Rhodium‐catalyzed Asymmetric Hydrogenation of α‐Dehydroamino Ketones: A General Approach to Chiral α‐amino Ketones

Rhodium/DuanPhos‐catalyzed asymmetric hydrogenation of aliphatic α‐dehydroamino ketones has been achieved and afforded chiral α‐amino ketones in high yields and excellent enantioselectives (up to 99 % ee), which could be reduced further to chiral β‐amino alcohols by LiAlH(tBuO)₃ with good yields_. This protocol provides a readily accessible route for the synthesis of chiral α‐amino ketones and chiral β‐amino alcohols.     

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.     

Titanyl Acetylacetonate as an Efficient Catalyst for Regioselective 1,2‐Reduction of α,β‐Unsaturated Carbonyl Compounds and Conversion of α‐Diketones & Acyloins to Vicinal Diols with Sodium Borohydride

α,β‐Unsaturated aldehydes and ketones were reduced readily and exclusively to their corresponding allylic alcohols with NaBH₄ and catalytic amounts of titanyl acetylacetonate at room temperature. Reduction reactions were carried out in CH₃CN or THF. This reducing system was also efficient for the reduction of α‐diketones and acyloins to their corresponding vicinal diols in CH₃CN.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.     

A Convenient Halogenation Procedure for the Preparation of α-Halocarbonyl Compounds

Except for substituted acetophenones (p-Y-C₆H₄COCH₃, Y=H, Br, CH₃O), simple ketones, β-ketoesters and 1,3-diketones reacted smoothly with a preformed homogeneous mixture of hydrochloric acid and potassium permanganate in acetonitrile to give moderate to good yields of the corresponding α-chlorocarbonyl compounds. Mixtures of α-chloro- and α,α-dichlorocarbonyl compounds were obtained for substituted acetophenones. Brominations proceeded similarly with higher yields when the hydrochloric acid was replaced with hydrobromic acid.     

MgCl2/Et3N Base System as a New Catalyst for the Synthesis of α‐Hydroxyphosphonate

An efficient and simple synthesis of α‐hydroxyphosphonates via reaction of aldehydes and ketones with dimethylphosphite in the presence of MgCl₂/Et₃N base system is reported. The use of readily available and easy to handle reagent MgCl₂/Et₃N makes this method simple, convenient, and practical.     

Palladium‐catalyzed cyclization of β‐bromo‐α,β‐unsaturated ketones with arylhydrazines leading to 3‐substituted 1‐aryl‐1 H‐pyrazoles

β‐Bromo‐α,β‐unsaturated ketones are condensed with arylhydrazines to form hydrazones, which are in situ intramolecularly cyclized into 3‐substituted 1‐aryl‐1 H‐pyrazoles under a catalytic system of Pd(OAc)₂/1,3‐bis(diphenylhosphino)propane (dppp)/NaO^tBu. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis of β‐Haloketones by β‐Addition Reactions of α,β‐Unsaturated Ketones with BX3 (X = Br,Cl) as Halide Source

A series of β‐bromoketones and β‐chloroketones were synthesized by the addition reactions of α,β‐unsaturated ketones under BX₃ (X = Br, Cl) and ethylene glycol reaction system. The α,β‐unsaturated ester also was successfully converted to its corresponding β‐bromoester under the reaction condition.     

Catalytic Asymmetric Intramolecular Homologation of Ketones with α‐Diazoesters: Synthesis of Cyclic α‐Aryl/Alkyl β‐Ketoesters

A catalytic asymmetric intramolecular homologation of simple ketones with α‐diazoesters was firstly accomplished with a chiral N,N′‐dioxide–Sc(OTf)₃ complex. This method provides an efficient access to chiral cyclic α‐aryl/alkyl β‐ketoesters containing an all‐carbon quaternary stereocenter. Under mild conditions, a variety of aryl‐ and alkyl‐substituted ketone groups reacted with α‐diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β‐ketoesters in high yield and enantiomeric excess.     

Reduction of α,β unsaturated carbonyl compounds by Ni–BH4

The reduction of α,β unsaturated carbonyl compounds by sodiumborohydride is catalysed by Ni(bpy)Cl₂ (bpy=2,2′-bipyridine). Various carbonyl compounds having the general formula R₁CH=CHCRO [where R₁, R=C₆H₅, H; p-MeO---C₆H₄---,C₆H₄; p-CH₃---C₆H₄, C₆H₅; (m-OMe---)(p-OMe---)C₆H₃, C₆H₅; C₆H₅, (CH₃)₂CH---; CH₃, H; m-Br---C₆H₄---, C₆H₅] are reduced to corresponding allylicalcohol [R₁CH=CHCRHOH] at 25°C within half an hour. During these reductions the double bond is partially reduced to give saturated alcohols as minor products having the molecular formula R₁CH₂CH₂CRHOH. The reduction of trans-3-phenyl-2-propenal with NaBH₄ and catalytic amounts of Ni(bpy)Cl₂ in solvents containing active deuterium (D₂O, CD₃OD), leads to the partial incorporation of deuterium at the α and γ positions to give C---D bonded alcohols.     

Synthesis of Three‐, Five‐, and Six‐Membered Heterocycles Derived from New β‐Amino‐α‐(trifluoromethyl) Alcohols

Nucleophilic trifluoromethylation of α‐imino ketones 2 , derived from arylglyoxal, with Ruppert–Prakash reagent (CF₃SiMe₃) offers a convenient access to the corresponding O‐silylated β‐imino‐α‐(trifluoromethyl) alcohols. In a ‘one‐pot’ procedure, by treatment with NaBH₄, these products smoothly undergo reduction and desilylation yielding the expected β‐amino‐α‐(trifluoromethyl) alcohols 4 . The latter were used as starting materials for the synthesis of diverse trifluoromethylated heterocycles, including aziridines 5 , 1,3‐oxazolidines 8 , 1,3‐oxazolidin‐2‐ones 9 , 1,3,2‐oxazaphospholidine 2‐oxides 10 , 1,2,3‐oxathiazolidine 2‐oxides 11 , and morpholine‐2,3‐diones 12 . An optically active 5‐(trifluoromethyl)‐substituted 1,3‐oxazolidin‐2‐one 9g was also obtained.     

Transition Metal Free Chemoselective Reduction of α,β‐Unsaturated Ketones to Saturated Ketones Using Tosyl Hydrazide as a Hydrogen Donor

An efficient, inexpensive and simple method for the reduction of various α,β‐unsaturated ketones to corresponding saturated ketones using tosyl hydrazide as a hydrogen donor in DMF using calcium oxide powder has been reported. A variety of enones underwent reduction without forming undesirable side products. High chemoselectivity, broad functional group tolerance and good yields are the noteworthy features of this protocol.     

Highly Efficient Synthesis of α‐Halomethylketones via Ce(SO4)2/Acid Co‐Catalyzed Hydration of Alkynes

A general atom‐economical approach for the synthesis of α‐halomethyl ketones is demonstrated through Ce(SO₄)₂/acid co‐catalyzed hydration of a wide range of haloalkynes. The reactions are conducted under convenient conditions and provide products with excellent regioselectivity in good to excellent yields, with broad substrate scope. This protocol is an alternative to conventional α‐halogenation of ketones.     

An Efficient α‐Alkylation of Aromatic Ketones with Primary Alcohols Catalyzed by [Cp∗︁IrCl2]2 without Solvent

Aromatic ketones are directly alkylated at α position with primary alcohols at 110°C in the presence of catalytic amount of KOH and [Cp??IrCl₂]₂ (Cp??=pentamethylcyclopentadienyl) catalyst. The reaction is carried out in the absence of any solvent or additive, which generates only water as the byproduct in theory. It is very efficient and generally completed in 10 min in good isolated yields. The reaction is believed to undergo successive hydrogen transfer and cross aldol condensation processes.     

Copper‐Catalysed Decarboxylative Trifluoromethylation of β‐Ketoacids

An efficient method for Cu‐catalyzed decarboxylative trifluoromethylation of β ‐ketoacids to achieve α ‐trifluoromethyl ketones was developed. A wide variety of synthetically useful α ‐trifluoromethyl ketones were obtained in modest to good yields under mild reaction conditions. The present method also exhibits good functional‐group compatibility.     

Synthesis of new optically active α,α′,β‐trisubstituted‐β‐lactones as monomers for stereoregular biopolyesters

Various optically active (4R)‐alkyloxycarbonyl‐3,3‐dialkyl‐2‐oxetanones as monomers were synthesized from L‐(S)‐malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by ¹H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2586–2597     

Reaction of α,β‐unsaturated ketones using cerium (IV) sulfate tetrahydrate in acetic acid

The reaction of α,β‐unsaturated ketones with cerium (IV) sulfate tetrahydrate [Ce(SO₄)₂·4H₂O, CS] in acetic acid gave the corresponding β‐acetoxy ketones. In the case of 2‐cyclohexen‐1‐one with CS in acetic acid, benzobicyclo[2.2.2]octen‐2‐one was obtained. The reaction mechanism also was proposed. Moreover, we report the aromatization and esterification of (R)‐(?)‐carvone by CS in acetic acid. Copyright © 2007 John Wiley & Sons, Ltd.     

A novel method for the synthesis of (Z)-α-selenyl-α,β-unsaturated ketones via acylation of (E)-α-selanylvinylstannanes

The (E)-α-selenylvinylstannanes react with acyl halides in presence of a catalytic amount of Pd(PPh₃)₄ to give the corresponding (Z)-α-selenyl-α,β-unsaturated ketones in good yield.     

Recent Applications of α-Metalated Isocyanides in Organic Synthesis

Being both nucleophilic and electrophilic, α-metalated isocyanides can add to polar double bonds, forming heterocycles. They are also synthons for α-metalated primary amines. This article describes recent or improved procedures for their use in organic synthesis: (1) In heterocyclic syntheses to give 2-oxazolines, 2-imidazolines, 2-thiazolines, oxazoles and oligooxazoles, thiazoles, triazoles, imidazolinones, pyrroles, 5,6-dihydro-1,3-oxazines and -thiazines, and (via cycloaddition with nitrones) 2-imidazolidinones. (2) In the field of formylaminomethylenation, for example transformation of estrone methyl ether and a keto sugar into the corresponding α-formylaminoacrylic esters, and the conversion of aldehydes and ketones by 3- and 4-pyridyl-methyl isocyanides into N-(1-pyridyl-1-alkenyl)formamides and their hydrolysis to 3- and 4-acylpyridines. (3) In connection with the use of α-metalated isocyanides as synthons for α-metalated primary amines, the author demonstrates how they may be used for preparation of 1,2- and 1,3-amino alcohols, 1,2-diamines, 2,3-diaminoalkanoic acids and for synthesis of higher amino acids starting from simple amino acids.     

Oxidative acylation of α,α‐diarylallylic alcohols: Synthesis of 1,2,4‐triarylbutane‐1,4‐diones

A metal‐free mediated oxidative acylation of α,α‐diarylallylic alcohols with simple aromatic aldehydes for the synthesis of 1,2,4‐triphenylbutane‐1,4‐diones is presented. In the presence of TBPB (tert‐butyl peroxybenzoate), desired products were obtained in good to excellent yields for 28 examples. This protocol features high regioselectivity, wide functional group tolerance and atom economy.