Anti-addition of Dimethylsulfoxonium Methylide to Acyclic α,β-Unsaturated Ketones and Its Application in Formal Synthesis of an Eicosanoid

Abstract

Cyclopropanation using dimethylsulfoxonium methylide (Corey–Chaykovsky reaction) was examined with a series of linear α,β-unsaturated ketones, and the results showed that the major trajectory for the addition of the sulfur ylide to the enones is anti, related to the γ-substituent. The stereochemical assignment for the generated cyclopropanes was achieved by X-ray crystallography or comparing with the reported spectroscopic data. We found that the diastereoselectivity was influenced by several factors, including the protecting groups, solvents, and temperatures, and good anti/syn ratios (>10:1) were often obtained using the tert -butyldimethylsilyl and tert -butyldiphenylsilyl-protected substrates. The method was applied to a formal synthesis of a natural eicosanoid with good efficiency.

Coupling of Sulfoxonium Ylides with Arynes: A Direct Synthesis of Pro-Chiral Aryl Ketosulfoxonium Ylides and Its Application in the Preparation of α-Aryl Ketones

“…Sulfonium and sulfoxonium ylides , have played significant roles in organic synthesis as important building blocks in total synthesis, − chemical materials, − and pharmaceuticals, − among others. , These ylides have also proven to be alternative metallocarbene surrogates to diazo compounds, having many reactions in common such as insertion, − cyclopropanation, epoxidation, aziridination, dimerizations, and Wolff , and Stevens rearrangements. , Furthermore, when compared with diazo compounds, these ylides are generally crystalline solids, more stable, have already been used in industrial scales, and are easier/safer to prepare (since they do not involve the use of potentially explosive compounds such as azides, diazomethane, and its derivatives) …”

Chiral cyclopentadienyl RhIII-catalyzed enantioselective cyclopropanation of electron-deficient olefins enable rapid access to UPF-648 and oxylipin natural products

“…Constanolactones 19 and ent -eicosanoid 8 20 are marine oxylipins 21 containing a trans -cyclopropane. Previous syntheses 22 , 23 used lactone 7 as common intermediate which could be accessed in 6 23a or 13 steps. 22 c In a streamlined access to required N -enoxysuccinimide 2n , we developed a gold( i )-catalyzed addition of N -hydroxysuccinimide to terminal alkyne 5 which directly provided substrate 2n in 68% yield ( Scheme 2 ).…”

Unveiling the beauty of cyclopropane formation: a comprehensive survey of enantioselective Michael initiated ring closure (MIRC) reactions

“…Enantioenriched cyclopropanes have also been successfully synthesized using a variety of chiral building blocks containing acyclic enones, [62][63][64][65][66][67][68][69] cyclic enones, [70][71][72][73][74][75][76][77] acyclic enoates, [78][79][80][81][82][83][84][85][86][87][88][89][90][91][92] unsaturated lactones, [93][94][95] and amides as electron-withdrawing groups, in addition to employing chiral auxiliaries. This versatile synthetic method serves as a crucial step in the synthesis of numerous biologically important compounds and natural products.…”

“…This versatile synthetic method serves as a crucial step in the synthesis of numerous biologically important compounds and natural products. Notable examples include the synthesis of potent taxol analogues, 62 glutamate analogues, 78 l -DCG-IV, 63 l -CCGI (selective activators of specific isotypes of metabotropic glutamate receptors), 89 24,25-ethanovitamin D3 lactones (novel vitamin D receptor antagonists), 68 eicosanoids, 69 17 S ,20 S -methanofusidic acid (a fusidic acid antibiotic), 93 and majusculoic acid (an antifungal agent), 94 among many others (Fig. 4).…”