An N-aryl-substituted oxazolidinone-containing ketone-catalyzed asymmetric epoxidation with hydrogen peroxide as the primary oxidant

Asymmetric epoxidation of various olefins with an N-aryl-substituted oxazolidinone-containing ketone as catalyst and hydrogen peroxide as the primary oxidant has been investigated, and up to 96% ee was obtained.     

Effective asymmetric epoxidation of styrenes by chiral dioxirane

High enantioselectivity (80-92% enantiomeric excess (ee)) has been obtained for the epoxidation of various styrenes using an easily prepared ketone (4) catalyst.     

Synthesis of chiral isoindolinones via asymmetric propargylation/lactamization cascade

A Zn-mediated propargylation/lactamization cascade reaction with chiral 2-formylbenzoate derived N-tert-butanesulfinyl imines was realized, which provided a practical and efficient method for the synthesis of chiral isoindolinones. High diastereoselectivities (up to 97:3 dr) and good reaction yields were observed for most examined cases.     

Enantioselective synthesis of 3-demethoxyaranciamycinone via asymmetric epoxidation

The tetracyclic olefin 1 was enantioselectively epoxidized using a molybdenum(VI)- oxodiperoxo complex containing a chiral lactamide. Conversion to the glycosides 8 and 9 showed the epoxide 2 to be the predominant (3 : 1) enantiomer.     

Synthesis of new macrocyclic chiral manganese(III) Schiff bases as catalysts for asymmetric epoxidation

We describe a general synthetic strategy for the preparation of a series of macrocyclic chiral manganese(III) salen complexes. The developed reaction pathway allows the modulation of the different key groups, namely, the chiral diimine, the bulky substituents in positions 3 and 3', and the linker used in the macrocyclization of the Schiff base. The different complexes presented here illustrate these readily available structural variations. The catalytic properties of the catalysts (5 mol %) were improved for the asymmetric epoxidation of 2,2'-dimethylchromene with NaOCl or H2O2 as oxygen atom donor. A large range of enantiomeric excesses was obtained (ee values from 30% to 96%), depending on the features and the stability of the complexes. The most efficient catalyst, in terms of stereoinduction (ee value = 96%), contains a diiminocyclohexyl moiety, ethyl groups in positions 3 and 3', and a short polyether junction arm.     

Enantioselective total synthesis of (+)-scuteflorin A using organocatalytic asymmetric epoxidation

We report the first enantioselective total synthesis of (+)-scuteflorin A in 14% overall yield, employing a chiral iminium salt to effect an organocatalytic asymmetric epoxidation of xanthyletin in >99% ee as the key step.     

A catalytic asymmetric synthesis of chiral glycidic acid derivatives through chiral dioxirane-mediated catalytic asymmetric epoxidation of cinnamic acid derivatives

A novel and practical asymmetric synthesis of chiral glycidic acid derivatives involving methyl (2R,3S)-3-(4-methoxyphenyl)glycidate ((2R,3S)-2a), a key intermediate for diltiazem hydrochloride (1), was developed. Treatment of methyl (E)-4-methoxycinnamate ((E)-3a) with chiral dioxirane, generated in situ from a catalytic amount (5 mol %) of an 11-membered C(2)-symmetric binaphthyl ketone (R)-7a, provided (2R,3S)-2a in 92% yield and 80% ee. Other cinnamic acid esters and amides were epoxidized by the use of the same procedure to give the corresponding chiral glycidic acid derivatives with up to 95% yield and 92% ee. Higher enantioselectivities in the asymmetric epoxidation of (E)-cinnamates than that of (E)-stilbene derivatives were observed and were proposed to be attributed to a dipole-dipole repulsion between oxygen atoms of an ester group in the cinnamates and those of the lactone moieties in the binaphthyl dioxirane.     

New chiral binaphthalene-derived iminium salt organocatalysts for asymmetric epoxidation of alkenes

A series of binaphthalene-fused azepinium salts has been generated and used as organocatalysts in the asymmetric epoxidation of unfunctionalized alkenes, giving rise to ees of up to 84%.     

Synthesis of (+)-patulolide C via an asymmetric hydroformylation/macrocyclization cascade

A highly atom-economical total synthesis of (+)-patulolide C has been accomplished in three steps from the known (2R)-8-nonyn-2-ol in 49% overall yield and 93% de. A Rh(I)-catalyzed asymmetric hydroformylation (AHF)/ intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry and E-olefin geometry as well as form the macrolactone.     

Studies of substituent effect on asymmetric epoxidation of chromenes by chiral dioxirane

A series of 6- and 8-substituted chromenes has been investigated for asymmetric epoxidation using chiral ketone catalysts. Up to 93% ee was achieved. Higher ee's are obtained when substrates are substituted at the 6-position. The enhanced enantioselectivity is likely due to the beneficial interaction between the 6-substituent of the substrate and the N-aryl or alkyl group of the ketone catalyst.     

C-Galactosylceramide diastereomers via Sharpless asymmetric epoxidation chemistry

C-Glycoside analogs of α-galactosylceramide (KRN7000) were synthesized in 19 linear steps with Sharpless asymmetric epoxidation as a key reaction. Opening of a hydroxy epoxide with sodium azide provided an anti vicinal azido diol with inversion of configuration at the azide-bearing carbon while opening with Ti(O-i-Pr)₂(N₃)₂ gave syn vicinal azido diol with retention. The latter, unusual outcome could be rationalized either by invoking Ti-catalyzed intramolecular double S_N2 inversion or by epoxide opening/intramolecular delivery of azide from the Ti complex.     

Synthesis of chiral 1-ferrocenylaldols and 1-ferrocenyl-1,3-diols via asymmetric reductions

The asymmetric transfer hydrogenation promoted by the (R,R)-(Ts-DPEN)–Ru complex of some 1-ferrocenyl-1,3-diketones was investigated and in all the cases only the carbonyl group distant to the metallocene moiety was reduced with variable selectivity depending on the C-3 substituent. The CBS-catalyzed reduction of 1-ferrocenyl-β-hydroxy-1-ketones, previously protected as acetates, was also found effective, giving both the corresponding syn- and anti-1,3-diols in satisfactory enantiomeric purity.     

Synthesis of P-chiral phosphines via chiral metal template promoted asymmetric furan Diels-Alder reaction

The organoplatinum complex containing ortho-metalated (S)-(1-(dimethylamino)ethyl)-naphthalene as the chiral auxiliary has been used to promote the asymmetric [4+2] Diels-Alder reaction between phenyldivinylphosphine and 2-diphenylphosphinofuran. The reaction was complete in 6 days at room temperature, with the formation of four isomeric diphosphino-substituted oxanorbornene metal complexes in the ratio of 4:2:2:1. Only the exo-cycloaddition products were formed. The formation of stereogenic carbon centers within the oxanorbornene skeleton are highly stereoselective, with all four cycloadducts adopting the same absolute configurations. However, the stereocontrol at the external phosphorus stereogenic center is less efficient (S_p:R_p = 2:1 for the template cycloadducts). The chiral naphthylamine auxiliary could be removed chemoselectively by treatment with concentrated hydrochloric acid, and further ligand liberation of the dichloro complexes with aqueous cyanide gave the diphosphino-substituted oxanorbornene ligands. Hydrogenation of the double bonds in the cycloadduct stabilizes the phosphorus stereogenic center of the free diphosphine ligand which otherwise undergoes inversion of absolute configuration.     

Novel chiral calix[4]arenes by direct asymmetric epoxidation reaction

We report the first asymmetric synthesis of trans optically active (+) C 2 1,3-bisarylepoxide of calix[4]arene in excellent chemical yield and >99% ee, and its enantiospecific conversion to the corresponding bis-dioxolane.     

An approach to a chiral cycloalkanone-mediated asymmetric epoxidation of stilbene with oxone.

Chiral and C2-symmetric seven-membered cycloalkanones 2--6 bearing 1,2-diphenylethane-1,2-diamine and cyclohexane-1,2-diamine backbones were synthesized and evaluated their asymmetry inductive behaviours in an asymmetric epoxidation of stilbene with oxone. Although the reaction of the ketones 2 and 3 of a 1,2-diphenylethane-1,2-diamine backbone gave stilbene oxide in trace to 31% yield, those of the ketones 4-6 of a cyclohexane-1,2-diamine backbone gave the epoxide in satisfactorily high yield up to 98%. It is noteworthy that both reactions with use of stoichiometric and substoichiometric amounts of a ketone 4 gave the epoxide in the essentially same enantioselectivity, 17 and 18%. Eleven-membered cyclic ketones 7 and 8 bearing a binaphthalene backbone were also synthesized and examined their behaviours, while the enantioselectivity turned out to be marginal.     

Synthesis of chiral γ-lactones via a RuPHOX-Ru catalyzed asymmetric hydrogenation of aroylacrylic acids

An asymmetric hydrogenation of aroylacrylic acids catalyzed by RuPHOX-Ru catalyst has been developed, affording the corresponding chiral γ-lactones in high yields and with up to 93% ee. The methodology has the advantage of utilizing easily accessible substrates and has therefore expand the scope of the resulting chiral γ-lactones. Furthermore, high catalytic efficiency was achieved in that the reduction of both the CC and CO double bonds was achieved in one step. The current work provides an alternative and convenient pathway for the synthesis of a wide range of chiral γ-lactones.     

Enantioselective epoxidation by the chiral auxiliary approach: Asymmetric total synthesis of (+)-Ambrisentan

Enantioselective and a highly concise total synthesis of Ambrisentan are described. The chiral auxiliary controlled enantioselective epoxidation (Azerad protocol), photochemical regioselective epoxide opening, and base mediated ester hydrolysis reactions are the key reactions.     

A new class of chiral tetrahydropyran-4-one catalyst for asymmetric epoxidation of alkenes

A new class of chiral α-oxygenated-tetrahydropyran-4-ones for asymmetric epoxidation of alkenes using Oxone^® is described, affording epoxides with up to 83% ee.