Highly Diastereo‐ and Enantioselective Organocatalytic One‐Pot Sequential 1,4‐Addition/Dearomative‐Fluorination Transformation

Abstract

Fluorination: A wide range of nitroolefins and pyrazol-5-ones undergo a sequential 1,4-addition/dearomative-fluorination transformation when treated with a catalytic amount of a tertiary-amine-thiourea compound and the terminal electrophile, N-fluorobenzenesulfonimide, to give fluorinated products in 72-95% yield with up to 99:1 d.r. and 98% ee. Notably, these products contain adjacent tertiary and α-fluoro quaternary stereocenters (see scheme).

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.…”

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

“…To begin our initial investigation, several bifunctional organocatalysts ( Figure 2) were screened to evaluate their ability to promote the model reaction of 2-tosylaminochalcone (2 a) with the unsaturated pyrazolone 1 a in the presence of 5 mol % of the catalyst at room temperature in dichloromethane ( Table 1, entries [1][2][3][4][5][6][7][8][9]. To our delight, by using squaramide III derived from quinidine, the cascade aza-Michael/ Michael addition reaction proceeded well to give the desired adduct 3 a in excellent yield with almost complete diastereoselectivity and high enantioselectivity (> 99:1 dr, 84 % ee).…”

“…[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.…”

“…In 2010 Yuan and co-workers employed pyrazolones as nucleophiles in organocatalytic asymmetric Michael addition to nitroalkenes and highly enantioselectivities were obtained. [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. At the same time, Rios et al reported the first use of unsaturated pyrazolones as electrophiles in the secondary aminecatalyzed cascade Michael/Michael/Aldol reaction to synthesize chiral spiropyrazolones in 2011.…”

Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions

“…In 2012, Ma and co-workers reported an organocatalytic, asymmetric, one-pot sequential 1,4-addition/dearomative-fluorination transformation using pyrazolones ( 208a , X = NR) as the aromatic partners, thus leading to optically active fluorine-containing products with two adjacent stereogenic centers (Scheme 75 ). 87 This transformation is catalyzed by a chiral tertiary-amine-thiourea compound 211a in combination with benzoic acid. Other nucleophilic donors were also tested for the sequential reaction, and similarly high levels of reactivity and stereocontrol were observed.…”