Recent Advances in Reductive Desymmetrization of Diketones

Abstract

Reductive desymmetrization of achiral or meso diketones has attracted considerable attention due to these motifs which play important roles in organic synthesis, pharmaceuticals and functional materials. This review focuses on recent advances in homogeneous reductive desymmetrization of 1,2-, 1,3-and 1,4-diketones, which provides an efficient and practical access to structurally diverse chiral α-, βor γ-hydroxy ketone derivatives. Scheme 2. Reduction of 1,2-Diketones with PseDH or EDH. Scheme 3. Bioreduction of 1,3-Diphenyl-1,3-propandione. Scheme 4. Enantioselective Synthesis of (+)-Crotogoudin.

The Phosphinamide-Based Catalysts: Discovery, Methodology Development, and Applications in Natural Product Synthesis

“…Through a patient optimization of various reaction parameters, we eventually established an efficient protocol for the desymmetric enantioselective reduction of cyclic 1,3-diketones using 28′o (Scheme ) as an optimal catalyst with only 5 mol % loading (Schemes and ). Compared with the reported methods, this new protocol exhibited broad compatibility for both five- and six-membered diketones, affording the products with high to excellent enantio- and diastereoselectivity for a series of substrates of both types. In addition, a rich variety of functional groups were also well tolerated.…”

“…Desymmetric enantioselective reduction of cyclic 1,3-diketones is an important transformation in the area of asymmetric synthesis because the corresponding chiral cyclic 3-hydroxyl ketone products are widely used as important chiral intermediates in the synthesis of various types of natural products . General methods include Corey–Bakshi–Shibata (CBS) and enzyme-catalyzed reduction and transition-metal-catalyzed hydrogenation .…”

“…Desymmetric enantioselective reduction of cyclic 1,3-diketones is an important transformation in the area of asymmetric synthesis because the corresponding chiral cyclic 3-hydroxyl ketone products are widely used as important chiral intermediates in the synthesis of various types of natural products . General methods include Corey–Bakshi–Shibata (CBS) and enzyme-catalyzed reduction and transition-metal-catalyzed hydrogenation . In our efforts toward synthesizing cyathane and hamigeran terpenoids, we designed the desymmetric enantioselective reduction of 1,3-cyclopentanediones as one of strategic transformations and examined CBS and enzyme-catalyzed reductions.…”

“…Allylation of 52 with prenyl bromide 53 afforded 2,2-disubstituted cyclopentanedione 44a in high yields. Desymmetric enantioselective reduction of 44a was carried out by enzyme-catalyzed reduction , before the P -stereogenic phosphinamide-catalyzed method was established. , While excellent stereoselectivity of up to 99% ee and ca. 25:1 dr could be obtained for 45a , the method is time- and solvent-consuming due to the long reaction time (ca.…”

“…intermediates in the synthesis of various types of natural products. 58 General methods include Corey−Bakshi−Shibata (CBS) and enzyme-catalyzed reduction and transition-metalcatalyzed hydrogenation. 58 In our efforts toward synthesizing cyathane and hamigeran terpenoids, we designed the desymmetric enantioselective reduction of 1,3-cyclopentanediones as one of strategic transformations and examined CBS and enzymecatalyzed reductions.…”