Insertion reactions of nitrenes

Nitrenes like carbenes readily insert into single bonds. Carbonyl nitrenes are very reactive species and insert into the C-H bonds of alkanes to give amides or carbamates. The order of reactivity among alkane C-H bonds is 

For all nitrenes studied, the selectivity of C-H insertion follows the expected pattern of reactivity, decreasing in the order tertiary secondary primary C-H, although there is considerable variation in the degree of selectivity. For example, the relative reactivities of tertiary, secondary, and primary C-H bonds in 2-methylbutane toward ethoxycarbonylnitrene is approximately 30 10 1, whereas the corresponding values for methanesulfonylnitrene are 10 4 1. 

Although aryl nitrenes often give poor yields of intermolecular C-H insertion products, the intramolecular reaction works well, and proceeds with retention 

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Mechanisms [i] and [II] may occur through the recombination of unpaired electrons which are formed by the hydrogen abstraction of nitrenes, and the insertion reaction of nitrenes to C-H bonds, respectively. However, it has not been revealed in this study which C-H bond is attacked by the nitrene. 

The C—H insertion reaction of nitrenes is a potentially useful way of functionalizing unactivated C—H bonds, converting hydrocarbons into amine derivatives. In its intermolecular form the synthetic utility of the reaction is highly dependent on the substituents on the nitrene, and on the manner in which it is generated. To exemplify these effects, the results for the functionalization of cyclohexane by insertion of various nitrenes (equation 1) are summarized in Table 1. 

The pyranofurooxazoline 109 can be prepared by a nitrene insertion reaction of the corresponding furan 110 upon treatment with ethyl azidoformate at — 50 °C under photolysis conditions. Compound 109 is moisture sensitive, and upon treatment with wet acidic THF was converted quantitatively to the more polar furanopyran 111. The structure and stereochemistry of 109 were proved unambiguously by X-ray diffraction, showing that the nitrene inserted anti to the bridgehead methyl group <1999JOC736> (Scheme 30). 

The transition metal-catalyzed C-H insertion reaction of carbenes to organic compounds is a well-established synthetic method, as shown in the first two sections in this chapter. However, nitrene C-H insertion, the corresponding reaction of carbene analog, is much less known. In the past decade, considerable advances have been made in the development of this chemistry into a generally useful C-H amination process by using improved catalysts and protocols, in which readily available amines or amides are used as the starting substrates. Moreover,... 

As shown in the previous two sections, rhodium(n) dimers are superior catalysts for metal carbene C-H insertion reactions. For nitrene C-H insertion reactions, many catalysts found to be effective for carbene transfer are also effective for these reactions. Particularly, Rh2(OAc)4 has demonstrated great effectiveness in the inter- and intramolecular nitrene C-H insertions. The exploration of enantioselective C-H amination using chiral rhodium catalysts has been reported by several groups.225,244,253-255 Hashimoto s dirhodium tetrakis[A-tetrachlorophthaloyl-(A)-/ r/-leuci-nate], Rh2(derived rhodium complex, Rh2(i -BNP)4 48,244 afforded moderate enantiomeric excess for amidation of benzylic C-H bonds with NsN=IPh. 

Among these, a variety of oxygen atom transfer reactions have been described [la,b] and highly stereoselective reactions have been reported [2]. Although the formation of aziridines by the reaction of nitrenes with olefins is well known, the efficiency is moderate, because of the competition between hydrogen abstraction and insertion processes [3]. A typical example is shown (Eq. 2) [3d]. 

The typical reactions of nitrenes generated from aliphatic azide precursors are shown below and include isomerization to imines (a), intramolecular insertion into C—H bonds (b) has been questioned (see 1. c. n> p. 57) and intermolecular hydrogen abstraction (c). 

The four ttutin characteristic reactions of nitrenes are summarized in Scheme 2. All of these reactions have parallels in carbene chemistry for example, a full discussion of the C—insertion reaction of car-benes is given in Volume 3, Ch ter 4.2. The first reaction, the addition to an alkene to form an aziridine, is covered in detail in Volume 7, Chapter 3.S. The C—insertion reaction, the subject of this chapter, can, in principle, occur by severid mechanisms. However nx>st of the reactions are believed to involve... 

Thus the intramolecular reaction of nitrenes with sp C—H bonds, although it may not involve a genuine C—insertion mechanism, is a useful synthetic method, which extends and complements the nitrene insertions into unaedvated sp C—bonds discussed in earlier sections. 

The intramolecular insertion reaction of arylnitrenes proceeds with retention of configuration at carbon. For example, heating the (S)-aryl azide (11 X = Na) in the vapor phase gives 2-ethyl-2-methylin-doline in 50- % yield in ca. 100% optical purity.The optical purity of the product is lower if the azide is heated in solution, or if the nitrene is generated from the corresponding nitro compoimd (11 X = NO2) with triethyl phosphite. ... 

Better yields have been obtained in the insertion reactions of car-boalkoxy nitrenes. Pyrolysis of -octadecylazidoformate (35) in cyclohexane gave 60% of (JV-cyclohexyl)-R-octadecyl carbamate (36) zilong with 23% of the abstraction product 37 . 

We expect that this is the case for singlet and triplet phenyl carbene as well. Intermolecular C—H bond insertion reactions of phenyl carbene are well known but are unknown for singlet phenyl nitrene at ambient temperature, presumably due to the rapid rate of the competitive ring expansion process which forms dehydroazepine. 

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