Novel efficient synthesis of β-fluoro-β-(trifluoromethyl)styrenes

CF₃CFBr₂ was employed in catalytic olefination reactions of aromatic aldehydes. In situ prepared hydrazones of aldehydes were transformed to β-fluoro-β-(trifluoromethyl)styrenes by reaction with CF₃CFBr₂ under CuCl catalysis. Based on this reaction, a novel stereoselective approach towards β-fluoro-β-(trifluoromethyl)styrenes was elaborated. Nucleophilic vinylic substitution of fluorine by secondary amines, thiolates and alkoxides in β-fluoro-β-(trifluoromethyl)styrenes was also tested.     

α-Phenylselanyl imines: preparation of β-phenylselanyl amines and original synthesis of allylaziridines

Resorting to suitable methods, a wide variety of α-phenylselanyl imines 2-5 were prepared from α-phenylselanyl aldehydes and α-phenylselanyl ketones 1. These compounds were reduced to afford β-phenylselanyl amines 6-9. Our experimental conditions have limited the well known deselenenylation side-reaction occurring with most hydrides. On the other hand, the reaction of α-phenylselanyl imines 2 with organometallics led to the expected addition products only in the case of allylated derivatives. Depending on the temperature, either β-phenylselanyl amines 11 or unexpected allylaziridines 12 were recovered.     

Convenient synthesis of fluoroalkyl α- and β-aminophosphonates

Addition of both alkyl phosphites and phosphonate α-carbanions to N-substituted aldimines derived from fluoroalkyl aldehydes presents a convenient method for synthesis of fluoroalkyl α- and β-aminophosphonates in good yield (55-86%) under mild conditions.     

Efficient synthesis of fluorinated α- and β-amino nitriles from fluoroalkylated α,β-unsaturated imines

A simple and efficient synthesis of fluoroalkylated α-amino nitrile (4) derivatives by regioselective 1,2-addition of trimethylsilyl cyanide to fluoroalkylated α,β-unsaturated imines (1) is described. Fluoroalkylated β-amino nitriles (7) are also prepared by regioselective 1,2-addition of α-carbanions derived from acetonitrile to fluoroalkylated α,β-unsaturated imines (1). Fluoroalkylated α-(4) and β-amino nitriles (7) are also prepared through an ‘one pot’ procedure by reaction of enaminophosphonate 2 with BuLi, addition of aldehydes and subsequent addition of either trimethylsilyl cyanide or α-carbanion derived from acetonitrile. Basic hydrolysis of α-(4) and β-amino nitriles (7) gives fluoroalkylated α-(5) and β-amino acids (8).     

Synthesis of α-trifluoromethyl-phenethylamines from α-trifluoromethyl β-aryl enamines and β-chloro-β-(trifluoromethyl)styrenes

A novel synthetic approach towards α-trifluoromethyl-phenethylamines was elaborated by reduction of the electron deficient β-aryl-α-trifluoromethyl enamines and imines with sodium cyanoborohydride in the presence of trifluoroacetic acid. The starting imines were prepared by the reaction of primary amines with β-aryl-α-trifluoromethyl enamines or β-chloro-β-(trifluoromethyl)styrenes.     

Highly diastereoselective indium-mediated synthesis of β-lactam carbohydrates from imines

A simple and very effective approach to versatile carbohydrate β-lactam synthons of predictable absolute configuration has been developed. The procedure, which is based on the indium-mediated reaction of imines and bromoesters, was applied to the enantioselective synthesis of 3-monosubstituted and 3-disubstituted β-lactams from readily available carbohydrates. The opening of the β-lactamic ring gave rise to the corresponding sugar-derived β-amino acids. Transformation of the β-lactams into the corresponding azetidines was also achieved.     

Highly diastereoselective synthesis of enantiopure β-trifluoromethyl β-amino alcohols from chiral trifluoromethyl oxazolidines (Fox)

The organolithium species addition to 2-hydroxymethyl fluorinated oxazolidines (Fox) provides a highly diastereoselective and straightforward route for the synthesis of enantiopure trifluoromethyl β-amino alcohols quaternarized at the β-position.     

Direct synthesis of imines from primary alcohols and amines using an active ruthenium(II) NNN–pincer complex

An easy and direct access to ruthenium(II) NNN pincer complex, [RuCO(PPh₃)₂(NNN)] (NNN = bis(benzimidazole)pyridine) is reported. The formation of imines by coupling of primary alcohols and amines was studied using the title complex under atmospheric air without any additives. The effect of solvent, reaction temperature, time, and catalyst loading was also investigated.     

Diastereoselective synthesis of β-aminosulfones from the 1,2-addition to N-(para-methoxyphenyl) imines

The base-promoted 1,2-addition of alkyl phenylsulfones to N-(para-methoxyphenyl) imines was investigated as a direct route to stereochemically defined β-aminosulfones. Using ⁿBuLi as base, 2-(phenylsulfonyl)ethylbenzene was added to a range of N-(para-methoxyphenyl) imines to give β-aminosulfone products in high yields as single anti-diastereoisomers. Other less substituted alkyl phenylsulfones were not as successful.     

Facile synthetic pathway to β-hydroxy-β-trifluoromethyl imines and their derivatives

Synthetic approach based on mediated addition of different trifluoromethylated building blocks to selected acyclic imines giving access to a variety of β-hydroxy-β-trifluoromethyl imines are elaborated. A reaction between fluorinated adducts and imines proceed easily giving the condensation products in good to excellent yields. β-Hydroxy-β-trifluoromethyl imines possessing trifluoromethyl group and exhibiting strong intramolecular hydrogen bonding are great precursors to different β-hydroxy-β-trifluoromethyl ketones and alcohols.     

Facile synthesis of β,β′-diketophosphine sulfides from imines and Lawesson’s reagent

In a convenient one-pot sequence, treatment of imines with Lawesson’s reagent (LR) followed by hydrolytic work-up leads to β,β′-diketophosphine sulfides in good to excellent yields. These compounds were isolated exclusively in their tautomeric β-keto-β′-enol form as was evident from IR and NMR spectroscopic data.     

Stereoselective synthesis of α-hydroxy-β-amino acid derivatives from β-hydroxy-γ,δ-unsaturated sulfilimine

The first report on the use of N-sulfinyl benzylcarbamate for the preparation of N-Cbz sulfilimine from the corresponding sulfoxide is reported. The sulfilimine moiety is utilized as an intramolecular nucleophile for the regio- and stereoselective heterofunctionalization of an alkene to furnish a bromo carbamate which is used as a key advanced intermediate in the synthesis of representative α-hydroxy-β-amino acid derivatives.     

Synthesis of fluorinated α-amino ketones part I: α-benzamidoalkyl mono- di- and trifluoromethyl ketones

2-Phenyl-5(4H)-oxazolones, obtained from α-amino acids, are reacted with di- and trifluoro acetic anhydride by a modified Dakin-West procedure to yield in a one-pot reaction α-benzamidoalkyl-di- and trifluoromethyl ketones in good yields. The monofluoromethyl analogues were also prepared from α-amino acids, however the use of the highly toxic fluoroacetic anhydride was avoided. The key step is the halogen exchange reaction on the corresponding bromomethyl ketone.     

Diastereoselective synthesis of β- and γ2-muurolene: a carbocationic pathway from mono- to sesquiterpenes

The Lewis acid catalysed addition of the piperityl chlorides6 to isoprene yields adduct7, which undergoes a cis-stereoselective cyclisation to give the diastereoisomeric muurolene monohydrochlorides8. Treatment with potassium tert-butoxide affords β- and γ₂- muurolene 2.     

Gold(III) N-heterocyclic carbene complexes mediated synthesis of β-enaminones from 1,3-dicarbonyl compounds and aliphatic amines

A series of gold(III) N-heterocyclic carbene complexes [1-(R(1))-3-(R(2))imidazol-2-ylidene]AuBr(3) [R(1) = i-Pr, R(2) = CH(2)Ph (1c); R(1) = mesityl, R(2) = CH(2)Ph (2c); R(1) = i-Pr, R(2) = CH(2)COt-Bu (3c), and R(1) = t-Bu, R(2) = CH(2)COt-Bu (4c)] act as effective precatalysts in the synthesis of β-enaminones from 1,3-dicarbonyl compounds and primary amines under ambient conditions. Specifically the 1c-4c complexes efficiently catalyzed the condensation of a variety of cyclic as well as acyclic 1,3-dicarbonyl compounds, namely, acetyl acetone, benzoylacetone, 2-acetylcyclopentanone, and ethyl-2-oxocyclopentanecarboxylate with primary aliphatic amines, viz., methylamine, ethylamine, n-propylamine, i-propylamine, and n-butylamine, yielding β-enamines at room temperature. Interestingly enough, the more electrophilic gold(III) 1c-4c complexes exhibited superior activity in comparison to the gold(I) counterparts 1b-4b. A comparison along a representative 4a-c series further underscored the importance of gold in the reaction as both the gold(I) 4b and gold(III) 4c complexes were more effective than the silver analogue 4a. The density functional theory (DFT) study revealed that the strong σ-donating nature of the N-heterocyclic carbene ligand results in a strong C(carbene)-Au(III) interaction in the 1c-4c complexes.     

Asymmetric synthesis of α- and β-amino acids by diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines

The diastereoselective addition of triorganozincates to (R)-N-(tert-butanesulfinyl)imines has been used as a key step to achieve the synthesis of highly enantiomerically enriched N-protected α- and β-amino acids. Desulfinylation of the addition products followed by benzoylation of the nitrogen atom of the obtained primary amines and oxidation of one of the substituents on the carbon atom connected to the nitrogen complete the sequence. Using the same configuration in the sulfinyl chiral auxiliary, α-amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α-Disubstituted α-amino esters with high enantiomeric purity can also be prepared when α-imino esters are the starting substrates.     

A short synthesis of (S)-α-(diphenylmethyl)alkyl amines from amino acids

A range of (S)-α-(diphenylmethyl)alkyl amines were prepared from the corresponding (S)-α-amino acid ester hydrochlorides. These amines were derived by direct hydrogenation of their precursor oxazolidinones.     

Convenient Syntheses of Perdeuterioacrylonitrile and β,β-Dideuterioacrylonitrile

Perdeuterioacrylonitrile can be prepared conveniently from succinonitrile in a two-step process. Succinonitrile is exchanged with D₂O to obtain perdeuteriosuccinonitrile, which is then pyrolyzed at ～550°C to obtain perdeuterioacrylonitrile and DCN. CDBCN and CzDsCN are by-products of this reaction. A chemical procedure for separating perdeuterioacrylonitrile from these materials was developed. This involved formation of the Diels-Alder adduct of cyclopentadiene with perdeuterioacrylonitrile, followed by pyrolysis of the purified adduct at -330°C. Cyclopentadiene was removed from the resulting pyrolyzate by reaction with maleic anhydride. Purified perdeuterioacrylonitrile exchanged with H₂O to yield β,β-dideuterioacrylonitrile in good yield and good isotopic purity.     

β, β-Bis(trifluoromethyl)glycidic ester

Conclusions ,-Bis(trifluoromethyl)glycidic ester is far more active than ,-dimethylglycidic ester and is opened by amines on the side of the -carbon atom.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8 pp. 1529–1530, August, 1964