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.     

Inverse solvent effects in carbocation carbanion combination reactions: the unique behavior of trifluoromethylsulfonyl stabilized carbanions

Second-order rate constants for the reactions of the trifluoromethylsulfonyl substituted benzyl anions 1a-e (CF3SO2CH(-)-C6H4-X) with the benzhydrylium ions 2f-j and structurally related quinone methides 2a-e have been determined by UV-vis spectroscopy. The reactions proceed approximately 10-40 times faster in methanol than in DMSO leading to the unique situation that these carbocation carbanion combinations are faster in protic than in dipolar aprotic media. The pK(a) values of some benzyl trifluoromethylsulfones were determined in methanol (1c-H, 17.1; 1d-H, 16.0; 1e-H, 15.0) and found to be 5 units larger than the corresponding values in DMSO. Rate and equilibrium measurements thus agree that the trifluoromethylsulfonyl substituted benzyl anions 1a-e are more effectively solvated by ion-dipole interactions in DMSO than by hydrogen bonding in methanol. Br?nsted correlations show that in DMSO the trifluoromethylsulfonyl substituted carbanions 1 are less nucleophilic than most other types of carbanions of similar basicity, indicating that in DMSO the intrinsic barriers for the reactions of the localized carbanions 1 are higher than those of delocalized carbanions, including nitroalkyl anions. The situation is reversed in methanol, where the reactions of the localized carbanions 1 possess lower intrinsic barriers than those of delocalized carbanions as commonly found for proton-transfer processes. As a consequence, the relative magnitudes of intrinsic barriers are strongly dependent on the solvent.     

Reactions of α-chloro β-oxo aldehydes with CH-acid anions

The reactions of α-chloro and α,α-dichloro β-oxo aldehydes with carbanions are accompanied by the cleavage of the carbon-carbon bond in the chloro aldehydes and result in formylation of CH-acids. These electrophiles react with carbanions, which are generatedin situ from CH-acids in the presence of AcONa in aprotic solvents, to form polyfunctional hydroxy compounds.     

One-pot regioselective synthesis of nitrophenyloxazolinyl styrene oxides by the Darzens reaction of vicarious nucleophilic substitution-formed carbanions of 2-dichloromethyl-4,4-dimethyloxazoline

The vicarious nucleophilic substitution reaction of dichloromethyloxazoline 2 with nitrobenzene has been investigated. Treatment of 2 with t-BuOK followed by the addition of nitrobenzene leads to benzylic carbanions 4 or 9 depending upon the solvent used (DMSO, DMF, or THF). Subsequent treatment of 4 or 9 with aldehydes, in a Darzens-like reaction, furnishes very good yields of nitrophenyl oxazolinyloxiranes 8 and 11. 1,2-Dioxazolinyl-1,2-dinitrophenylethene 7 forms quantitatively when carbanion 4 is allowed to warm to room temperature in the absence of external electrophiles.     

Exploring the Reactivity of α‐Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]‐Wittig Rearrangement and the Mechanistic Proposal Revisited

By carefully controlling the reaction temperature, treatment of aryl benzyl ethers with tBuLi selectively leads to α‐lithiation, generating stable organolithiums that can be directly trapped with a variety of selected electrophiles, before they can undergo the expected [1,2]‐Wittig rearrangement. This rearrangement has been deeply studied, both experimentally and computationally, with aryl α‐lithiated benzyl ethers bearing different substituents at the aryl ring. The obtained results support the competence of a concerted anionic intramolecular addition/elimination sequence and a radical dissociation/recombination sequence for explaining the tendency of migration for aryl groups. The more favored rearrangements are found for substrates with electron‐poor aryl groups that favor the anionic pathway.     

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     

Unique Structural Properties of 2,4,6‐Tri‐tert‐butylanilide: Isomerization and Switching between Separable Amide Rotamers through the Reaction of Anilide Enolates

Herein, we report a unique structural property of 2,4,6‐tri‐tert‐butylanilide, which can be separated into its amide rotamers at room temperature. Interconversion between the rotamers of anilide enolates occurs readily at room temperature and their reaction with electrophiles gives mixtures of the rotamers in a ratio that depends on the reactivity of the corresponding electrophile. That is, the reaction of the 2,4,6‐tri‐tert‐butylacetanilide enolate with reactive electrophiles, such as allyl bromide or protic acids, gives mixtures of the anilide rotamers in which the E rotamer is the major component, whereas less‐reactive electrophiles, such as 1‐bromopropane and 2‐iodopropane, yield mixtures of the rotamers in which the Z rotamer is the major component. The rotameric ratio of the product is also strongly dependent on the reactivity of the anilide enolate. Switching between the anilide rotamers can be achieved through protonation of a less‐reactive enolate by a less‐reactive protic acid and thermal isomerization of the anilide.     

The rearrangement route to 2-azabicyclo[2.1.1]hexanes. Solvent and electrophile control of neighboring group participation

The reactions of N-(alkoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 5 with halonium ion electrophiles were studied in polar and nonpolar aprotic solvents and also in protic media with the aim of controlling nitrogen neighboring group participation. Specifically, for bromonium ions nitrogen participation is facilitated by the polar aprotic solvent nitromethane and by the poorly nucleophilic protic solvent acetic acid. Alkene 5b and bromine/nitromethane afford only the rearranged anti,anti-5,6-dibromo-2-azabicyclo[2.1.1]hexane 6b, and NBS/acetic acid gives an 8:1 mixture favoring rearranged 5-bromo-6-acetate 6f. Conversely, pyridinium bromide perbromide/CH(2)Cl(2) is selective for only unrearranged 5,6-dibromide 7. Iodonium and phenylselenonium ions react with alkenes 5 to give only unrearranged 1,2-addition products 9 and 10, regardless of solvent. Chloronium and fluoronium ions react with alkenes 5 to give 4-aminomethyl-3-hydroxycyclobutene 11, derived by ring cleavage.     

Zur Photochemie von Allylaryläthern. 55. Mitteilung über Photoreaktionen

The photochemical reactions of different allyl aryl ethers (Scheme 3) were investigated in hydrocarbons (Chap. 3.1) and in alcoholic solvents (Chap. 3.2). The composition of the photoproducts depended very much on the nature of the solvent. Irradiation (3–95 h) of different methyl substituted allyl aryl ethers ( 1, 3, 5, 7 and 11 ) with a low pressure mercury lamp (λ_Emiss. = 254 nm; 6 or 15 Watt) under argon (quartz vessel) resulted in the formation of 2-, 3– and 4-substituted phenols, dienones and products of consecutive reactions (Tables 1–4 and 6). The results suggested that all products were formed by homolytic cleavage of the C? O bond in the singlet state of the ethers to intermediate radical-geminates (Scheme 5) followed by radical recombination of the two fragments. No products were formed by concerted processes (Table 5, Schemes 5 and 6). Upon irradiation of allyl aryl ethers lacking alkyl substituents at position 4 ( 1 and 5 ) in protic solvents, mainly 2- and 4-allylated phenols were obtained (Tables 1 and 4); 3-allylated phenols were formed only in small amounts (0.02%). However, in aromatic hydrocarbons or cyclohexane 3-allylated phenols were obtained from 1 , 5 and 11 in significant amounts (3–11%; Tables 1, 4 and 6). E.g., upon irradiation of allyl-2,6-dimethyl-2,4-cyclohexadien-1-one ( 6 ) besides 3- and 4-allyl-2, 6-dimethyl-phenol ( 23 and 24 ). Irradiation of 5 in methanol afforded 23 and 6 only in traces, whereas 24 was the main product.     

Regio- and diastereoselective functionalization of (−)-cytisine

(−)-N-Benzyl cytisine has been stereoselectively substituted in moderate to high yields on its carbon 6 (Csp³ α to the pyridone nitrogen). The reaction involved the in situ trapping of the carbanion formed by reaction of lithium diisopropyl amide (LDA) and its reaction with electrophiles (alkyl, allyl, benzyl halides, non-enolizable aldehydes, and Weinreb amide). In the absence of an electrophile or with its addition after the formation of the carbanion, a dimeric structure was isolated (yield: 42%) resulting from the 1,4-addition of the carbanion on the pyridone ring of another cytisine molecule. Deprotection of the benzyl group (Olofson's reagent) allowed the formation of 6-substituted derivatives of the natural product, cytisine, a potent agonist of nicotinic receptors of subtype α₄β₂.     

The psuedo‐michael reaction of 2‐aminoimidazolines 2. Part 1. Synthesis and structure assignment of isomeric 5(1H)‐Oxo and 7(1H)‐Oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates

The pseudo‐Michael reaction of 1‐aryl‐2‐aminoimidazolines‐2 with diethyl ethoxymethylenemalonate (DEEM) was investigated. Extensive structural studies were performed to confirm the reaction course. For derivatives with N1 aromatic substituents, it was found that the reaction course was temperature dependent. When the reaction temperature was held at ?10 °C only the formation of 1‐aryl‐7(1H)‐oxo‐2,3‐dihydroimi‐dazo[1,2‐a]pyrimidine‐6‐carboxylates ( 4 ) was observed in contrast to earlier suggestions. Under the room temperature conditions, the same reaction yielded mixtures, with varying ratio, of isomeric 1‐aryl‐7(1H)‐oxo‐ ( 4a‐4f ) and 1‐aryl‐5(1H)‐oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates ( 5a‐5f ). The molecular structure of selected isomers, 4b and 5c , was confirmed by X‐ray crystallography. Frontal chro‐matography with delivery from the edge was applied for the separation of the isomeric esters. The isomer ratio of the reaction products depended on the character of the substituents on the phenyl ring. The 1‐aryl‐7(1H)‐oxo‐carboxylates ( 4a‐4f ) were preferably when the phenyl ring contained H, 4‐CH₃, 4‐OCH₃ and 3,4‐Cl₂ substituents. Chloro substitution at either position 3 or 4 in the phenyl ring favored the formation of isomers 5a‐5f . The isomer ratios were confirmed both by ¹H NMR and chromatography. The reaction of the respective hydrobromides of 1‐aryl‐2‐aminoimidazoline‐2 with DEEM, in the presence of triethylamine, gave selectively 5(1H)‐oxo‐esters ( 5a‐5f ).     

Selectfluor-mediated mild oxidative halogenation and thiocyanation of 1-aryl-allenes with TMSX (X = Cl,Br, I,NCS) and NH4SCN

Presence of TMSX (X = Cl, Br, I) unleashes the oxidative character of Selectfluor and provides a mild dihalogenation method for 1-arylallenes. Preference for 2,3-addition was observed with TMSCl in MeCN irrespective of the nature of the substituent on the aryl moiety, whereas 1,2-addition was preferred in [BMIM][BF₄]. With TMSBr and TMSI only products corresponding to 2,3-addition were observed. Reactions carried out with TMSBr in IL solvents gave the corresponding monobromoalkenes as a major product along with the isomeric dibromo-alkenes. Reaction with NH₄SCN provided convenient access to dithiocyanate derivatives. The same products were formed via TMS-NCS/Selectfluor. Formation of common products via TMSNCS and NH₄SCN points to the formation and interplay of SCN⁺/NCS⁺ as incipient electrophiles.     

Rearrangements of organometallic compounds : X. The mechanism of 1,2-aryl migration in the Wittig rearrangement of α-metallated benzyl aryl ethers

The mechanism of 1,2-aryl shifts in the Wittig rearrangement of α-metallated benzyl aryl ethers has been investigated by a detailed examination of the behavior of the following ethers: benzyl phenyl ether, benzyl para-tert-butyl- and meta-tert-butyl-phenyl ethers, benzyl 2-bromo-4-tert-butylphenyl ether and dibenzo[b,d] pyran. The failure to trap any aldehyde intermediate, the ease of rearrangement for the pyran, the lack of evidence for an aryne intermediate with the benzyl butyl ethers and other circumstantial evidence have led to the proposal of an intramolecular pathway in which radical pairs are generated and then collapse to the isomeric carbinolate.     

Photochemical naphthylation at(α-carbon atom of carbonyl and its equivalences

The photostimulated reaction of halonaphthalene with a series of carbanions derived from,propionic acid derivatives in liquid ammonia led to the naphthylation at a-carbon of the carbanions inan isolated yield ranging from 25％ to 86％.In all cases,the dehalonaphthalenes were found to,be by-products and the reaction was inhibited by p-dinitrobenzere.An electron transfer from thecarbanion to the halonaphthalene followed by ejection of halogen led to naphtbyl radical,as predictedby comparing the LUMOs of the carbanions and the halonaphthalenes,was involved in the process.Absence of the alkylnaphthalene and 1,2-dinaphthylalkane in the products indicates the smoothelectron transfer between(Naph-Nu)~+ and Naph-X.C-vs.O-naphthylation is fully addressed interms of MNDO calculations and acid-base principle.     

Lithium Choreography: Intramolecular Arylations of Carbamate‐Stabilised Carbanions and Their Mechanisms Probed by In Situ IR Spectroscopy and DFT Calculations

Deprotonation of O‐allyl, O‐propargyl or O‐benzyl carbamates in the presence of a lithium counterion leads to carbamate‐stabilised organolithium compounds that may be quenched with electrophiles. We now report that when the allylic, propargylic or benzylic carbamate bears an N‐aryl substituent, an aryl migration takes place, leading to stereochemical inversion and C‐arylation of the carbamate α to oxygen. The aryl migration is an intramolecular S_NAr reaction, despite the lack of anion‐stabilising aryl substituents. Our in situ IR studies reveal a number of intermediates along the rearrangement pathway, including a “pre‐lithiation complex,” the deprotonated carbamate, the rearranged anion, and the final arylated carbamate. No evidence was obtained for a dearomatised intermediate during the aryl migration. DFT calculations predict that during the reaction the solvated Li cation moves from the carbanion centre, thus freeing its lone pair for nucleophilic attack on the remote phenyl ring. This charge separation leads to several alternative conformations. The one having Li⁺ bound to the carbamate oxygen gives rise to the lowest‐energy transition structure, and also leads to inversion of the configuration. In agreement with the IR studies, the DFT calculations fail to locate a dearomatised intermediate.     

1,6-Eliminationsreaktionen an Spirocoleonon; Charakterisierung der ersten Spiro[(methylcyclopropan)-phenanthren]-1,3-dion-Derivate

Preparation of the First Spiro[(methylcyclopropan)-phenanthrene]-1,3-dione Derivatives by 1,6-Elimination Reactions of Spirocoleons Spirocoleons, e.g. coleon J ( 1 ), on treatment with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) in aprotic solvents, undergo enolization followed by a rapid 1,6-elimination with formation of the hitherto unknown 2-methyl-spiro[cyclopropane-1,2′(1′H)-phenanthrene]-1′,3′(4′bH)-dione system, e.g. 3 . In protic solvents, base-catalyzed solvolysis of the spirocyclopropane predominates.     

Role of base in palladium-catalyzed arylation of carbanions

The arylation reaction of carbanions, derived from certain sulfones, cyanoacetic ester and malononitrile, with aryl bromides (using the catalytic system of Pd₂dba₃/3L, L=PPh₃, PtBu₃) as well as the reaction of the carbanions with one equivalent of 4-CF₃C₆H₄ Pd(PPh₃)₂Br has been studied. These reactions proceed smoothly provided that the base stronger than the initial carbanion is present in the reaction mixture. In the absence of the above type of base the reactions do not proceed at all. Taking that into account we have proposed a novel mechanism of palladium-catalyzed arylation of CH-acids. The main feature of this mechanism is the accelaration of the reductive elimination due to the deprotonation of the intermediate ArPdL₂CHXY. The correlation between the carbanion reactivity and the pK_a values for related CH-acids as well as the ligand effect are discussed in the framework of the proposed mechanism.     

Three-component coupling polymerization of bisallene,aryl dihalides,and nucleophiles via π-allylpalladium complex. II. Effect of nucleophiles on polymerization

A novel palladium-catalyzed three-component polycondensation of 1,2,10,11-dodecatetraene, 4,4′-diiodobiphenyl, and nucleophiles was carried out using various carbanions and amines as a nucleophilic part. The polymerization with various sodium diethyl malonates produced polymers in high yields. Particularly, no exo-double bond was detected in the polymers prepared from sodium diethyl malonates bearing substituents directly on the carbanion center. The ratios of E- and Z- isomeric units in the polymers were dependent on the structure of the nucleophiles used. Other carbanions with appropriate electron-withdrawing groups such as sulphones and ketones can be also used as a nucleophile for the present polycondensation. Within heteronucleophiles examined, cyclic amines were suitable to produce polymers in high yields. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1211–1218, 1997     

Absolute rate constants for water protonation of 1-(3-benzoylphenyl)alkyl carbanions

[reaction: see text] Efficient photodecarboxylation of (3-benzoylphenyl)alkanoic acids with formation of carbanions has enabled the determination of their protonation rate constants in water; the values obtained show that the reactivity toward protonation is determined by the size of the alkyl groups attached to the carbanion center.     

Comparative study of the reactivities of substituted 3-(benzoyl)benzyl carbanions in water and in DMSO

Benzyl-substituted carbanions produced by photodecarboxylation of ketoprofen derivatives have been examined in basic aqueous and DMSO solutions. Product studies, combined with kinetic measurements from laser flash photolysis, have allowed the determination of absolute rate constants for protonation and intra-S(N)2 reactions leading to five- and six-membered ring cyclizations; the former are significantly faster. Many of the well-known trends in carbanion reactivity are placed on an absolute rate basis; thus, intra-S(N)2 are favored in polar nonprotic solvents, and the effect is larger for the more hindered carbanion centers. Protonation by water is slightly dependent on the nature of the carbanion center and is approximately 400 times faster in nonhydroxylic solvents, compared with bulk water. As expected, the reactivity for halide leaving groups follows the usual order of decreasing bond strengths, i.e., I(-) > Br(-) > Cl(-).