Han-Young Kang

Reductive decyanation of α-cyano and α-alkoxycarbonyl substituted nitriles promoted by samarium(II) iodide

Abstract Decyanation of geminal dinitriles and α-alkoxycarbonyl substituted nitriles promoted by samarium(II) iodide has been efficiently achieved. This method has advantages over the previously known radical route using tin hydride with respect to applicable substrates and the reaction temperature employed. This decyanation could broaden the synthetic applicability of the nitrile derivatives.

Indium-mediated diastereoselective allylation reactions: preparation of tert-α-hydroxy acids

Indium-mediated allylation reactions of α-ketoimides derived from Oppolzers sultam were accomplished in aqueous THF in good yields and excellent diastereomeric excesses. It could be a useful method for the preparation of enantiopure t-α-hydroxy acids. When the substituent of α-ketoimides was changed from phenyl to thiophenyl or furyl group, diastereoselectivity decreased in comparison to N-phenyl derivatives, but changing solvent to aqueous ethanol provided improved levels of diastereoselectivity.

Total synthesis of 10-deoxymethynolide and narbonolide.

A flexible and convenient approach was developed for the synthesis of 10-deoxymethynolide (1) and narbonolide (2), which are aglycones of the methymycin and the pikromycin families of macrolide antibiotics. These lactones are produced by pikromycin polyketide synthase from Streptomyces venezuelae. Polyketide lactones, 10-deoxymethynolide and narbonolide, which contain 12- and 14-membered rings, respectively, were synthesized efficiently. These target lactones were retrosynthetically divided into three parts and assembled by using an asymmetric aldol reaction, the Yamaguchi esterification, and ring-closing metathesis. The ring-closing metathesis reaction catalyzed by the second-generation Grubbs catalyst is particularly efficient in preparing these macrocyclic polyketide lactones.

Synthesis of (-)-oseltamivir phosphate (Tamiflu) starting from cis-2,3-bis(hydroxymethyl)aziridine.

Oseltamivir phosphate (Tamiflu) has been synthesized from cis-2,3-bis(hydroxymethyl)aziridine. After protection of the cis-2,3-bis(hydroxymethyl)aziridine with a Boc group, desymmetrization provided a chiral aziridine, which was a key intermediate to install the required stereogenic center containing a nitrogen atom. Allylation and ring closing metathesis are the key reactions to obtain the cyclic product that was successfully converted to the desired oseltamivir phosphate.

Total synthesis of methymycin

Methynolide and 10-epi-methynolide were synthesized from the necessary segments, which were prepared by the addition of Grignard reagents to the corresponding alpha-alkoxyketones utilizing 1,2-stereochemical selection based on Cram chelation control. Ring-closing metathesis, as the key reaction, was carried out to combine the segments for the synthesis of methynolide and 10-epi-methynolide. The total synthesis of methymycin was also achieved by the glycosylation of methynolide with the trichloroimidate derivative of D-desosamine.

Total Synthesis of Pikromycin

The total synthesis of pikromycin (6), the first isolated macrolide antibiotic, was achieved. The target macrolide was retrosynthetically divided into two parts, pikronolide (6a) (aglycon) and D-desosamine. The aglycon was synthesized using key reactions such as an asymmetric aldol reaction, Yamaguchi esterification, and ring-closing metathesis. The aglycon was coupled successfully with the trichloroacetimidate derivative of D-desosamine under Lewis acidic conditions to afford pikromycin. Narbomycin (5) was also synthesized from narbonolide (5a) under identical conditions.

Synthesis of 3-Alkylidenecepham-4-carboxylic Acid derivatives by Samarium(II) Iodide Reduction

Abstract Samarium(II) iodide promoted reductive deacetoxylation of 7-aminocephalosporanic acid derivatives to synthesize 3-alkylidenecepham-4-carboxylates, which could be valuable intermediates for the synthesis of new cephalosporin antibiotics, was investigated.

Barbier-type reactions of nitriles and alkyl iodides mediated by samarium(II) iodide in the presence of catalytic nickel(II) iodide

Abstract The samarium(II) iodide-mediated intermolecular Barbier-type reactions of nitriles and alkyl iodides have been investigated. In the presence of a catalytic amount of nickel(II) iodide, the reaction proceeded smoothly to provide the corresponding ketones. Amides also reacted to give ketones under the same Barbier-type conditions.

Indium-mediated allylation reactions of α-chlorocarbonyl compounds and preparation of allylic epoxides

Indium-mediated allylation of α-chlorocarbonyl compounds with various allyl bromides in aqueous media gave the corresponding homoallylic chlorohydrins, which could be transformed into the corresponding epoxides in the presence of a base. These reactions were strongly dependent upon both the substituents at the carbon bearing chlorine and the allyl bromides used.

Isonitrile–nitrile rearrangement promoted by samarium(ii)iodide

A samarium(II) iodide-promoted rearrangement of isonitriles to nitriles, which requires an α-alkoxycarbonyl group at the carbon atom bearing the isonitrile group, occurs under very mild conditions and contrasts with the thermal version of the rearrangement, which usually requires high temperature.