Diazirines rearrangement

An especially strict partition between carbene and excited state diazirine rearrangements occurs in the photolysis of r-butylchlorodiazirine, 24 Eq. 14.27... 

Recently, diazirine rearrangement in the excited state (RIES) that mimics the result of cyclopropylcarbene fragmentation has been postulated. For examples, see (a) Ref. 128d,e (b) Thamattoor, D.M., Jones Jr., M., Pan, W. and Shevlin, P.B. (1996). Tetrahedron Lett. 37, 8333-8336... 

Methylvinyldiazirine (199) rearranges at room temperature in the course of some days. Formation of the linear isomer is followed by electrocyclic ring closure to give 3-methyl-pyrazole. The linear diazo compound could be trapped by its reaction with acids to form esters, while the starting diazirine (199) is inert towards acids (B-71MI50801). 

Diazirine, fluoromethoxy-nitrogen extrusion, 7, 224 Diazirine, methylvinyl-rearrangement, 7, 221 Diazirines addition reactions to Grignard compounds, 7, 2 0 as carbene precursors, 7, 236 IR spectra, 7, 203 microwave spectrum, 7, 199 molecular spectra, 7, 202-204 nitrogen extrusion, 7, 223 NMR, 7, 202 photoconversion to diazoalkanes, 7, 234 photoisomerization, 7, 221 photolysis, 7, 225-227 quantum chemical investigations, 7, 197 reactions... 

Correlation diagrams include the product orbitals while perturbation approaches require knowledge of the empty orbitals of the reactant. However, the occupied molecular orbitals of diazirine (II), compared with those of cyclopropene (I), do seem to give some indication of a preferred thermal decomposition of (II) compared with the rearrangement of (I). Moreover these molecular orbitals are a typical illustration of the localization obtained in the presence of an electronegativity perturbation. 

Photolysis of diazirine 75 in N2 at 9 K produced carbene 76, whose IR and UV/Vis spectra fit predictions by DFT calculations. The IR spectra were most consistent with a carbene conformation with Cl aligned 90° to the adjacent C-CH bond. The carbene was found, by IR spectroscopy, to rearrange to chloroadamantene 77 slowly at 9 K in the dark. The rate of rearrangement was somewhat faster in Ar matrices at 9 K or at higher temperatures in N2. 

Photoelimination of nitrogen from diazirines, for example, proceeds via carbene intermediates. 3-tert-Butyldiazirine (395) is converted into the cyclopropane 396 and the alkene 397 with the formation of the carbene insertion product being favored from the singlet state.328 3-Cyclopropyl-3-chlorodiazirine (398) has similarly been converted to the carbene 399 which undergoes both rearrangement to l-chlorocyclobutene(400)329 and addition... 

Some diazirines, particularly the 3-trifluoromethyl-3-aryldiazirines, can rearrange upon photolysis to a linear diazo derivative, similar in structure to the photosensitive end of the crosslinker PNP-DTP (Chapter 5, Section 3.12). These isomerized products themselves can be photolyzed to the reactive carbene. 

The photolysis of cyclic diazo ketones in hydroxylic solvents leads to ring contracted carboxylic acid derivatives via this ketocarbene -> ketene rearrangement. Examples of such reactions are given in (2.24)239) and (2.25) 240). In this last example a photoequilibrium between the diazo ketone and its valence isomer, a diazirine, has been observed, both products then eliminating nitrogen to afford the cyclobutane carboxylic acid. 

Knowledge of the intramolecular product distribution may allow for the partitioning of k between competitive intramolecular reactions, but one must be certain that noncarbenic routes to the products do not compete with the carbenic pathways. In particular, we must be concerned with the possible intervention of RIES (cf. Section m.C), especially when diazirines or diazoalkanes are the carbene precursors. Again, corrections for RIES can be made to quantitate the carbenic routes see, for example, the discussion of the cyclobutylhalocarbene rearrangements (Section m.C.1). 

Additional evidence for a second intermediate in supposed carbene reactions comes from numerous studies.17-29 In the earliest experimental approach, the carbene precursor, frequently a diazirine, was photolyzed in the presence of increasing quantities of an alkene, which trapped the carbene with the formation of a cyclopropane (5 in Scheme 1). If carbene 2 were the sole product-forming intermediate, as depicted in Scheme 1, then the ratio of its alkene addition product (5) to its 1,2-H shift rearrangement product (4) would vary linearly with alkene concentration Eq. 9. 

The second intermediate s identity has been debated since the mid-1980s. In 1984, Liu and Tomioka suggested that it was a carbene-alkenc complex (CAC).17 Similar complexes had been previously postulated to rationalize the negative activation energies observed in certain carbene-alkene addition reactions.11,30 A second intermediate is not limited to the CAC, however. In fact any other intermediate, in addition to the carbene, will satisfy the kinetic observations i.e., that a correlation of addn/rearr vs. [alkene] is curved, whereas the double reciprocal plot is linear.31 Proposed second intermediates include the CAC,17 an excited carbene,31 a diazo compound,23 or an excited diazirine.22,26 We will consider the last three proposals collectively below as rearrangements in the excited state (RIES). 

Although the RIES mechanism of Scheme 3 fits the overall kinetic results, and is strongly supported by spectroscopic and chemical evidence presented below, there are loose ends . For example, k /k, the Y-intercept of Eq. 13, gives the partition between rearrangement of the excited diazirine (1 ) and its loss of nitrogen to carbene 2. It is difficult to see why this should depend on alkene identity, yet small dependences have been observed.19,33-37 The behavior can be understood in terms of the CAC mechanism (Scheme 2, Eq. 11), where the Y-intercept is dependent on the rate of rearrangement of the CAC. On the other hand, there are reports that the Y-intercept does not vary in experiments with benzylchlorocarbene and (e.g.) 1-hexene, a-chloroacrylonitrile, or TME.23... 

The Y-intercept ( 3 /k Eq. 13) of the reciprocal correlation for the photolysis of diazirine 21-C1 in TME was 2.18, which translated into a 68% incursion of diazirine excited state in the genesis of the rearrangement products, 22-C1 and 23-C1 carbene 17-C1 only accounted for 32% of these products.28 A similar conclusion followed from the ratio of rearr/addn (68 32) at a high concentration (6.7 M) of TME in pentane, where carbene 17-C1 was almost completely diverted to the cyclopropane, and 22 and 23 were exclusively derived from the excited diazirine.28... 

If Scheme 2 accurately represented the PhCH2CCl chemistry, curvature in the addn/rearr vs. [alkene] correlation would persist when the carbene was generated from 37. The absence of curvature in this case counts against Scheme 2 (and the CAC mechanism), but accords with the RIES mechanism, Scheme 3. Elimination of the diazirine precursor eliminates the diazirine excited state. From 37, both cyclopropane formation and 1,2-H rearrangement proceed from a single (carbene) intermediate, and addn/rearr vs. [alkene] is linear.25... 

Clearly, rearrangements do occur in the excited states of diazirine and diazo carbene precursors. Kinetic studies of carbenic rearrangements need to consider the possible intervention of RIES when absolute rate constants are partitioned between competitive rearrangement pathways on the basis of product distributions.28... 

Although the carbenes are generated by diazirine photolysis, RIES is an unlikely complication because the alkylacetoxycarbenes (e.g., 76) can be almost completely scavenged by added alkenes, with the suppression of rearrangement products.81... 

Generation of 78 by thermolysis or photolysis of a diazoalkane or diazirine precursor, however, affords the singlet carbene, whose 1,2-H shift to ethene is opposed by a barrier of only 0.678 to 1.298 kcal/mol. Consequently, even in cryogenic matrices, singlet 78 rearranges more rapidly than it intersystem crosses to the triplet, which has therefore not been detected by UV or ESR in either an Ar matrix at 8 K or a Xe matrix at 15 K." The lifetime of singlet 78 at ambient temperature has been estimated at <0.5 ns.89,98b (Note the enormous spectator substituent effect of Cl the lifetime of MeCCl is 740 ns,60 at least 1500 times longer than that of MeCH.)... 

Several comparative studies are available in the literature, which clearly shows that, according to the latest results, tetrafluoro-pheny/ azides (AZ), trifluoro-methyl-phenyl diazirines (DZR), and particularly benzophenone (BP) are the best choice (Scheme 3.). Diazocarbonyl compounds, which played a historically role in the evolution of PAL, can also be considered together with aryl-diazonium salts [6] (not shown). For aryl azides the more common unsubstituted photophore is presented. It should be noted that tetrafluoro-phenyl azides have an increased reactivity towards CH-groups and they do not rearrange. Other substituted phenyl azides can readily alter the excitation wavelength allowing the application of milder or differential photoactivation. 

Photolysis ofbenzylchlorodiazirine (3) in the presence of tetramethylethylene (TME) is known to produce ( )- and (Z)-/l-chlorostyrene (4) and the cyclopropane (5). Plots of [5]/[4] vs [TME] are curved, consistent with the existence of two pathways for the formation of the alkenes (4). Benzylchlorocarbene (BnClC ) was generated by laser flash photolysis of the phenanthrene (6) in the presence of TME. In this case, plots of [5]/[4] vs [TME] are linear, mling out the possibility that the second pathway to the alkenes (4) involves reaction of a carbene-alkene complex. Time-resolved IR spectroscopy revealed that diazirine (3) rearranges to the corresponding diazo compound, but this process is too inefficient to account for the curvatures. It is proposed that the second pathway to alkene formation involves the excited state of the diazirine. 

Photolysis of dialkyl- and alkyl-diazirines has been broadly investigated since the products formed gave evidence of shortlived intermediates possessing excess vibrational energy. As shown in Scheme 1 diazirines (3) were photoactivated to (235) by irradiation with a medium pressure mercury lamp with quantum yields smaller than one this means reversibly. Nitrogen extrusion yielded carbenes (236). These rearranged to the primary products, alkenes and... 

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