Design, Synthesis of Chiral Ketone and Application in Asymmetric Epoxidation

A class of chiral ketone was synthesized for asymmetric epoxidation. High ee values have been obtained for a number of cis olefin and trans olefin. The epoxidation was stereospecific with no isomerizatiom observed in the epoxidation of acyclic system. Encourageingly high ee value has also been obtained for a number of terminal olefins. Mechanistic studies show that electronic interactions play an important role in the stereodifferentiation. O O O O O O NBoc O O t-BuO2CH2CN O O O …     

Iron-catalyzed asymmetric epoxidation of β,β-disubstituted enones

The combination of Fe(OTf)(2) and novel phenanthroline ligands enables the catalytic asymmetric epoxidation of acyclic β,β-disubstituted enones, which have been a heretofore inaccessible substrate class. The reaction provides highly enantioenriched α,β-epoxyketones (up to 92% ee) that can be further converted to functionalized β-ketoaldehydes with an all-carbon quaternary center.     

Highly enantioselective epoxidation of alpha,beta-unsaturated esters by chiral dioxirane

This paper describes a highly enantioselective epoxidation of alpha,beta-unsaturated esters using the fructose-derived ketone 2 as catalyst and Oxone as oxidant. High ee's have been obtained for a number of trans and trisubstituted substrates (82-98% ee). The results described show that it is feasible for dioxiranes to effectively epoxidize electron-deficient olefins with high ee's.     

A cyclodextrin-modified ketoester for stereoselective epoxidation of alkenes

A beta-cyclodextrin-modified ketoester 2 was prepared by covalent attachment of a reactive ketone moiety to beta-cyclodextrin. Treatment of 2 with Oxone as terminal oxidant would produce CD-substituted dioxirane, which can effect stereoselective alkene epoxidation. The 2-mediated (S)-alpha-terpineol epoxidations proceeded to give terpineol oxides in high yields, and the stereoselectivities (i.e., cis-/trans-epoxide ratio) decreased from 2.5:1 to 1:1.2 with increasing steric bulkiness of the terpenes. This steric-dependent stereoselectivity can be understood based on different binding geometries of the 2/terpene inclusion complexes according to the (1)H NMR titration and 2D ROESY experiments. Enantioselective epoxidation of styrenes has also been achieved with 2 as catalyst (20-50 mol %) in aqueous acetonitrile solution, and up to 40% ee was obtained in 4-chlorostyrene epoxidation at 0 degrees C. Similar enantioselectivities were also obtained for the 2-mediated epoxidation of 1,2-dihydronaphthalene (37% ee), 4-chlorostyrene (36% ee), and trans-stilbene (31% ee).     

Synthesis of a new chiral N,N,N-tridentate pyridinebisimidazoline ligand library and its application in Ru-catalyzed asymmetric epoxidation

A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (>99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins. [reaction: see text]     

An improved heterogeneous asymmetric epoxidation of homoallylic alcohols using polymer-supported Ti(IV) catalysts

Heterogeneous asymmetric epoxidation of homoallylic alcohols has been achieved using polymer-supported Ti(IV) catalysts with tert-butyl hydroperoxide as oxidant. The enantioselectivities and chemical yields obtained are significantly higher (ee values up to 80%) than with monomeric tartrate ligands.     

Effective and recyclable dendritic ligands for the enantioselective epoxidation of enones

An operationally simple and mild protocol for the catalytic enantioselective epoxidation of enones has been established using a series of chiral pyrrolidinylmethanol-based dendritic catalysts and tert-butyl hydroperoxide (TBHP) as an oxidant. The epoxides have been obtained in good yields and ee up to 78%.     

Theoretical investigations of Rh-catalyzed asymmetric 1,4-addition to enones using planar-chiral phosphine-olefin ligands

Recently, planar-chiral phosphine-olefin ligands based on (η⁶-arene)chromium(0) and (η⁵-cyclopentadienyl)manganese(I), which are known as first- and second-generation, respectively, have been developed. These ligands were employed for Rh-catalyzed asymmetric 1,4-addition to enones. First-generation ligands involve high enantioselectivity for cyclic enones (>98% ee). Second-generation ligands involve high enantioselectivity for not only cyclic enones but also for acyclic enones (>98% ee). In this study, we have performed DFT calculations to investigate the origin of enantioselectivity. The theoretical values of enantioselectivities were found to be in good agreement with the experimental values obtained for a cyclic enone, 2-cyclopenten-1-one, using both the first- and second-generation ligands. Regarding an acyclic enone, 3-penten-2-one, it was found that the s-cis type decreases the enantioselectivity because the transition states in the s-cis type have a large steric repulsion. Energy decomposition analysis (EDA) and natural bond orbital (NBO) analysis indicate that it is important to study the orbital interactions in the transition states of the insertion step for the acyclic enone attacked from si-face with the second-generation ligand. © 2018 Wiley Periodicals, Inc.     

Enantioselective epoxidation of alpha,beta-enones promoted by alpha,alpha-diphenyl-L-prolinol as bifunctional organocatalyst

[reaction: see text] An operationally simple and mild protocol for the catalytic enantioselective epoxidation of alpha,beta-unsaturated ketones has been estabilished using commercially available alpha,alpha-diphenyl-l-prolinol as bifunctional organocatalyst and tert-butyl hydroperoxide (TBHP) as oxidant. The epoxides have been obtained in good yields and with up to 80% ee.     

Alpha-fluorotropinone immobilized on silica: a new stereoselective heterogeneous catalyst for epoxidation of alkenes with oxone

The dioxirane-mediated epoxidation of alkenes in the presence of supported alpha-fluorotropinones 5 and 9 has been evaluated. The catalysts anchored onto silica supports 5 have shown comparable activity with respect to the homogeneous counterpart 10 and good stability on recycling. In the second part of this paper the enantiomerically enriched alpha-fluorotropinone 4 was anchored onto both mesoporous MCM-41 and amorphous KG-60 silicas. The chiral-supported catalysts promoted the stereoselective epoxidation of several trans-substituted and trisubstituted alkenes with ee values up to 80% and were perfectly reusable with the same performance for at least three catalytic cycles.     

beta-peptides as catalysts: poly-beta-leucine as a catalyst for the Juliá-Colonna asymmetric epoxidation of enones

Poly-beta-leucines have been evaluated as catalysts for the Juliá-Colonna asymmetric epoxidation of enones; the beta 3-isomer was found to be an effective catalyst for the epoxidation of chalcone (70% ee) and some analogues.     

Asymmetric epoxidation of 6-cyano-2,2-dimethylchromene on Mn(salen) catalyst immobilized in mesoporous materials

This article reports our recent work on the heterogeneous asymmetric epoxidation catalyzed by chiral Mn(salen) catalyst axially immobilized via phenoxyl groups and organic sulfonic groups. The asymmetric epoxidation of 6-cyano-2,2-dimethylchromene was especially presented in detail. The factors that affected the asymmetric induction, such as the nanopores and the external surface, the linkage length, and the modification of nanopores with methyl groups were discussed. It was found that the enantioselectivities increased with decreasing the nanopore sizes or increasing the linkage length in nanopore, and the Mn(salen) catalyst immobilized into nanopores generally gave higher ee values than those on the external surface. The heterogeneous Mn(salen) catalysts with modified nanopores gave a TOF of 14.8 h⁻¹ and an ee value of 90.6% for the asymmetric epoxidation of 6-cyano-2,2-dimethylchromene, which were higher than the results (TOF 10.8 h⁻¹, ee 80.1%) obtained for the homogeneous catalyst.     

Organocatalytic stereoselective epoxidation of trisubstituted acrylonitriles

The first diastereospecific and enantioselective epoxidation of trans-2-aroyl-3-arylacrylonitriles by means of the commercially available diaryl L-prolinol/tert-butyl hydroperoxide system has been developed. These diversely functionalized epoxides were obtained in excellent yield (up to 99%), complete diastereoselectivity for the trans-isomer, and good enantioselectivity (up to 84% ee). Highly enantioenriched epoxides can be easily obtained after a single crystallization (ee > 90%).     

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.     

High enantioselectivities in an (E)-alkene epoxidation by catalytically active chromium salen complexes. Insight into the catalytic cycle

[structure: see text]. The epoxidation of (E)-beta-methylstyrene mediated by an oxochromium salen complex yields the epoxide in 92% ee in stoichiometric mode, the highest ee yet reported for a metal-mediated epoxidation of an (E)-alkene. The effect of added donor ligands, previously substantial, has reached a ceiling with this complex. In catalytic mode a slightly reduced ee and higher yield is obtained, indicating both the presence of a second oxidation cycle and that the major oxidant reacts with its reduced form.     

Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: asymmetric synthesis of allylic sulfides,allylic sulfones,and allylic alcohols

We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac-1 a-c and racemic acyclic allylic carbonates rac-3 aa and rac-3 ba through reaction with tert-butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2-pyrimidinethiol by using N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)-benzamide] (BPA) as ligand. Selectivities are expressed in yields and ee values of recovered substrate and product and in selectivity factors S. The reaction of the cyclohexenyl carbonate 1 a (>/=99 % ee) with 2-pyrimidinethiol in the presence of BPA was shown to exhibit, under the conditions used, an overall pseudo-zero order kinetics in regard to the allylic substrate. Also described are the highly selective palladium catalyzed asymmetric syntheses of the cyclic and acyclic allylic tert-butylsulfones 2 aa, 2 b, 2 c, 2 d and 4 a-c, respectively, and of the cyclic and acyclic allylic 2-pyrimidyl-, 2-pyridyl-, and 4-chlorophenylsulfides 5 aa, 5 b, 5 ab, 6 aa-ac, 6 ba and 6 bb, respectively, from the corresponding racemic carbonates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E-configured allylic sulfides 6 aa, 6 ab, 6 ac and 6 bb was accompanied by the formation of minor amounts of the corresponding Z isomers. The analogous synthesis of allylic tert-butylsulfides from allylic carbonates and tert-butylthiol by using BPA could not be achieved. Reaction of the cyclopentenyl esters rac-1 da and rac-1 db with 2-pyrimidinethiol gave the allylic sulfide 5 c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac-1 a and of the acyclic carbonates rac-3 aa and rac-3 ba with 2-pyridinethiol and lead to the formation of the sulfides 5 ab, 6 ab, and 6 bb, respectively. The low ee values may be ascribed to the operating of a "memory effect", that is, both enantiomers of the substrate give the substitution product with different enantioselectivities. However, in the reaction of the racemic carbonate rac-1 a as well as of the highly enriched enantiomers 1 a (>/=99 % ee) and ent-1 a (>/=99 % ee) with 2-pyrimidinethiol the ee values of the substrates and the substitution product remained constant until complete conversion. Similar results were obtained in the reaction of the cyclic carbonates rac-1 a, ent-1 a (>/=99 % ee) and ent-1 c (>/=99 % ee) with lithium tert-butylsulfinate. Thus, in the case of rac-1 a and 2-pyrimidinthiol and tert-butylsulfinate anion as nucleophiles the enantioselectivity of the substitution step is, under the conditions used, independent of the chirality of the substrate; this shows that no "memory effect" is operating in this case. Hydrolysis of the carbonates ent-1 a-c, ent-3 aa and ent-3 ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9 a-c (>/=99 % ee) and acyclic allylic alcohols 10 a (>/=99 % ee) and 10 b (99 % ee), respectively.     

Construction of the tricyclic furanochroman skeleton of phomactin A via the Prins/Conia-ene cascade cyclization approach

A substrate-controlled asymmetric Prins/Conia-ene cascade cyclization has been developed with In(OTf)(3) in CH(3)CN from 0 to 70 °C. These conditions afforded very good yields of the 1-oxadecalin product in one pot and effectively suppressed the racemization of the 1-oxadecalin product with almost no enantiomeric excess (ee) loss. This cascade cyclization has been successfully employed for the construction of the highly functionalized 1-oxadecalin unit of phomactin A with an acyclic β-keto ester and an alkynal as the substrates via a one-pot operation (66% yield, single diastereomer). The 1-oxadecalin moiety has been readily converted to the tricyclic furanochroman skeleton of phomactin A via the epoxidation/dealkoxycarbonylation protocol under very mild conditions with 52% yield in three steps.     

Iminium salt catalysts for asymmetric epoxidation: the first high enantioselectivities

A highly enantioselective iminium salt catalyst has been prepared and tested in the catalytic asymmetric epoxidation of unfunctionalized alkenes, giving up to 95% ee, the highest ee yet reported for iminium salt-catalyzed epoxidation. Catalyst loadings as low as 0.1 mol % may be used.     

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.     

Enantioselective epoxidation of terminal olefins by chiral dioxirane

[see reaction]. This paper describes an enantioselective epoxidation of terminal olefins using chiral ketone 3 as catalyst and Oxone as oxidant. Up to 85% ee has been obtained.