Fe‐Catalyzed Anaerobic Mukaiyama‐Type Hydration of Alkenes using Nitroarenes

Abstract

Hydration of alkenes using first row transition metals (Fe, Co,M n) under oxygen atmosphere (Mukaiyamatype hydration) is highly practical for alkene functionalization in complex synthesis.Different hydration protocols have been developed, however,c ontrol of the stereoselectivity remains ac hallenge.H erein, highly diastereoselective Fe-catalyzed anaerobic Markovnikov-selective hydration of alkenes using nitroarenes as oxygenation reagents is reported. The nitro moiety is not well explored in radical chemistry and nitroarenes are knownt os uppress free radical processes.O ur findings show the potential of cheap nitroarenes as oxygen donors in radical transformations.S econdary and tertiary alcohols were prepared with excellent Markovnikov-selectivity.T he method features large functional group tolerance and is also applicable for late-stage chemical functionalization. The anaerobic protocol outperforms existing hydration methodology in terms of reaction efficiency and selectivity. Scheme 1. Literature backgrounda nd suggestedp rocess.

Synthesis of Cardiotonic Steroids Oleandrigenin and Rhodexin B

“…Arguing that a larger trapping agent may result in a better β14-selectivity, we examined anaerobic conditions by Studer (entry 3). 18 conditions indeed resulted in the improved β:α selectivity (β:α = 10:1); however, despite the complete conversion, the product 11 was isolated in only 37% yield. With these results in hand, our subsequent studies focused on using Co(acac)2/PhSiH3/O2 conditions developed above and the hydration of 9 was carried on 1.2 g scale providing the mixture of epimers at the C14 position (14β:14α = 2.9:1).…”

Skeleton‐Reorganizing Coupling Reactions of Cycloheptatriene and Cycloalkenones with Amines

“…After acylation, the N ‐acetyl product 22 underwent allylic hydroxylation smoothly to give product 23 in 83 % yield. On the other hand, an iron‐catalyzed alkene hydration of compound 22 furnished tertiary alcohol 24 with 56 % yield [19] . In addition, the alkene epoxidation reaction also proceeded efficiently with the aid of m ‐CPBA and the epoxide 25 was obtained in 80 % yield.…”

“…Similar diversification was also applicable for sulfalen (16 a) and lenalidomide (17), both bearing reactive amidated NÀ H bonds. Other molecular drugs with an arylamine framework, such as coumarin 120, procaine, and dimethocaine, all successfully delivered the ring-fused products in 25-42 % yield (18)(19)(20). Likewise, with cyclooct-2-en-1-one 9 as the editing unit, aminoglutethimide and sulfalen could also be converted into ring-fused products in 65 % and 32 % yield, respectively (15 b and 16 b).…”

“…Reaction conditions: 1 (0.40 mmol), 2 a (0.20 mmol), [Rh(COD)Cl] 2 (2.5 mol %), ligand (5 mol %), MeCN 0.4 mL, 100 °C, 24 h. Unless otherwise noted, yields were determined by19 F NMR analysis of the crude reaction mixture using 4-fluorobiphenyl as the internal standard. [a] In NMP/ dioxane (1/1, v/v).…”

Toward Renewable Amines: Recent Advances in the Catalytic Amination of Biomass-Derived Oxygenates

“…Among the several suggestions on the synthetic methodologies for amines, the catalytic amination of alcohols using NH 3 has received the most significant attention, especially for large-scale production. , Generally, it is considered an important process due to the wide availability of alcohols industrially produced by hydroformylation of olefins followed by hydrogenation, , hydration of alkenes, or catalytic conversion of syngas . These processes produce alcohols ranging from lower to higher carbon numbers, requiring multiple energy extensive steps.…”