Reactions of heterocumulenes with organometallic reagents: XIX. Quantum-chemical study on S-alkylation and intramolecular cyclization of lithiated methoxyallene adducts with methyl, phenyl, and 3-(methylsulfanyl)phenyl isothiocyanates. Concurrent formation of pyrrole and/or thiophene rings

Concurrent reaction paths leading to the formation of thiophene and/or pyrrole rings from adducts of lithiated methoxyallene with methyl, phenyl, and 3-(methylsulfanyl)phenyl isothiocyanates were simulated by quantum-chemical methods. According to the calculations, pyrrole ring closure is kinetically more favorable for the adduct of 1-lithio-1-methoxyallene with methyl isothiocyanate, both reaction channels are equally probable for the adduct with phenyl isothiocyanate, and thiophene ring closure is the main reaction path for the adduct with 3-(methylsulfanyl)phenyl isothiocyanate.     

Reactions of heterocumulenes with organometallic reagents: XVIII. Quantum-chemical study on the mechanisms of formation of thiophene ring from lithium and potassium buta-2,3-dienimidothioates

Thermodynamic stabilities of different isomers and tautomers of lithium and potassium buta-2,3-dienimidothioates (ambident N,S-centered anionic adducts derived from methoxyallenyl carbanion and methyl isothiocyanate) as real or potential precursors of 3-methoxy-N,N-dimethylthiophen-2-amine were estimated by quantum-chemical calculations in terms of the density functional theory. Gradient channels corresponding to concerted (one-step) and stepwise (two-step) mechanisms of formation of thiophene ring from the most stable conformers and tautomers were localized. The formation of thiophene structure from lithium and potassium buta-2,3-dienimidothioates in two steps via intramolecular cyclization to thiophen-2(5H)-ylidene anion and its isomerization into thienylamide was found to be more probable. The activation barriers in both stepwise and concerted cyclization mechanisms considerably decrease in going from lithium to potassium as counterion.     

Reactions of heterocumulenes with organometallic reagents: XII. Reaction of metallated vinyl ethers with isocyanates: Ingenious synthesis of pyruvic acid amides

Acid hydrolysis of 2-alkoxy-N-substituted acrylamides easily obtained by reacting α-metallated vinyl ethers with isocyanates proceeded regiospecifically leading to the formation in a high yield of virtually undescribed and difficultly available 2-oxo-N-substituted propanamides.     

Heterocumulenes reactions with organometallic reagents: XX. Quantum-chemical study of concurrent processes of structural reorganization of N-Methyl-2-methoxy- and 2-(methylsulfanyl)buta-2,3-dienimidothioates into pyrroles and/or 2,3-dihydropyridines

Utilizing the MP2/6-31G(d,p) method a quantum-chemical investigation was performed of thermally induced formation of pyrrole and/or 2,3-dihydropyridine structures from methyl N-methyl-2-methoxy- and 2-(methylsulfanyl)buta-2,3-dienimidothioates (1-aza-1,3,4-trienes). According to calculations the pyrrole and dihydropyridine cyclization of a methoxy-substituted 1-aza-1,3,4-triene is both kinetically and thermodynamically virtually equally probable with a little prevalence of the first pathway. The main direction of the structural reorganization of methylsulfanyl-substituted 1-aza-1,3,4-triene is the kinetically controlled formation of the dihydropyridine ring.     

Reactions of heterocumulenes with organometallic reagents: XXIV. Quantum-chemical study of the effect of the substituent nature at sulfur atom in buta-2,3-dienimidothioates on the direction of their structural transformations

Applying B3LYP/6-31G(d,p) method we have performed a quantum-chemical study of structural transformations of propargyl and acetyl 2-methoxy-N-methylbuta-2,3-dienimidothioates (1-aza-1,3,4-trienes) into pyrroles and thiophenes. Heterocyclization mechanisms have been analyzed, thermodynamic and kinetic characteristics were obtained for the gradient channels of aza- and thiaheterocycles formation.     

Reactions of group IV organometallic compounds : XXIX. Insertion reactions of (trimethylsilylmethylene)phosphorane with heterocumulenes. Inhibition of Wittig type reactions

A reaction of (trimethylsilylmethylene)dimethylphenylphosphorane, PhMe₂PCHSiMe₃ (I), with phenyl isocyanate affords a 2/1 insertion product, which results from insertion of phenyl isocyanate into both the CSi and CH bonds of I. By way of contrast, a reaction of isothiocyanate and carbon disulfide with I affords 1/1 products by insertion of these heterocumulenes into the CSi bond of I. In these reactions, Wittig-type elimination of dimethylphenylphosphine oxide or sulfide did not occur because of irreversible migrations of the trimethylsilyl group to the anionic centers of the Zwitterionic intermediates.     

Catalytic asymmetric ring opening of 2,3-substituted norbornenes with organometallic reagents: a new formal aza functionalization of cyclopentadiene

An unprecedented regioselective and anti stereoselective asymmetric ring opening of 1,3-cyclopentadiene-heterodienophile cycloadducts, including also 2,3-diazabicyclo[2.2.1]heptenes, with hard alkylmetals and copper-phosphoramidite catalysts, is reported. The induced ring opening, in conjunction with C-C bond formation, gives a catalytic and practical access to new heterofunctionalized cyclopentenes in an enantioenriched form (up to 86% ee). [reaction: see text]     

Reactions of heterocumulenes with organometallic reagents: XIII. Quantum-chemical study on the mechanisms of syn -( Z )/ anti -( E )-isomerization of methyl 2-methoxy- N -methylbuta-2,3-dienimidothioate

Mechanisms of syn-(Z)/anti-(E) isomerization of methyl 2-methoxy-N-methylbuta-2,3-dienimidothioate, including rotational, inversion, promoted by N-protonation, and nucleophile-catalyzed, were studied by quantum-chemical methods, and the corresponding thermodynamic and kinetic parameters were calculated. The most probable mechanisms of isomerization of buta-2,3-dienimidothioates were found to be inversion (E _a = 74.4 kJ/mol) and nucleophile-catalyzed (E _a = 61.6 kJ/mol). Original Russian Text ? V.A. Shagun, N.A. Nedolya, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 11, pp. 1591–1600. For communication XII, see [1].     

Reactions of heterocumulenes with organometallic reagents: XI. Quantum-chemical study on the mechanism of noncatalytic cyclization of methyl 2-methoxy-<Emphasis Type="Italic">N</Emphasis>-methylbuta-2,3-dienimidothioate (1-aza-1,3,4-triene) into substituted pyrrole

Rotational isomerism of methyl 2-methoxy-N-methylbuta-2,3-dienimidothioate (1-aza-1,3,4-triene), which is readily available from 1-lithio-1-methoxyallene, methyl isothiocyanate, and methyl iodide, was studied by quantum-chemical methods. Four most stable rotamers with the energies of activation of their mutual transformations exceeding 35 kJ/mol were identified. The potential energy surfaces for the formation of pyrrole structure from 1-aza-1,3,4-triene via different ring closure channels were analyzed. According to the results of calculations, the most probable is direct [1,5]-cyclization of 1-aza-1,3,4-triene through a cyclic carbene species.     

A stereoselective and short total synthesis of the polyhydroxylated gamma-amino acid (-)-detoxinine,based on stereoselective preparation of dihydropyrrole derivatives from lithiated alkoxyallenes

Based on our earlier results employing lithiated methoxyallene 2 as C(3) building block and imines 3 for the synthesis of dihydropyrrole derivatives 5, we have investigated chiral imines 6, 10, and 15 as electrophilic components. Combined with lithiated alkoxyallenes, these imines provide the corresponding primary adducts and finally the dihydropyrrole derivatives 8, 12, 17, 20, and 22 in good yields and with high to excellent syn selectivities. This stereochemical outcome is interpreted as a result of alpha-chelate control. Treatment with hydrochloric acid converted syn-8 and syn-12 into bicyclic compounds 9 and 13, whereas under more mildly acidic conditions adduct syn-17 was transformed into diol syn-18. The total synthesis of the uncommon gamma-amino acid (-)-detoxinine could be achieved by starting from (S)-malic acid, which was converted into imine 15 in four steps. Lithiated benzyloxyallene added to imine 15 and efficiently furnished the crucial dihydropyrrole derivative syn-22. The hydrogenolysis of this compound did not directly provide the protected triol 29 as anticipated, but a stepwise protocol made the triol available in a fairly satisfactory manner. A second crucial step of the synthesis was the selective oxidation of 29, which could be achieved by employing platinum dioxide and oxygen. The resulting bicyclic lactone 30 was smoothly transformed into enantiopure (-)-detoxinine. Thus, a fairly short synthesis of this natural product based on a lithiated alkoxyallene could be performed, demonstrating the potential of these intermediates for syntheses of interesting functionalized heterocyclic compounds.     

One-pot synthesis of aromatic homoallylic alcohols from aldehydes and Grignard reagents promoted by Titanium(IV) tetraisopropanolate

An efficient method of Titanium(IV) mediated one-pot reaction approaching aromatic homoallylic alcohols from aldehydes and dual Grignard reagents was developed with good isolated yields. This method could use aromatic-, heteroaromatic-, or aliphatic-aldehydes as starting materials. However, electron-riched benzaldehyde or cinnamaldehyde tended to precede further hydroxyl eliminations to give all conjugated structures as demonstrated.     

Reaction of organometallic reagents with triethoxyacetonitrile. A new and short synthesis of α-ketoesters.

Grignard reagents react with triethoxyacetonitrile to give esters, while organolithium reagents provide α-ketoesters in excellent yields.     

Reactions of heterocumulenes with organometallic reagents: XIV. Quantum-chemical study on the mechanism of unusual thermally induced transformation of methyl <Emphasis Type="Italic">N</Emphasis>-Methylbuta-2,3-dienimidothioates into iminocyclobutenes with migration of the methylsulfanyl group

The mechanism of formation of cyclobutene ring from methyl 2-methoxy-and 2-phenyl-N-methylbuta-2,3-dienimidothioates (H₂C=C=C(R)-C(SMe)=NMe, 1-aza-1,3,4-trienes) was studied by quantum-chemical methods. The limiting stage in the [1,3]-sigmatropic migration of the methylsulfanyl group was found to follow a reaction path involving a “collapsed” state of the azatriene with linear configuration of the C=N-Me fragment, which is characterized by reduced activation barrier. The results of calculations substantiate preferential formation of pyrrole and dihydropyridine heterorings in the thermolysis of methyl 2-methoxy-N-methylbuta-2,3-dienimidothioate and of dihydropyridine and cyclobutene structures in the thermolysis of methyl N-methyl-2-phenylbuta-2,3-dienimidothioate.     

Nickel(0)-catalyzed diastereoselective three-component coupling of 1,3-dienes, aldehydes, and organometallic reagents: influence of organometallic reagents on diastereoselectivity

A nickel-catalyzed diastereoselective alkylative three-component coupling of 1,3-diene and aldehyde with organoboron or organosilicon reagents has been realized. The diastereoselectivity was dramatically changed depending on the class of organometallic reagents. The reaction using ArB(OH)₂ in the presence of PPh₃ afforded 1,3-syn-substituted 4-penten-1-ol derivative as a single diastereomer. On the other hand, the coupling reaction with tetraorganosilicon reagent using NHC as a ligand under similar conditions exclusively produced the corresponding 1,3-anti isomer.     

Reactions of alkoxy(chloromethyl)methylsilanes with sodium diethyl phosphate and with sodium dimethylphosphinate

Summary The reactions of alkoxy(chloromethyl)methylsilanes with sodium diethyl phosphate and with sodium dimethylphosphinate provide a method for the preparation of some silicon-phosphorus organic compounds containing an Si-C-O-P linkage and functional groups attached to the silicon atom.     

Synthesis and easy aromatisation of 5-substituted 6-(alkylthio)-2-methoxy-2,3-dihydropyridines. A new approach to the pyridine ring

Reaction of lithiated methoxyallene, 1-ethoxyethoxyallene, 1-(methylthio)propyne and 2-butyne with methoxymethyl isothiocyanate, MeOCH₂N=C=S followed by methylation affords the imidothioates H₂C=C=C(R)C(SMe)=NCH₂OMe [R=Me, OMe, OCH(Me)OEt, SMe]. Rearrangement to the fully conjugated systems H₂C=CH---C(R)=C(SMe)---N=CHOMe and subsequent electrocyclisation of these compounds leads to the 5-substituted 6-(methylthio)-2-methoxy-2,3-dihydropyridines with good to excellent yields. In the presence of acidic catalysts or by heating at elevated temperatures these dihydropyridines eliminate methanol to afford 3-substituted 2-(methylthio)pyridines. The aroma compound 2-(methylthio)-3-pyridinol was obtained by acid-catalysed treatment of 3-(1-ethoxyethoxy)-2-(methylthio)pyridine.     

Reactions of (chlorodifluoromethyl)benzene and (chlorodifluoromethoxy)benzene with nucleophilic reagents

Condensation reactions of (chlorodifluoromethyl)benzene and (chlorodifluoromethoxy)benzene with phenoxide and thiophenoxide ions have been performed in DMF or NMP with heating. In these conditions, the reaction between phenylselenide ion and (chlorodifluoromethyl)benzene did not occur. This latter reaction requires an additional visible light irradiation to proceed, as reported by Yoshida et al.     

Fluorine-containing heterocycles: XV. Reactions of polyfluorobenzoyl isothiocyanates with aminoazines and aminoazoles

Reactions of tetra-and pentafluorobenzoyl isothiocyanates with aminoazoles and aminoazines led to the formation of fluorinated 1,3-benzothiazin-4-ones which reacted with cyclic amines in different ways. Replacement of the N=C=S fragment was observed in some reactions of polyfluorobenzoyl isothiocyanates with nucleophiles.