Transformation of 1,2,3‐Thiadiazolyl Hydrazones as Method for Preparation of 1,2,3‐Triazolo[5,1‐b][1,3,4]thiadiazines

The transformation of 1,2,3‐thiadiazolyl hydrazones of aldehydes and ketones including Dimroth rearrangement giving 1‐alkylidenamino‐5‐mercapto‐1,2,3‐triazoles, alkylation of mercapto group of these heterocyclic compounds by α‐bromoacetophenones and cyclization giving 6,7‐dihydro‐5H‐[1,2,3]triazolo[5,1‐b ][1,3,4]thiadizines have been investigated. It was shown that the reaction for hydrazones of acetophenones and benzoaldehydes is diastereoselective. Triazolothiadiazine spiro derivatives were prepared with transformation of hydrazones of cyclic ketones.     

Scope and Mechanism on Iridium‐f‐Amphamide Catalyzed Asymmetric Hydrogenation of Ketones

A series of novel and easily accessed ferrocene‐based amino‐phosphine‐sulfonamide (f‐Amphamide) ligands have been developed and applied in Ir‐catalyzed asymmetric hydrogenation of aryl ketones, affording the corresponding chiral secondary alcohols with excellent results (up to >99% conversion, >99% ee and TON up to 200 000). DFT calculations suggest an activating model involving an alkali cation Li⁺.     

Enolizable Carbonyls and N,O‐Acetals: A Rational Approach for Room‐Temperature Lewis Superacid‐Catalyzed Direct α‐Amidoalkylation of Ketones and Aldehydes

An efficient catalytic room‐temperature direct α‐amidoalkylation of carbonyl donors, that is, ketones and aldehydes with unbiased N,O‐acetals, is described. Sn(NTf₂)₄ is an optimal catalyst to promote this challenging transformation at low loading and the reaction shows promising scope. A comprehensive and rational evaluation of this reaction has led to the establishment of an empirical scale of nucleophilic reactivity for a broad set of ketones that should be helpful in the synthetic design and development of carbonyl α‐functionalization methods.     

Chiral Silver Phosphate Catalyzed Transformation of ortho‐Alkynylaryl Ketones into 1H‐Isochromene Derivatives through an Intramolecular‐Cyclization/Enantioselective‐Reduction Sequence

The transformation of ortho‐alkynylaryl ketones through a cyclization/enantioselective‐reduction sequence in the presence of a chiral silver phosphate catalyst afforded 1H‐isochromene derivatives in high yield with fairly good to high enantioselectivity. An asymmetric synthesis of the 9‐oxabicyclo[3.3.1]nona‐2,6‐diene framework, which has been found in some biologically active molecules, is presented as a demonstration of the synthetic utility of this method.     

Synthesis of β‐Chlorohydrins in Water

2,4,6‐Trichloro‐1,3,5‐triazine (TCT, cyanuric chloride) was found to mediate the regio‐ and stereoselective ring opening of epoxides in H₂O in the presence of morpholine at room temperature to afford the corresponding β‐chlorohydrins in excellent yields (Table). The transformation is very simple, fast, efficient, and ecologically beneficial.     

An Efficient One-pot Synthesis of β-Amino/β-Acetamido Carbonyl Compounds via ZrCl4-catalyzed Mannich-type Reaction

Zirconium(IV) chloride catalyzed efficient one-pot synthesis of β-amino/β-acetamido carbonyl compounds at room temperature is described. In the presence of ZrCl4, the three-component Mannich-type reaction via a variety of in situ generated aldimines, with various ketones, aromatic aldehydes and aromatic amines in ethanol, led to the formation of β-amino carbonyl compounds and the four-component Mannich-type reaction of aromatic aldehydes with various ketones, acetonitrile and acetyl chloride resulted in the corresponding β-acetamido carbonyl compounds in high to excellent yields. This methodology has also been applied towards the synthesis of dimeric β-amino/β-acetamido carbonyl compounds.     

Efficient iridium and rhodium‐catalyzed asymmetric transfer hydrogenation using 9‐amino(9‐deoxy) cinchona alkaloids as chiral ligands

9‐Amino (9‐deoxy) cinchona alkaloids, derived from natural cinchona alkaloids, were applied in asymmetric transfer hydrogenation in both iridium and rhodium catalytic systems using i‐propanol as the hydrogen source. A series of aromatic ketones was examined, and good to excellent conversions and enantioselectivities were observed. The best results were achieved using 9‐amino(9‐deoxy) epicinchonine 2a as the ligand and [Ir(COD)Cl]₂ as the metal precursor, and for the isobutylphenone, the conversion and enantioselectivity were obtained in 90 and 97% e.e. respectively. Copyright © 2006 John Wiley & Sons, Ltd.     

Asymmetric anti‐Selective Michael Reaction of Imidazole‐Modified Ketones with trans‐β‐Nitroalkenes

The successful application of imidazole‐modified ketones in asymmetric anti‐selective Michael reactions with trans‐β‐nitroalkenes is presented by employing a newly developed 3‐bromothiophene‐modified chiral diamine ligand. The corresponding conjugate adduct was submitted to further transformations with Grignard reagents to solve the problem of α‐site selectivity of simple linear ketones. Additionally, the syn‐selective product was obtained by treating the anti‐selective adduct with a simple base. In this way, the site‐specific products for both diastereomers in the asymmetric conjugate addition of simple ketones to nitroalkenes can be obtained.     

Enantio‐ and Site‐Selective α‐Fluorination of N‐Acyl 3,5‐Dimethylpyrazoles Catalyzed by Chiral π–CuII Complexes

Catalytic enantioselective α‐fluorination reactions of carbonyl compounds are among the most powerful and efficient synthetic methods for constructing optically active α‐fluorinated carbonyl compounds. Nevertheless, α‐fluorination of α‐nonbranched carboxylic acid derivatives is still a big challenge because of relatively high pK_a values of their α‐hydrogen atoms and difficulty of subsequent synthetic transformation without epimerization. Herein we show that chiral copper(II) complexes of 3‐(2‐naphthyl)‐l ‐alanine‐derived amides are highly effective catalysts for the enantio‐ and site‐selective α‐fluorination of N‐(α‐arylacetyl) and N‐(α‐alkylacetyl) 3,5‐dimethylpyrazoles. The substrate scope of the transformation is very broad (25 examples including a quaternary α‐fluorinated α‐amino acid derivative). α‐Fluorinated products were converted into the corresponding esters, secondary amides, tertiary amides, ketones, and alcohols with almost no epimerization in high yield.     

Synthesis of a Pyridine–Zinc‐Based Porous Organic Polymer for the Co‐catalyst‐Free Cycloaddition of Epoxides

The synthesis of solid catalysts for the co‐catalyst‐free cycloaddition of CO₂ has attracted much attention. Herein, we report a hierarchical porous organic polymer, Py‐Zn@MA, that is able to catalyze the cycloaddition reaction of epoxides and CO₂ without using any additives or co‐catalyst to afford turnover frequency (TOF) values as high as 250 and 97 h⁻¹ at 130 °C by using pure and diluted CO₂ (simulating flue gas), respectively. These results are superior to those obtained from previously reported heterogeneous co‐catalyst‐free systems. The high activity of Py‐Zn@MA is mainly attributed to its bifunctional nature with ZnBr₂ and pyridine activating the epoxide in a cooperative way. Notably, Py‐Zn@MA can be easily prepared on a large scale without using any catalyst and the chemicals are cost effective. Moreover, Py‐Zn@MA shows good substrate universality for the cycloaddition reactions of epoxides. Our designed porous organic polymer Py‐Zn@MA material has the potential to serve as an efficient catalyst for the direct conversion of flue gas with epoxides into value‐added cyclic carbonates.     

Synthesis of (+)‐13‐Stemarene and (+)‐18‐Deoxystemarin: Expeditious Preparation of the Key 6‐exo‐Hydroxybicyclo[2.2.2]octan‐2‐one Ethylene Dithioacetal

An expeditious preparation of the 6‐exo‐hydroxybicyclo[2.2.2]octan‐2‐one ethylene dithioacetal 2b , a key intermediate in the synthesis of (+)‐13‐stemarene ( 4 ) and (+)‐18‐deoxystemarin ( 5 ) is described. Compound 2b was obtained as the major product by equilibrating the endo rich mixture of 6‐hydroxybicyclo[2.2.2]octan‐2‐one ethylene dithioacetals 2 with TsOH in benzene at reflux, easily available from the corresponding hydroxy ketones 9 . The model experiments which preceeded the above transformation, not previously described in the literature, are also presented.     

Synthesis of 1‐Aryl‐1H‐indazoles via a Ligand‐Free Copper‐ Catalyzed Intramolecular Amination Reaction

A general synthesis of 1‐aryl‐1‐H‐indazoles from o‐halogenated aryl aldehydes or ketones and aryl hydrazines was described. This protocol included an intermolecular condensation and a ligand‐free copper‐catalyzed intramolecular Ullmann‐type coupling reaction. This method was applied to a wide range of substrates to produce the indazole products in good yields.     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

gem‐Difluoroolefination of Diaryl Ketones and Enolizable Aldehydes with Difluoromethyl 2‐Pyridyl Sulfone: New Insights into the Julia–Kocienski Reaction

The direct conversion of diaryl ketones and enolizable aliphatic aldehydes into gem‐difluoroalkenes has been a long‐standing challenge in organofluorine chemistry. Herein, we report efficient strategies to tackle this problem by using difluoromethyl 2‐pyridyl sulfone as a general gem‐difluoroolefination reagent. The gem‐difluoroolefination of diaryl ketones proceeds by acid‐promoted Smiles rearrangement of the carbinol intermediate; the gem‐difluoroolefination is otherwise difficult to achieve through a conventional Julia–Kocienski olefination protocol under basic conditions due to the retro‐aldol type decomposition of the key intermediate. Efficient gem‐difluoroolefination of aliphatic aldehydes was achieved by the use of an amide base generated in situ (from CsF and tris(trimethylsilyl)amine), which diminishes the undesired enolization of aliphatic aldehydes and provides a powerful synthetic method for chemoselective gem‐difluoroolefination of multi‐carbonyl compounds. Our results provide new insights into the mechanistic understanding of the classical Julia–Kocienski reaction.     

Thionation of ω‐Acylamino Ketones with Lawesson's Reagent: Convenient Synthesis of 1,3‐Thiazoles and 4H‐1,3‐Thiazines

The reaction of ω‐acylamino ketones with Lawesson's reagent (=2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide; LR ) is described. Treatment of 2‐acylamino ketones 1 (n=0) with LR gave 1,3‐thiazole derivatives 3 in good yields (Scheme 1 and Table 1). The 4H‐1,3‐thiazines 4 were obtained as main products by treatment of 3‐acylamino ketones 2 (n=1) with an equimolar amount of LR , while mainly the corresponding 3‐(thioacyl)amino ketones 5 were isolated when 0.5 equiv. of LR was used. The 3‐acylamino esters 7 also reacted with LR to give the corresponding 3‐(thioacyl)amino esters 8 (Scheme 3 and Table 2).     

Rhodium‐Catalyzed Regioselective C7‐Functionalization of N‐Pivaloylindoles

An efficient rhodium‐catalyzed method for direct C? H functionalization at the C7 position of a wide range of indoles has been developed. Good to excellent yields of alkenylation products were observed with acrylates, styrenes, and vinyl phenyl sulfones, whereas the saturated alkylation products were obtained in good yield with α,β‐unsaturated ketones. Both the N‐pivaloyl directing group and the rhodium catalyst proved to be crucial for high regioselectivity and conversion.     

Disulfonimide‐Catalyzed Asymmetric Reduction of N‐Alkyl Imines

A chiral disulfonimide (DSI)‐catalyzed asymmetric reduction of N‐alkyl imines with Hantzsch esters as a hydrogen source in the presence of Boc₂O has been developed. The reaction delivers Boc‐protected N‐alkyl amines with excellent yields and enantioselectivity. The method tolerates a large variety of alkyl amines, thus illustrating potential for a general reductive cross‐coupling of ketones with diverse amines, and it was applied in the synthesis of the pharmaceuticals (S)‐Rivastigmine, NPS R‐568 Hydrochloride, and (R)‐Fendiline.     

Metal‐Free Oxidation of α‐Hydroxy Ketones to 1,2‐Diketones Catalyzed by Mesoporous Carbon Nitride with Visible Light

As a photocatalyst, mesoporous carbon nitride (mpg‐C₃N₄) shows higher photocatalytic activities in organic synthesis. Herein we report an mpg‐C₃N₄‐catalyzed oxidation of α‐hydroxy ketones to synthesize 1,2‐diketones using visible light. This transformation represents a green and highly efficient synthetic route to synthesize 1,2‐diketones for which catalytic approaches are scarce.     

A copper diimine‐based honeycomb‐like porous network as an efficient reduction catalyst

Nitrophenols are among the widely used industrial chemicals worldwide; however, their hazardous effects on environment are a major concern nowadays. Therefore, the conversion of environmentally detrimental p‐nitrophenol (PNP) to industrially valuable p‐aminophenol (PAP), a prototype reaction, is an important organic transformation reaction. However, the traditional conversion of PNP to PAP is an expensive and environmentally unfriendly process. Here, we report a honeycomb‐like porous network with zeolite‐like channels formed by the self‐organization of copper, 1,10‐phenanthroline, 4,4′‐bipyridine, and water. This porous network effectively catalyzed the transformation of hazardous PNP to pharmaceutically valued PAP. In the presence of complex, PNP to PAP conversion occurred in a few minutes, which is otherwise a very sluggish process. To assess the kinetics, the catalytic conversion of PNP to PAP was studied at five different temperatures. The linearity of lnC_t/C_o versus temperature plot indicated pseudo‐first‐order kinetics. The copper complex with zeolite like channels may find applications as a reduction catalyst both on laboratory and industrial scales and in green chemistry for the remediation of pollutants.     

Pyrazole‐4‐carboxylic Acids from Vanadium‐catalyzed Chemical Transformation of Pyrazole‐4‐carbaldehydes

The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole‐4‐aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H₂O₂ as an oxidant is described. The catalytic technology was successfully applied to a range of various 4‐formylpyrazoles, and plausible mechanism is also discussed.