Diazirines, generation carbenes

Surface-introduced photoreactive group, aryl diazirine, can generate carbenes by 365 nm UV exposure. However, gold-sulfiir bonds, which support photolinker on gold, can be easily broken by UV light below 300 nm. Therefore, UV transmission filter is essential in UV irradiation. 

The photolysis or thermolysis of 3-chloro-3-cyclobutyl- and 3-chloro-3-cyclopropyl-3/7-diazirine " generates chloro(cycloalkyl)carbenes which react with alkenes to form 1-chloro-l-cyclobutyl- or 1-chloro-l-cyclopropylcyclopropanes 1 and 2, respectively (Houben-Weyl, Vol. E19b, pp 1520-1521). 

The state of the arylhalocarbene generated depends on the method applied. If potassium tcrt-butoxide is used for the a-elimination of aryldihalomethanes 1, carbenoids rather than free carbenes are generated. When the same process is carried out with a crown ether, free carbenes are formed. The state of the carbene is not a decisive factor as far as its addition to alkenes is concerned from a preparative point of view. In the decomposition of 3//-diazirines, free carbenes are generated, therefore this method is widely applied for mechanistic investigations. 

In the 1950s and 1960s chemists learned how to generate carbenes from haloform, diazirine and diazo compound precursors as transient intermediates in solution. [1,5,6] The chemists of this era identified the products of carbene reactions and learned how to make these reactions synthetically useful. They postulated a framework for carbenes (Scheme 1) with ground or low lying triplet states which is still the starting point in all mechanistic discussions. 

Carbenes are conveniently generated from nitrogenous precursors such as diazo compounds [23] or diazirines [24] upon irradiation or thermolysis, which takes place very cleanly and efficiently. Therefore, it is possible to generate carbenes even at very low temperature in rigid matrix once those precursors are prepared. This makes it very easy to assign and characterize the carbenes spectroscopically, which is a very important point since we will then have to assign only triplet states of carbenes and to estimate their stability. 

A prominent strategy in matrix isolation photochemistry has been the expulsion of N2 from stable precursors. Both diazo/diazirine precursors and 1,2-diazene precursors have been useful. The former generate carbenes and related species, while the latter are useful precursors to biradicals. 

The reactions of carbenes depend appreciably on the means by which they are generated. Carbenes for example, which result from the photolysis of diazirines exhibit... 

Substituted fluorocarbenes have been generated by several methods, but organometallic transfer reagents again are most useful synthetieally [64, 65, 66, 67, 68] (equations 25-27) Diazirines cleanly produce carbenes thermally [69, 71] or... 

Singlet halo(trifluoromethyl)carbenes [33a]-[33c], which were characterized by IR and UV spectroscopies and chemical trapping with HCl, have been generated from respective 3-halo-3-(trifluoromethyl)diazirines [34a]-[34c] frozen in an argon matrix at 12 K and irradiated with UV light at... 

Finally, in some cases diradical negative ions can even be generated directly npon ionization of appropriate precnrsors. For example, nitrene and carbene anions can be formed by El of organic azides, diazo-compounds, and diazirines, whereas Branman and co-workers have reported the formation of oxyallyl anions by El of flnorinated acetyl componnds (Eq. 5.12). ... 

As shown in Table 1, however, the product distribution depends on the method of carbene generation. Whereas thermolysis of either tosylhydrazone salt (7) or methylethyldiazirine (8) affords essentially the same product distribution (in which 95% of the products are the 2-butenes), photolysis of diazirine 8 is quite different. 

Photolytic generation of carbene 19 from a precursor diazirine afforded cyclobutenes 27 (68%) and 28 (14%) via CH2 and CMe2 migrations, respectively cf. Eq. 15.45... 

Cyclopropanated phenanthrenes revert to phenanthrene and carbenes on photolysis CH2,49 CC12,50 CBr2,51 CBrCl,51 and f-BuCH15d have been generated this way. Platz et al.25 used 37 (R=PhCH2) to generate benzylchlorocarbene (10a) for comparison with 10a generated from diazirine 9a cf. Scheme 2. 

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... 

It is suggested that the real carbene, generated by thermolysis of the diazo or diazirine precursors or photolysis of 40, gives mostly 1,3-insertion, whereas photolysis of either the diazoalkane or diazirine yields much 1,2-Me migration directly from precursor excited states.15 1 An analogous intervention of 1,2-Me migration via RIES was also observed in the photolytic decomposition of f-butylchlorodiazirine (24) to f-butylchlorocarbene (18) cf. Eq. 14.27... 

Accordingly, a re-examination of the benzylchlorocarbene system was performed, with close attention paid to the products formed at low temperature.71 Carbene 10a was photolytically generated from diazirine 9a in isooctane, methylcyclohexane, and tetrachloroethane at temperatures ranging from 30 to —75°C. At —70°C in isooctane, the products included 47% of P-chlorostyrenes 11a and 12a, 2.4% of a-chlorostyrene (49), 2% of dichloride 50, 5.5% of a C-H insertion product of 10a and isooctane, 4% of the dimers of 10a, and 30% of azine 48.71 The sum of the intermolecular products at —70°C was thus 41.5%, of which azine was the principal component. 

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.)... 

In general, 1,2-C shifts do not compete effectively with the 1,2-H shifts of acyclic alkyl and alkylhalocarbenes. However, r-butylchlorocarbene (18) lacks the a-H needed for a 1,2-H shift, and so affords 1,3-CH insertion and 1,2-Me migration Eq. 14. Note that only for the thermally generated 18 is the 1,2-Me shift product (26) derived from the carbene. Photolytic generation of 18 from diazirine 24 gives only 1,3-CH insertion to dimethylchlorocyclopropane 25 in this case, the 1,2-Me shift product is formed by RIES of the diazirine.27 Based on the rate constant for the 1,3-CH insertion of t-BuCCl at 25°C (9.3 x 105 s 1), we can estimate A 105 s 1 for the 1,2-Me shift at 78°C. 

It has been found that the catalytic activity of PKC is enhanced by a lipid component of the cell membrane, namely phosphatidylserine. This activity is further stimulated by sn-1,2-diacylglycerol. Oleic acid also activates the enzyme in the presence of 1,2-diacylglycerol, and thus it is presumed to mimic phosphatidylserine. In order to identify that modulating binding site for oleic acid on PKC, a photoaffinity analogue was devised. A carbene generating photophore, diazirine was placed in the apolar terminus of the unsaturated fatty acid ligand (30, Fig. 12). The synthesis and the photochemical activation properties were reported by Ruhmann and Wentrup [113]. 

Vasella et al. introduced an approach to glycoside synthesis using the glycosylidene carbene generated from the diazirine sugar as a novel type of glycosyl donor. The... 

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. 

The absolute rate constants for reaction of /t-tolyl(trifluoromethyl)carbene, generated by laser flash photolysis of the corresponding diazirine, with pyridine (4 x lO lmor s ... 

Furylchorocarbene (11), generated by irradiation of the corresponding diazirine in a nitrogen matrix at 8K, was characterized by IR spectroscopy, which revealed two species, one of which was destroyed on irradiation to form the aldehyde (12). The experimental and calculated spectra were in accord with two conformations of the carbene, one of which decomposes to the aldehyde. 

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