Pyridine ylide method

The pyridine ylide method also allows determination of the rate constants for the intermolecular reactions of carbenes with alkenes, alcohols, or other carbene... 

The pyridine ylide method depends on the effective trapping of the carbene by pyridine. At high pyridine concentrations every carbene produced by the laser pulse will be trapped as ylide, and the ylide s absorbance (Ay) will saturate or reach a plateau (A °). The magnitude of A ° will vary with carbene structure it will decrease with both the increasing ease of carbene rearrangement and the intervention of RIES during carbene generation.3... 

When the diazirine was decomposed thermally, avoiding its electronically excited state, the yield of fragmentation products dropped to 1-2%. Further analysis revealed that, under photolytic conditions, cyclobutenes 27 and 28 were formed from both the carbene (63%) and directly from the excited diazirine (17%) fragmentation accounted for the remainder of the material balance. LFP studies by the pyridine ylide method gave rate constants for 19 —> 27 (1.3 x 106 s-1) and 19 — 28 (2.5 x 105 s-1), with the 5-fold preference for CH2 migration to 27 over CMe2 migration to 28 attributed to differential steric effects.45... 

Carbene 103 undergoes 1,3-CH insertion to nortricyclene (105), but this reaction is either too rapid for LFP measurement by the pyridine ylide method (r <0.1 ns), or the insertion occurs by RIES of the precursor 2-norbomyldiazirine. Theoretically, a short lifetime is expected for 103 AG for the carbene insertion into the 6-endo-CU bond (103 — 105) is computed at 5.2 kcal/mol, about 6.7 kcal/mol less than the (unobserved) exo- 1,2-H shift to norbomene.16... 

C-C3H5 = cyclopropyl. m By pyridine ylide method. n By direct observation. 

The lifetime of formylcarbene was determined by transient absorption and grating spectroscopies.39 Photolysis of formyldiazomethane produces formylcarbene which can isomerize, kr, to ketene or react with pyridine (Scheme 4). Using the pyridine ylide method, the lifetime of singlet formylcarbene was estimated to be 150-730 ps in CH2CI2. This is in reasonable agreement with the lifetime of 900 ps determined by transient grating spectroscopy. 

Alkylcarbenes generally lack useful UV signals for LFP studies, but they can be indirectly visualized by the pyridine ylide method in which their intramolecular reactions compete kinetically with capture of the carbene by added pyridine. 

One of the most interesting products obtained from the capture of singlet nitrene 16e is ylide 22e produced by photolysis of 15e in pyridine (Scheme 4). Ylide 22e has a very intense absorption band with maximum absorption at 390 nm. The pyridine-ylide method was successfully used by our group to probe the dynamics of the fluoro-substituted singlet arylnitrenes - " -" ... 

Marcinek and Platz used the pyridine-ylide method to measure absolute rate constants of reactions of two para-substituted perfluorophenylnitrenes (16h, 16j) with pyridine, amines, isoprene. 2,3-dimethyl-2-butene and other quenchers (Table 11). 

In summary, the pyridine ylide method has told us quite a lot about 1,2-hydrogen migration reactions of invisible carbenes. We learned that simple aUcyl and dialkyl carbenes are true intermediates with nanosecond lifetimes. The pyridine ylide method revealed that the rate of rearrangement of alkylcarbenes are influenced by the cationic stabilizing power of X k. increases as X = FI < CH ... 

Spectroscopically invisible carbenes can be monitored by the ylide method .92 Here, the carbene reacts with a nucleophile Y to form a strongly absorbing and long-lived ylide, competitively with all other routes of decay. Although pyridine (Py) stands out as the most popular probe, nitriles and thiones have also been used. In the presence of an additional quencher, the observed pseudo-first-order rate constant for ylide formation is given by Eq. 2.92,93 A plot of obs vs. [Q] at constant [Y ] will provide kq. With Q = HX, complications can arise from protonation of Y and/or the derived ylides. The available data indicate that alcohols are compatible with the pyridine-ylide probe technique. 

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. 

In the 1988-1999 period, almost all absolute kinetic studies of carbenic reactions employed LFP with UV detection. Carbenes that contain a UV chromophore (e.g., PhCCl) are easily observed, and their decay kinetics during reaction can be readily followed by LFP.11 However, alkyl, alkylhalo, and alkylacyloxycarbenes are generally transparent in the most useful UV region. To follow their kinetics, Jackson et al. made use of the ylide method, 12 in which the laser-generated carbene (2) is competitively captured by (e.g.) pyridine, forming a chromophoric ylide (3, cf. Scheme 1). The observed pseudo first order rate constants (kobs) for the growth of ylide 3 at various concentrations of pyridine are monitored by UV spectroscopy, and obey Eq. 1. 

Pyridinium ylide is considered to be the adduct car-bene to the lone pair of nitrogen in pyridine. The validity of this assumption was confirmed by Tozume et al. [12J. They obtained pyridinium bis-(methoxycarbonyl) meth-ylide by the photolysis of dimethyl diazomalonate in pyridine. Matsuyama et al. [13] reported that the pyridinium ylide was produced quantitatively by the transylidalion of sulfonium ylide with pyridine in the presence of some sulfides. However, in their method it was not easy to separate the end products. Kondo and his coworkers [14] noticed that this disadvantage was overcome by the use of carbon disulfide as a catalyst. Therefore, they used this reaction to prepare poly[4-vinylpyridinium bis-(methoxycarbonyl) methylide (Scheme 12) by stirring a solution of poly(4-vinylpyridine), methylphenylsulfo-nium bis-(methoxycarbonyl)methylide, and carbon disulfide in chloroform for 2 days at room temperature. 

A useful method for the synthesis of 1-unsubstituted 2-arylindolizines is provided by the 1,5-dipolar cyclization of pyridinium ylides derived from 181, in the presence of the oxidant tetrakis(pyridine)cobalt(ll) dichromate (TPCD), which oxidizes the intermediate dihydroindolizine 182 (Scheme 43). The study demonstrated that the presence of an aryl group on the double bond was necessary for the reaction to occur. 

Because of the presence of a lone pair and a vacant orbital, singlet carbenes are supposed to be able to react with both Lewis bases and acids. Transient electrophilic carbenes are known to react with Lewis bases to give normal ylides (Scheme 8.19). For example, carbene-pyridine adducts have been spectroscopically characterized and used as a proof for the formation of carbenes,and the reaction of transient dihalogenocarbenes with phosphines is even a preparative method for C-dihalogeno phosphorus ylides. Little is known about the reactivity of transient carbenes with Lewis acids. 

Reaction with acetylenic dipolarophiles represents an efficient method for the preparation of 2,5-dihydrothiophenes. These products can be either isolated or directly converted to thiophene derivatives by dehydration procedures. The most frequently used dipolarophile is dimethyl acetylenedicarboxylate (DMAD), which easily combines with thiocarbonyl ylides generated by the extrusion of nitrogen from 2,5-dihydro-1,3,4-thiadiazoles (8,25,28,36,41,92,94,152). Other methods involve the desilylation (31,53,129) protocol as well as the reaction with 1,3-dithiolium-4-olates and l,3-thiazolium-4-olates (153-158). Cycloaddition of (S)-methylides formed by the N2-extrusion or desilylation method leads to stable 2,5-dihydrothiophenes of type 98 and 99. In contrast, bicyclic cycloadducts of type 100 usually decompose to give thiophene (101) or pyridine derivatives (102) (Scheme 5.37). 

The intrinsic acidity of dimethylhalonium ions has been determined, both by theoretical methods and by gas-phase reactions of the isolated ions with pyridine bases.135 The calculated geometry of the dimethylhalonium ions shows a bent structure with the C-X-C angle decreasing in the order Cl > Br > I. Thermochemical calculations for the reaction of the dimethylhalonium ions with pyridine, 2,6-dimethylpyridine, and 2,6-di-r-butylpyridinc indicated that proton transfer, with the formation of the dimethylhalonium ylide, is endothermic, whereas methyl transfer, with formation of methyl halide, is exothermic. The endothermicities for proton transfer are, nevertheless,... 

One of the oldest and most popular methods for oxidizing activated halides is the three-step KrShnke oxidation. The individual steps are (i) quatemization of the halide with pyridine (ii) deprotonadon in base and reaction of the resulting pyridinium ylide with AfJV-dimethyl-4-nitrosoaniline and (iii) acid hydrolysis of the nitrone to the carbonyl compound (Scheme S). 

The oxidation of alkyl halides to carbonyl compounds with pyridine or 2-picoline N-oxide is a popular and general method, applicable even to unactivated substrates. The reaction may be performed in two ways. In the first, the halide is heated with the N-oxide in the presence of a base such as sodium hydrogen carbonate. In the second, the intermediate N-alkoxypyridinium salt is isolated before base treatment. The reaction has been shown by labeling to proceed via the pyridinium ylide, or, in the case of picoline N-oxide, via the anhydrobase (Scheme 8). Some typicd examples are shown in equations (23)-(25). ... 

The formation of bonds c and b can take a couple of forms, either a Darzens-type approach (i.e., addition of a nucleophile bearing a leaving group) or addition of a carbene. Both of these routes have been used in the synthesis of fused-ring aziridines as well as monocyclic aziridines. The addition of a carbene or nucleophile such as an ylide to an imine can provide a nice route to fused-ring aziridines. The necessary cyclic imines are sometimes more readily obtained and used than the acyclic imines. These methods have largely been used on pyridine and quinoline derivatives. 

Azomethine ylides of pyridine, quinoline, isoquinoline, and related nitrogen heterocycles undergo [3 -1- 2] cycloaddition with a variety of dipolarophiles leading to fused heterocycles <73S469>. This method has been extended to the use of a phosphaalkyne as dipolarophile. 

H-D exchange via an electrophilic substitution process, such as will operate for benzene, does not take place with pyridine. A special mechanism allows selective exchange at the two a-positions in DCI-D2O, or even in water at 200 °C, the key species being an ylide formed by 2/6-deprotonation of the 1//-pyridinium cation (see also 8.11). Efficient exchange at aU positions can be achieved at 110 °C in D2O in the presence of hydrogen and paUadium-on-carbon (a method which also works for other heterocycles, including indoles). ... 

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