Simple Cyclic Ketones Research Articles

Mechanochemical asymmetric three-component Mannich reaction involving unreactive arylamines.

We report here a mechanochemical protocol for an asymmetric three-component Mannich reaction involving unreactive arylamines with simple cyclic ketones and arylaldehydes catalyzed by (S)-proline with a chiral diol. In this mechanochemical protocol, ball milling enables reaction acceleration and enantioselectivity control. The reported asymmetric three-component Mannich reactions usually involve reactive arylamines such as p-anisidine and phenylamine, while the catalytic asymmetric Mannich reactions involving unreactive arylamines in solution did not proceed smoothly or gave low yields and enantioselectivities. However, the use of ball-milling techniques overcomes the deficiency of the batch systems in solution and avoids the use of toxic organic solvents. The desired products were obtained in moderate-to-good yields (49%-80%) with good-to-high enantioselectivities (up to 99% ee). This is the first example of a mechanochemically activated catalytic asymmetric three-component Mannich reaction involving unreactive arylamines.

Cover Picture: A Stepwise Annulation for the Transformation of Cyclic Ketones to Fused 6 and 7‐Membered Cyclic Enimines and Enones (Chin. J. Chem. 4/2019)

The cover picture shows a typical building within the Campus of Xiamen University displaying Chen Jiageng (Tan Kah Kee)'s style. Just like many beautiful buildings designed and constructed by human, Nature “designs and constructs” a huge number of useful molecules with fascinating structures called natural products. Many natural products possess a fused six or seven‐membered carbocyclic unity. On page 315–322, the Huang's group disclosed a three‐step “[2+n]” annulation method for the construction of fused six and seven‐membered carbocyclic enimines and enones. The method starts from simple cyclic ketones and terminal olefinic amides, and relies on both the Suzuki coupling reaction and the olefin‐amide based Friedel‐Crafts type acylating reaction, a method developed by Huang and coworkers. image

Fungal BVMOs as alternatives to cyclohexanone monooxygenase.

FAD-dependent Baeyer-Villiger monooxygenases (BVMOs) have proven to be useful biocatalysts in the selective and specific oxygenation of various ketones. Despite the cloning, heterologous expression and characterization of close to 80 members of this enzyme family, some sub-groups of BVMOs still remain underrepresented and their evolutionary relationship uncertain. Until recently, very few fungal BVMOs have been described. Our previous investigations into BVMOs from the fungus Aspergillus flavus, yielded very little activity on simple cyclic ketones. Here we report on another four BVMOs from A. flavus that are more closely related to cyclohexanone monooxygenase (CHMO) from Acinetobacter sp. NCIMB 9871. Evolutionary analysis with other characterized BVMOs show their closest relationship to be with either cycloalkanone monooxygenase (CAMO) or 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-coenzyme A monooxygenase (OTEMO). The OTEMO-related BVMOAFL706 and BVMOAFL334 were heterologously expressed in E. coli, purified and shown to be able to convert a range of cyclic and substituted cyclic ketones. Of the unsubstituted cyclic ketones, cyclohexanone showed the highest conversion with maximum turnover frequencies reaching 4.3s-1 for BVMOAFL706. Unlike CHMOacinet, and many of the closely related BVMOs, no substrate inhibition was observed with cyclohexanone to a concentration of up to 30mM, creating the possibility for applications requiring high substrate loading. Aliphatic ketones were also readily converted with excellent regioselectivity. Similar to CHMOacinet, acetophenones were not converted and the oxidation of rac-cis-bicyclo[3.2.0]hept-2-en-6-one occurs enantiodivergently, with the (1R,5S) isomer converted to the "normal" lactone and the (1S,5R) isomer to the "abnormal" lactone.

Enantio‐ and Diastereoselective Dehydrative “One‐Step” Construction of Spirocarbocycles via a Ru/H+‐Catalyzed Tsuji–Trost Approach

Chiral spirocarbocyclic skeletons are ubiquitous in natural products. An intramolecular Tsuji-Trost (T-T) α-allylation of simple cyclic ketones is a reasonable approach to construct chiral spriocarbocyclic motifs; however, it has been a challenging approach despite many excellent intermolecular examples. For the first time, this has been achieved by a Ru/H+ combined catalyst that dehydratively cyclizes racemic allylic alcohols comprising a simple ketone via simultaneous activation of the C=O and OH groups. This chiral technology facilitates the construction of various spirocarbocycles containing two contiguous spiro all-carbon quaternary and tertiary stereocenters. Among four possible stereoisomers, one stereoisomer can be selectively produced in high yield, enhancing the feasibility of the T-T strategy, particularly in the synthesis of spirocarbocycles.

Combinatorial approach for the synthesis of precursors for chirality-controlled synthesis of SWCNTs

We report a theoretical approach for synthesis of precursors for the rational synthesis of chirality-pure single-walled carbon nanotubes (SWCNT) by surface-assisted method. The presented combinatorial strategy in combination with the mass-selective deposition technique provides a simple access to precursors for SWCNT of various chiralities, including large diameter tubes. The synthetic strategy provides a simple access to the robust SWCNT precursors “preprogrammed” for 54 different chiralities, starting from just four simple cyclic ketones. The molecules exhibit a rigid and fully fused structure which is expected to be important for a highly efficient conversion to ultra-short SWCNTs and for high yield of the respective isomer-pure tubes. The advantages and limitations of the approach for the preparative production of chirality pure SWCNTs are discussed.

Dibutyltin oxide mediated diastereoselective cyclodehydration/sulfonylation of 1,2,4-triols

Dibutyltin oxide (Bu2SnO) mediated cyclodehydration or sulfonylation of 1,2,4-triols is predictably diastereoselective depending on the steric bulk of the substituents at C4. A larger difference (ΔA-value >1kcal/mol) leads to the syn-1,2,4-triols favouring cyclodehydration (78–85%) to form 3-hydroxytetrahydrofurans, with the anti-1,2,4-triols favouring monosulfonylation (66–87%). Triols from symmetrical ketones preferentially undergo cyclodehydration in high yield (>75%) due to a gem-disubstituent effect. Thus, the 1,2,4-triols derived from simple cyclic ketones also favour cyclodehydration to form spirocyclic 3-hydroxytetrahydrofurans in 72–79% yields.

Catalytic Direct β-Arylation of Simple Ketones with Aryl Iodides

Herein we report a direct β-arylation of simple ketones with widely available aryl iodides, combining palladium-catalyzed ketone oxidation, aryl-halide activation, and conjugate addition through a single catalytic cycle. Simple cyclic ketones with different ring-sizes, as well as acyclic ketones, can be directly arylated at the β-position with complete site-selectivity and excellent functional group tolerance.

Iodine‐Catalyzed Selective Synthesis of 2‐Sulfanylphenols via Oxidative Aromatization of Cyclohexanones and Disulfides

AbstractIodine‐catalyzed intermolecular dehydrogenative aromatizations of six‐membered cyclohexanones for the selective synthesis of 2‐sulfanylphenols have been developed. Both aryl and alkyl disulfides can be used as sulfanylation reagents to give the desired products in good yields under the optimized reaction conditions. The catalytic reaction uses dimethyl sulfoxide or oxygen as the terminal oxidant and avoids the use of transition metal catalysts. In addition, α‐sulfanyl enones could also be obtained via an iodine‐catalyzed oxidative system from simple cyclic ketones using dimethyl sulfoxide as the oxidant.magnified image

ChemInform Abstract: Silver‐Catalyzed Direct Addition of Terminal Alkynes to Simple Cyclic Ketones in Water.

AbstractUnder conditions A), cyclohexane (Ia) and some derivatives (no stereochemistries indicated) can be easily transformed to propargyl alcohol systems.

Silver-Catalyzed Direct Addition of Terminal Alkynes to Simple Cyclic Ketones in Water

The first catalytic addition of terminal alkynes to simple cyclic ketones in water catalyzed by silver was developed. Cyclic ketones were reacted with terminal alkynes efficiently in water to give the corresponding propargyl alcohols.

Strigolactone Analogs Derived from Ketones Using a Working Model for Germination Stimulants as a Blueprint

Strigolactones are important signaling compounds in the plant kingdom. Here we focus on their germination stimulatory effect on seeds of the parasitic weeds Striga and Orobanche spp. and more particularly on the design and synthesis of new active strigolactone analogs derived from simple cyclic ketones. New analogs derived from 1-indanone, 1-tetralone, cyclopentanone, cyclohexanone and a series of substituted cyclohexanones (including carvone and pulegone) are prepared by formylation of the ketones with ethyl formate followed by coupling with a halo butenolide. Both enantiomers of the analog derived from 1-tetralone have been prepared by employing a homochiral synthon for the coupling reaction. For three other strigolactone analogs the antipodes have been obtained by chromatography on a chiral column. All analogs have an appreciable germinating activity towards seeds of Striga hermomonthica and Orobanche crenata and O. cernua. Stereoisomers having the same configuration at the D-ring as in naturally occurring strigol have a higher stimulatory effect than the corresponding antipodes. The analogs obtained from 1-indanone and 1-tetralone have an activity comparable with that of the well known stimulant GR 24. Analogs derived from 2-phenyl-cylohexanone, carvone and pulegone also have a good germinating response. The results show that the working model for designing new bioactive strigolactones is applicable.

Liquid phase synthesis of annelated pyridines over molecular sieve catalyst

Simple and selective single step synthesis of substituted octahydrophenanthridines and annelated pyridines was achieved using simple cyclic ketones, aliphatic aldehydes and ammonia over zeolites as catalyst under high pressure (autogeneous pressure) conditions with high yields and high conversions for the first time. The catalyst was inexpensive, environmentally friendly and could be reused many times without significant loss of activity.

Ring fused 1,2,5-thiadiazoles from oximes and trithiazyl trichloride

Trithiazyl chloride 1 converts the oximes of simple cyclic ketones into fused 1,2,5-thiadiazoles and bis-1,2,5-thiadiazoles in mild one-pot reactions. Cyclopentanone oxime gives the bisthiadiazole 3 (20%) in which all four methylene groups have been functionalised. Indan-1-one oxime 4 gives the thiadiazole 5 (63%), and tetralone oximes 6 and 8 give the bisthiadiazole 7 in low yields (20%) in complex reactions. Benzosuberone oxime 11 however gives only the monothiadiazole 12 (30%) which is not converted further with more trimer 1. These reactions probably occur by mechanisms analogous to those proposed earlier for the conversion of alkenes, alkynes, active methylene compounds and enamines into 1,2,5-thiadiazoles. Bisthiadiazole 3, a reactive analogue of fluorene, condenses with p-anisaldehyde to give 13 and is oxidised by PCC to the fluorenone analogue 15 in low yield; 15 is formed directly from cyclopentane-1,3-dione with trimer 1. Ketone 15 condenses with malononitrile and Hunig's base to give the dicyanomethylene derivative 17 (94%) which forms a black metallic 1 ∶ 1 complex with TTF at room temperature.

Eu(fod) 3 and SnCl 4-catalyzed heterocycloadditions of O-silyl enol ethers deriving from cyclic ketones

O-t-Butyldimethylsilyl enol ethers deriving from simple cyclic ketones acted as efficient dienophiles in the Lewis acid-catalyzed heterocycloadditions with methyl benzylidenepyruvate 1. Good selectivities were observed with cyclohexanone derivatives. Using Eu(fod) 3, the dienophile 2b led to the expected endo adduct 3b (93–97%). When using SnCl 4, the major product (89–95%) was found to be the “abnormal” adduct 5b with a trans ring junction.

Baeyer-Villiger oxidation of cyclic ketones with hydrogen peroxide catalyzed by cationic complexes of platinum(II): selectivity properties and mechanistic studies

The catalytic oxidation of simple cyclic ketones with hydrogen peroxide to give the corresponding lactones is reported. The reaction is catalyzed by complexes of Pt(II) of the type [(P-P)Pt(CF[sub 3])(solv)][sup +] (P-P = diphosphine) that may be deactivated by the hydroxy acids formed by hydrolysis of the lactones. The selectivity of the catalyst is studied in the oxidation of substrates like camphor, 2-cyclohexene-1-one, menthone, carvone, and indanones. Cyclobutanone is used to determine the mechanism of the reaction from initial rates studies. The reaction scheme proposed, which accounts for the observed effects of the various reactants, involves the coordination of the ketone on the vacant coordination site of the complex followed by nucleophilic attack of free hydrogen peroxide on the carbonyl carbon. The involvement of a quasi-peroxymetallacyclic intermediate is suggested which rearranges to give the lactone and the starting complex. A comparison with the mechanistic behavior of organic peroxy acids is given. 24 refs., 10 figs., 3 tabs.

ChemInform Abstract: ELECTRIC DICHROISM SPECTROSCOPY IN THE VACUUM ULTRAVIOLET. I. CYCLOBUTANONE, CYCLOPENTANONE, CYCLOHEXANONE, AND CYCLOHEPTANONE

Electrochromism and electric linear dichroism have been used in a study of transitions to the second excited singlet of a series of simple cyclic ketones. The results of the work show that the transition under investigation is polarized perpendicular to the direction of the dipole moment in the ground state of cyclobutanone, cyclopentanone, cyclohexanone, and cycloheptanone, where the dipole moment changes for the transition to the second excited singlet state from ground state are found to be 1.44, 1.63, 4.30, and 4.92 D, respectively. The magnitude of the changes in dipole moment and mean polarizability support the perpendicular B2←A1,3sa1←nb2 molecular Rydberg assignment. The larger dipole moment changes for the larger compounds are attributed to ring delocalization of the positive core charges in this extravalent state, a situation that appears unfavorable in the small ring compounds.

Electric dichroism spectroscopy in the vacuum ultraviolet. I. Cyclobutanone, cyclopentanone, cyclohexanone, and cycloheptanone

Electrochromism and electric linear dichroism have been used in a study of transitions to the second excited singlet of a series of simple cyclic ketones. The results of the work show that the transition under investigation is polarized perpendicular to the direction of the dipole moment in the ground state of cyclobutanone, cyclopentanone, cyclohexanone, and cycloheptanone, where the dipole moment changes for the transition to the second excited singlet state from ground state are found to be 1.44, 1.63, 4.30, and 4.92 D, respectively. The magnitude of the changes in dipole moment and mean polarizability support the perpendicular B2←A1,3sa1←nb2 molecular Rydberg assignment. The larger dipole moment changes for the larger compounds are attributed to ring delocalization of the positive core charges in this extravalent state, a situation that appears unfavorable in the small ring compounds.

Reactions of Per Acids. II. The Reaction of Perbenzoic Acid with Simple Cyclic Ketones. Kinetic Studies

Reactions of Per Acids. II. The Reaction of Perbenzoic Acid with Simple Cyclic Ketones. Kinetic Studies