Isocyanates, addition nitrenes

Reductive carbonylation of nitro compounds is catalyzed by various Pd catalysts. Phenyl isocyanate (93) is produced by the PdCl2-catalyzed reductive carbonylation (deoxygenation) of nitrobenzene with CO, probably via nitrene formation. Extensive studies have been carried out to develop the phosgene-free commercial process for phenyl isocyanate production from nitroben-zene[76]. Effects of various additives such as phenanthroline have been stu-died[77-79]. The co-catalysts of montmorillonite-bipyridylpalladium acetate and Ru3(CO) 2 are used for the reductive carbonylation oLnitroarenes[80,81]. Extensive studies on the reaction in alcohol to form the A -phenylurethane 94 have also been carried out[82-87]. Reaction of nitrobenzene with CO in the presence of aniline affords diphenylurea (95)[88]. 

The outcome of the nitrene addition reaction depends on the type of 7i-bond involved. In contrast to electron deficient olefins [26] and nonpolar olefins forming aziridines, electron rich olefins react with alkoxycarbonyl nitrenes to give oxazolines (Sch. 14) [22]. The same type of cycloaddition reaction leading to the production of five-membered rings has also been observed with nitriles [27] (such as compound 35 in Sch. 14) and isocyanates [28] as illustrated in Sch. 15. 

In the direct photolysis the main products are isocyanates. Two lactames 57 and 58 and the insertion product 59 are formed in addition. The sensitized photolysis, in striking contrast to the direct photolysis, leads only to abstraction products 60,34 and 61 in good yields arising from a triplet nitrene. No lactames could... 

The azabicyclononane system is a common structural feature in diterpene alkaloids, and the nitrene insertion route to the ring system has been studied in detail in model decalins as well as in steroids (Scheme 11). Thus irradiation of the rrans-acyl azide (21) gave, in addition to isocyanate (30-33%), a mixture of Ae 7- and 8-lactams (22) and (23). The y-lactam (22) predominated, dthough the overall yield was poor. > The corresponding c/s-azide (24), however, gave the 8-lactam (25) as Ae major product, again in low yield. One elegant application of this type of intramolecular nitrene insertion reaction... 

When stericaUy demanding peptide fragments are coupled in the presence of HOSu, a side reaction that leads to a P-alanine derivative becomes donninant (Scheme In this side reaction, HOSu is activated by DCC and attacked by a second equivalent of HOSu. The nitrene is probably not a real intermediate as it is rearranged conconoitantly to its formation to an isocyanate moiety, which is trapped by a third equivalent of HOSu.t By replacing the HOSu additive with A-hydroxy-5-norbornene-2,3-dicarboximide (18)t or other dinucleo-phUes, this side reaction is efficiently bypassed. 

The Curtius rearrangement also occurs in the direct photolysis of acylazides, but additional products have been isolated and have been shown to arise from typical nitrene reactions . For example, Horner et have trapped benzoyl nitrene with a variety of scavengers. Similarly to the Wolff rearrangement (vide infra) it has been shown ° that the Curtius rearrangement occius via a singlet intermediate this intermediate can be a nitrene or an excited azide molecule in which a concerted decomposition leads to isocyanate derivatives. This reaction could occur in competition with nitrene formation or, alternatively, originate from a vibrationally-excited ground state azide molecule. 

An internal addition of nitrenes is also possible, when the double bond is located at a suitable distance. The highly strained fused aziridines formed undergo immediate hydrolysis to hydroxymethyl pyrrolidines. With acyl azides yields were low, as the respective isocyanates were the major products. Examples are the conversions... 

The photolysis of benzoyl azide (PhCON3) has been investigated by means of matrix isolation, time-resolved IR spectroscopy, and computations at various levels of theory.In argon at 12 K, formation of two species was observed. One of these was phenyl isocyanate (PhCNO), while the other had an IR spectrum consistent with the predicted spectrum of the reactive singlet species PhCON, which appears to have a structure intermediate between that of a carbonyl nitrene and an oxazirene. Analogous observations were also made for 4-acetyl-benzoyl azide. Time-resolved IR spectroscopy on the nanosecond time scale provided additional evidence for the singlet ground state of benzoylnitrene. 

The parallel to the photochemistry of azides found in the arylimines is also observed on irradiation of 1,2,4-triazole 4-acyl-,129 133 4-sulfonyl-,81 and 4-carbamoylimines.133 In methanol the same products are generated as in the photolysis of the corresponding azides. Their formation is consistent with the mechanism given in Scheme 15 the AT-acyl- and sulfonyl-imines afford 1,2,4-triazole and a nitrene which yields the typical nitrene products 107a-d with methanol. Furthermore, carbamic esters (109) are formed, by addition of methanol to an isocyanate (108). These isocyanates can originate directly from the N-imine by a synchronous reaction or from the nitrene by a sextet rearrangement. Although irradiation of s-triazole... 

K. In addition, it was found that the irradiation of 22 in benzene in the presence of both cis- and rans-pentenes (0.05 to 3 M) produces a mixtiu-e of aziridines, which is typical of the presence of both singlet and triplet nitrene cycloaddition reactions. The triplet-triplet absorption spectrum of azide 22 was detected, and it was found that naphthalene inhibits the photoreaction of 22 by quenching of its triplet state. It was concluded, therefore, that the ground state of nitrene 23 is a triplet and that it is formed exclusively upon sensitized photolysis of azide 22 through the triplet state of 22. 21 Nq isocyanate was detected in the photolysis products of 22. 

Two main pathways for the formation of the rearranged sulphamide 434 can be considered (equation 144). Path B involves an intramolecular path for the formation of the sulphamide 434. However, when the reaction was carried out in the presence of phenyl isocyanate, the urea (441) was isolated from the reaction mixture. This provided evidence for the existence of free 2,2,4,4-tetramethylpyrrolidine (440), which was considered to arise from the tert-octyl nitrene (438) by y-hydrogen insertion. Later work401, however, showed that when the rearranged sulphamide is heated in the presence of phenylisocyanate under identical conditions to those for its formation, pyrrolidinylurea (441) is formed in 60% yield. Thus the formation of 441 is not evidence of the existence of free 440, because 434 once formed is capable of dissociation and reaction with phenylisocyanate to give 441. In addition, attempts to independently generate tert-oc y nitrene failed to produce any... 

More recent matrix isolation studies on benzoyl nitrene, however, did show conversion to the isocyanate. Calculations show that the acyl nitrene has oxazirene (108) character and that this 0-N interaction stabilizes the singlet state of the nitrene. Interestingly, a reexamination of benzoyl nitrene, trapped in an argon matrix and irradiated at 308 nm, revealed that in addition to phenyl isocyanate, a small amoimt of phenyl cyanate (110) was formed. Direct irradiation of benzoyl azide (254 nm) also generated the... 

---