Ylides, pyridine

Further studies were carried out with halocarbene amides 34 and 357 Although again no direct spectroscopic signatures for specifically solvated carbenes were found, compelling evidence for such solvation was obtained with a combination of laser flash photolysis (LFP) with UV-VIS detection via pyridine ylides, TRIR spectroscopy, density functional theory (DFT) calculations, and kinetic simulations. Carbenes 34 and 35 were generated by photolysis of indan-based precursors (Scheme 4.7) and were directly observed by TRIR spectroscopy in Freon-113 at 1635 and 1650 cm , respectively. The addition of small amounts of dioxane or THF significantly retarded the rate of biomolecular reaction with both pyridine and TME in Freon-113. Also, the addition of dioxane increased the observed lifetime of carbene 34 in Freon-113. These are both unprecedented observations. 

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. 

Although we are not specifically concerned here with kpp and the kinedcs of carbene-pyridine ylide formation, we note that the magnitude of is directly related to the structure and reactivity of the carbene. fcpyr ranges from 105 M s-1 for ambiphilic alkoxycarbenes to 109-10I° M-1 s 1 for electrophilic halocarbenes or alkylcarbenes. Very nucleophilic carbenes (MeOCOMe) do not react with pyridine.13... 

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... 

One can correct the observed distribution of 1,2-C and 1,2-H products so as to reflect only the carbenic pathway.28 The corrected 1,2-C/1,2-H ratio (4.8), coupled with a pyridine ylide absolute rate constant for overall carbene rearrangement (kc + % = 6.8 x 107 s 1), gives the partitioned rate constants kc = 5.6 x 107 s 1 and ifeH = 1.2 x 107 s-1.28 The dominance of 1,2-C over 1,2-H in this system will be discussed below. 

In pentane, the distribution of 1,3-insertion product 25 to 1,2-Me shift product 26 is 91 9. Upon addition of 2-methyl-1-butene, the yield of 25 smoothly decreases (to 19% with 4 M alkene), but the yield of 26 is unaffected 1 Moreover, correlation of addn/l,3-CH insertion (to 25) for 18 is nicely linear. The simplest interpretation is that 25 comes directly from carbene 18, whereas the 1,2-Me shift product 26 comes from the excited diazirine.27 Interestingly, thermolysis of 24 at 79°C produces 90% of 25 and 10% of 26, but now the yields of both products smoothly decrease in the presence of an alkene. In thermolysis the (electronically) excited diazirine is unavailable, both 25 and 26 stem from the carbene, and their formation is suppressed by the alkene s interception of the carbene. A pyridine ylide kinetic study gave the 1,3-CH insertion rate constant (18 - 25) as 9.3 x 10s s"1.27-47... 

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... 

Despite its fleetingness, 78 has been captured by CO in a matrix at 10 K, affording low yields of ketene." Modarelli and Platz were unable to observe the formation of a pyridine ylide upon LFP generation of 78 in pyridine/pentane at —40°C. However, with perdeuterated methylcarbene (78- 4) a weak pyridine ylide signal was detected, and the rate constant of the 1,2-D shift could be estimated as ito 2 x 109 s-1 (r 0.5 ns) using a Stem-Volmer analysis (see Eqs. 3-6 in Section II).89 The activation energy for this 1,2-D shift was estimated at 2.3 kcal/mol, assuming A 1011 s-1.89 However, it seems likely that both 2sa and A are somewhat lower, with A 108 to 109 s (AS = —17 e.u.).89... 

Pyridine ylide/LFP studies of 83-85 in pentane or isooctane afforded carbene lifetimes of 21-24 ns (k 4 to 5 x 107 s 1), similar to the lifetime of dimethylcarbene under these conditions. Unfortunately, these lifetimes are limited by reactions with the hydrocarbon solvents the lifetime of 83 is 1.5 times longer in cyclohexane-d12 than in cyclohexane. The observation that the lifetimes of 55-CI ( 1000 ns) and 55-F (—7000 ns) are considerably longer than those of 83 and 84 could reflect the superior stabilization provided by the halogen spectator substituents of 55, but this conclusion is tentative in the absence of definitive intramolecularly controlled lifetimes for 83-85. 

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 pyridine ylide of la is the parent compound of the Dimroth-Reichardt betaine dyes used to probe solvent polarity.71,72 These dyes show a very pronounced solvatochromism, and the shifts of the absorption maxima as a function of the solvent polarity has been used to establish the quantitative ET30 scale. 

The reaction of carbenes 1, generated either thermally or photochemically from the corresponding quinone diazides 2, with pyridine results in the formation of the deeply colored betaines which can be isolated in substance from the reaction mixture.73,62 This alternative synthesis of the betaines opens a general route to pyridine ylides unsubstituted at the pyridine ring. 

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. 

Ab initio and RRKM calculations indicate that the reactions of C, CH, and (H2C ) with acetylene occur with no barrier." Laser flash photolysis of the cyclopropanes (69) and (70) was used to generate the corresponding dihalocarbenes. The absolute rate constant for the formation of a pyridine ylide from Br2C was (4-11) x 10 lmoP s. The rates of additions of these carbenes to alkenes were measured by competition with pyridine ylide formation and the reactivity of BrClC was found to resemble that of Br2C rather than CI2C . 

Previous studies of the photochemistry of alkylchlorodiazirines have shown that the yield of trappable carbene is sensitive to the alkylcarbene structure. A laser flash photolysis study of phenanthridenes (91), precursors of alkylchlorocarbenes, in the presence of pyridine, has ruled out the intermediacy of a carbene-pyridine complex which partitions between pyridine-ylide formation and [1,2]-H shift. ... 

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. 

All this is not to say that dialkylcarbenes are incapable of the reactions formerly attributed to them exclusively. They often—usually—are able to do the reactions, even in cases in which diazo compound chemistry pre-empts their doing so. For example, homocubylidenes (65) are not the first-formed intermediates from the diazohomocubane precursor (66). The bridgehead alkenes, homocubenes (67) are. However, it was possible to use a complex kinetic analysis involving both the pyridine ylide technique and the alternative hydrocarbon precursor 68 to show that in the parent system the two reactive intermediates 65 and 67 are in... 

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). 

It is known that irradiation of perfluorophenyl azide in the presence of diethylamine results in the formation of hydrazine along with some other products. LFP of azides 16f, 16g demonstrates that in the presence of amines (piperidine and morpholine) the decay of the aryinitrene absorption (Figure 17, Spectrum 1) is accompanied by formation of the transient absorption with maximum at 320 nm (Figure 17, Spectrum 2). Unlike the adduct of singlet aryinitrene with pyridine (ylide 22e), this intermediate is unstable and its lifetime is about 2.5 ps. The product of its transformations absorbs slightly in the near-UV region (Figure 17, Spectrum 3), which is typical of hydrazines (24). 

A situation in which the pyridine nitrogen is not strictly the reaction site, but where the inductive stabilization of negative charge by the azonium site is the key role leading to reactivity is that of pyridine ylide formation, by deprotonation of the 2- and 6-positions of 3-substituted 1-methylpyridinium ions in D20 buffer solution catalyzed by OD. A reasonable correlation is produced using ox (p = 8.9) for the reactivity of... 

Since their introduction in I960,88 pyridine ylides have become increasingly popular probes into the dynamics of carbenes which lack chromophores.89 94 The combination of high reactivity, favorable spec-... 

In the presence of pyridine, photolysis of benzocyclobutene-l,2-dione (196) leads to the formation of pyridine ylide (197), and this is thought to arise by reaction with bisketene formed from the substrate dione rather than from an oxacarbene (198). 3-(2-Hydroxy-4-methoxyphenyl)-4-phenyl-2(5H)-fura-none, one of the photoproducts of 6-methoxybenzofuran-2,3-dione and styrene, has now been synthesised. ... 

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