Showing papers on "Nucleophile published in 1999"

Ligand-Accelerated Catalysis of the Ullmann Condensation: Application to Hole Conducting Triarylamines

Abstract: High-purity triarylamines find employment in xerographic photoreceptors where, as concentrated solid solutions in polymeric transport layers, they function as efficient hole conductors.1,2 Under the influence of an applied electric field, injected positive charge migrates through such layers by a hopping mechanism to create latent electrostatic images.3 This process occurs readily since triarylamines possess an easily accessible oxidation potential and on hole injection give up a nonbonding electron to generate amine cation radicals, the stable spin centers responsible for transport. Triarylamines are also important to a number of emerging technologies. Transport layers are equally fundamental to electroluminescent devices where, in essentially the reverse of electrophotography, electrons and holes are separately injected and transported to an emitting species where their recombination produces singlet excitons whose radiative decay results in visible light.4 They are also constituents of nonlinear optical chromophores useful in the design of integrated electrooptic switches and modulators.5 In each of these applications, achievement of an electronic grade purity level is required for optimal device performance. Thus, clean and efficient syntheses which can be readily scaled to multi-kilogram lot sizes are desirable. Despite their structural simplicity, synthetic protocols which satisfy these criteria are uncommon and the heightened importance of triarylamines has led to extensive recent research attention. The classic technique for the construction of triarylamines has been the venerable Ullmann condensation.6 As usually practiced, the reaction entails the condensation of a diphenylamine and an unactivated aryl halide with catalysis by some form of copper (metal, alloy, copper(I) or -(II) salt) in the presence of added base. The reaction is noted for its capricious nature and sensitivity to catalyst type. Strongly aggressive conditions involving high temperature and extended reaction times are generally needed to secure at best moderate yields. Although halide reduction and homocoupling often negatively impact yields, control of the substitution pattern of all three rings is afforded. In a variant, bis(arylation) of a substituted aniline with 2 equiv of an aromatic halide allows access, depending on reactants, to products in which two or perhaps all three of the aromatic ring are identically substituted. Yields tend to be substantially poorer in these cases. Attempts have been made to moderate the harshness of the reaction conditions. Frechet and Gauthier reported that crown ethers induce rate accelerations and improve yields in certain Ullmann condensations.7 The procedure, however, does not obviate the requirement for high temperature, and the long reaction times (15 h in the best case) make it unattractive for large scale industrial applications. Catalyst effects still persist, as is common when potassium carbonate is used as base, and the high cost of the crown would necessitate its recovery and reuse. An area of research showing rapid progress is the application of transition metal catalysis to the formation of the aromatic carbon-nitrogen bond. Palladiumcatalyzed aromatic amination reactions, as described by both Buchwald and Hartwig,8 have created interesting new possibilities. Aromatic amines with a wide structural variation have been successfully synthesized under exceptionally mild reaction conditions. It is as yet premature to judge whether this chemistry will supplant the Ullmann condensation as the robustness and economics of a method requiring noble metal catalysis in a large scale industrial application requires demonstration, particularly in the commodity chemicals arena.9 Background. Important information on the kinetics of amine Ullmann condensations is available. The reaction is zero order in amine with the rate-determining step being the loss of halide from the substrate with the reactivity order being I > Br > Cl . F.6a,10 Detailed kinetics have proven difficult to extract under the heterogeneous conditions normally employed. Paine, by studying a homogeneous but synthetically nonviable reaction surrogate, concluded that only copper(I) states actively participate as catalysts regardless of the oxidation level of the added copper. Additionally, despite the apparent heterogeneity of the reaction, the nucleophilic species is posited to be a soluble amine cuprate.11 Rate accelerations have been reported in the related, industrially important Ullmann condensation of phenols leading to diphenyl ethers. Careful work by Weingarten clearly demonstrated that impurities present in his reaction solvent, diglyme, imparted enhanced catalytic activity. Such activity was destroyed by LAH treatment † Tel. (905) 823-7091. Fax: (905) 822-7022. E-mail: Bruce.Goodbrand@crt.xerox.com. (1) Borsenberger, P. M.; Weiss, D. S. Organic Photoreceptors for Imaging Systems; Marcel Dekker: New York, 1993. (2) Law, K.-Y. Chem. Rev. 1993, 93, 449. (3) (a) Facci, J. S.; Stolka, M. Philos. Mag. B 1986, 54, 1. (b) Abkowitz, M.; Bassler, H.; Stolka, M. Philos. Mag. B 1991, 63, 201. (4) (a) Thelekkat, M.; Fink, R.; Haubner, F.; Schmidt, H.-W. Macromol. Symp. 1997, 125, 157-164. (b) Tamato, N.; Adachi, C.; Nagai, K. Chem. Mater. 1997, 9, 1077-1085. (c) Tanaka, H.; Tokito, S.; Taga, Y.; Okada A. Chem. Commun. 1996, 2175-2176. (d) Chen, C.; Shi, J.; Tang, C. W. Macromol. Symp. 1997, 125, 1-48. (e) Tsutsui, T. MRS Bull. 1997, 39. (f) Bellmann, E.; Shaheen, S.; Thayumanavan, S.; Barlow, S.; Grubbs, R.; Marder, S.; Kippelen, B.; Peyghambarian, N. Chem. Mater. 1998, 10, 1668-1676. (5) Miller, R. D.; Lee, V. Y.; Twieg, R. J. Chem. Commun. 1995, 245246. (6) For general reviews of Ullmann condensation chemistry, see: (a) Lindley, J. Tetrahedron 1984, 40, 1433-1456. (b) Fanta, P. E. Synthesis 1974, 1-21. (c) Bacon, R. G. R.; Hill, H. A. O. Q. Rev. 1965, 19, 95125. (7) Gauthier, S.; Frechet, J. M. J. Synthesis 1987, 383-385. (8) For leading references, see: (a) Hartwig, J. F. Angew. Chem., Int. Ed. Engl. 1998, 37, 2046-2067. (9) (a) Beller, M. Angew. Chem., Int. Ed. Engl. 1995, 34, 1316-1317. (b) Reaction modifications with a view to accommodating large scale work have recently been described, see: Wullner, G.; Jansch, H.; Kannenberg, S.; Schubert, F.; Boche, G. Chem. Commun. 1998, 15091510. (10) Weingarten, H. J. Org. Chem. 1964, 29, 977-978. (11) Paine, A. J. J. Am. Chem. Soc. 1987, 109, 1496-1502. 670 J. Org. Chem. 1999, 64, 670-674

N,N'-Bis(2,2-dimethylpropyl)benzimidazolin-2-ylidene: a stable nucleophilic carbene derived from benzimidazole.

Abstract: N,N'-Dialkylated benzimidazol-2-thiones I (R = CH2CMe3, Me) can be prepd. in a three-step procedure from o-phenylenediamine. Thione I (R = CH2CMe3) was reduced with sodium/potassium under desulfurization leading to carbene II. Compd. II is the first stable free carbene derived from benzimidazole. It exhibits the topol. of an unsatd. carbene, including a short C4-C5 bond. Its 13C NMR spectrum [d(C2) = 231.47] and selected structural parameters [angle N1-C2-N3 103.5(1) Deg and 104.2(1) Deg], however, correspond to those of satd. carbenes of the imidazolidin-2-ylidene type. The observation that II behaves like a satd. imidazolidin-2-ylidene is corroborated by the tendency of the sterically less bulky I (R = Me) to yield olefin III after redn. with Na/K. Carbene II can be coordinated to a W(CO)5 fragment yielding a complex which contains a nonplanar carbene ring.

Highly Enantio- and Diastereoselective Hetero-Diels-Alder Reactions Catalyzed by New Chiral Tridentate Chromium(III) Catalysts.

Abstract: Even moderately nucleophilic dienes react with simple aldehydes in the presence of a new CrIII catalyst in a hetero-Diels–Alder reaction [Eq. (1)]. Tetrahydropyranyl products with up to three stereogenic centers are generated in near-perfect diastereoselectivities and with greater than 90 % ee (99 % ee for the example shown). TBAF=tetrabutylammonium fluoride; TBS=tert-butyldimethylsilyl; TES=triethylsilyl.

Facile, Novel Methodology for the Synthesis of Spiro[pyrrolidin‐3,3′‐oxindoles]: Catalyzed Ring Expansion Reactions of Cyclopropanes by Aldimines

Abstract: The role of the bifunctional catalyst is decisive: The magnesium ion as Lewis acid and its nucleophilic iodide counterion contribute in synergy to the successful ring expansion of the cyclopropane 1 by aldimine 2 [Eq. (1)]. This reaction offers a novel route to spiro[pyrrolidin-3,3'-oxindoles] 3.

An Alkanesulfonamide “Safety-Catch” Linker for Solid-Phase Synthesis

Abstract: An alkanesulfonamide “safety-catch” linker has been developed for tethering carboxylic acids to support. Acylation of the sulfonamide support provides a support-bound N-acylsulfonamide that is stable to both basic and strongly nucleophilic reaction conditions. At the end of a solid-phase synthesis sequence, treatment with iodoacetonitrile provides N-cyanomethyl derivatives that can be cleaved by nucleophiles under mild reaction conditions to release the target compounds. Coupling conditions have been developed to load Boc- and Fmoc-amino acids to the alkanesulfonamide resin with high loading efficiencies and minimal racemization. A number of support-bound amino acids incorporating diverse side-chain functionality have been subjected to a short synthesis sequence, followed by iodoacetonitrile activation and nucleophilic displacement to provide dipeptide products. All 20 of the proteinogenic amino acids, when suitably protected, are compatible with the loading and activation steps. Finally, displacement wit...

Direct Oxidative Carbon−Carbon Bond Formation Using the “Cation Pool” Method. 1. Generation of Iminium Cation Pools and Their Reaction with Carbon Nucleophiles

Abstract: We have developed a method that involves the generation of a “cation pool” using low-temperature electrolysis, and then its reaction with nucleophiles under non-oxidative conditions. This one-pot method solves problems associated with conventional oxidative generation of cations and their in situ reaction with nucleophiles, and provides an efficient method for direct oxidative carbon−carbon bond formation. As an example of this method, generation of cation pools from carbamates by low-temperature electrolysis (−72 °C) and their reactions with carbon nucleophiles such as allylsilanes, enol silyl ethers, and enol acetates were examined and the desired products were obtained in good yields. Aromatic compounds and 1,3-dicarbonyl compounds can also be utilized as carbon nucleophiles. The present method was also applied to combinatorial parallel synthesis using a robotic synthesizer.

The chemistry of the metabolites of cyclophosphamide.

Abstract: This is primarily an overview of the spontaneous (non-enzymatic) chemistry of the metabolites of cyclophosphamide, viz., cis- and trans-4-hydroxycyclophosphamide, aldophosphamide (and its hydrate), iminophosphamide, phosphoramide mustard, acrolein, and chloroethylaziridine. A brief description of detoxification products obtained through enzyme catalyzed reactions appears. Included as the historical basis for the development of cyclophosphamide is the chemistry of nitrogen mustards. Among the topics covered are: perturbations to metabolite distributions and half-lives effected by buffer, structure, pH and nucleophiles; effects of pH on mechanism; alkylation versus P-N bond hydrolysis; the influence of nucleophiles on alkylation product distributions; the influence of substituents on alkylation rates; and preactivated forms of cyclophosphamide as metabolite precursors (4-hydroperoxycyclophosphamide and mafosfamide). A review with 66 references.

Recent advances in the enantioselective synthesis of beta-amino acids.

Abstract: The introductory section of this review presents some of the currently most compelling beta-amino acid targets, according to their structural types: alpha- and beta-aryl substituted, olefinic and alkynyl, alpha, alpha- and alpha,beta-disubstituted, cyclic and conformationally restricted, fluorine-containing, and phosphonic analogous beta-amino acids. The main section highlights some of the very new (1996-1998), promising methodology for the enantioselective synthesis of beta-amino acids, with especial emphasis on catalytic and enzymatic processes, as well as methods based on "chiral pool", self-regeneration of stereogenic centers , diastereoselective nucleophilic additions to prochiral double bonds, and enantioselective reactions in the presence of chiral additives.

High-yielding rotaxane synthesis with an anion template

Abstract: An electrophile caught like a mouse in a trap! An anionic stopper-wheel complex acts as a supramolecular nucleophile in an almost quantitative synthesis of a phenyl ether rotaxane. The electrophilic semiaxle has to thread through the macrocycle in order to contact the bulky phenolate group that is positioned on the other side, and probably tightly held in place by hydrogen bonds.

Electrophilic Fluorination-Nucleophilic Addition Reaction Mediated by Selectfluor: Mechanistic Studies and New Applications.

Abstract: The electrophilic fluorination-nucleophilic addition reaction with Selectfluor-type reagents upon glycals has been studied and optimized. This reaction leads to selective fluorination at the 2-position with concomitant nucleophilic addition to the anomeric center. To understand the stereochemical outcome of this process, a mechanistic study has led to the discovery that, in the fucose series, Selectfluor adds specifically in a syn manner, yielding a 1-[TEDA-CH2Cl]-2-fluoro saccharide that anomerizes slowly to a more stable intermediate. The anomeric α/β distribution was studied as a function of reactants and conditions, and it was found that a judicious choice of protective group strategy can improve the stereoselectivity of both fluorination and nucleophilic addition. Furthermore, a hypersensitive radical probe was used to probe the reaction, and no product characteristic of a radical process was isolated, suggesting that no single electron transfer occurs during the attack of the glycal on Selectfluor. The importance of solvent effect, Selectfluor counterion, and stepwise procedure has also been discussed. This study has brought an important improvement of yields and a broader range of allowed nucleophiles such as secondary alcohols of carbohydrates, amino acids, phosphates, or phosphonates. This optimized process was further applied to the modification of important bioactive molecules, including the synthesis of fluorinated daunomycin and oleandrin analogues and the oxidation of thioglycosides to the corresponding sulfoxides.

The Allyl Leaving Group Approach to Tricoordinate Silyl, Germyl, and Stannyl Cations

Abstract: A group 14 atom bonded to three mesityl groups (2,4,6-trimethylphenyl) and to one allyl group serves as a novel precursor to tricoordinate group 14 cations, the analogues of the carbocation. The double bond of the allyl group provides an accessible reaction site that is located beyond the ortho methyl groups. Reaction of various electrophiles with the double bond releases the allyl group and leads to formation of the group 14 cations. The mesityl groups then are of sufficient steric bulk to protect the tricoordinate metal center from attack by nucleophiles. This approach is used herein with silicon, germanium, and tin as the central atom. The 29Si chemical shift (δ 225) indicates full cationic character for the silicon system. The 119Sn chemical shift (δ 806) indicates less than full cationic character for the tin system. The positive charge for the germanium system has been assessed by examination of the aromatic 13C chemical shifts. These results provide the highest current cationic character for silyli...

Azide and Cyanide Displacements via Hypervalent Silicate Intermediates

Abstract: Hypervalent azido- and cyanosilicate derivatives, prepared in situ by the reaction of trimethylsilyl azide or trimethylsilyl cyanide, respectively, with tetrabutylammonium fluoride, are effective sources of nucleophilic azide or cyanide. Primary and secondary alkyl halides and sulfonates undergo rapid and efficient azide or cyanide displacement in the absence of phase transfer catalysts with the silicate derivatives. Application of these reagents to the stereoselective synthesis of glycosyl azide derivatives is reported.

General Syntheses of Optically Active α-Trifluoromethylated Amines via Ring-Opening Reactions of N-Benzyl-2-trifluoromethylaziridine

Abstract: Syntheses of optically active trifluoromethylated amines via ring-opening reactions of optically active N-benzyl-2-trifluoromethylaziridine were achieved. Proton-catalyzed ring-opening reactions of the 2-trifluoromethylaziridine proceeded very smoothly, while the compound was found to be inert toward nucleophiles; thus, the trifluoromethylaziridine itself cannot be ring-opened by nitrogen or carbon nucleophiles. The N-alkylated aziridinium ion of trifluoromethylaziridine was highly reactive to undergo smooth ring-opening by nitrogen and carbon nucleophiles.

C−H Insertion Reactions of Nucleophilic Carbenes

Abstract: Syntheses and characterizations are described for C−H insertion products derived from 1,3-dimesityldihydroimidazol-2-ylidene (1) with acetylene, acetonitrile, methyl phenyl sulfone, and chloroform. In the reaction with acetylene, both acetylenic H-atoms are reactive so that 1 : 1 and 2 : 1 adducts can be obtained. The acetylene and methyl-phenyl-sulfone adducts are structurally characterized by means of single-crystal X-ray structure determinations. The reactions of 1,3,4,5-tetramethylimidazolidin-2-ylidene (8) with chloroform or chlorodifluoromethane are shown to yield 2-(dihaloalkyl)imidazolium salts that arise from a failure of the intermediate 2-protioimidazolium salt to capture the initially formed halocarbanion.

Configurationally Stable Biaryl Analogues of 4-(Dimethylamino)pyridine: A Novel Class of Chiral Nucleophilic Catalysts

Abstract: A short synthetic approach toward a novel class of chiral nucleophilic catalysts, the dissymmetry of which stems from restricted rotation about an Ar−Ar bond, has been developed. The key steps of the synthesis include preparation of a nucleophilic 1-methyl-2-pyrrolino[3,2-c]pyridine core 16 by ortho-lithiation and creation of the biaryl axes via Suzuki cross-coupling reactions. Comparative HPLC studies of racemization for configurationally labile biaryls 31, 38, and 43 containing 1-methyl-2-pyrrolino[3,2-c]pyridine, 4-(dimethylamino)pyridine, and 4-(1-pyrrolidino)pyridine cores, respectively, have demonstrated that a pyrrolidino substituent ortho to the biaryl axis is optimal for slowing Ar−Ar rotation. Biaryls containing all three cores have been shown to retain DMAP-like catalytic activity in the acylation of a hindered alcohol. Biaryls 55 and 56, which are configurationally stable at ambient temperature, have also been prepared via modification of configurationally labile derivatives. Compounds 55 and ...

Nucleophilic ring opening of aziridines

Abstract: This account of research work on nucleophilic ring opening (NRO) of aziridines (Az's) demonstrates the broad synthetic scope of this reaction, inclusive secondary reactions, and it discusses the special mechanistic fundamentals and details as well as mechanistic variants. Formation of a C–C bond by NRO is the red thread in this report. A central mechanistic aspect is the quality of the leaving group in Az bases, aziridinium ions and activated Az's (acyl, sulfonyl; double activation). Factors controlling the regioselectivity of NRO are dealt with as well as the influence of the nitrogen pyramid. Competing reactions include carbonyl attack (acylated Az's) and electron transfer with cases of pseudo-NRO (multistep radical paths).

Palladium-Catalyzed, Asymmetric Hetero- and Carboannulation of Allenes Using Functionally-Substituted Aryl and Vinylic Iodides

Abstract: Aryl and vinylic iodides with a nucleophilic substituent in the ortho or allylic position, respectively, react with 1,2-dienes in the presence of a palladium catalyst and a chiral bisoxazoline ligand to afford five- and six-membered ring heterocycles and carbocycles in good yields and 46−88% enantiomeric excess. The generality of this process has been demonstrated by the use of nucleophilic substituents as varied as tosylamides, alcohols, phenols, carboxylic acids, and stabilized carbanions.

Organic Synthesis in Water/Carbon Dioxide Microemulsions

Abstract: Nucleophilic substitution reactions were performed in H2O/CO2 (w/c) microemulsions formed with an anionic perfluoropolyether ammonium carboxylate (PFPE COO-NH4+) surfactant. These reactions between hydrophilic nucleophiles and hydrophobic substrates were accomplished in an environmentally benign microemulsion without requiring toxic organic solvents or phase transfer catalysts. For the synthesis of benzyl bromide from benzyl chloride and KBr, the yield was an order of magnitude higher in w/c microemulsions versus conventional water-in-oil (w/o) microemulsions. Benzoyl chloride and p-nitrophenyl chloroformate were hydrolyzed in w/c microemulsions with rate constants an order of magnitude faster than those in w/o microemulsions.

Transferring iodine: more than a simple functional group exchange in organic synthesis

Abstract: Some synthetic features of the IPy2BF4 reagent are presented. Among others, its utility to promote unusual ‘carbon-carbon’ coupling processes will be discussed. Furthermore, the unique iodinating ability of this reagent towards aromatic and other unsaturated systems will be summarized. The rich chemistry of the carbon-iodine bond has made it a particularly rewarding synthetic tool of routine use for the purpose of functional group interconversion. Iodinated compounds are also credited as helpful diagnostic aids when the radioactive isotopes of the element are used [1]. Moreover, the growing presence and impact of hypervalent iodine compounds represents an additional source of interest in iodine containing reagents [2]. The bis(pyridinium) iodonium (I) tetrafluoroborate (IPy2BF4) is a stable and solid reagent, that acts as a mild source of iodonium ions towards different types of unsaturated compounds, as it will be shown in this article. Initial efforts were devoted to the development of a methodology that can be useful to accomplish vicinal iodofunctionalization of an alkene. Thus, when the reagent is mixed in CH2Cl2 with an alkene and a nucleophile the corresponding products derived from the addition of an iodine atom and the nucleophile across the double bond are formed, for instance MeOH for 1a, in Scheme 1 [3]. Usually, an acid is required to neutralize the supply of pyridine molecules from the iodinating reagent, avoiding the formation of adducts, such as 1b, that incorporate pyridine as a nucleophile through a competition process for the capture of the intermediate iodonium ion. In this regard, tetrafluoroboric acid is very useful due to the low nucleophilic character of the BF4 1 counteranion. When simply the reagent, the acid and the alkene are mixed at low temperature, a clean, regioand stereoselective iodofluorination takes place [3,4], as also depicted in Scheme 1 for the case of 1c. *Lecture presented at the 5th International Conference on Heteroatom Chemistry (ICHAC-5), London, Ontario, Canada, 5–10 July 1998, pp. 369–512. Scheme 1 Addition is the usual outcome of the reaction of IPy2BF4 with alkenes. However, starting from vinylsilanes an easy substitution process occurs, resulting in a very efficient and simple procedure for the iodo-silicon exchange from E 2a, and Z 2b monosubstituted trimethylsilylalkenes, giving rise stereospecifically to the formation of compounds 3a and 3b, respectively (Scheme 2) [5]. Otherwise, this is known to be an elusive transformation. Interestingly, the reagent is also an efficient iodinating agent promoting addition reactions of alcohols to the same alkenylsilanes furnishing compounds 4 (Scheme 3), by simply running the transformation in the presence of the corresponding alcohol as cosolvent [6]. The resulting adducts can be dehydroiodinated with the tertiary base 1,8-diazobicyclo[5.4.0]undec-7-ene (DBU), giving the stereochemically well-defined trisubstituted enol ethers, in a stereospecific manner. The same sequence, but requiring t-butyldimethylsilyl derivatives, gives aryl-substituted enol ethers. Adducts 6a and 6b are stereospecifically formed [6], now by a syn addition (Scheme 4). It was reported that the IPy2BF4 reagent promotes electrophilic addition of iodine and nucleophiles to alkynes in a similar way, a process where the stereochemistry of the resulting alkenyliodides relies on the structure of both the alkyne and the nucleophile [7]. These functionalization reactions can be equally achieved using heteroatom-substituted alkynes as iodonium acceptors. The regiochemistry of the products formed upon addition to these substrates nicely illustrates the electronic tuning of the process (Fig. 1) [8]. Thus, 1-iodoalkynes are transformed into 2-functionalized-1,1-diiodoalkenes, whereas for alkynylsulfides the regiochemistry switches, yielding the corresponding 2-iodovinylsulfides [8b]. 432 J. BARLUENGA q 1999 IUPAC, Pure Appl. Chem. 71, 431–436 Scheme 2

Concerted Organic and Bio-Organic Mechanisms

Abstract: DEFINITIONS Origin of the Concept Mechanism and its Description The Definition of Concertedness Bond Order and Coupling Potential energy or Free Energy? Classes of Concerted Reactions TECHNIQUES Detection of Intermediates Exclusion of Stepwise Mechanisms Transition State Structure PROTON TRANSFER Proton Transfer between Bases Proton Transfer and Displacement Reactions at Saturated Carbon Centers Proton Transfer and Double Bond Changes Non-Perfect Synchronization NUCLEOPHILIC DISPLACEMENTS AT UNSATURATED CARBON Displacements at the Carbonyl Group Vinyl Group Transfer Nucleophilic Aromatic Substitution Nucleophilic Substitution at Diagonal Carbon NUCLEOPHILIC DISPLACEMENTS AT SATURATED CARBON Mechanisms The Carbenium Ion Ion-Pair Intermediates The Concerted Mechanism DISPLACEMENT REACTIONS AT HETEROATOMS Electophilic Displacement at Hydrogen Nucleophilic Displacement at Saturated Nitrogen Nucleophilc Displacement at Silicon Nuleophilic Displacement at Phosphorus(V) Displacement at Sulfur CYCLIC REACTIONS Intermediates Clock Reactions Energetic Relationships Nascent Products Isotope Effects Theoretical Methods ENZYME REACTIONS Proton Transfer Theoretical Calculations Isotopes Carbohydrases Aspartyl Proteases Hydride Transfer Amine Oxidases Carbon-Carbon Bond Formation Clocks Cyclic Reactions

Catalytic enantioselective formation of aziridines from α-imino esters

Abstract: A new catalytic enantioselective aziridination reaction of α-imino esters with diazo compounds catalyzed by chiral Lewis acid complexes is presented. A series of N-substituted α-imino esters has been tested as substrates for the aziridination reaction using trimethylsilyldiazomethane as the carbenoid fragment donor catalyzed by various chiral complexes. Both chiral BINAP and bisoxazoline† ligands, in combination with copper(I) salts in particular can catalyze the aziridination reaction leading to the cis-aziridine with up to 72% ee applying BINAP–copper(I) complexes as the catalyst, while the bisoxazoline–copper(I) catalysts give an aziridination reaction with lower diastereoselectivity, however, the trans-aziridine was formed in 69% ee. The influence of diazo compounds, Lewis acids, chiral ligands, solvents and counterion on the reaction course has been investigated and a mechanism for the reaction is discussed in which the α-imino ester coordinates to the chiral catalyst. For trimethylsilyldiazomethane, nucleophilic attack on the coordinated α-imino ester probably takes place in the case of copper(I) as the Lewis acid, while for ethyl diazoacetate the reaction course is dependent on the Lewis acid; for silver(I) a nucleophilic attack is probably also operating, while a metal–carbene intermediate is involved when copper(I) is used.