pyrazolones as nucleophiles in organocatalytic asymmetric Michael addition to nitroalkenes and highly enantioselectivities were obtained.…”