C—H Insertion

More recently, both our group and Perez s group have demonstrated that Ag complexes 22 and 33 containing scorpionate ligands are effective for C-H insertion 

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The photolytic and thermolytic decomposition of azides in the presence of olefins has been applied to aziridine synthesis. However, only a limited number of steroid aziridines have been prepared in this manner. The patent literature reports the use of cyanogen azide at ca. 50° for 24 hours in ethyl acetate for the preparation of an A-nor- and a B-norsteroidal aziridine. The addition is believed to proceed via a triazoline. The reaction of cholest-2-ene with ethyl azidoformate takes place in a nonselective manner to produce a mixture of substances, including C—H insertion products. 

Transannular C—H Insertions in Epoxides of Medium-sized Cydoalkenes... 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

A significant effect of Lewis acids on such transamiular C-H insertion reactions has been demonstrated. Treatment of 5,6-epoxycydooctene (31) with s-BuLi/ (-)-sparteine gave allylic alcohol 32, formally the product of P-elimination, in good yield (and ee) (Scheme 5.9). In the presence of BF3-Et20, however, alcohol 33 was produced as a result of a-lithiation, in 75% yield and 71 % ee [16]. 

To extend the scope of asymmetric transannular C-H insertions, more highly functionalized medium-sized cyclic epoxides have been investigated. A triad of cydooctene oxides 34, 36, and 38, possessing protected diol units, gave the expected alcohols 35, 37, and 39 (Scheme 5.10) [17, 18] an asymmetric synthesis of (-)-xialenon A has been achieved starting from alcohol 39 [19]. In comparison,... 

Limited examples of nontransannular C-H insertions occurring in metalated epoxides exist. Treatment of trons-di-tert-butylethylene oxide 56 with t-BuLi predominantly gave the diastereomeric alcohols 58 and 59 (Scheme 5.13) [27]. Mioskowski... 

Whereas exo-norbornene oxide rearranges to nortricyclanol on treatment with strong base through transannular C-H insertion (Scheme 5.11), endo-norbornene oxide 64 gives norcamphor 65 as the major product (Scheme 5.14) [15, 22]. This product arises from 1,2-hydrogen migration very little transannular rearrangement is observed. These two reaction pathways are often found to be in competition with one another, and subtle differences in substrate structure, and even in the base employed, can have a profound influence on product distribution. 

Interestingly, the use of (S,S)-bis(l-phenyl)ethylamide as base with epoxide 70 predominantly yields ketone 71. Where the possibility for competing C-H insertion is removed (e. g., with epoxide 73), isomerization to ketone 74 occurs in excellent yield. 

Mioskowski et al. have demonstrated a route to spirocyclopropanes. As an example, treatment of epoxide 100 with n-BuLi in pentane stereoselectively gave tricyclic alcohol 101, albeit in only 47% yield (Scheme 5.21) [29]. With a related substrate, epoxide 102 stereoselectively gave dicydopropane 103 on treatment with PhLi uniquely, the product was isolable after column chromatography in 74% yield [35]. As was also seen with attempts to perform C-H insertion reactions in a non-transannular sense, one should note that steps were taken to minimize the formation of olefin products, either by the use of a base with low nudeophilicity (LTM P) and/or by slow addition of the base to a dilute solution (10-3 m in the case of 102) of the epoxide. 

The chemistry of metalated aziridines is far less developed than the chemistry of metalated epoxides, although from what is known [lb], it is obvious that their chemistry is similar. Like metalated epoxides, metalated aziridines can act as classical nucleophiles with a variety of electrophiles to give more highly substituted aziridines (Scheme 5.56, Path A). A small amount is known about how they can act as electrophiles with strong nucleophiles to undergo reductive alkylation (Path B), and undergo C-H insertion reactions (Path C). 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

Tetraphenylmolybdenocene dihydride Mo(r 5-C5HPh4)CpH2 (45) was formed by addition of diphenylacetylene to MoCpL(PhC CPh)CH3 (L = P(OMe)3) (Eq. 15), presumably via an ot-hydrogen abstraction to an intermediate methylidene hydrido complex, followed by addition of two equivalents of diphenylacetylene and C — H insertion with concomitant elimination of L [57 b],... 

There are numerous examples of metal carbene insertion reactions, usually requiring a catalyst. " The C—H insertion reactions of metal carbenes can be highly selective. Intramolecular insertion reactions are very versatile and tolerate a... 

Many other reagents for converting alkenes to epoxides,including H2O2 and Oxone , VO(0-isopropyl)3 in liquid C02, ° polymer-supported cobalt (II) acetate and 02, ° and dimethyl dioxirane.This reagent is rather versatile, and converts methylene oxiranes to spiro-epoxides. ° ° One problem with dimethyloxirane is C—H insertion reactions rather than epoxidation. Magnesium monoperoxyphthalate is commercially available, and has been shown to be a good substitute for m-chloroperoxybenzoic acid in a number of reactions. 

Feldman reported a route to dihydropyrroles, pyrroles, and indoles via the reaction of sulfonamide anions with alkynyliodonium triflates <96JOC5440>. Thus, upon nucleophilic addition of the anion of 91 to the p-carbon of the alkynyliodonium salt, the alkylidene carbene 92 is generated which can the undergo C-H insertion to the desired product 93. 

The only other reaction with an aromatic substance is the C-H insertion into ferrocene [85], giving 41,which illustrates the highly electrophilic character of the phosphinidene complex. Other aromatic C-H insertions have been observed, but these likely occur by means of intermediate P,0- and P,N-ylids,such as the reaction of (0C)5W=PR withbenzophenone and azobenzene that give 42 and 43,respectively [56a, 86]. 

C-H insertion also occurs in the reactions with acetone and acetophenone, presumably through the rearrangement of transient OH-substituted phosphi-ranes [87]. C-C insertions occur for diketones to give 45 and have been postulated to occur via initial 1,2-addition to the conjugated enol 44 [87]. Diimines 46 also undergo C-C insertions [88]. Based on a theoretical evaluation, the products 47 are considered to result from a 2,3-sigmatropic rearrangement of initial formed P,N-ylids. 

Transition metal-catalyzed carbenoid transfer reactions, such as alkene cyclopro-panation, C-H insertion, X-H insertion (X = heteroatom), ylide formation, and cycloaddition, are powerful methods for the construction of C-C and C-heteroatom bonds [1-6]. In contrast to a free carbene, metallocarbene-mediated reactions often proceed stereo- and regioselectively under mild conditions with tolerance to a wide range of functionalities. The reactivity and selectivity of metallocarbenes can be... 

Interestingly, [Ee(F20-TPP)C(Ph)CO2Et] and [Fe(p2o-TPP)CPh2] can react with cyclohexene, THF, and cumene, leading to C-H insertion products (Table 3) [22]. The carbenoid insertion reactions were found to occur at allylic C-H bond of cyclohexene, benzylic C-H bond of cumene, and ot C-H bond of THF. This is the first example of isolated iron carbene complex to undergo intermolecular carbenoid insertion to saturated C-H bonds. 

Table 3 Stoichiometric C-H Insertion Reactions of [Fe(F20-TPP)C(Ph)CO2Et] 2 and [(MeIm)Fe (F2o-TPP)CPli2] 4 with Alkenes or Tetrahydrofuran...

With the iron complex [Fe(Cl3terpy)2]( 104)2 (Clsterpy = 4,4, 4"-trichloro-2,2 6, 2"-terpyridine) as catalyst, sulfamate esters react with Phl(OAc)2 to generate iminoiodanes in situ which subsequently undergo intramolecular nitrenoid C-H insertion to give amidation products in good yields (Scheme 30) [48]. 

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