Nucleophilic reaction with ylide

As well as the Bingel reaction and its modifications some more reactions that involve the addition-elimination mechanism have been discovered. 1,2-Methano-[60]fullerenes are obtainable in good yields by reaction with phosphorus- [44] or sulfur-ylides [45,46] or by fluorine-ion-mediated reaction with silylated nucleophiles [47]. The reaction with ylides requires stabilized sulfur or phosphorus ylides (Scheme 3.9). As well as representing a new route to l,2-methano[60]fullerenes, the synthesis of methanofullerenes with a formyl group at the bridgehead-carbon is possible. This formyl-group can be easily transformed into imines with various aromatic amines. 

CHMe, cyclopropylidene, and CMe2 to activated double bonds.1075 Similar reactions have been performed with phosphorus ylides, 076 with pyridinium ylides,1077 and with the compounds (PhS)3CLi and Me3Si(PhS)2CLi.1078 The reactions with ylides are of course nucleophilic addition. 

The Michael addition represents an extremely efficient synthetic method for achieving chain elongation by adding a three (or more) carbon fragment electrophile to a nucleophilic moiety. Notice that the typical Michael electrophiles (e.g. 90) are products of condensation of carbonyl compounds and can be easily formed via the aldol-like condensation, the Wittig reaction (with ylides like 81), the Perkin reaction, or the Mannich reaction (see below). 

In the synthesis of molecules without functional groups the application of the usual polar synthetic reactions may be cumbersome, since the final elimination of hetero atoms can be difficult. Two solutions for this problem have been given in the previous sections, namely alkylation with nucleophilic carbanions and alkenylation with ylides. Another direct approach is to combine radical synthons in a non-polar reaction. Carbon radicals are. however, inherently short-lived and tend to undergo complex secondary reactions. Escheirmoser s principle (p. 34f) again provides a way out. If one connects both carbon atoms via a metal atom which (i) forms and stabilizes the carbon radicals and (ii) can be easily eliminated, the intermolecular reaction is made intramolecular, and good yields may be obtained. 

In contrast reaction with aprotic nucleophiles, e.g. alkoxides, LiAlILt and sulfur ylides (Z ), yields amino acid derivatives (341), resulting from sp C—N bond scission. The third possible way of ring opening, namely at the C—C bond, has also been observed in certain cases, i.e. (342) -> (343) (67TL5033). 

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

With Af-acyl or Af-sulfonyl hydrazines as nucleophiles, Zincke salts serve as sources of iminopyridinium ylides and ylide precursors.Reaction of the nicotinamide-derived Zincke salt 8 with ethyl hydrazino urethane 42 provided salt 43, while the tosyl hydrazine gave ylide 44 (Scheme 8.4.14). ° Benzoyl hydrazines have also been used in reactions with Zincke salts under similar conditions.Af-amino-1,2,3,6-tetrahydropyridine derivatives such as 47 (Scheme 8.4.15), which showed antiinflammatory activity, are also accessible via this route, with borohydride reduction of the initially formed ylide 46. ... 

On treatment with a strong base such as sodium hydride or sodium amide, dimethyl sulfoxide yields a proton to form the methylsulfinyl carbanion (dimsyl ion), a strongly basic reagent. Reaction of dimsyl ion with triphenylalkylphosphonium halides provides a convenient route to ylides (see Chapter 11, Section III), and with triphenylmethane the reagent affords a high concentration of triphenylmethyl carbanion. Of immediate interest, however, is the nucleophilic reaction of dimsyl ion with aldehydes, ketones, and particularly esters (//). The reaction of dimsyl ion with nonenolizable ketones and... 

Finally, an intramolecular reaction of an oxygen nucleophile to give 2,5-dihy-drofuran derivatives 146 is shown in Scheme 2.37. Since the vinylaziridines were generated in situ by treatment of imines 143 with ylide 144, this ylide is formally acting as an equivalent of the 2,5-dihydrofuran anion [57]. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Sulfur-stabilized ylides underwent photodriven reaction with chromium alkoxy-carbenes to produce 2-acyl vinyl ethers as E/Z mixtures with the E isomer predominating (Table 22) [ 121-123]. The reaction is thought to proceed by nucleophilic attack of the ylide carbon at the chromium carbene carbon followed by elimination of (CO)5CrSMe2. The same reaction occurred thermally, but at a reduced rate. Sulfilimines underwent a similar addition/elimination process to produce imidates or their hydrolysis products (Table 23) [ 124,125]. Again the reaction also proceeded thermally but much more slowly. Less basic sulfilimines having acyl or sulfonyl groups on nitrogen failed to react. 

This reaction may be visualized as proceeding by nucleophilic attack of tervalent phosphorus at the carbonyl group to give an intermediate such as (15). The structure of (16) was deduced from the fact that it was hydrolysed to the known phosphine oxide (17). Methylenephosphoranes (phosphorus ylides) may also be converted into monophosphazenes by reaction with benzonitrile ... 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

Highly stabilized phosphorus ylides are prepared from acetylenic esters, a carbon-based nucleophile, and triphenylphosphine in aqueous media.40 In acetone-water (2 1) solvent, the reaction proceeds via the conjugate addition of triphenylphosphine to dialkyl acetylenedicarboxy-lates the resulting vinyl triphenylphosphonium salts undergo Michael addition reaction with a carbon-nucleophile to give the corresponding highly stabilized phosphorus ylides. 

The reaction of the same ylide 63 with dimethyl acetylenedicarboxylate (DMAD) in chloroform afforded the cyclazine 67, through aromatization of monoadduct 66 the azocine 69, which is formed through a second nucleophilic attack with ring expansion in the bis-adduct 68 and the pyrrolo derivative 71, which is formed by evolution of the bis-adduct 70 through a retro-Diels-Alder reaction (Scheme 3) <2001JOC1638>. 

The ylide obtained from (methyl)triphenylphosphonium bromide reacts with morpholine derivatives 597 to give phosphonium salts 598 which upon treatment with -butyllithium are converted to new ylides 599. In a reaction with aldehydes, ylides 599 form iV-(l,3-disubstituted allyl)-morpholines 602 (Scheme 94) <1996AQ138>. Another less common nucleophile that can be used for substitution of the benzotriazolyl moiety in Af-(a-aminoalkyl)benzotriazoles is an adduct of iV-benzylthiazolium salt to an aldehyde which reacts with compounds 597 to produce adducts 600. Under the reaction conditions, refluxing in acetonitrile, salts 600 decompose to liberate aminoketones 601 <1996H(42)273>. 

The first silicon-organophosphorus betaine with a thiolate center (15a) was synthesized by the reaction of stable silanethione (14) with trimethyl-methylenephosphorane (Scheme 8) and characterized by multinuclear NMR spectroscopy.14 Compound 15a is formed under kinetic control and is transformed, under the thermodynamically controlled conditions, into the silaacenaphthene salt (16). The processes presented in this scheme reflect the competition of the basicity and nucleophilicity of phosphorus ylides. Betaine 15b prepared from less nucleophilic and less basic ylide with phenyl substituents at the phosphorus atom is much less resistant toward retro-decomposition compared to the alkyl analog. Its equilibrium concentration does not exceed 6%. 

Aryl(trimethylsiloxy)carbenes. Acylsilanes (153) undergo a photoinduced C —> O silyl shift leading to aryl(trimethylsiloxy)carbenes (154).73,74 The carbenes 154 can be captured by alcohols to form acetals (157) 73 or by pyridine to give transient ylides (Scheme 29).75 LFP of 153 in TFE produced transient absorptions of the carbocations 155 which were characterized by their reactions with nucleophiles.76 The cations 155 are more reactive than ArPhCH+, but only by factors < 10. Comparison of 154 and 155 with Ar(RO)C and Ar(RO)CH+, respectively, would be of interest. Although LFP was applied to generate methoxy(phenyl)carbene and to monitor its reaction with alcohols,77 no attempt was made to detect the analogous carbocation. 

Relative rates of some prototypical carbenes, obtained by Stem-Volmer methods, are listed in Table 2. Although many of these carbenes have triplet ground states, reaction with nucleophiles Y occurs prior to spin equilibration. Most often, ylide formation with solvent molecules was analysed in terms of Eq. 3. The pyridine-ylide served as the probe for 154. 

Cyclodditions to Carbonyl Derivatives. Electrophilic transient carbenes are known to react with carbonyl derivatives through the oxygen lone pair to give carbonyl ylides 26.43 These 1,3-dipolar species are usually characterized by [3 + 2]-cycloaddition reactions or can even be isolated44 a small amount of the corresponding oxiranes is sometimes obtained.433,45 To date, no reaction of transient nucleophilic carbenes with carbonyl derivatives has been reported. 

Cyclodditions to Carbon-Heteroatom Triple Bonds. Transient electrophilic carbenes are known to react with nitriles to give transient46 or even stable nitrile ylides 30.47 No reaction of transient nucleophilic carbenes with nitriles has been reported. 

The mechanism sketched in Figure 3.18 implies that the starting complex L M has a free coordination site (or a readily replaceable ligand) and can act as an electrophile. Therefore reactions of this type will occur more readily with increasing nucleophilicity of the ylide and increasing electrophilicity of the metal complex... 

The reaction of chloromethyl aryl ethers with nucleophilic reagents has been described by Barber et al Thus, by reaction with thiourea, potassium thiocyanate, or sodium cyanide, there arc obtained aryloxyalkylisothiouronium salts, aryloxyalkyl thiocyanates, and aryloxyalkylacetonitriles, respectively. The reaction of chloromethyl aryl ethers with butyllithium leads to an aryloxycarbene which on reaction with olefins gives aryloxy-cyclopropanes. The ethers react with triphenylphosphine and a base to give phcnoxymethylene ylides which arc useful in con-... 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

Closely related with the synthesis of ylides from carbenes is the use of ylides as carbene transfer reagents (CTR), that is processes in which the ylide is cleaved homolytically, liberating the nucleophile and the carbene, which could remain both coordinated to the metal or not (Scheme 10). Diphosphirane (34) can be obtained from the diphosphene by reaction with sulfur ylide Me2S(0)=CH2, which behave as a carrier of the CH2 unit [95]. Recent work of Milstein et al. shows that sulfur ylides decompose in the presence of Rh derivatives with vacant coordination sites affording Rh(l)-carbene complexes [96, 97]. Complexes (35-37) can be obtained from... 

The attack of nucleophiles on unsaturated ligands or functional groups bonded to metallic centers, exemplified in Scheme 9 (reaction of metallic carbenes with phosphines or pyridines) or in Scheme 15 (Wittig reaction) can be extended to a wide variety of reagents. Two main groups of reactions can be considered (1) those in which the nucleophile is an ylide and (2) those in which the nucleophile is a phosphine (and less commonly other nucleophiles). Usually these reactions give metallated ylides (type III), that is, species in which the ylide substituents are metallic centers. 

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