Diazirines cyclopropanes

Later there was an attempt by ab initio calculation to fit the electron structure of diazirine into the Walsh model of cyclopropane (69MI50800). According to these SCF-LCAO-MO calculations three MOs add to the description of the lone electron pairs, all of which also contribute to some extent to ring bonding. As to strain, 7r-character and conjugative effect, the term pseudo-rr-character was used. 

Two other fluorine-containing diazirines give similar results. Cyanofluorodiazirine (223) and fluoromethoxydiazirine (224) release nitrogen at 100 °C the carbenes formed can be trapped by tetrafluoroethylene to give cyclopropanes (65JHC371). Without a carbene trap alkenes are obtained. 

The stabilization of chloromethoxycarbene (234) was intensively studied. It is formed from diazirine (233) in a first order reaction with fi/2 = 34h at 20 C. It reacts either as a nucleophile, adding to electron poor alkenes like acrylonitrile with cyclopropanation, or as an electrophile, giving diphenylcyclopropenone with the electron rich diphenylacetylene. In the absence of reaction partners (234) decomposes to carbon monoxide and methyl chloride (78TL1931, 1935). 

The methylethylcarbene which is formed thermally from methyl-ethyldiazirine at 160°C gives the same products as that from butanone p-toluenesulfonylhydrazone and bases in aprotic solvents." However, photolysis of the same diazirine gives a different mixture of C4H8 hydrocarbons. Considerable amounts of 1-butene are formed, the trans-butene content is reduced by half, and the amount of methyl cyclopropane increased fivefold. ... 

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... 

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 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... 

In addition, 18-19% of isobutene and chloroacetylene formed via fragmentation. Photolysis of the diazirine in up to 9 M trimethylethylene in pentane led to a sharp decrease in 27 and 28 (to 32% and 8.5%), along with 40% of cyclopropanes formed via the capture of 19. However, the yield of isobutene and chloroacetylene was unchanged, indicating that these products did not stem from the carbene, but arose directly by fragmentation of its excited diazirine precursor.45... 

Addition of up to 0.42 M TME did not much affect the yields, even though up to 37% of the cyclopropane adduct of carbene 20 formed, presumably at the expense of freon-carbene (C-Cl) insertion products which form in the absence of TME. The yield of 30, but not f-butylethene, was also minimally affected by TME when the diazirine was thermally decomposed at 100°C.46... 

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... 

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 non-nitrogenous carbene precursor (102) was used for the photochemical generation of the carbene (103) without complications due to reactions of diazirine or diazo species. In the presence of alkenes, carbene (103) gave rise to cyclopropanes and in the absence of alkenes was proposed to undergo [1,2]-C shift to form (104), which suffered retro-Diels-Alder reaction to give a triene. 

Other methods for the formation of carbenes that have seen at least limited application in cyclopropanation reactions include the use of diazirines, epoxides, ketenes and W-nitrosoureas.lhi8e-8f,8l 8m,8P... 

Kinetic analysis of the rearrangement of benzylfluorocarbene, generated by laser flash photolysis of the corresponding diazirine, gave a rate constant of 9.2 x 106 s 1 at 26 °C with activation entropy —17.2 eu and activation energy 3.25 0.34 kcal mol-1, very similar to the values for the chlorocarbene.80 A product analysis study of the thermolysis and photolysis of the diazirine (73) in the presence of tetramethylethylene showed tiiat die ring-expanded cyclobutene and the cyclopropanation products do not arise via a common intermediate.81 The ring expansion was proposed to occur by loss of N2 from the diradical intermediate (74). 

In an attempt to reduce the size of the photoreactive group, Emi and Khorana (1980) investigated the properties of tetrafluorodialkyl diazirines. Unfortunately these compact molecules (Fig. 3.17) did not yield insertion products on photolysis, but rearranged internally by alkyl migration to give olefins, and underwent intramolecular insertion to yield cyclopropanes. 

The diazirine from Step 1 (9.5 mmol) was dissolved in methylacrylate (90 mmol) and 10 ml tetrachloroethylene then refluxed 20 minutes. The crude products consisted of an isomeric cyclopropane mixture with a syn/anti ratio of 3.8 1. The mixture was purified by chromatography on silica with light petroleum/EtOAc, 5 1, and the product mixture isolated 68% yield with no change in the isomer ratio. H-NMR and data supplied. 

Diazirines are thermally unstable and generate a carbine radical intermediate. This property has been used with hydrazones as a route for forming cyclopropanes (2) as illustrated in Eq. 2 ... 

Another more recent example of a cheletropic reaction, studied in various solvents, is the addition of aryl-halocarbenes (generated photolytically from diazirines) to tetramethylethene to give the corresponding cyclopropane derivatives [820], The addition of chlorophenylcarbene is only about three times faster in ethyl acetate than in pentane, as befits an isopolar activated complex. 

Depending on the mode of generation, a carbene may be initially formed in either the singlet or triplet state, irrespective of its stability. Common methods used for the generation of carbenes include photolytic, thermal, or metal catalyzed decomposition of diazocompounds, elimination of halogenfrom gem-dihalides, elimination of Hx from CHX3, decomposition of ketenes, thermolysis of a-halo-mercury compounds and cycloelimination of shelf stable substrates such as cyclopropanes, epoxides, aziridines and diazirines. 

Cyclopropan l-Chlor-2-cyan-l-methoxy- E14a/3, 73 (En —CN -I- 3-C1 —3-OR—3H-diazirin) E19b, 1660 (Carben + En-CN)... 

Cyclopropan 1-Cyan-l-methoxy-trimethyl- E17a, 759 (3-CN —3-OR —3H-diazirin/Base + En) Furan 2-(Dimethylamino-methyl)-5-methyl- Xl/1, 783 (H - CH2 —NR2) E6a,... 

Cyclopropan 2-Cyan-l-fluor-l-phenoxy- E17a, 743 (3-F —3-OR —3H-diazirin/A + En)... 

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