Desymmetrization of cyclic 1,3-diketones via Ir-catalyzed hydrogenation: an efficient approach to cyclic hydroxy ketones with a chiral quaternary carbon

Abstract

We herein report an efficient method to synthesize cyclic hydroxy ketones with a chiral quaternary center.

Escaping from Flatland: Stereoconvergent Synthesis of Three‐Dimensional Scaffolds via Ruthenium(II)‐Catalyzed Noyori–Ikariya Transfer Hydrogenation

“…In their earlier report, using ( S , S )‐ A for desymmetrization of cyclopentane‐1,3‐dione 129 , the corresponding monoalcohol 130 was obtained with 93 % ee [53] . To illustrate superiority of ATH over other reduction methods: Corey–Bakshi–Shibata reduction provided for transformation of 126 to 127 78 % yield, d.r.=86:14, 94 % ee ; [54] and recently, Zhang reported for this transformation 93 % yield, d.r.=89:11 and 96 % ee employing KO t Bu‐promoted (5 mol %), Ir/f‐ampha‐catalyzed (0.5 mol %) hydrogenation (40 atm H 2 ), which required glove box operation under argon and use of anhydrous solvents [55] …”

“…= 89:11a nd 96 % ee employing KOtBu-promoted (5 mol %), Ir/f-ampha-catalyzed (0.5 mol %) hydrogenation (40 atm H 2 ), which required glove box operation under argon and use of anhydrous solvents. [55] Transfer hydrogenation of the simple cyclopentane-1,3dione 126 is very intriguing because it gives the corresponding mono-alcohol 127 in excellent enantiopurity without the typical attractive electrostatic interaction in the hydrogen transfer step. Ag lance at the transition state geometries, leading to each of the four possible stereomeric products reveals that enantio-and diastereoselection is solely sterically driven (Figure 31).…”

Recent Advances in Reductive Desymmetrization of Diketones

“…They offered a straightforward and facile access to a wide range of chiral hydroxy ketones which were widespread in nature and considered as significant motifs in drugs owing to the pharmaceutical and biological activities [9,10,12,15,20] . The desymmetrization of diketones also provided a novel and highly efficient strategy for the construction of all carbon quaternary stereocenters and multiple stereogenic centers [9–13,15,18–23,25,27] …”

Synthesis of cis β‐Hydroxy Ketones by Desymmetrization of 1,3‐Cyclopentanediones through Ruthenium‐Catalyzed Hydrogen Transfer

“…In 2009, Metz and Chiu's groups reported ruthenium‐catalyzed transfer hydrogenative desymmetrization of a 1,3‐cyclopentanedione substrate with 12/1 dr and 93% ee at 11% catalyst loading (Scheme a) . In 2019, Zhang's group disclosed iridium‐catalyzed hydrogenative desymmetrization of 1,3‐cyclopentanediones (Scheme b) with high cis diastereo‐selectivities and enantioselectivities. Recently, our group reported a palladium‐catalyzed hydrogenative desymmetrization of 1,3‐indanediones (Scheme c) .…”

“…Chiral hydroxy ketone cis ‐ 4 was obtained with 98% ee and 6 : 1 dr. Using the chiral 4 as key intermediate, (+)‐estrone can be synthesized through the known four‐step transformations …”