Azides fluorophenyl azide

Our prediction, that 2-fluorophenylnitrene (lOf) should preferentially cyclize away from the fluorine, was subsequently verified experimentally by Leyva and Sagredo.89 They photolyzed 2-fluorophenyl azide in diethylamine and isolated the trapping product expected from cyclization of the nitrene away from the fluoro substituent (Scheme 20).89... 

As mentioned previously, unique kinetic results were obtained upon LFP of o-fluorophenyl azide,in that the singlet nitrene decays faster than the ketenimine is formed. This finding requires the presence of an intermediate, presumably ben-zazirine 40, between the singlet nitrene and ketenimine 42. The data could be interpreted by assuming that azirine 40 reverts easily to singlet nitrene according to the scheme below.The equilibrium constant is equal to the ratio of [40]/[39s] and was deduced to be 0.5 with AG 350 caFmol. Younger and Bell have also reported a system in which a benzazirine and ketenimine interconvert. 

INTERCONVERSION OF SINGLET NITRENE AND AZIRINE IN THE CASE OF ORTHO-FLUOROPHENYL AZIDE EXPERIMENT AND THEORY... 

Unique kinetic results were obtained upon LFP of ortho-fluorophenyl azide 15a. Figure 15 displays the typical kinetics of the decay of singlet 2-fluorophenylnitrene (16a) and the formation of products (ketenimine 18a and... 

Fig. 16 The temperature dependencies of the rate constant of decay of singlet 2-fluorophenyInitrene 15a (1) and the apparent rate constant of formation of triplet 2-fluorophenylnitrene (20a) and ketenimine (18a) (2). Solid lines (1) and (2) results of non-linear global fit of the data to analytical solutions. Insert transient absorption spectra produced by LFP at 295 K (1) of 2-fluorophenyl azide 15a in pentane, detected 500 ns after the laser pulse (2) 4-fluorophenyl azide 15b detected 50 ns after the laser pulse and (3) persistent spectrum detected after 20 s of photolysis of 2-fluorophenyl azide 15a in methylcyclohexane at 77 K.

This hypothesis was supported by analysis of the transient spectrum obtained upon LFP of 2-fluorophenyl azide, which reveals the presence of triplet nitrene 20a despite the small ratio of kisc/koss- This is clearly evident in Fig. 16 (Insert Spectrum 1), which presents the spectrum of the products formed from the decay of singlet nitrene 16a at room temperature. This spectrum is the sum of the spectrum of triplet nitrene 20a (narrow band at 303 nm and weak absorption below 450 nm) and ketenimine 18a (broad band at 350 nm). This complicated spectrum can be eompared with the simpler spectrum of ketenimine 18b (Spectrum 2) and the spectrum of triplet nitrene 20a observed as a persistent species in a low-temperature matrix (Spectrum 3). It is clear that the yield of triplet nitrene 20a is significant at room temperature. However, if one postulates that azirine 17a does not inter-eonvert with singlet nitrene 16a (Scheme 6, -r). then the yield of... 

Levya, E. Sagredo, R. Photochanistiy of fluorophenyl azides in diethylamine. Nitrene reaction vCTsns ring expansion, Tetrahedron 1998,54, 7367-7374. 

The initial synthesis of aprepitant (1), which relies on a Tebbe olefination and reduction to install a methyl group on the benzyl ether side chain, is shown in Scheme 3.8,19 The initial steps are from a literature-precedented synthesis of p-fluorophenyl glycine based on conversion of chiral oxazolidinone 33 to azide 34. Formation of morpholinone intermediate 36 proceeds via benzylation and reaction with 1,2-dibromoethane. 

Intermediate (5)-l is simply yV-benzyl-4-fluorophenylglycine that has been capped with an ethylene unit. The original synthesis in which 4-fluorophenylacetic acid was transformed to the corresponding chiral oxazolidinone 6 is depicted in Scheme 2. Masked a-azido acid 7 was formed diastereoselectively from this intermediate. Hydrolysis and azide reduction afforded enantiomerically pure (5)-4-fluorophenyl glycine (8). Reductive amination with benzaldehyde introduced the V-benzyl unit and subsequent A, 0-dialkylation with ethylene dibromide provided chiral oxazinone 1. 

A soln. of N-(p-fluorophenyl)dichloroazomethine in dimethoxyethane stirred overnight with hydrazine-activated Na-azide crude l-(p-fluorophenyl)-5-chlorotetrazole. Y 79%. F. e. s. J. G. Kauer and W. A. Sheppard, J. Org. Ghem. 32, 3580 (1967). 

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