Energetic study of diastereoselective thio-Claisen rearrangement

Molecular simulation is applied to explain the diastereoselective thio-Claisen rearrangement results of various S-allyl γ-hydroxy ketene dithioacetals. We show that the experimental results of Sreekumar et al. in the absence and in the presence of zeolite catalyst can be rationalized in terms of the energetics of the steric of the reactant and the transition-state structure and of the non-bonding interactions of zeolite–reactant and zeolite–transition-state structure. The procedures used can successfully identify optimum products for a given diastereoselective thio-Claisen rearrangement.     

Thio-Claisen rearrangement used in preparing anti-β-functionalized γ,δ-unsaturated amino acids: scope and limitations

Multifunctionalized amino acids, especially amino acids with unsaturation, are important, demanding building blocks in peptide chemistry. Here we present a summary of our most recent study using the thio-Claisen rearrangement for the synthesis of anti-β-functionalized γ,δ-unsaturated amino acids. Investigations on scope, limitations, chemoselectivities and stereoselectivities regarding an FeBr(3)-catalyzed allylation strategy and a thio-enolate dianion formation strategy for asymmetric thio-Claisen rearrangement are documented. An explanation of the chirality crossover observed between the Eschenmoser-Claisen rearrangement and the thio-Claisen rearrangement is proposed. Novel optically active N(α)-protected amino acids with biologically interesting functional groups were prepared for the first time.     

The acid-catalyzed rearrangement of 1-N-allylindolines

Zinc chloride-catalyzed rearrangement of 1-N-allylindoline and 1-N-(2-methylallyl)indoline proceeds readily in refluxing xylene to give 7-allylindoline and 7-(2-methylallyl)indoline in 73% and 86% yields, respectively. The reaction of 1-N-2-butenylindoline and zinc chloride give rise to the mixture of 7-(1-methylallyl)indoline, 7-(cis- and trans-1-methyl-1-propenyl)indoline, and 7-(trans-2-butenyl)indoline. On the other hand, the similar reaction of 1-N-(3-methyl-2-butenyl)indoline with zinc chloride led to the formation of a mixture of 1,2,5,6-tetrahydro-4,4-dimethyl-4H-pyrrolo[3,2,1-ij]quinoline and 7-(3-methyl-2-butenyl)indoline.     

Developments of Asymmetric Synthesis Mediated by Chiral Sulfur Reagents

Abstract

Our work on the thio-Claisen rearrangement mediated by an adjacent sulfinyl group is reviewed. The substrates could easily be prepared on a large scale from diacetone-D-glucose. The rearrangement was effected with a diastereoselectivity of 95:5, in favor of the (S,S) or the (R,R) isomer. An approach to natural bis(lactones) was investigated, using a halolactonization reaction and a second [3,3] sigmatropic shift, again mediated by the sulfinyl group. The second part deals with the catalytic enantioselective benzylidenation of aldehydes, mediated by chiral sulfur ylides. We have introduced simple C ₂ symmetric thiolanes for that purpose. The procedure is very practical and enantiomeric excesses up to 96% have been reported for the model of stilbene oxide. A series of ferrocenyl sulfides with planar chirality has also been investigated, leading to unexpected diastereoselectivities and enantiomeric excesses up to 94%.     

Sigmatropic rearrangements of alkenyl benzofuryl and benzothienyl sulfides

The thio Claisen rearrangement of 2-butenyl 2-benzofuryl sulfide, cyclopenten-2-yl 2-benzofuryl sulfide, 2-butenyl 2-benzothienyl sulfide, and cyclopenten-2-yl 2-benzothienyl sulfide was investigated. The rates, energies and entropies of activation of the process were calculated, and the effect of the structure of the sulfide, the polarity of the solvent, and the temperature was demonstrated by comparison of these values. The 1,3-thioallyl rearrangement of 1-methylallyl 3-methyl-2-benzothienyl sulfide was studied, and it was shown that this reaction competes with the thio Claisen rearrangement.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1338–1341, October, 1982.     

Nitration of 7- and 8-methyl-4-R-1H-2, 3-dihydro-1,5-benzodiazepin-2-ones

4-R-8-Methyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones are nitrated in the 7 position, whereas their 7-methyl analogs are nitrated in the 1, 8, or 9 position. The nitration of 4,8-dimethyldihydrobenzodiazepinone proceeds as primary substitution at the N₁ atom of the amide group. The resulting N₁-nitroamide undergoes prototropic rearrangement to the 9-nitro isomer in strongly acidic media.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 122–126, January, 1978.     

Reactions of β-ketoesters and nitriles with carbon disulphide : Tautomerism of dithioesters and thio-Claisen rearrangement of ketene mercaptals

By use of the ion pair extraction technique tetrabutylammonium salts of ethyl and methyl acetoacetate, ethyl benzoylacetate, and cyanoacetone were reacted with CS₂ to give salts of dithioacids. Alkylation gave dithio-esters and ketene mercaptals. Rearrangements of allyl and crotyl ketene mercaptals of ethyl and methyl acetoacetate and ethyl benzoylacetate were studied. In the rearrangement of the dicrotyl ketene mercaptal of methyl acetoacetate an intermediate was detected supporting a four-step thio-Claisen rearrangement mechanism for dicrotyl ketene mercaptals, giving α-crotyl dithioesters with retention of the crotyl group.     

Synthesis of symmetric HIJ-ring model of ciguatoxin

A tricyclic model ether compound comprising 6/8/6 ether rings was synthesized via a new route including conjugate addition to form a symmetric eight-membered ether-ketone with syn/trans stereochemistry in selective manner. The corresponding vinyl triflate of this ketone was allowed to convert to the vinyl methyl derivative via cross-coupling reaction. This endo-olefinic tetrahydro-2H-oxocin was selectively reduced to afford α-methyl product. The corresponding exo-olefinic oxocane derivative, on the other hand, provided the β-methyl isomer as the major diastereoisomer (2/1). Our previous report on the synthesis of this final product was revised due to some rearrangement and the mechanisms are discussed.     

Synthesis of 4,7,9-trimethyl-2H-thieno[3,2-g]-1-benzopyran-2-one. A psoralen isostere

The title compound, an isostere of 4,5′,8-trimethylpsoralen, was prepared in good yield from 7-[(2-bromo-allyl)thio]-4,8-dimethylcoumarin via a thio-Claisen rearrangement. The structure of the final product was determined by proton nmr decoupling experiments.     

Thio-claisen rearrangements of some ketene derivatives

A number of 1-allylthio and 1-crotylthio 1-aminoalkenes derived from ketones and active methylene compounds has been prepared and rearranged to the corresponding thioamides (thio-Claisen rearrangement). Besides rearrangement products, small amounts of 1-alkyl-thio-N-alkyl-N-phenyl-1-aminoalkenes have also been isolated. When the ketene derivatives did possess a H-atom on nitrogen, cleavage of the formed thioamide produced phenyl isothiocyanate and substituted active methylene compounds.     

Cis-trans isomerization of chemically activated 1-methylallyl radical and fate of the resulting 2-buten-1-peroxy radical

The cis-trans isomerization of chemically activated 1-methylallyl is investigated using RRKM/Master Equation methods for a range of pressures and temperatures. This system is a prototype for a large range of allylic radicals formed from highly exothermic (～35 kcal/mol) OH + alkene reactions. Energies, vibrational frequencies, anharmonic constants, and the torsional potential of the methyl group are computed with density functional theory for both isomers and the transition state connecting them. Chemically activated radicals are found to undergo rapid cis-trans isomerization leading to stabilization of significant amounts of both isomers. In addition, the thermal rate constant for trans → cis isomerization of 1-methylallyl is computed to be high enough to dominate reaction with O(2) in 10 atm of air at 700 K, so models of the chemistry of the (more abundant and more commonly studied) trans-alkenes may need to be modified to include the cis isomers of the corresponding allylic radicals. Addition of molecular oxygen to 1-methylallyl radical can form 2-butene-1-peroxy radical (CH(3)CH═CHCH(2)OO(?)), and quantum chemistry is used to thoroughly explore the possible unimolecular reactions of the cis and trans isomers of this radical. The cis isomer of the 2-butene-1-peroxy radical has the lowest barrier (via 1,6 H-shift) to further reaction, but this barrier appears to be too high to compete with loss of O(2).     

Effect of the position of the asymmetric center on the chiral-optical properties of seven-membered benzolactams

The synthesis and chiral-optical properties of (+) -3-methyl- and (+) -4-methyl-2,3,4,5-tetrahydro-1H-benz [c] azepin-1-ones are described. A weak Cotton effect (CE) at 270 nm and a more intense positive CE are observed for both compounds in the 250 nm region. The considerably lower CE at 250 nm in the case of the 4-methyl isomer as compared with the 3-methyl isomer is explained by the remoteness of the asymmetric center in the 4-methyl isomer from the conjugated benzamide chromophore and the absence of the preferred conformation, which determines the sign of the CE.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 675–677, May, 1981.     

Stereoselective synthesis of some cis 2,3- disubstituted cyclanones : Ring size influence on the stereoselectivity of 2-substituted endocyclic enolates protonation

Conjugate addition of carbanionic reagents formed from aryl-or phenyl-thioacetonitriles 1a–1c and 2 to 2-methyl and 2-phenyl 2-cyclohexenone or 2-methyl 2-cyclopentenone, followed by acidic quench, under kinetic control, leads to different ratios of cis and trans 2,3-disubstituted cyclanones according to ring size. From 2-methyl and 2-phenyl 2-cyclohexenone, the cis isomer is highly predominant (85 to 98%). From 2-methyl 2-cyclopentenone a cis/trans mixture is obtained: the cis isomer only predominates when a bulky reagent (1c) is used (80%); in the other cases a mixture of nearly 1:1 is obtained.     

Enantioselective synthesis of anti-beta-substituted gamma,delta-unsaturated amino acids: a highly selective asymmetric thio-Claisen rearrangement

A novel synthesis of optically active anti-beta-substituted gamma,delta-unsaturated amino acids via a thio-Claisen rearrangement has been achieved. A 2,5-diphenylpyrrolidine was used as a C2-symmetric chiral auxiliary to control the stereochemistry, giving good yields and excellent diastereoselectivities and enantioselectivities.     

Stereoselective generation of Z-ketene S,N-acetal from S-alkyl onium salt of thioamide and its application to diastereoselective α-allylation of thioamide

Highly diastereoselective α-allylation of thioamides has been achieved via S-allylation of thioamide, dehydrohalogenation, and thio-Claisen rearrangement sequences in one pot.     

A new entry into the synthesis of the strychnos indole alkaloids containing 19,20-double bond via the thio-claiser rearrangement

A simple and selective route to the Strychnos framework containing 19,20-double bond has been developed employing the thio-Claisen rearrangement.     

A versatile one-pot synthesis of 2,3,5-tri-substituted thiophenes from thiomorpholides

An efficient method for the preparation of 2,3,5-trisubstituted thiophenes in a one-pot synthesis from thiomorpholides via the thio-Claisen rearrangement was developed.     

Thio-claisen rearrangement in the synthesis of sulfur-containing heterocyclic compounds (review)

The review is devoted to literature information on the mechanism of the thio-Claisen rearrangement of allyl aryl (heteryl) sulfides and their use in the synthesis of five- and six-membered sulfur-containing heterocyclic compounds, including derivatives of dihydrobenzothiophene and thiochromane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 435–449, April, 1980.     

Thermal (1,3)-allylic rearrangements in sulfoxides and sulfones

Rates and activation parameters for thermal (1,3)-allylic rearrangement have been determined for the systems β-methylallyl phenyl sulfoxide ($\text{2}$) and the corresponding sulfone ($\text{3}$), with evidence presented for a dissociative reaction mechanism.     

呋喃碳苷衍生物的合成及主产物构型的确认

在三氯氧磷催化下将2-甲基-5-(2′-氯-2′-脱氧-D-半乳糖-1-丁醇基)-3-乙酰基呋喃经脱水反应得到呋喃碳苷衍生物(2-甲基-5-[(4′-α-羟基-3′-β-氯)-2′-四氢呋喃基]-3-乙酰基呋喃),并对反应机理进行了讨论.通过2D NMR图谱确认了主产物的构型为α构型.