γ‐Pyronecarbaldehyde‐Based Practical Asymmetric Catalytic Synthesis of Chiral 2,4‐Dihydroxycarboxylic Acids andα‐Hydroxy‐γ‐lactones

Abstract

Biomass derived γ-pyrone-2-carbaldehydes were proposed as robust heterocyclic platform for carrying out organocatalytic asymmetric cross-aldol reactions with various aldehydes and ketones in high yield with excellent diastereoselectivity and enantioselectivity. Origins of efficient stereoinduction were revealed by quantum-chemical calculations of four possible transition states. The products were converted to synthetically useful chiral 2,4-dihydroxy carboxylic acid derivatives via protection/deprotection and Ru III -catalyzed oxidative fragmentation steps without racemization of stereogenic centers. The developed approach was applied for asymmetric synthesis of chiral pantolactones, valuable precursors of biologically active substances and natural products, and for synthesis of Dexpanthenol, a medication used for treating defects in the barrier function of skin.

Asymmetric Synthesis of Functionalized α-Amino Acid Derivatives via the γ-Pyrone Carbaldimine-Based Organocatalytic Mannich Reaction

“…It potentially opens the gate for the straightforward asymmetric synthesis of α-amino acid derivatives bearing a carbonyl or hydroxyl group at the γ-position with respect to the pyrone fragment. Asymmetric synthesis of functionalized aldols from γ-pyrone-carbaldehyde 1 and carbonyl compounds in the presence of prolinamide-type organocatalysts recently developed by our group 14 provided evidence of the feasibility of the proposed approach. Organocatalytic asymmetric Mannich-type reactions of γpyrone-carbaldimines with carbonyls have not yet been reported.…”

“…3-(Methoxy)-6-methyl-4-oxo-4H-pyran-2-carbaldehyde (1′) was prepared by a literature procedure: 14 2, 159.3, 153.2, 143.4, 140.4, 137.2, 128.7, 128.7, 128.5, 115.9, 114.9, 114.8, 73.7, 62.6, 55.7, 54.8, 46.0, 19.7, 19.3, 11.9 175.7, 164.2, 159.5, 153.1, 143.3, 140.5, 137.2, 128.7, 128.5, 115.8, 114.9, 114.8, 73.7, 65.7, 55.7, 54.6, 39.4, 19.7, 12.8 NO 5 410.1962NO 5 410. , found 410.1963.…”

“…3-(Benzyloxy)-6-methyl-4-oxo-4 H -pyran-2-carbaldehyde ( 1 ) was prepared by a literature procedure: 1 H NMR (300 MHz, CDCl 3 ) δ 9.84 (s, 1H), 7.35 (m, 5H), 6.30 (s, 1H), 5.49 (s, 2H), 2.32 (s, 3H).…”

Asymmetric Synthesis of Pantolactone: Recent Advances

“…Recently, the Zlotin group employed prolinamide 110 to catalyze the cross‐aldol reaction of alkyl aldehydes with γ‐pyrone‐2‐carbaldehydes 109 , giving high yields and excellent stereoselectivities. The aldol adducts were subsequently reduced with NaBH 4 to generate 1,3‐diols 111 (Scheme 34), [96] which were in turn converted into synthetically useful chiral 2,4‐dihydroxycarboxylic acids 114 . In the following steps, these 2,4‐dihydroxycarboxylic acid derivatives were converted into enantiomerically enriched pantolactones, namely D‐panthenol 119 and the chiral 2‐(1,2,3‐triazol‐1‐yl)pantolactone 118 in high diastereoselectivities.…”

Oxidative Ring-Opening Transformation of 5-Acyl-4-pyrones as an Approach for the Tunable Synthesis of Hydroxylated Pyrones and Furans

“…Taking into account the actively developing approaches for direct hydroxylation of heterocyclic and polycarbonyl compounds, we suggested to apply oxidation of 4-pyrones as a method for the synthesis of various OH-substituted structures. These reactions are not typical for 4-pyrones due to the high acceptor nature of the heterocycles and have been included in the complete destructive processes, which were used for the introduction of the carboxyl group . To the best of our knowledge, in 1981, Ross et al described the synthesis of ethyl 5-hydroxy-6-phenyl-comanate as the only example via the epoxide of ethyl 6-bezoylcomanate without indication of reaction conditions and the yields (Scheme ).…”