1,4-Conjugate addition of allyltrimethylsilane to α,β-unsaturated ketones

α,β-Unsaturated ketones smoothly undergo conjugate addition with allyltrimethylsilane in the presence of a catalytic amount of elemental iodine under very mild and convenient conditions to afford the corresponding Michael adducts in high yields with high selectivity.     

Synthesis of α,β-unsaturated ketone from α-iodo ketone using photoirradiation

Irradiation of α-iodo ketone in hexane under a nitrogen atmosphere with a high-pressure mercury lamp (λ>300nm) at room temperature afforded the corresponding α,β-unsaturated ketones in good yield. This reaction affords a new, clean and convenient synthetic method for the α,β-unsaturated ketone.     

The clemmensen reduction of α,β-unsaturated ketones

The deoxygenation of the α,β-unsaturated ketones (1) and (5) under the Clemmensen condition yielded the olefins (2) and (6) along with their respective dimers (3+4) and (8+9). The α , β-unsaturated ketone (13) under similar treatment yielded the olefin (14) in satisfactory yield but the dimer could not be characterized. The deoxygenation of the α,β-unsaturated ketones (10) and (16) under similar con- ditions afforded the olefins (12) and (15) respectively in satisfactory yield along with the rearranged olefins (11) and (17) respectively. Epox-idation of the olefin (17) followed by heating with p-toluenesulfonic acid yielded the ketone (18).     

Spectral correlations for β-chlorovinyl ketones

The IR and UV spectroscopic data of a series of alkyl substituted β-chlorovinyl ketones have been determined. Some of the IR and UV spectroscopic criteria, developed for the S-cis or S-trans conformation of ordinary α,β-unsaturated ketones, seem to be applicable for the β-chlorovinyl ketones: the S-cis conformer shows a low ratio (rⁱ) of the integrated intensities of the carbonyl and double bond stretching vibrations and a relatively low UV ε value; whereas high rⁱ and ε values are found for the S-trans conformer; non-planarity increases the rⁱ value and decreases the ε value.The prefered conformations as determined by the IR and UV spectral data have led to the presentation of benzene solvation models for a series of β-chlorovinyl ketones. These models made it possible to assign thecis ortrans structure to α,β-dialkyl-β-chlorovinyl ketones on the basis of the NMR aromatic solvent induced shifts of the β-alkyl group: high solvent shifts to a higher field (0·31–0·66 ppm) are found forcis-β-chlorovinyl ketones, whereas low solvent shifts (0·040·15) are found for thetrans-β-chlorovinyl ketones. Assignments based on the chemical shifts alone can lead to erroneous interpretations.     

Highly enantioselective reduction of achiral ketones with NaBH4/Me3SiCl catalyzed by (S)-α,α-diphenylpyrrolidinemethanol

The reducing agent prepared from sodium borohydride, trimethylsilyl chloride and a catalytic amount of (S)-α,α-diphenylpyrrolidinemethanol has been successfully applied to the enantioselective reduction of ketones. The optically active secondary alcohols were obtained in excellent enantiomeric excess and almost quantitative chemical yield.     

Potassium phosphate or silica sulfuric acid catalyzed conjugate addition of thiols to α,β-unsaturated ketones at room temperature under solvent-free conditions

Potassium phosphate and silica sulfuric acid have been found to be useful and highly efficient catalysts for conjugate addition of thiols to α,β-unsaturated ketones under solvent-free conditions, at room temperature. Silica sulfuric acid (SSA) was found to be suitable for electron-deficient enones while potassium phosphate was found to effect thia-Michael addition with both, electron-deficient as well as electron-rich conjugated ketones.     

Synthesis of α-phosphorylated cyclopentanones by intramolecularcarbenoid cyclizations of α-diazo β-keto alkylphosphonates and phosphine oxides

α-diazo β-ketoalkylphosphonates and phosphine oxides undergo intramolecular carbenoīd cyclizations under rhodium (II) catalysis to afford substituted diethoxyphosphono-2 and diphenylphosphono-2 cyclopentanones which, under Wittig-Horner conditions, lead to α-methylene cyclopentanones.     

Phosphonates containing sulfur and selenium. Synthesis of vinylphosphonates bearing α-sulfenyl, α-selenenyl, α-sulfinyl and α-seleninyl moieties and studies on nucleophilic addition

The selenenylation of racemic and optically active α-phosphoryl sulfoxides is a key step leading efficiently to α-phosphorylvinyl sulfoxides or α-phosphorylvinyl selenides depending on the reaction conditions. Oxidation of α-phosphorylvinyl selenides and subsequent thermolysis of selenoxides afford alkynylphosphonates. Studies of the stereochemical course of nucleophilic addition to α-phosphoryl sulfoxides show high facial stereoselectivity of the reaction, however, epimerisation at the α-carbon atom leads to mixtures of diastereomers.     

Rhodium(III) iodide hydrate catalyzed three-component coupling reaction: synthesis of α-aminonitriles from aldehydes, amines, and trimethylsilyl cyanide

Aryl imines formed from aldehydes and amines undergo smoothly in situ nucleophilic addition with trimethylsilyl cyanide (TMSCN) in the presence of catalytic amount of hydrated rhodium(III) iodide to afford the corresponding α-aminonitriles in excellent yield. The low catalytic loading (2 mol %), mild experimental conditions, and short reaction time (mostly within 13 min) represent the key features of this novel catalytic system.     

Dual-activation protocol for tandem cross-aldol condensation: An easy and highly efficient synthesis of α,α′-bis(aryl/alkylmethylidene)ketones

Commercially available lithium hydroxide monohydrate (LiOH·H₂O) was found to be a novel ‘dual activation’ catalyst for tandem cross-aldol condensation between cyclic/acyclic ketones and aromatic/heteroaromatic/styryl/alkyl aldehydes leading to an efficient and easy synthesis of α,α′-bis(aryl/alkylmethylidene)ketones at r.t. in short times. The reaction of aryl, heteroaryl, styryl and alkyl aldehydes with acyclic and five/six-membered cyclic ketones afforded excellent yields after 2 min to 1.25 h. The reaction conditions were compatible with various electron withdrawing and electron donating substituents, e.g. Cl, F, NO₂, OMe and NMe₂. The rate of the cross-aldol condensation was influenced by the nature of the ketone and electronic and steric factors associated with the aldehyde. The reaction took place at a faster rate for acyclic ketone (e.g., acetone) than that for cyclic ketone (e.g., cyclohexanone). In case of cycloalkanones, the rate of the reaction was dependent on the size of the ring of the cycloalkanone. The cross-aldol condensation of cyclopentanone was faster than that of cyclohexanone for a common aldehyde. In case of reactions involving aliphatic aldehyde having α-hydrogen atom no self-aldol condensation of the aldehyde took place.     

H-bond donor-directed switching of diastereoselectivity in the Michael addition of α-azido ketones to nitroolefins

The development of catalyst-controlled stereodivergent asymmetric catalysis is important for providing facile access to all stereoisomers of chiral products with multiple stereocenters from the same starting materials. Despite progress, new design strategies for diastereodivergent asymmetric catalysis are still highly desirable. Here we report the potency of H-bond donors as the governing factor to tune diastereoselectivity in a highly diastereoselective switchable enantioselective Michael addition of α-azido ketones to nitroolefins. While a newly developed bifunctional tertiary amine, phosphoramide, preferentially afforded syn-adducts, an analogous squaramide catalyst selectively gave anti-adducts. The resulting multifunctional tertiary azides can be converted to spiro-pyrrolidines with four continuous stereocenters in a one-pot operation. Mechanistic studies cast light on the control of diastereoselectivity by H-bond donors. While the squaramide-catalyzed reaction proceeded with a transition state with both squaramide N–H bonds binding to an enolate intermediate, an unprecedented model was proposed for the phosphoramide-mediated reaction wherein an amide N–H bond and an alkylammonium ion formed in situ interact with nitroolefins, with the enolate stabilized by nonclassical C–H⋯O hydrogen-bonding interactions.

We report the successful reversal of the diastereoselectivity in an unprecedented Michael addition of α-azido ketones to nitroolefins catalyzed by bifunctional tertiary amines, simply by varying the H-bond donor from phosphoramide to squaramide.     

Substoichiometric TiCl4-mediated vicinal difunctionalization of α,β-acetylenic ketones for the synthesis of β-halo Baylis–Hillman olefins

A substoichiometric amount of titanium tetrachloride was found to be effective to promote and participate in the tandem α-hydroxyalkylation/β-chlorination of α,β-acetylenic ketones in the presence of (n-Bu)₄NI. This method provides the concise synthesis of (E)-β-halo Baylis–Hillman adducts. No β-iodo products were detected when using this combination of halogen sources. The reaction process involves 1,4-addition of chloro anion released from TiCl₄ onto α,β-acetylenic ketones to give TiCl₃–allenolate intermediates followed by the titanium Lewis acid-promoted carbonyl addition. Modest to good yields (53–77%) and excellent E/Z stereoselectivity (>95%) have been obtained for 10 examples.     

A novel synthesis of α-hydroxy- and α,α′-dihydroxyketone from α-iodo and α,α′-diiodo ketone using photoirradiation

A novel reaction of α-iodo ketone (α-iodocycloalkanone, α-iodo-β-alkoxy ester, and α-iodoacyclicketone) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketone in good yields. In the case of α,α′-diiodo ketone, α,α′-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′-dihydroxyketone.     

Preparation of α-amino ketones, β-amino hydroxylamines using asymmetric aza-Henry reactions of N-p-tolylsulfinylimines with nitroethane

N-Sulfinylimines derived from aromatic and aliphatic aldehydes react with nitroethane and NaOH, yielding mainly two diastereoisomeric β-nitroamines as the result of a highly diastereoselective reaction and further epimerization of the carbon linked to the nitro group. The resulting β-nitroamines are used as precursors of N-sulfonyl α-amino methyl ketones and β-amino hydroxylamines.     

Microwave-assisted synthesis of α-hydroxy ketone and α-diketone and pyrazine derivatives from α-halo and α,α′-dibromo ketone

A novel reaction of α-halo ketone (α-bromo and α-chloro ketone) with irradiation under microwave gave the corresponding α-hydroxyketone and pyrazine derivative in good yields. In the case of α,α′-dibromo ketone, α-diketone was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxyketone, α-diketone, α-chloro ketone and pyrazine derivative.     

Chlorotrimethylsilane promoted asymmetric Michael reaction of chiral enamines of α-alkyl β-keto esters

By the promotion of chlorotrimethylsilane, asymmetric Michael reaction of the chiral enamines (2) of α-alkyl β-keto esters (1) with methyl vinyl ketone and ethyl acrylate proceeded to afford, after hydrolysis, either enantiomer of the corresponding adducts (4) in a good enantioselectivity.     

Catalytic cyanosilylation of ketones using organic catalyst 1,1,3,3-tetramethylguanidine

1,1,3,3-Tetramethylguanidine acts as a highly effective catalyst for cyanosilylation of various ketones and aldehydes to the corresponding cyanohydrin trimethylsilyl ethers in up to 99% yield. The reaction proceeds smoothly with 0.1 mol % catalyst loading at 25 °C under solvent-free conditions.     

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.     

TiO2 as a new and reusable catalyst for one-pot three-component syntheses of α-aminophosphonates in solvent-free conditions

Commercially available titania (TiO₂) is reported as an extremely efficient catalyst for the synthesis of α-aminophosphonates. A three-component reaction of an amine, an aldehyde or a ketone and a dialkyl phosphite (Kabachnik–Fields reaction) took place in one-pot, under solvent-free conditions to afford the corresponding α-aminophosphonates in high yields and short times. The TiO₂ catalyzed α-aminophosphonate synthesis in the present study perhaps represents a true three-component reaction as no intermediate formation of either an imine or α-hydroxyphosphonate was observed that indicated the simultaneous involvement of the carbonyl compound, the amine and the phosphite in the transition state. Furthermore, the catalyst can be reused for several times without any significant loss of catalytic activity.     

Synthesis of β-keto-sulfones using ionic liquid [TPA][Pro] as an efficient and reusable reaction medium

Facile and an efficient synthesis of β-keto-sulfones is described by the reaction of α-haloketone with sodium alkyl/aryl sulphinates in ionic liquid [TPA][Pro] as an efficient and reusable reaction medium to afford the corresponding β-keto-sulfones in excellent yields.