Relative tendency of carbonyl compounds to form enamines

Equilibria between carbonyl compounds and their enamines (from O-TBDPS-derived prolinol) have been examined by NMR spectroscopy in DMSO-d(6). By comparing the exchange reactions between pairs (enamine A + carbonyl B → carbonyl A + enamine B), a quite general scale of the tendency of carbonyl groups to form enamines has been established. Aldehydes quickly give enamines that are relatively more stable than those of ketones, but there are exceptions to this expected rule; for example, 1,3-dihydroxyacetone acetals or 3,5-dioxacyclohexanones (2-phenyl-1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one) show a greater tendency to afford enamines than many α-substituted aldehydes.     

Catalyst-free conjugated addition of thiols to alpha,beta-unsaturated carbonyl compounds in water

[reaction: see text] Catalyst-free conjugate addition of thiols to alpha,beta-unsaturated carbonyl compounds in water is reported. beta-Sulfido carbonyl compounds were formed at room temperature, in short times and with excellent chemoselectivity. Competitive dithiane/dithiolane formation, transesterification, and ester cleavage were not observed. Water played a dual role in simultaneously activating the alpha,beta-unsaturated carbonyl compound and the thiol. This new methodology constitutes an easy, highly efficient, and green synthesis of beta-sulfido carbonyl compounds.     

An acetylenic approach to patulin derivatives

A new route for the preparation of patulin-oxime, and other carbonyl derivatives of patulin, in a substantial yield, starting from acetylenic compounds, is described.

Chemical and theoretical evidence is presented for stereomutation in the preparation of carbonyl derivatives from patulin.     

The binding sites of carboxylic acid group contacting to Cu electrode

In this work, the binding sites of carboxylic acid binding to Cu electrode are explored by electrochemical jump-to-contact STM break junction. Single molecular conductance of benzene-based molecules with ending groups of carboxylic acid, carbonyl and hydroxyl are measured and compared. The conductance values of 1,4-benzenedicarboxaldehyde can be found in those of 1,4-benzenedicarboxylic acid, which shows that carboxylic acid can bind to Cu electrode through carbonyl group. Carboxylic acid can also bind to the electrode through carboxylate group, and gives out larger conductance values than those of carbonyl group. However, molecule with hydroxyl group is difficult to form single molecular junction with Cu. The current work demonstrates that the carboxylic acid can bind to the electrode through carbonyl and carboxylate groups, and a new anchoring group of carbonyl group can be used to form effective single molecular junction.     

Dialkylaluminum N,O-dimethylhydroxylamine complex as a reagent to mask reactive carbonyl groups in situ from nucleophiles

Aluminum complexes of N,O-dimethylhydroxylamine are effective reagents to mask carbonyl groups in situ from nucleophilic addition by organolithiums, Grignard reagents, and borohydrides. The utility of this process by selectively adding nucleophiles into carbonyl groups on a variety of structures as well as distinguishing between carbonyl groups on a sensitive natural product is demonstrated. (1)H NMR analysis supports the in situ masking of the more reactive carbonyl group.     

Tetracyanoethylene oxide not only oxidizes sulfides to sulfoxides but also reduces sulfoxides to sulfides

It was found that tetracyanoethylene oxide not only oxidizes sulfides to sulfoxides but also reduces sulfoxides to sulfides with generation of two molecules of carbonyl cyanide. The reaction thus also functions as a new method for generation of carbonyl cyanide.     

New approach to the synthesis of 1,3-dioxolanes

Application of ethanol to the synthesis of 1,3-dioxolanes by the condensation of carbonyl compounds with vicinal diols results in a high yield of the reaction product and considerably reduces the duration of the process. It is assumed that the effect of the ethanol is caused by the adduct formation with carbonyl compounds (hemiacetals) which behave as active intermediates of the condensation. A cyclic ketal of acetone with glycerol obtained with the help of ethanol was used as a basis component in the synthesis of a series of ketals substituting diol or carbonyl components by transketalyzation mechanism proceeding without water liberation.     

Electroinduced Addition of Fluoroalkyltrimethylsilanes to Carbonyl Compounds

Generation of a radical anion of a carbonyl compound in the presence of fluoroalkyltrimethylsilanes results in a chain reaction of addition to the carbonyl group with the generation of corresponding silyl ethers at a current efficiency of up to 7000%. A similar reaction is realized when zinc dust is used as the reductant.     

Carbonyl groups as molecular valves to regulate chloride binding to squaramides

Environment-sensitive binding of anions to synthetic receptors is important for the functional mimicry of ion channels. We describe new squaramide-based chloride ion receptors whose anion binding cavity can be opened and closed by using carbonyl groups as valves. In nonpolar solvents, the carbonyls preclude chloride binding via intramolecular hydrogen bonding with the squaramide NHs. In polar solvents, disruption of the intramolecular hydrogen bonds reorients the carbonyl groups and opens the anion-binding cavity.     

Desulfurization of mercaptans to hydrocarbons by carbon monoxide and water in the presence of cobalt carbonyl

Benzylic mercaptans and thiophenols undergo desulfurization when exposed to carbon monoxide and water, with cobalt carbonyl as the catalyst; carbonyl sulfide is evolved in these reactions.     

DBU-catalyzed condensation of acyldiazomethanes to aldehydes in water and a new approach to ethyl β-hydroxy α-arylacrylates

DBU-catalyzed condensation of ethyl diazoacetate (EDA) with aldehydes in pure water afforded corresponding β-hydroxy α-diazo carbonyl compounds. The β-hydroxy group of the products was further converted into β-siloxy group. The Rh(II)-catalyzed reaction of the β-aryl β-siloxy α-diazo carbonyl compounds gave 1,2-aryl shift products predominantly. The three-step transformation constitutes an efficient synthesis of ethyl β-hydroxy α-arylacrylates.     

A General Strategy to Enhance Donor‐Acceptor Molecules Using Solvent‐Excluding Substituents

While organic donor‐acceptor (D‐A) molecules are widely employed in multiple areas, the application of more D‐A molecules could be limited because of an inherent polarity sensitivity that inhibits photochemical processes. Presented here is a facile chemical modification to attenuate solvent‐dependent mechanisms of excited‐state quenching through addition of a β‐carbonyl‐based polar substituent. The results reveal a mechanism wherein the β‐carbonyl substituent creates a structural buffer between the donor and the surrounding solvent. Through computational and experimental analyses, it is demonstrated that the β‐carbonyl simultaneously attenuates two distinct solvent‐dependent quenching mechanisms. Using the β‐carbonyl substituent, improvements in the photophysical properties of commonly used D‐A fluorophores and their enhanced performance in biological imaging are shown.     

Molecular recognition of alpha,beta-unsaturated carbonyl compounds using aluminum tris(2,6-diphenylphenoxide) (ATPH): structural and conformational analysis of ATPH complexes and application to the selective vinylogous aldol reaction

Various alpha,beta-unsaturated carbonyl compounds were coordinated with aluminum tris(2,6-diphenylphenoxide) (ATPH) to give the corresponding Lewis acid-base complexes in a distinctive coordination fashion (selective coordination). ATPH recognizes carbonyl substrates and subsequently orients itself as it forms a stable complex through selective coordination with the carbonyl oxygen. Selective coordination also confers a conformational preference to each carbonyl compound under the steric and electronic influence of ATPH, which enables the vinylogous aldol reaction of alpha,beta-unsaturated carbonyl compounds to give the corresponding gamma-aldol products with different regio- and stereoselectivities.     

Facile Conversion of Tosylhydrazones to Carbonyl Compounds by the Potassium Peroxymonosulfate-Acetone System

Tosylhydrazones of carbonyl compounds were found to be readily cleaved into the corresponding carbonyl compounds in good yields under the mild conditions by treatment with dimethyldioxirane which is generated in situ from the reaction of acetone with potassium peroxymonosulfate.     

A computational study on addition of Grignard reagents to carbonyl compounds

The mechanism of stereoselective addition of Grignard reagents to carbonyl compounds has been investigated using B3LYP density functional theory calculations. The study of the reaction of methylmagnesium chloride and formaldehyde in dimethyl ether revealed a new reaction path involving carbonyl compound coordination to magnesium atoms in a dimeric Grignard reagent. The structure of the transition state for the addition step shows that an interaction between a vicinal-magnesium bonding alkyl group and C=O causes the C-C bond formation. The simplified mechanism shown by this model is in accord with the aggregation nature of Grignard reagents and their high reactivities toward carbonyl compounds. Concerted and four-centered formation of strong O-Mg and C-C bonds was suggested as a polar mechanism. When the alkyl group is bulky, C-C bond formation is blocked and the Mg-O bond formation takes precedence. A diradical is formed with the odd spins localized on the alkyl group and carbonyl moiety. Diradical formation and its recombination were suggested to be a single electron transfer (SET) process. The criteria for the concerted polar and stepwise SET processes were discussed in terms of precursor geometries and relative energies.     

Stereoselective Carbonyl Olefination with Fluorosulfoximines: Facile Access to Z or E Terminal Monofluoroalkenes

Terminal monofluoroalkenes are important structural motifs in the design of bioactive compounds, such as homeostasis regulators and mechanism‐based enzyme inhibitors. However, it is difficult to control the stereoselectivity of known carbonyl olefination reactions, and olefin metathesis is limited to disubstituted terminal monofluoroalkenes. Although sulfoximines have been used extensively in organic synthesis, reports on their use in carbonyl olefination reactions have not appeared to date. Herein, we report highly stereoselective carbonyl monofluoroolefination with a fluorosulfoximine reagent. The potential of this method is demonstrated by the synthesis of MDL 72161 and by the late‐stage monofluoromethylenation of complex molecules, such as haloperidol and steroid derivatives.     

Unusually low barrier to carbamate C-N rotation

The barrier for rotation about an N-alkylcarbamate C(carbonyl)-N bond is around 16 kcal/mol. In the case of an N-phenylcarbamate, the rotational barrier is lowered to 12.5 kcal/mol, but with N-(2-pyrimidyl)carbamates the barriers are so low (<9 kcal/mol) that the syn and anti rotamers cannot be observed as separate signals by 500 MHz NMR spectroscopy at 183 K. X-ray and computational data show that the N-(2-pyrimidyl) carbamates have C(carbonyl)-N bonds that are on average 0.03 A longer than for related N-phenylcarbamates. The computational results trace the origin of the effect to increased single bond character for the C(carbonyl)-N bond due to the increased electron-withdrawing ability of the pyrimidyl ring.     

From ketenimines to ketenes to quinolones: two consecutive pseudopericyclic events

[reaction: see text] N-[2-(Alkyl- or arylthio)carbonyl]phenyl ketenimines undergo cyclization under mild thermal conditions to afford 2-alkyl(aryl)thio-3H-quinolin-4-ones by means of the 1,5-migration of the alkyl(aryl)thio group from the carbonyl carbon to the central carbon atom of the ketenimine fragment followed by the 6pi-electrocyclization of the resulting vinyliminoketene. These 1,5-migration and electrocyclization processes occur via transition states whose pseudopericyclic characteristics have been established on the basis of their magnetic properties, geometries, and NBO analyses.     

Multicomponent approach to unique 1,4-diazepine-2-amines

Isocyanide-based multicomponent reaction (IMCR) of 1,3-diaminopropane with carbonyl compounds has been developed as an efficient strategy for the synthesis of 1,4-diazepine-2-amines. Brønsted and Lewis acids are able to promote the reaction, and TMSCl has been found to be the most efficient among them. The IMCR is applicable to a variety of carbonyl compounds and isocyanides.     

18O-tracer study on the rearrangement of carbonyl oxide intermediates to esters

A tracer study for the rearrangement of carbonyl oxides to esters using doubly-labeled oxygen lead to a conclusion that carbonyl oxides do not isomerize directly to dioxyranes and the rearrangement to esters proceeds via a cyclic tetroxide.