Asymmetric synthesis of alpha-amino 1,3-dithioketals from sulfinimines (N-sulfinyl imines). Synthesis of (2S,3R)-(-)-3-hydroxy-3-methylproline

[reaction: see text] N-Sulfinyl alpha-amino 1,3-dithioketals are prepared in high de and good yield by treating sulfinimines with lithio-1,3-dithianes. Selective removal of the N-sulfinyl or the thioketal groups affords stable alpha-amino 1,3-dithioketals and N-sulfinyl alpha-amino ketones, respectively. This new sulfinimine-derived chiral building block is employed in the asymmetric synthesis of polyoxypeptin amino acid (2S,3R)-(-)-3-hydroxy-3-methylproline.     

Totally selective ring-opening of amino epoxides with ketones: a general entry to enantiopure (2R,3S)- and (2S,3S)-3-aminoalkano-1,2-diols

[Reaction: see text] Transformation of enantiopure diastereoisomers (2R,1'S)- and (2S,1'S)-2-(1-aminoalkyl)epoxides into the corresponding 4-(1-aminoalkyl)-1,3-dioxolanes is achieved by reaction with different ketones in the presence of BF3.Et2O. The conversion takes place in very high yields, total selectivity, and without epimerization. A mechanism to explain this transformation is proposed. The obtained 1,3-dioxolanes can be deprotected, and (2R,3S)- and (2S,3S)-3-aminoalkano-1,2-diols were isolated.     

Highly regioselective, catalytic asymmetric reductive coupling of 1,3-enynes and ketones

[reaction: see text] Highly regioselective, catalytic asymmetric reductive coupling reactions of 1,3-enynes and ketones have been achieved using catalytic amounts of Ni(cod)(2) and a P-chiral, monodentate ferrocenyl phosphine ligand. These couplings represent the first examples of catalytic, intermolecular reductive coupling of alkynes and ketones, enantioselective or otherwise, and afford synthetically useful 1,3-dienes possessing a quaternary carbinol stereogenic center in up to 70% ee.     

The first nonthiolic, odorless 1,3-propanedithiol equivalent and its application in thioacetalization

2-[2-Chloro-1-(1-chlorovinyl)allylidene]-1,3-dithiane 1 was synthesized by the chlorination of 3-(1,3)-dithianylidenepentane-2,4-dione 2 using the Vilsmeier-Haack reagent in 99% yield. As a novel nonthiolic, odorless 1,3-propanedithiol equivalent, 1 was investigated in the thioacetalization reaction. Various types of aldehydes and ketones 3 were converted to the corresponding dithianes 4 in the presence of 1 in high yields (79-97%). Moreover, 1 exhibited obvious chemoselectivity between aldehyde and ketone in this thioacetalization reaction. A mechanism for this thioacetalization reaction is proposed.     

Highly enantioselective michael addition of cyclic 1,3-dicarbonyl compounds to alpha,beta-unsaturated ketones

[reaction: see text] The highly enantioselective Michael addition of 1,3-cyclic dicarbonyl compounds to alpha,beta-unsaturated ketones was reported to be catalyzed by an organic primary amine derived from quinine. A chiral anticoagulant drug, (S)-warfarin, was directly prepared in 96% ee, and other related important adducts were also obtained in excellent enantioselectivity (89-99% ee).     

Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral ruthenium catalysts. dynamic kinetic resolution

The reduction of 2-alkyl-1,3-diketones using (R,R)- or (S,S)-RuCl[N-(tosyl)-1,2-diphenylethylenediamine](p-cymene) in the presence of formic acid and triethylamine affords syn-2-alkyl-3-hydroxy ketones as the major products with high enantioselectivity. [reaction: see text]     

New Approach to the Synthesis of 1,3-Chloroisothiocyanatoalkanes. Synthesis of Tetrahydro-1,3-thiazine-2-thiones and 2-Alkylamino-5,6-dihydro-1,3-thiazines

A method was developed to prepare 1,3-chloroisothiocyanatoalkanes by reducing 1,3-isothiocyanato ketones using sodium borohydride at pH ~7 and subsequent treatment of the resultant 1,3-isothiocyanato alcohols with thionyl chloride. The reaction of 1,3-chloroisothiocyanatoalkanes with sodium hydrosulfide or amines gives substituted tetrahydro-1,3-thiazine-2-thiones or 2-amino-5,6-dihydro-1,3-thiazines.     

Expeditious copper-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to alpha,beta-cycloalkenones and subsequent transformations

Expeditious CuI-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to the five-, six-, seven-, and eight-membered alpha,beta-cycloalkenones is described. The reaction times are decreased dramatically compared to CuBr-(CH(3))(2)S catalysis. The resulting ketoacetals were subsequently cyclized to bicyclic beta-hydroxy ketones and alpha,beta-enones, followed by further transformations.     

Synthesis of 1,3-dithianes and 1,3-dithiolanes. Baker's yeast reduction and lipase-catalyzed resolution for synthesis of enantiopure derivatives.

Three 1,3-dithiolanes and four 1,3-dithianes have been synthesised from 1-(1,3-dithiolan-2-yl)-2-propanone and 1-(1,3-dithian-2-yl)-2-propanone, respectively. Asymmetric reductions of these ketones using baker's yeast gave the corresponding enantiopure (S)-alcohols. Baker's yeast also reduced the double bond in 3-(1,3-dithian-2-yl)-3-buten-2-one enantioselectively to give (S)-3-(1,3-dithian-2-yl)-2-butanone. 3-(1,3-Dithian-2-yl)-3-buten-2-one was also reduced chemo-selectively and the resulting 3-(1,3-dithian-2-yl)-3-buten-2-ol was resolved by transesterification in organic solvent using lipase B from Candida antarctica to yield the (S)-alcohol and the (R)-acetate with very high enantiomeric ratio, E. Racemic 1-(1,3-dithiolan-2-yl)-2-propanol and 1-(1,3-dithian-2-yl)-2-propanol were also resolved under similar conditions to give the (S)-alcohols and the corresponding (R)-acetates.     

Synthesis of 2-phenylethynyl-1,3-dioxanes and their hydrolysis

2-Phenylethynyl substituted 1,3-dioxanes were obtained by the reaction of 1,3-dioxanium salts with an lotsich reagent. It was shown that they are readily hydrolyzed with the formation of a-acerylenic ketones. A simple new method is proposed for the synthesis of the latter without isolating the intermediate 1,3-dioxanes using the reaction of 4 substituted 2-methyl(phenyl, furyl)-1,3-dioxanium salts with hydroxymethyl- and phenylethynylmagnesium bromide as examples.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 193–197, February, 1996.     

Direct synthesis of 1,3-diketones by Rh-catalyzed reductive alpha-acylation of enones

1,3-Diketones were synthesized from alpha,beta-unsaturated ketones by treatment with acid chlorides and Et(2)Zn in the presence of RhCl(PPh(3))3. This is a very simple and extremely chemoselective reaction to give the adduct at the alpha-position of alpha,beta-unsaturated ketones.     

Studies on the intramolecular C[bond]H...X (X = O,S) interactions in (S)-N-acyl- 4-isopropyl-1,3-thiazolidine-2-thiones and related 1,3-oxazolidin-2-ones

[reaction: see text] Two intramolecular C[bond]H...X (X = O, S) interactions in (S)-N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones are documented through crystallographic and spectroscopic evidence and high-level theoretical calculations. The key role played by the sulfur atoms has been made clear by comparison with structurally related (S)-N-acyl-4-isopropyl-1,3-oxazolidin-2-ones.     

Reactions of 1,3-isothiocyanato ketones with mineral acids. Synthesis of 3,4-dihydro-2H,1,3-thiazin-2-ones

Reactions of 1, 3-isothiocyanato ketones with mineral acids formed 3, 4-dihydro-2H, 1, 3-thiazin-2-ones or their mixtures with 6-alkylidenetetrahydro-1, 3-thiazin-2-ones. Subsequent acid hydrolysis of the thiazines obtained formed salts of 1,3-amino ketones. The direction and extent of the transformation depend on the nature of the acid, reaction temperature, and structure of the 1,3-isothiocyanato ketones.Omsk State University, Omsk 644077. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 850–854, June, 1996. Original article submitted October 18, 1995.Deceased.     

1,3-dioxenium cations: Synthesis and properties

The features and prospects of the new reaction of 1,3-keto-enols, ketones, and acids yielding 1,3-dioxenium salts were investigated. The results of studies of the structure, topomerization, and transformations of 1,3-dioxenium cations — a new family of stable heterocyclic cations of the allyl type — were generalized.     

Enolate addition to a 2-alkylidene[1,3]dithiane-derived bissulfoxide. A new a(2)-acceptor

Reaction of enolates derived from esters and ketones to an easily prepared alkylidene[1,3]dithiane-1,3-dioxide afforded the respective adducts with good yields and selectivities generally exceeding 85:15. The base used for enolate addition played no significant role for the reaction outcome, and addition of a silyl enole ether gave similar results. The thus formed oxygenated S,S-acetals were transformed into the corresponding 1,4-dicarbonyls by a reduction/oxidation sequence with 84% yield. [reaction: see text]     

1,3-Heterocumulene-to-alkyne

Transition structures and energy barriers of the concerted prototypical cycloaddition reaction of 1,3-heterocumulenes (S=C=S, S=C=NR, RN=C=NR, and heteroanalogs) to acetylene resulting in nucleophilic carbenes were calculated by G2(MP2) and CBS-Q ab initio quantum chemical and by density functional theory (DFT) methods. According to the calculations the activation energies (activation enthalpies) of the homoheteroatomic cumulenes decrease in the order O > S > Se and NH > PH and the reaction energies in the order O > S approximately Se and PH > NH. The reaction of carbon disulfide and acetylene has a lower reaction barrier than that of carbodiimide and acetylene although the first reaction is less exothermic than the second one. The stronger cyclic stabilization of the 1, 3-dithiol-2-ylidene in the transition state is discussed in terms of deformation and stabilization energies and of bond indices. The known reactions of carbon disulfide with ring-strained cycloheptynes were examined by DFT and by DFT:PM3 two-layered hybrid ONIOM methods. In agreement with qualitative experimental findings the activation energy increases and the reaction energy decreases in the sequence S, SO(2), and SiMe(2) if CH(2) in the 5-position of 3,3,7, 7-tetramethyl-1-cycloheptyne is replaced by a heteroatom or heteroatomic group, respectively. The results of these calculations were corroborated by experimental studies with carbon diselenide and isothiocyanates as 1,3-heterocumulenes. The cycloaddition of carbon diselenide to cyclooctyne proceeded faster than with carbon disulfide, the main product being the 1,3-diselenol-2-selone. Under more drastic conditions it was possible to add methyl and phenyl isothiocyanate, respectively, to 3,3,6, 6-tetramethyl-1-thia-4-cycloheptyne. The products are 1:3 adducts (cycloalkyne:isothiocyanate) whose formation is explained by a trapping reaction of the first formed 1,3-thiazol-2-ylidenes.     

Reactions of 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine with linear and cyclic 1,3-diketones

Ketones are known to be unreactive toward α-fluoroamines such as Ishikawa's Reagent or 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA). On the other hand, 1,3-diketones were found to undergo fluorination with TFEDMA. In the case of linear 1,3-diketones, the proposed mechanism involves the formation of β-fluoro-α,β-unsaturated ketones followed by the addition of HF to selectively give the product β,β-difluoroketone. Interestingly, when the 1,3-diketone is cyclic (i.e. 1,3-cyclohexadione) the outcome of the reaction is different and results in the formation of a product with a 2,2-difluoroacetyl group on the 2-carbon.     

New Chiral Diamines of the Dioxolane Series: (+)-(4S,5S)-2,2-Dimethyl-4,5-bis(diphenylaminomethyl)- 1,3-dioxolane and (+)-(4S,5S)-2,2-Dimethyl-4,5-bis(methyl- aminomethyl)-1,3-dioxolane

The reaction of sodium diphenylamide with 2,2-dimethyl-4,5-bis(tosyloxymethyl)-1,3-dioxolane gave (+)-(4S,5S)-2,2-dimethyl-4,5-bis(diphenylaminomethyl)-1,3-dioxolane, which was brought into complex formation with cobalt chloride. Treatment of 2,2-dimethyl-4,5-bis(tosyloxymethyl)-1,3-dioxolane with sodium N-methylanilide resulted in cleavage of the SÄO bond in the p-toluenesulfonate moiety with formation of N-methyl-N-phenyl-p-toluenesulfonamide and 4,5-bis(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane disodium salt. Diethyl (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate reacted with methylamine to give the corresponding dicarboxamide which was reduced with lithium aluminum hydride to (4S,5S)-2,2-dimethyl-4,5-bis(methylaminomethyl)-1,3-dioxolane having chiral carbon and nitrogen atoms.     

Manipulation of electrocatalytic reaction pathways through surface chemistry: in situ Fourier transform infrared spectroscopic studies of 1,3-butanediol oxidation on a Pt surface modified with Sb and S adatoms

Cyclic voltammetry and in situ Fourier transform infrared (FTIR) spectroscopy were employed to study the electrocatalytic properties of a Pt electrode modified with adatoms of antimony (Sb) or sulfur (S) for 1,3-butanediol (1,3-BD) oxidation. The results demonstrated the possibility of manipulating the reaction pathways involved in 1,3-BD oxidation through chemical modification of the Pt electrode surface. Both Sb and S adatoms (Sb(ad) and S(ad)) can inhibit the dissociative reaction of 1,3-BD into CO, which is the main source of self-poisoning in electrocatalysis of small organic molecules. On Pt electrodes modified with a high coverage of Sb(ad) (Pt/Sb(ad)) the onset oxidation potential of 1,3-BD has been significantly decreased, which is attributed to the fact that the oxidation of Sb(ad) occurs at lower potentials than that of the Pt surface. In situ FTIR results illustrated that, although at potentials below 0.5 V (vs a saturated calomel electrode), at which the Sb(ad) is stable on the Pt electrode surface, both carbonyl and CO2 species have been observed, the principal oxidation products of 1,3-BD are carbonyl species. Such results indicate that the reaction is mainly the dehydrogenation of 1,3-BD molecules. However, at potentials above 0.5 V the proportion of CO2 species in the oxidation products increases quickly, implying that the reaction has turned to the breakage of C-C bonds in 1,3-BD molecules and the subsequent oxidation of the cleaved fragments. In contrast with the cases of 1,3-BD oxidation on Pt and Pt/Sb(ad) electrodes, the reaction of 1,3-BD oxidation on a Pt electrode modified with S adatoms (Pt/S(ad)) is oriented completely to the production of carbonyl species when electrode potentials are below 0.9 V, though the reaction activity is relatively low. When the electrode potential is increased above 0.9 V, the intensity of the CO2 IR band in the FTIR spectra increases rapidly, corresponding to a fast oxidation of 1,3-BD on surface Pt sites recovered by the oxidation and desorption of S(ad) from the Pt surface.     

Reactions of substituted (1,3-butadiene-1,4-diyl)magnesium, 1,4-bis(bromomagnesio)butadienes and 1,4-dilithiobutadienes with ketones, aldehydes and PhNO to yield cyclopentadiene derivatives and N-Ph pyrroles by cyclodialkenylation

1,4-Dilithiobutadiene derivatives 1, 1,4-bis(bromomagnesio)butadiene derivatives 2 and metallacyclic (1,3-butadiene-1,4-diyl)magnesium reagents 3 were prepared and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply substituted cyclopentadienes and N-Ph pyrroles were formed by unprecedented reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated during the reaction and behaved formally as a one-carbon unit; the N==O moiety of PhNO was cleaved to afford N-Ph pyrrole derivatives. Furthermore, different reactivities among these three types of reagents 1, 2 and 3 were revealed. The 1,4-dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4-dimagnesium reagents 2 reacted with aldehydes, but not ketones; the metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did react with ketones.