Desymmetrization of Cyclopentenediones via Organocatalytic Cross‐Dehydrogenative Coupling

Abstract

An enantioselective synthesis of cyclopentenediones bearing a pyrazole unit has been achieved through an organocatalytic Michael addition/oxidation process. This desymmetrization reaction led to the desired pyrazole-cyclopentenediones with high yield and good enantioselectivities. The postulated cross-dehydrogenative coupling-mechanism has been investigated via preliminary control experiments.

Recent advances towards organocatalytic enantioselective desymmetrizing reactions

“…Besides the aforementioned frameworks, symmetric cyclopentenediones are extremely reactive substrates as well and an array of correlative transformations have been conducted (Figure 3E). In 2017, Enders and coworkers disclosed a formal cross-dehydrogenative coupling of cyclopentenediones (32) with pyrazoles [51]. This thiourea-catalyzed process proceeded via cascade Michael addition/ oxidation to forge functionalized compounds (33) in 14-95% yields with 50-87% enantioselectivities.…”

“…Subsequently in 2018, the Li group presented an NHC-catalyzed desymmetrization reaction of diarylalkane-bisphenols with aldehydes [67]. A series of substrates bearing electron-donating and -withdrawing substituents on the aryl rings were exposed to the system and the corresponding products (51) were obtained smoothly under the optimal conditions. Apart from aldehydes, Morita-Baylis-Hillman carbonates could also act as the substrates and an asymmetric allylic alkylation was conducted via the catalysis of commercially available (DHQ) 2 PHAL by Li [68].…”

New Trends in Enantioselective Cross-Dehydrogenative Coupling

“…Other approaches to organocatalyzed CDC have been reported since. One of these was reported by Enders and coworkers in 2017 [90]. It involved a desymmetrization reaction of cyclopentene diones with pyrazoles via organocatalytic Michael addition/oxidation, catalyzed by chiral bifunctional thiourea (136) (Figure 45).…”

Organocatalytic Enantioselective Michael Addition of Pyrazol‐5‐ones to β‐Silylmethylene Malonates: Synthesis of Chiral Organosilanes Under Metal‐ free Conditions

“…In recent years, the nucleophilic C-4 center on pyrazolin-5-ones has been exploited in the asymmetric catalytic enantioselective reactions for the synthesis of chiral pyrazole derivatives. [16,17] However, we are not aware of any reports on organocatalyzed or metal-catalyzed Michael reaction of pyrazolin-5-ones to βsilylmethylene malonates. In line with our interest in the synthesis of enantioenriched organosilanes under catalytic conditions [18] and in general organocatalysis, [18,19] herein, we disclose quinidine-derived squaramide and quinine-derived thiourea catalyzed enantioselective Michael addition of pyrazol-5-ones to β-silylmethylene malonates to access both enantiomers of chiral organosilanes appendage with pyrazoles.…”