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The enantioselective formal synthesis of (−)-aurantioclavine is described. The core tricyclic skeleton was synthesized using a Pd-catalyzed Heck insertion–allylic amination cascade. The stereocenter was constructed by a highly enantioselective organocatalytic asymmetric aziridination reaction.

We developed a highly effective organocatalytic system for asymmetric aziridination of cyclic enones. Catalytic asymmetric aziridination of 2-cyclopenten-1-one with t-butyl p-toluenesulfonyloxy carbamate proceeded using 20 mol % of (1R,2R)-1,2-diphenylethylenediamine derivative with an N-4,4-dimethylcyclohexyl group 1h, producing chiral aziridine ketone (1R,5R)-4 in 82% yield with 99% ee. Organocatalyst 1h was also an effective catalyst for the asymmetric aziridination of other cyclic enones. The obtained chiral aziridine ketone (1R,5R)-4 could be successfully transformed into the key intermediate for the synthesis of (−)-allosamizoline, demonstrating the utility of this asymmetric aziridination for the synthesis of aminocyclopentitol derivatives.

A formal synthesis of anatoxin-a was accomplished by using rhodium-catalyzed formal amide insertion reaction. The key reaction was performed on a gram scale using 0.4 mol % of Rh 2 (NHCO t Bu) 4 catalyst, affording a 9-azabicyclo[4.2.1]nonane derivative in good yield. The nitrogen-bridged molecule was converted to Wiseman's intermediate through diastereoselective reduction, site-selective deoxygenation and functional group interconversions.

We previously reported a synthetic method of spirocyclohexadienones using an Pd-catalyzed intramolecular ipso-Friedel–Crafts allylic alkylation of para-substituted phenol derivatives. However, the mechanism for the step leading to spirocyclization and driving force behind the remarkably easier formation of the five-membered spirocyclohexadienone as compared with the six-membered spirocyclohexadienone were unclear. Herein, detailed density functional theory (DFT) calculations for the spirocyclization were performed to obtain a plausible reason for the observed behavior. In addition, the mechanistic basis of the characteristic ortho-selectivity in the related Pd-catalyzed intramolecular Friedel–Crafts allylic alkylation of meta-substituted phenol derivatives was elucidated. DFT calculations and experimental studies revealed that the ortho-selective allylation proceeded via an unexpected eleven-membered oxapalladacycle-mediated intramolecular Friedel–Crafts type process.

In this study, the fluidization characteristics for fine cohesive powders under mechanical vibrating conditions were experimentally investigated. In a case of handling of fine cohesive powders with fluidized bed, stable gas channels and cracks were easily formed in the bed due to the strong cohesiveness acting among particles. A mechanical vibration is one of the methods to improve the fluidity of fine cohesive powders. In this study, we focused on the transition of the dominant bed flow pattern induced by mechanical bed vibrating conditions. The powders used in this study were different sizes (0.7 – 20 μm) and materials (silica, alumina, polymer). All powders belonged to group-C in the Geldart classification. The bed expansion ratio was lower in the relatively smaller vibration strengths regardless of the gas velocity, however, it steeply increased with larger a certain vibration strength. Form the visual observation of the bed, the bubble formation appeared with larger than such a critical vibration strength. This implied that the dominant bed fluidization pattern was transitioned from channeling behavior (group-C) to bubbling behavior (group-A or –AC) by the addition of the mechanical vibration.

Functionalized quinolizidin-4-ones and indolizidin-3-ones were synthesized from mixed N,O-acetals with a terminal alkyne unit and nucleophiles with two reactive sites by a gold(I)/Bronsted acid relay catalysis with 40–90% yield. The reactions are proposed to proceed through gold-catalyzed carboalkoxylation of the alkynes with the internal mixed N,O-acetals, giving the corresponding cyclic enols, which are transformed to spirocyclic compounds by a Bronsted acid catalyst. The latter spirocyclization process occurs under thermodynamic control, providing polycyclic quinolizidin-4-one and indolizidin-3-one derivatives diastereoselectively.

Herein we report an enantioselective synthesis of ( R )-Sumanirole wherein an organocatalytic asymmetric aziridination of 2-nitrocinnamaldehyde was the key step.

We developed a novel method for synthesizing fused-tricyclic indole derivatives with a 3-aminomethyl indole motif through a reaction cascade involving ipso -Friedel–Crafts alkylation of phenols, rearomatization of the spirocyclohexadienone unit, and iso -Pictet–Spengler reaction. Using TFA as an acid promoter, six-, seven-, and eight-membered ring-fused indoles were obtained in 31–99% yield.

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 method for synthesizing 4,5-fused tricyclic quinoline derivatives based on an acid-promoted intramolecular Friedel–Crafts allenylation of anilines. Using aryl group-substituted propargyl alcohol derivatives with a meta-substituted N-Boc aniline unit as substrates, a four-step reaction sequence involving an acid-promoted intramolecular Friedel–Crafts allenylation of anilines, an acid-promoted intramolecular C–N bond formation, deprotection of the Boc group, and air oxidation proceeded in a single pot, producing the corresponding 4,5-fused tricyclic quinoline derivatives in 31–84% yield.

We report the first enantioselective total syntheses of cedrelin A and methylated paralycolin B, wherein Pd-catalyzed asymmetric intramolecular Friedel–Crafts allylic alkylation of phenols was the key step.

We developed a novel synthetic method for allenyl spiro[4.5]cyclohexadienone derivatives based on a base-promoted intramolecular ipso-Friedel–Crafts addition of phenols to propargyl bromides. The present spirocyclization proceeded in a CH2Cl2–tert-BuOH mixed solvent system using potassium tert-butoxide as the base, and produced the corresponding spiro[4.5]cyclohexadienone derivatives with an allene motif in up to 99% yield. This-type allenyl spirocycle was also accessible through Pd-catalyzed intramolecular ipso-Friedel–Crafts alkylation when a propargyl carbonate derivative with a naphthol unit was used as a substrate. Acid-promoted skeletal rearrangement of the reaction adducts was also examined.

A novel method for synthesizing 3-arylpyrrolidine and 4-arylpiperidine derivatives through an acid-promoted skeletal rearrangement is described. Using trifluoroacetic acid as the acid promoter, an intramolecular ipso -Friedel–Crafts-type addition of phenols to allyl cations, formation of iminium cations through rearomatization of the spirocyclohexadienone units, and an intramolecular aza-Prins reaction, proceeded sequentially to afford 3-arylpyrrolidine and 4-arylpiperidine derivatives in good yield with high diastereoselectivity.

A novel catalytic asymmetric synthetic method for making spirocyclohexadienones with an all-carbon quaternary spirocenter was developed based on the Pd-catalyzed intramolecular ipso -Friedel–Crafts allylic alkylation of phenols. When 5 mol % of the Pd catalyst and 12 mol % of (−)-9-NapBN (−)- 3e were used, the spirocyclic adduct was obtained with up to 93% ee, albeit with low chemical yield. On the other hand, when using 6 mol% of the Trost ligand ( R , R )- 3k , the spirocyclic adducts were obtained in good yields with up to 89% ee (diastereoselectivity = 9.2:1).

Novel chiral hydrogen bond donor catalysts based on a 4,5-diamino-9,9′-dimethylxanthene skeleton were designed and synthesized. Among the phenylurea-amide hybrid molecules prepared from various natural/unnatural chiral amino acids, the phenylalanine-derived catalyst, and the proline-derived catalyst were successfully applied to enantioselective conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes. Using 2-acetylcyclopentanone and 2-methoxycarbonylcyclopentanone as prochiral nucleophiles, asymmetric conjugate addition to β-aryl nitroalkenes proceeded with good diastereoselectivity to provide the corresponding products bearing an all-carbon quaternary stereocenter in excellent yield with up to 95% ee.

(2S,3R)- and (2R,3R)-2,3-Diaminobutanoic acid (Dab) derivatives were efficiently synthesized from Cbz-(R)-alanine using the proline-catalyzed diastereoselective α-hydrazination reaction and the SmI2-promoted reductive cleavage of the N–N bond as the key steps.

An organocatalytic enantioselective aziridination reaction of α,β-unsaturated aldehydes including aromatic substrates using N-arenesulfonyloxycarbamates in the presence of diphenylprolinol triethylsilyl ether and sodium carbonate or sodium acetate is described.

The asymmetric hydrogenation of α-amino-β-keto esters using ruthenium (Ru) anti -selectively proceeds via a dynamic kinetic resolution to afford anti -β-hydroxy-α-amino acids with high enantiomeric purities, which are important chiral building blocks for the synthesis of medicines and natural products. A mechanistic investigation has revealed that the Ru-catalyzed asymmetric hydrogenation takes place via the hydrogenation of the double bond in the enol tautomer of the substrate.

The martinelline chiral core 3 and its diastereomer were synthesized by using the asymmetric tandem Michael–aldol reaction as the key step from 4-methoxycarbonylanthranilaldehyde and the α,β-unsaturated aldehyde.

Asymmetric allylic aminations with aromatic amine nucleophiles using Pd–DIAPHOX catalyst systems are described. The asymmetric allylic aminations of various allylic carbonates proceeded using 2–5 mol % of the catalyst and BSA, providing the corresponding N-aryl chiral allylic amines in up to 99% ee for cyclic substrates, and in up to 97% ee for acyclic substrates.

A Pd-catalyzed asymmetric allylic alkylation of 2-substituted cycloalkenyl carbonates using a chiral diaminophosphine oxide is described. Asymmetric allylic substitution of various cyclic substrates proceeded using 5 mol % of Pd catalyst, 10 mol % of (S,RP)-Ph-DIAPHOX 1, 10 mol % of LiOAc, and N,O-bis(trimethylsilyl)acetamide (BSA), to afford the corresponding products in excellent yields with up to 92% ee.

The synthesis of novel P-stereogenic phenylphosphonamides 3 and 11 via an intramolecular nucleophilic substitution of P-stereogenic phosphoramide 8 is described. These compounds were used as chiral Lewis basic catalysts for the asymmetric allylation of benzaldehyde, providing the corresponding homoallylic alcohol derivatives in up to 54% ee.

Synthesis of 2,6-dimethyl-9-aryl-9-phosphabicyclo[3.3.1]nonanes from 1,5-cyclooctadiene and their application to asymmetric cyclization leading to chiral tetrahydroquinolines and relatives through palladium-catalyzed allylic alkylation are described.

An Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxide is described. Asymmetric allylic amination of terminal allylic carbonates proceeded in the presence of 2 mol % of Ir catalyst, 2 mol % of chiral diaminophosphine oxide, 5 mol % of NaPF6, and BSA, affording the chiral branched allylic amines in up to 95% ee.

The stereoselective synthesis of (3R,5R)-5-hydroxypiperazic acid, a component of naturally occurring antibiotic cyclodepsipeptides, and its diastereomer was achieved via the use of Lewis acid-promoted diastereoselective Strecker synthesis as a key step, in which an interesting stereochemical reversal of diastereoselectivity by the choice of Lewis acid catalyst was observed.

We developed an efficient method for the synthesis of 3-substituted 2,3-dihydroquinolin-4-ones using a one-pot sequential multi-catalytic process: Pd-catalyzed allylic amination–thiazolium salt-catalyzed Stetter reaction cascade. Measurement of the initial rate of the developed sequential process revealed a significant increase in the reaction rate of the Stetter reaction in the presence of Pd(OAc)2 and AcOH·i-Pr2NEt, the constituents of the first Pd catalysis.

Total synthesis of halipeptin A, a potent anti-inflammatory cyclodepsipeptide, was achieved through proline-catalyzed asymmetric α-oxidation, diastereoselective aldol reaction, silver cyanide-mediated esterification, and macrolactamization.

(2S,3R)-3-Hydroxy-3-methylproline, a constituent of cyclodepsipeptides polyoxypeptins A and B, was efficiently synthesized by lithium chloride-induced diastereoselective tandem Michael-aldol reaction using methyl vinyl ketone and N-1-naphthylsulfonylglycine (R)-binaphthyl ester and subsequent hydrolysis of the product in 39% overall yield and five steps.

Four diastereomers, (2 R ,3 R ), (2 S ,3 S ), (2 S ,3 R ) and (2 R ,3 S ) at β-methoxytyrosine (β-OMeTyr), of the tripeptide hydrolysate, H-( S )- N -MeThr-β-OMeTyr-( S )-Hpr-OH, from papuamide A have been synthesized. Comparison of the 1 H NMR data of the natural hydrolysate with the four synthetic diastereomers unambiguously establishes the relative and absolute stereochemistry of the methoxytyrosine as 2 R ,3 R .

Titanium tetrachloride-mediated aza Diels–Alder cycloaddition using a chiral diene and an aza dienophile proceeds in highly diastereoselective manner to form a dehydropiperazic acid derivative in high yield, and diastereoselectivity of the reaction depends on the quantity of titanium tetrachloride.

The highly efficient synthesis of (R)- and (S)-piperazic acids, components of naturally occurring antibiotic cyclodepsipeptides, was achieved in 80% overall yield by the use of a proline-catalyzed asymmetric α-hydrazination as the key step.

The pyrrolo[3,2-c]quinoline consisting of a core structure of martinellines, the first naturally occurring heterocycle, was prepared through silicon-tether ring-closing metathesis reaction and intramolecular allylic amination as key steps.

The stereocontrolled synthesis of the protected (2S,3S)-N-methyl-5-hydroxyisoleucine, a component of halipeptins A and B with potent anti-inflammatory activity, has been achieved. The key steps include (i) installation of a double bond to bicyclic lactam 4 using N-tert-butyl phenylsulfinimidoyl chloride, (ii) highly exo-selective Michael reaction with lithium dimethylcuprate in the presence of chlorotrimethylsilane, and (iii) Ru-catalyzed oxidative deprotection of N,O-benzylidene acetal to the acid anhydride.

(2S,3R)-3-hydroxy-3-methylproline ones. The intriguing biological activities coupled with the unique structure of polyoxypeptins prompted us to synthesize these novel cyclodepsipetides. As studies directed towards the total synthesis of the polyoxypeptins, we have already reported efficient synthesis of (2S,3S)-3hydroxyleucine 2a using dynamic kinetic resolution and (2S,3R)-3-hydroxy-3-methylproline using SmI2-mediated cyclization. 2f We describe here stereoselective synthesis of the acyl side chain segment 2 from chiral 2,3-epoxy alcohol 6, easily prepared by Sharpless asymmetric epoxidation, through a regioselective ring-opening reaction. Kobayashi and Kurosu have indepen

Efficient synthesis of (S)-(+)-lycoperdic acid has been achieved by use of the stereoselective hydroxylation of the enolate derived from the bicyclic lactam 3 with the molybdenum oxidizing reagent, MoOPH (MoO5·Py·HMPA, oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide)), as a key step.

Stereoselective synthesis of (2 S ,3 R )-3-hydroxy-3-methylproline ( 3 ), a component of polyoxypeptins, has been achieved by use of SmI 2 -mediated diastereoselective cyclization reaction as a key step.

(2R,3R)- and (2S,3S)-3-Hydroxyleucines, components of cyclodepsipeptides, papuamides and polyoxypeptins, were efficiently synthesized along with their diastereomers from the corresponding β-keto-α-amino acid ester through dynamic kinetic resolution using RuCl2(binap)-catalyzed hydrogenation.

(3S,4R)-3,4-Dimethyl-(S)-glutamine, a common component of cyclodepsipeptides, papuamide A and callipeltin A, was stereoselectively prepared from (S)-pyroglutamic acid. The stereostructure of natural dimethylglutamine was unambiguously confirmed to be (2S,3S,4R) by comparison of the CD and NMR spectra of the synthetic 3,4-dimethylpyroglutamic acid with the hydrolysate of callipeltin A.

Asymmetric allylic substitution reactions between 1,3-diphenyl-2-propenyl acetate and various hetero nucleophiles were efficiently carried out using the catalysts derived from the monodentate phosphine ligands, (1R, 2S, 5R, 6S)-2,6-dimethyl-9-phenyl-9-phosphabicyclo[3.3.1] nonane and its enantiomer ((−)- and (+)-9-PBNs), and palladium (0).

Remarkable endo selectivity was observed during the hydroxylation of the enolates derived from the bicyclic lactam 1a and its relatives with molybdenum oxidizing reagents, MoOPD and MoOPH, showing that the molybdenum reagents approach the enolate from the sterically hindered concave face of the lactam in spite of their bulkiness.

The title acid, a component of microsclerodermins of marine sponge origin having five consecutive stereogenic centers, was efficiently synthesized as its proctected form 1 from the alcohol 5 utilizing the stereoselective addition of anisole to the acetylenic triple bond and the anti-aldol reaction as key steps.

The acyclic imides derived from primary benzylic amines and amino acid esters easily undergo the novel N → C acyl migration reaction via a base-generated carbanion, yielding the corresponding α-aminoketones which are expedient precursors for β-aminoalcohols.

New optically active bidentate phosphines, (S,S)- and (R,R)-2,7-di-tert-butyl-9,9-dimethyl-4,5-bis(methylphenylphosphino)xanthenes ( (S,S)- 1 and (R,R)- 1 ), were prepared through resolution of the corresponding phosphine oxides using (R,R)-(−)-dibenzoyl-tartaric acid and a preliminary experiment on asymmetric synthesis using an allyl substrate proved the utility of the new bidentate phosphines.

A core building block 3 for (2 S,3 R,4 S,5 S,6 S,11 E)-3-amino-6-methyl-12-(4-methoxyphenyl)-2,4,5-trihydroxydodec- 11-enoic acid (2, AMMTD) has been efficiently synthesized using the Sharpless asymmetric dihydroxylation and the Dondoni's furan addition to a nitrone derivative as key steps. The 2-furyl group has been used as the carboxyl synthon. © 1997 Elsevier Science Ltd.

New monodentate chiral phosphines, (+)- and (−)-2,6-dimethyl-9-phenyl-9-phosphabicyclo[3.3.1]nonanes ((+)- and (−)-9-PBNs), were prepared from 1,5-dimethyl-1,5-cyclooctadiene, and their application to the asymmetric allylic substitution reaction proved the utility of 9-PBNs as chiral phosphine ligands.

Optically active ethano Troger's base with configurationally stable stereogenic nitrogens and an ethylene bridge was synthesized by reaction with 1,2-dibromoethane and subsequent resolution using (−)- and (+)-di- p -toluoyl-D-tartaric acids from commercially available (±)-Troger's base in one step.

The C 20 –C 25 building blocks 2 and 3a for calyculin A, a protein phosphatase inhibitor, have been efficiently prepared from L-malic acid utilizing the Grignard reaction of the Weinreb amides 8 and 14 , followed by stereoselective reduction of the ketones 9 and 15 , respectively, as the key steps.

(+)-2-Hydroxy-3-pinanone ((+)-HyPN, (+)-2a) and (−)-3-hydroxy-2-caranone ((−) 2b) were respectively converted to the corresponding Schiff bases 18a and 18b with 1-(2 thiazolyl)methylamine (17). Alkylation followed by removal of the chiral auxiliaries (+)-2a and (−)-2b afforded (S)-dolaphenine (10) as an optically pure form. The method was applied to the asymmetric synthesis of the dolaphenine analogs 27ad.