Insertion into N-H bond

The ruthenium porphyrins, (TPP)Ru(CO) and (TMP)Ru(CO) also catalyze carbene insertion into N-H bonds [172]. Thus, the complex (TMP)Ru(CO)... 

Insertion into N-H bond. Of major importance is the recently developped intramolecular carbene insertion into N-H bond, which is the key step in the Merck Synthesis of the 1-carbapenam ring system from diazo precursors. Yields are high, and the reaction is always very selective in one isomer. 

Although Rh -catalyzed reaction of dimethyl diazomalonate with nitriles to afford 1,3-oxazoles (eq 4) generally gives high yields, it is incompatible with an a-amino function. Thus, an alternative route was proposed for preparation of oxazole derivatives of a-amino acids. This method involves Rh -catalyzed insertion into N-H bond of an amide, derived from the amino acid, followed by intramolecular condensation (eq 36). ... 

Table 18. Regioselectivity of ketocarbenoid insertion into C—H bonds of N-methylpyrrole.

H2, it does readily occur upon photolysis to generate [ReH-(dppe) ] as a very reactive photoproduct (13). As detailed below, this species rapidly adds substrate molecules (N, CO, C2H2, C H, and CO ) and inserts into C-H bonds of benzene solvent and the phenyl groups of the dppe ligands. 

Electrophilic carbene complexes can react with amines, alcohols or thiols to yield the products of a formal X-H bond insertion (X N, O, S). Unlike the insertion of carbene complexes into aliphatic C-H bonds, insertion into X-H bonds can proceed via intermediate formation of ylides (Figure 4.7). 

Functionalization of C-H bonds by metal carbenoid or nitrenoid insertions represents a promising alternative to the more traditional approach of direct activation by a metal center. Carbenoids and nitrenoids show unusual regio- and stereoselectivity in insertions into C-H bonds, and unlike insertions of metal centers, these are intrinsically functionalizations rather than activations, which must be followed by functionalization (although in either case, loss of the functionalized group, to regenerate the active metal complex, is still required for catalysis) [129]. The use of dimeric Rh(n) complexes in this area has been extensively developed [129]. 

An unusual reaction of carbenes is that of insertion into C—H bonds (2-20). Thus CH2 reacts with methane to give ethane and with propane to give n-butane and isobutane. 

Insertions into O—H bonds, N—H bonds and C—H bonds adjacent to oxygen and nitrogen have found use in the synthesis of a number of heterocycles (see Section 4.7.3.9).187-189 The reaction of alcohol (25) with methyllithium in ether, leading to the ketone (26), has been interpreted190 as involving the insertion of an intermediate carbenoid into a P-C—H bond followed by ring opening (equation 64). 

This process has found occasional use in the synthesis of heterocycles. The major product resulting from the reaction of MeLi on the dibromocarbene adduct (51) is the tetrahydrofuran (52), as shown in equation (105).189 In a novel approach to the synthesis of spiroacetal pheromones, caibene insertion into an acetal C—H bond was studied (equation 106).252 Unfortunately, the reaction proceeds in low yield and the approach is further hampered by the lack of stereocontrol in the ring opening of the cyclopropane. Carbene insertions into N—H and C—H bonds adjacent to nitrogen have been shown to give azabicyclo systems, as shown in equations (107) and (108).188... 

Scheme 7.8 Fe-corrole-catalyzed insertion of diazo compounds into N —H bonds.

Because C-H bonds are usually less reactive towards dioxirane oxidation than heteroatoms and C-C multiple bonds, it is instructive to give a few general guidelines on the compatibility of functional groups within the substrate to be submitted to oxidative C-H insertion Substances with low-valent heteroatoms (N, P, S, Se, I, etc.), C-C multiple bonds, and C=X groups (where X is a N or S heteroatom) are normally not suitable for C-H insertions, because these functionalities react preferably. Even heteroarenes are more susceptible to dioxirane oxidation than C-H bonds, whereas electron-rich and polycyclic arenes are only moderately tolerant, but electron-poor arenes usually resist oxidation by dioxiranes. N-oxides and N-oxyl radicals are not compatible because they catalyze the decomposition of the dioxirane. Oxygen insertion into Si-H bonds by dioxirane is more facile than into C-H bonds and, therefore, silanes are not compatible. Substance classes normally resistant towards dioxirane oxidation include the carboxylic acids and their derivatives (anhydrides, esters, amides, and nitriles), sulfonic acids and their de-... 

In addition to carbon monoxide, other unsaturated compounds, for example isonitriles and acetylenes, can also insert into C-H bonds to give aldimines and substituted alkenes, respectively [12, 13]. Similar to carbonylation, high terminal selectivity for n-alkanes were also observed in these reactions. 

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). 

In the carbene insertions to alkane C-H bonds the same concept as for the olefin cyclopropanations is applied. In that work, the gold-catalyzed carbene transfer is now used for insertions into C-H bonds (equation 150), with a selectivity that is influenced by the electronic properties of the ligand and the counterion employed. The carbene and nitrene insertion is not limited to Csp H bonds, but N H (equation 151), O H (equation 152), and aryl Csp -H bonds react as well (equation 153). ... 

No simple reactions between CO2 or CS2 and group IVB hydrides have been reported. On the other hand, a vast literature exists on insertion of CO2 and CS2 into N-H bonds. The reactions of NH3 with CO2 and CS2, to form ammonium carbamate and dithiocarbamate, respectively, are of commercial importance in the synthesis of urea, cyanates, and thiocyanates but are properly considered in the realm of organic chemistry. Secondary phosphines react with CS2 in the presence of a base ... 

Similar to singlet carbenes, singlet nitrenes (R-N ), the nitrogen analog of carbenes, are also known to insert into C-H bonds." Acyl nitrenes and sulfonyl nitrenes insert rather readily in C-H bonds [Eq. (6.133)] ... 

By using Cu complexes of chiral spiro bis(oxazoline) ligand S, S,S)-23a as catalysts, the enantioselective catalytic insertion of a-diazoesters into N—H bond of aromatic amines was realized in high yields and high enantioselectivities (Scheme 43) [25b, 108]. The chiral spiro Cu catalysts have unique binuclear structures, as showing in Figure 6, which may address the excellent performance of the Cu-(S, S,S)-23a catalyst for this challenging reaction. With the Cu-catalyzed asymmetric N—H... 

It is presumed that the production of other monovalent derivatives such as CaNH2 or CaC5H5 from NH3 or C5H6 may involve similar excited metal atom insertions into N—H or C—H bonds. Unlike the reactions with H20 and alcohols, however, no studies of the dynamics have been carried out and even the thermochemistry is very uncertain. Clearly, more experimental and theoretical work is necessary before any firm conclusions can be drawn about mechanisms. 

---