The stereoselective total synthesis of isocladosorpin

A highly stereoselective total synthesis of isocladosorpin is described. The key steps involved in this synthesis are oxa-Michael reaction, asymmetric propargylation, and Alder–Rickerts reaction.     

Asymmetric organocatalytic conjugate addition of dialkyl phosphites to N-unprotected isatylidene malononitriles: access to 3-phospho-2-oxindoles with chiral quaternary stereocenters

The enantioselective Michael addition of dialkyl phosphites to N-unprotected isatylidene malononitriles has been established for the first time by using a simple bifunctional tertiary amine–thiourea catalyst. The corresponding adducts, 3-phospho-2-oxindoles, containing a chiral quaternary carbon center at the 3-position of the oxindole, were obtained in good to excellent yields (up to 98%) with moderate to excellent enantioselectivities (up to 95% ee). In addition, optically active 3,3′-disubstituted oxindoles bearing carboxylate and phosphonate groups were facilely obtained by the oxidative degradation of the Michael adducts.     

Catalytic asymmetric one-pot synthesis of α-methylene-γ-lactams

An organocatalytic enantioselective synthesis of α-methylene-γ-lactams has been developed. The reaction between protected 2-aminomalonates and Morita–Baylis–Hillman carbonates is catalyzed by chiral Lewis bases to afford the corresponding lactams in excellent yields and moderate to good enantioselectivities, after work-up.     

Organocatalytic asymmetric Friedel–Crafts reaction of 1-naphthols with isatins: an enantioselective synthesis of 3-aryl-3-hydroxy-2-oxindoles

An organocatalytic enantioselective Friedel–Crafts reaction of 1-naphthols with isatins has been developed employing bifunctional thiourea–tertiary amine organocatalysts. A variety of isatin derivatives react well with 1-naphthols in the presence of Cinchona derived thiourea 1a to provide biologically important chiral 3-aryl-3-hydroxy-2-oxindoles (3a–zg) in good yield (70–84%) and moderate to good enantioselectivity (37–83%).     

Asymmetric aldol reactions catalyzed by the promiscuous aldo–ketoreductase enzyme

The promiscuous aldo–ketoreductase (AKR) enzyme is used as a sustainable biocatalyst for the first time to catalyze asymmetric aldol reactions in aqueous medium. The reactions between aromatic aldehydes and cyclic/acyclic ketones give the corresponding products in moderate yields and enantioselectivities in the presence of water. The influence of solvents, the mole ratio of substrates, and enzyme concentration are investigated. The mechanism of the AKR1A1-catalyzed aldol reaction is also discussed.     

Synthesis of Novel Thiazoline Catalysts and Their Application in Michael Addition Reaction

Several novel chiral thiazoline catalysts containing thiazoline, thiourea and proline were efficiently synthesized from commercially available L-cysteine. These ligands were subsequently applied to the asymmetric Michael reaction between cyclohexanone and various β-nitrostyrene. The result shows that the optimal catalyst for this reaction is ligand 18d, the organocatalyst with thiazoline, thiourea and chiral proline motif, which efficiently promotes the enantioselective conjugate addition of cyclohexanone to various nitroalkenes to yield the corresponding addition products in high to excellent yields with enantiomeric excess(e.e.) up to 95% and diastereoselectivity ratio(dr.) up to 99:1.     

Chiral cyclopentadienyl ruthenium(II) complexes with P,P-ligands derived from (1R,2R)-1,2-diaminocyclohexane: Synthesis,crystal structures and catalytic activity in Diels–Alder reactions

Chiral cyclopentadienyl ruthenium(II) complexes [CpRu(L1–L3)Cl] (5–7) have been prepared by reaction of [CpRu(PPh₃)₂Cl] with chiral P,P-ligands (1R,2R)-1,2-bis(diphenylphosphinamino)cyclohexane (L1), N,N′-[bis-(3,3′-bis-tert-butyl-5,5′-bis-methoxy-1,1′-biphenyl-2,2′-diyl)phosphite]-(1R,2R)-1,2-diaminocyclohexane (L2) and N,N′-[bis-(R)-1,1′-binaphtyl-2,2′-diyl)phosphite]-(1R,2R)-1,2-diaminocyclohexane (L3). The molecular structures of 5 and 6 have been determined by single-crystal X-ray analysis. Studies on catalytic activity of the cations derived from (5–7) by treatment with AgSbF₆, are also reported.     

Asymmetric synthesis of (−)-bissetone via a highly enantioselective hetero-Diels–Alder reaction

We demonstrate a new approach for the asymmetric synthesis of bissetone. The key reaction is the highly enantioselective hetero-Diels–Alder cycloaddition of triene 3 with ethyl glyoxylate catalyzed by readily available BINOL–Ti complexes. The HDA cycloadduct 4 was then transformed in five steps into O-protected bissetone (8) and its C5-epimer in good yield.     

Highly enantioselective Michael addition of isobutyraldehyde to nitroalkenes

The asymmetric catalytic Michael reaction between isobutyraldehyde and nitroalkanes with chiral primary amine thiourea organocatalysts was described. In the presence of 10 mol % of 1-((1R,2R)-2-amino-1,2-diphenylethyl)-3-benzylthiourea, the desired products were achieved in excellent enantioselectivity (up to>99% ee) with up to 98% yield.     

Total synthesis of (±)-antofine

An efficient preparation of (±)-antofine is described. The main steps involved in this synthesis are the Horner–Wadsworth–Emmons reaction, the intramolecular Schmidt reaction of an azido aldehyde, and the one-pot deprotection of the N-formyl group, followed by Pictet–Spengler cyclization. The asymmetric hydrogenation of the trisubstituted α,β-unsaturated ester is also explored, however only moderate enantio-control (55% ee) is obtained. Finally, (±)-antofine is prepared in six steps from the phenanthryl aldehyde 5 with an overall yield of 35%.     

Synthetic studies on polymaxenolides: model studies for constructing dihydropyran portion and synthesis of lower portion

With a goal of the total synthesis of polymaxenolide, the first hybrid marine natural product, the model studies for constructing the dihydropyran portion based on the originally proposed biosynthesis (C–C bond formation followed by dehydrative cyclization) and the synthesis of the lower portion (the C1–C3, C7–C17 portion) based on an iodide-induced Morita–Baylis–Hillman type reaction (a three-component assembly) followed by Suzuki–Miyaura cross-coupling are described.     

Organocatalytic asymmetric conjugate addition of thioacetic acid to β-nitrostyrenes

A method for organocatalytic, enantioselective Michael addition reactions of thioacetic acid with a range of trans-β-nitrostyrenes has been developed. The processes, promoted by the chiral amine thiourea organocatalyst, take place in high yields with up to 70% ee.     

Highly functionalised cyclohexa-1,3-dienes by sulfonyl Nazarov reagents

The Hayashi–Jørgensen organocatalyst has made possible a sulfonyl Nazarov analogue reagent to give a Diels–Alder reaction at the double bond, without involving the activated methylene affording chiral highly functionalised cyclohexa-1,3-dienes.     

Asymmetric aza-Henry reaction of fluoromethylated imines catalyzed by cinchona-derived bifunctional thiourea

The asymmetric aza-Henry reaction of fluoromethyl imines derived from 4-methoxyaniline with nitromethane was achieved under mild conditions using cinchona-derived bifunctional thiourea as catalyst. A series of chiral fluoromethylated β-nitroamines were synthesized and their transformation to optically pure 4-fluoromethyl-2-imidazolidones was illustrated.     

Electrochemical Detection of Asymmetric PCR Products by Labeling with Osmium Tetroxide

Single stranded DNA‐targets from asymmetric polymerase chain reaction (PCR) of a sequence of the gram positive, spore forming bacterium Clostridium acetobutylicum were detected by square‐wave voltammetry after labeling with osmium tetroxide bipyridine and hybridization with DNA capture probes immobilized on gold electrodes. The asymmetric PCR, performed with a 10‐fold excess of the forward‐primer, was used without any further purification for hybridization with protective strands and covalent labeling with osmium tetroxide bipyridine. Square‐wave voltammetric signals of 20 nmol/L targets were significantly higher at 50 °C compared with 23 °C hybridization temperature. A fully noncomplementary protective strand yielded thoroughly modified targets unable for further hybridization. Coupling this with thermal discrimination opens new opportunities for sequence specific DNA detection.     

Formal meta-specific intramolecular Friedel–Crafts allylic alkylation of phenols through a spirocyclization–dienone–phenol rearrangement cascade

Formal meta-specific intramolecular Friedel–Crafts allylic alkylation of phenols was achieved based on spirocyclization–dienone–phenol rearrangement cascades. Systematic screening of acid catalysts revealed that Sc(OTf)₃ was a highly effective catalyst for dienone–phenol rearrangement of spiro[4.5]cyclohexadienones. Using 5 mol % of Sc(OTf)₃ as the promoter, various spirocyclic substrates were transformed into the corresponding phenol derivatives in good to excellent yield. Furthermore, the one-pot sequential spirocyclization–dienone–phenol rearrangement proceeded using a palladium and scandium multi-catalytic system or a triphenylmethyl cation single-catalyst system, providing the corresponding meta-allylated phenol derivatives in excellent yield.     

A novel asymmetric organocatalytic Michael–aldol–dehydration domino reaction for the construction of spirocyclic benzofuranones

Organocatalytic Michael–aldol–dehydration domino reaction of 3-(1-hydroxyethylidene)benzofuran-2(3H)-ones and enones catalyzed by Cinchona-based primary amine has been developed. The desired chiral spirocyclic benzofuranones were obtained in excellent stereoselectivities (dr>20:1 and up to 96% ee) and moderate to excellent yields (up to 98%).     

Hexaphenylbenzene end-capped tri(p-phenylenevinylenes): synthesis and properties

Three new hexaphenylbenzene end-capped tri(p-phenylenevinylenes) were synthesized by the Horner–Wadsworth–Emmons reaction in good yields (86–76%). All compounds have bright fluorescent emissions in the blue to blue–green region in solution (λ_max = 445–492 nm in tetrahydrofuran) and also high emission efficiency (Φ_fl = 0.51–0.72 in tetrahydrofuran). They exhibit good electrochemical reversibility, high thermal stability, and have high HOMO value.     

Organocatalytic enantioselective Michael addition of thioacetic acid to enones

An enantioselective, organocatalytic Michael addition reaction of thioacetic acid with enones has been developed. The process, catalyzed by a chiral bifunctional amine thiourea, furnishes products in excellent yields with up to 63% ee.     

Stereoselective total synthesis of cananginones (D–I) using Ireland–Claisen rearrangement as a key step

A strategy for stereoselective total synthesis of α-substituted γ-hydroxymethyl γ-butyrolactone containing bioactive natural products cananginones (D–I) has been developed using cheap and commercially available d-mannitol as a chiral pool. The Ireland–Claisen rearrangement is utilized as a key step to generate the α-substituted chiral center of the core lactone moiety, while the elongation of aliphatic side chain by different C-8 hydrocarbon groups have been achieved by alkylation, Cadiot–Chodkiewicz, and Sonogashira reactions.