Stereochemistry in the reaction of alkylsulfinyl phenylmethyl carbanion with electrophiles

Stereochemistry of the reactions of methyl-, ethyl-, 2-propyl-, and 1,1-dimethylethylsulfinyl phenylmethyl carbanions with deuterium oxide and methyl iodide in tetrahydrofuran have been studied. The 2-propylsulfinyl phenylmethyl carbanion exerts abnormal behavior in the sense that the alkyl substituent herein has no ability to freeze the conformation of the carbanion. The results are interpreted in terms of hard and soft interactions. ⁷Li and ¹⁷O nuclear magnetic resonance (NMR) spectroscopy revealed that the carbanions derived from these sulfoxides behave as the oxylate form.     

Reaction of 1, 1-Bis(Methylthio)-3-Methyl-1, 3-Butadiene with Lithiated 3-Methyl-2-Butenyl Phenyl Sulfide. A Special Case of Cyclopropane Formation

Abstract

The conjugated ketene dithioacetal 2 is now available by three different procedures¹. This electrophilic isoprene compound has been shown to add smoothly some simple lithio derivatives, but the addition of 3-methyl-2-butenyl-lithium gave a product with total inversion of the starting allylic chain^1a.     

Polybromostryl macromers and their anionic polymerization

The decomposition of polybromostyryl carbanions (PBS^?), obtained by anionic polymerization of 4-bromostyrene in tetrahydrofuran (THF), was investigated in the dark in a temperature range of ?6–?21°C. It was accompanied by the evolution of bromine anions and by the formation of polymeric allylic carbanions (λ_max = 575 nm; ε_max = 6800 eq^?1·L·cm^?1). The reaction mechanism was elucidated. The rate constant of the unimolecular rate-determining step of the process was 1.3 × 10^?5 s^?1 and 9.7 × 10^?5 s^?1 at ?21 and ?6°C, respectively. Its apparent energy of activation E_app = 18.38 Kcal/mol. The polybromostyrenes with allylic carbanions at their ends may decompose further. Their “dark” decomposition yielded 1,3-butadiene-1,3-diphenyl-macromers. The mechanisms of decomposition of the PBS^? carbanions and the dark decomposition of the polybromostyryl allylic carbanions are analogous. The rate constant of the latter process was 2.5 × 10^?6 s^?1 at ?6°C. The anionic polymerization of prepared macromers can be initiated in THF at ?78°C by α-methylstyryl carbanions, which do not react, however, with PBS^? carbanions. “Comblike” polymacromers were prepared in which each branch had a molecular weight of about 50,000. The overall molecular weight of the polymacromer was estimated to be about 1 × 10⁶. It has been assumed that the 2–1 mode of addition to the diene group of the macromer is predominant during its polymerization. The 3–4 mode of addition followed by proton shift represents the termination step. The 4–3 mode of addition was ruled out on the basis of spectroscopic evidence.     

The Structure of Lithium Compounds of Sulfones,Sulfoximides, Sulfoxides,Thioethers and 1,3-Dithianes,Nitriles, Nitro Compounds and Hydrazones

Acceptor-substituted lithio compounds LiA? CR¹R², in which the acceptor A is an RC(0), N?C, RSO₂, RS(O)NR, RSO, RS, O₂N, or RC(N? NR₂) group, have long played an important role in organic synthesis. Their significance has grown still further in the last fifteen years, as one has increasingly learnt to employ them successfully in chemo-, regio-, diastereo-and enantioselective reactions. Remarkably, little if anything was known of the structures of these compounds. It is therefore not surprising that interest in the structures of this class of compounds has greatly increased in recent years. In the following review, we shall summarize recent research into the structures of the lithio compounds of sulfones, sulfoximides, sulfoxides, thioethers and 1,3-dithianes, nitriles, nitro compounds, and hydrazones. Crystal structure determinations from recent years are central to this study. They are supplemented by solution studies and by calculations of structures. Structural similarities and differences between the individual states of aggregation are pointed out wherever possible, as is also the relationship between structure and reactivity.     

Imine Anions Derived from 2° Allylic Amines

Abstract

The application of allylic carbanions to organic synthesis is extensive^2,3 and among the numerous variations are the generation and use of heteroallylic dianions. Noteworthy in this useful option is the ability of sulfide (?S^θ) to stabilize a developing adjacent carbanion,^4,5 while alkoxide (?0^θ) uniquely directs carbanion formation to a distal allylic position (Scheme I).^6,7 We now wish to report that under conditions typically used for hetero allylic dianion formation 2° allylic amides provide a third reaction pathway for this structural entity by isomerizing to the resonance-stabilized imine anions (Scheme I).^8,9 This overall conversion (presumably through an intermediate dianion) represents a heretofore unknown isomerization process that provides an alternative method for the generation of synthetically useful enolate equivalents.¹⁰     

Sulfoxides derived from Cinchona alkaloids—chiral ligands in palladium-catalyzed asymmetric allylic alkylation

Phenyl sulfides derived from Cinchona alkaloids, 9-PhS-epi-CD, 9-PhS-epi-QN, 9-PhS-epi-QD, and 9-PhS-QN were oxidized into the corresponding sulfoxides. Regardless of the oxidation system used (NaIO₄, TEMPO/NaOCl, VO(acac)₂/chiral Schiff base/H₂O₂) a similar stereochemical outcome of the oxidation was observed. Four pure epimers of sulfoxides 9-PhSO-epi-CD and 9-PhSO-epi-QN were isolated and fully characterized (X-ray, CD, ¹H NMR-pattern). The chiral sulfoxides as well as the corresponding sulfides and sulfones were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. The sulfoxides obtained from Cinchona alkaloids bearing the additional stereogenic center gave the main product of configuration dependent on the chirality of alkaloid framework only. Similar ees (up to 60%) but significantly higher yields (90%) were obtained as compared to the reaction with the corresponding thioethers. The results were in agreement with nucleophilic attack directed at the allylic carbon located trans to the sulfur atom in the M-shaped intermediate η³-allylpalladium complex.     

Oxidation of Tricarbonyl (η1 η2-but-3-en-1-yl)iron(0)and Tricarbonyl (η3-allyl)iron(0) Anion Complexes with Dioxygen

The addition of reactive carbanions to tricarbonyl(η⁴-1,3-diene)iron(0) complexes proceeded at ?78 °C to give putative tricarbonyl(η¹,η²-but-3-en-1-y1)iron(0) anion complexes and at 25 °C to produce postulated tricarbonyl(η³-allyl)iron(O) anion complexes; trapping of reactive intermediates with dioxygen produced γ,δ-unsaturated acids and allylic alcohols, respectively.     

Etude de la structure de carbanions en α du soufre

Carbanions α to sulfoxides and sulfones C₆H₅S(O)nCH₂M (n  1, 2; M  Li or K) have been studied by infrared and Raman spectroscopy. A strong increase of the force constant of the SCH₂M bond, and a similar decrease of that of the SO bond(s) are observed. This implies that the negative charge is delocalized over the carbon and oxygen atoms. ¹H NMR shows that carbanions α to sulfoxides are configurationally stable at low temperature. The interconversion energy depends on the polarizing ability of the counter-ion (Li⁺: ΔG

13.6 kcal mol^-1; K⁺: ΔG

10.7 kcal mol^-1). The coupling constant of the methylenic hydrogens (J_AB 2 Hz) confirms the nearly planar configuration of the anionic carbon in the α metallated sulfoxides.     

Sodium iodide/boron trifluoride etherate: A mild reagent system for the conversion of allylic and benzylic alcohols into corresponding iodides and sulfoxides into sulfides

A variety of allylic and benzylic alcohols have been converted into the corresponding iodides using NaI/BF₃.Et₂O. Selective conversion of allylic and benzylic alcohols in preference to primary saturated alcohols has also been demonstrated. Further, the same reagent system has been used to convert sulfoxides into sulfides under mild conditions.     

A new synthesis of 2-sulfanyl allylic alcohols and alpha-sulfanyl ketones from carbonyl compounds and 1-chloroalkyl p-tolyl sulfoxides with carbon-carbon bond-formation

Reaction of lithium alpha-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides with ketones or aldehydes at low temperature gave adducts in almost quantitative yields. Treatment of the adducts derived from ketones with trifluoroacetic anhydride (TFAA) in the presence of NaI in acetone gave alpha-sulfanyl allylic alcohols in good to quantitative yields. On the other hand, treatment of the adducts derived from aldehydes with TFAA and NaI resulted in the formation of alpha-sulfanyl ketones and/or alpha-sulfanyl allylic alcohols. These reactions offer a good method for the synthesis of the above-mentioned compounds from ketones and aldehydes with carbon-carbon bond-formation in two steps and in good yields.     

Sulfoxide-controlled SN2′ displacements between cuprates and vinyl and alkynyl epoxy sulfoxides

The S_N2′ displacement of readily available vinyl epoxy sulfoxides with organocopper reagents takes place in good yields with high anti selectivity and a good degree of E/Z stereocontrol to produce enantiopure α-hydroxy vinyl sulfoxides. A second allylic displacement on the related mesyloxy vinyl sulfoxides allows for the asymmetric construction of two adjacent chiral centers. In addition, cuprate mediated S_N2′ addition to alkynyl epoxy sulfoxides affords α-hydroxy allenyl sulfoxides in good yields.     

A new method for generation of non-stabilized α-amino-substituted carbanions by the reaction of magnesium carbenoids with N-lithio arylamines: their reactivity and a new synthesis of α-amino acid derivatives

Magnesium carbenoids were generated from aryl 1-chloroalkyl sulfoxides with i-PrMgCl in THF at low temperature in quantitative yields. The magnesium carbenoids were found to be reactive with N-lithio alkylamines to afford an olefin, which was derived from dimerization of the magnesium carbenoid, in moderate yield. On the other hand, reaction of the magnesium carbenoids with N-substituted N-lithio arylamines gave non-stabilized α-amino-substituted carbanions in good yields. Reactivity of the α-amino-substituted carbanions with some electrophiles was investigated and it was found that ethyl chloroformate reacted to give α-amino acid derivatives in good yields. As a whole, a new method for one-pot, three-component combined synthesis of α-amino acid derivatives from aryl 1-chloroalkyl sulfoxides was realized.     

The diastereospecific aprotic conjugate addition reactions of allylic anions-mechanistic aspects.

A ten-membered cyclic “chair-chair” - or “$\text{trans}$-decalyl”-like TS is proposed to account for the diastereospecific aprotic conjugate addition reactions of allylic carbanions bearing polar, charge-stabilizing groups.     

On the stabilization of carbanions by adjacent phenyl,cyano, methoxy-carbonyl,and nitro groups in the gas phase

Institute of Mass Spectrometry, University of Amsterdam, Amsterdam, The Netherlands By using the method of Fourier transform ion cyclotron resonance mass spectrometry, substituent stabilization energies of homologous series of cycloalkyl carbanions, Ξ-c-C_nH_2n?2 (n = 3, 4, 5, 6, 7) with π-accepting substituents (Ξ = Ph, CN, COOMe, NO₂) have been determined experimentally in the gas phase as the difference between the proton affinity of the substituted and corresponding unsubstituted (Ξ = H) cycloalkyl carbanions. The stabilization energy data have been analyzed in terms of Taft’s parametrization of polarizability, field/inductive, and resonance effects. The linear regression analyses show excellent correlations within the ΞCH₂ ^? Ξ-c-C_nH_2n?2 ^? (n = 4, 5, 6, 7), and Ξ-c-C₃H₄ ^? carbanion series, from which it appears that the contributions of polarizability effects are independent of the above type of carbanions and only depend on the nature of the substituent. Further, it follows that inductive stabilization is more effective in the substituted methyl, ΞCH₂ ^?, than in the substituted cycloalkyl, Ξ-c-C_nH_2n?2 ^? (n = 4, 5, 6, 7) carbanions. This result suggests that inductive stabilization is counteracted by the electron releasing effect of alkyl groups. Resonance stabilization is significantly more effective in the substituted cycloalkyl, Ξ-c-C_nH_2n?2 ^? (n = 4, 5, 6, 7), than in the substituted methyl, ΞCH₂ ^?, carbanions, which suggests that m contrast to inductive stabilization, resonance stabilization is assisted by the electron releasing effect of alkyl groups. Finally, it appears that substitutent stabilization in the geometrically restricted substituted cyclopropyl carbanions, Ξ-c-C₃H₄ ^?, is dramatically less effective than in the corresponding geometrically unrestricted larger substituted cycloalkyl carbanions, Ξ-c-C_nH_2n?2 ^? (n = 4, 5, 6, 7). The linear regression analyses of the substituted cycloalkyl carbanions indicate that reduction of the stabilization energy is caused not exclusively by a geometrically hindered resonance stabilization, but also to a smaller extent by a less efficient inductive stabilization in the substituted cyclopropyl carbanions.     

VICARIOUS NUCLEOPHILIC SUBSTITUTION WITH SULFUR CONTAINING CARBANIONS

Abstract

Carbanions stabilized with sulfur containing substituents are versatile intermedi-ates in organic synthesis. The great value and importance of such carbanions is connected with specific properties of the sulfur atom which is capable to exist in a variety of valent states and to form many functional groups. These various sulfur-containing groups exert different carbanion stabilizing effects and can also serve as leaving groups in nucleophilic substitution or elimination reactions. Taking into account numerous types of sulfur containing functional groups and a variety of reactions they can promote, it is well understandable that reactions of sulfur-containing carbanions have been thoroughly studied and widely exploited in organic synthesis. The reactions of such carbanions with aliphatic electrophilic partners: alkylating agents, carbonyl compounds and Michael acceptors consist a major section of this field and were subject of numerous studies as well as many monographs.¹ Contrary to that, not very much was known about reactions of such carbanions with electrophilic aromatic compounds. Actually, there are only few reports on nitroarylation of sulfur-containing carbanions via replacement of halogen orfho- or para- to the nitro group in halonitrocornpounds.² There are also some reports on the alkylation of nitroarenes and heterocyclic compounds in the reaction with sulfonium3 and sulfoxonium4 ylides, dimethylsulfoxide carbanion,⁵ and dialkyl or alkyl aryl sulfones carbanions.⁶     

Synthesis of functionalized allylic sulfoxides and their use in the construction of 2,3,4-trisubstituted furans via a [3 + 2] annulation

A route to 2,3,4-trisubstituted furan derivatives based on a [3 + 2] annulation of functionalized allylic sulfoxides and aldehydes is described. In this strategy, the precursors of allylic sulfoxides 4, allylic sulfides 3, were synthesized via a thiomethylation reaction of an alpha-EWG ketene-S,S-acetal 1 (EWG: electron-withdrawing group), formaldehyde, and a thiol 2 in high to excellent yields. Allylic sulfoxides 4 were prepared by a highly regioselective oxidation of 3, using m-chloroperoxybenzoic acid as oxidant. Thus, starting from these readily available sulfoxides 4, 2-alkylthio-3,4-disubstituted furans 6 were efficiently constructed via the [3 + 2] annulation reaction of 4 with aldehydes 5 under mild conditions. Further replacement of the 2-alkylthio group of 6 with amines led to the formation of 2-amino-3,4-disubstituted furan derivatives 7.     

The first example of racemization of the sulfur stereogenic center of α-sulfinyl carbanions at low temperatures

The treatment of enantiopure aryl dichloromethyl sulfoxides in THF with strong bases such as LDA, LiHMDS, NaHMDS, and KHMDS resulted in racemization of the sulfur stereogenic center of the sulfoxides even at ?78 °C. The rate of the racemization was found to be dependent on the alkali metal of the bases used. This is the first example of the racemization of the sulfur stereogenic center of α-sulfinyl carbanions at low temperatures.     

Quantification of Ion‐Pairing Effects on the Nucleophilic Reactivities of Benzoyl‐ and Phenyl‐Substituted Carbanions in Dimethylsulfoxide

Second‐order rate constants for the reactions of acceptor‐substituted phenacyl (PhCO?CH^??Acc) and benzyl anions (Ph?CH^??Acc) with diarylcarbenium ions and quinone methides (reference electrophiles) have been determined in dimethylsulfoxide (DMSO) solution at 20 °C. By studying the kinetics in the presence of variable concentrations of potassium, sodium and lithium salts (up to 10^?2 mol L^?1), the influence of ion‐pairing on the reaction rates was examined. As the concentration of K⁺ did not have any influence on the rate constants at carbanion concentrations in the range of 10^?4–10^?3 mol L^?1, the acquired rate constants could be assigned to the reactivities of the free carbanions. The counter ion effects increase, however, in the series K⁺<Na⁺<Li⁺, and the sensitivity of the carbanion reactivities toward variation of the counter ion strongly depends on the structure of the carbanions. The reactivity parameters N and s_N of the free carbanions were derived from the linear plots of log k₂ against the electrophilicity parameters E of the reference electrophiles, according to the linear‐free energy relationship log k₂(20 °C)=s_N(N+E). These reactivity parameters can be used to predict absolute rate constants for the reactions of these carbanions with other electrophiles of known E parameters.     

Homologous SNV Reaction: Synthesis of l‐Methyl‐4‐[4′‐phenylsulfonyl‐1′,3′‐butadienyl]pyridinium Iodide and Its Reactivity with Thiol Groups Giving Rise to the Chromophoric Thioether

Thioether 4‐[(1′E,3′E)‐4′‐phenylsulfanyl‐1,3′‐butadienyl]pyridine 8 and sulfone 4‐(4′‐phenylsulfonyl‐1′,3′‐butadienyl)pyridine 14 were prepared by reaction of the carbanions derived from allylic thioether or allylic sulfone with isonicotinaldehyde. The reaction with the sulfonyl carbanion occurred at the α position and on heating the alcolate gave the dienic sulfone 14 . The corresponding pyridinium iodide 10 and 15 were prepared by reaction with methyl iodide, respectively, on pyridine derivates 8 and 14 . The dienic pyridinium thioether 10 showed a long wavelength absorption band centered at 420 nm. The reaction of dienic pyridinium sulfone 15 with thiophenol gave the dienic pyridinium thioether 10 by a nucleophilic vinylic substitution. The reaction of sulfone 15 with glutathione was of second order and the rate constant was 8.5 M^?1s^?1 at 30°C and pH 7, about 500 times smaller than the rate constant observed with (E)‐1‐methyl‐4‐(2‐methylsulfonyl‐1‐ethenyl)pyridinium iodide 1 . The dienic pyridinium thioether 10 was a negative solvatochrome.     

Reaction of 4-methyl-5,6-dihydro-2h- and 4-methylenetetrahydropyrans with phenylsulfinyl chloride

4-Methyl-5,6-dihydro-2H- and 4-methylenetetrahydropyrans undergo an ene- type reaction with phenylsulfinyl chloride in the presence of ZnCl₂ to give the corresponding allylic sulfoxides.October Revolution Fortieth Anniversary, Bashkir State University, UfaTranslated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1446–1447, June, 1990.