Electrophiles carbenes

Heterocyclizations by reactions of electrophilic carbenes with a-amino acids derivatives 97T3425. 

The electrophilic carbene carbon atom of Fischer carbene complexes is usually stabilised through 7i-donation of an alkoxy or amino substituent. This type of electronic stabilisation renders carbene complexes thermostable nevertheless, they have to be stored and handled under inert gas in order to avoid oxidative decomposition. In a typical benzannulation protocol, the carbene complex is reacted with a 10% excess of the alkyne at a temperature between 45 and 60 °C in an ethereal solvent. On the other hand, the non-stabilised and highly electrophilic diphenylcarbene pentacarbonylchromium complex needs to be stored and handled at temperatures below -20 °C, which allows one to carry out benzannulation reactions at room temperature [34]. Recently, the first syntheses of tricyclic carbene complexes derived from diazo precursors have been performed and applied to benzannulation [35a,b]. The reaction of the non-planar dibenzocycloheptenylidene complex 28 with 1-hexyne afforded the Cr(CO)3-coordinated tetracyclic benzannulation product 29 in a completely regio- and diastereoselective way [35c] (Scheme 18). 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

The synthesis and X-ray structural determination of a stable Ir111 hydride/alkylidene complex, (165), has been reported, in which the tridentate N3 ligand is TpMe2. 9 The complex undergoes reversible hydride migration onto the electrophilic carbene atom, as shown in reaction Scheme 20. 

Metallacycle Formation Involving Electrophilic Carbene Addition to a Benzene Ring of the PPh3 Ligand... 

For very electrophilic carbene ligands bound to a metal center which also has coordinated an aromatic phosphine ligand,there is the possibility of the following intramolecular substitution reaction leading to a metallacycle ... 

The a-osmiumdiazo compound 91 decomposes in a thermal reaction to yield the metallacyclic complex 93 (130). This resembles the electrophilic carbene insertion reaction forming OsCl(CO)2(PPh2C6H4CHCl) (PPh3) (77) (see Section V,D,2), and we suggest that a similar insertion reaction of an electrophilic, cationic osmium carbyne 92 is the key step in this transformation. An X-ray structure determination has confirmed the formulation of 93. 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

Oxocyclohexadienylidene (la) and derivatives are highly reactive, electrophilic carbenes. Suitable precursors of these carbenes are quinone diazides... 

Many chemical reactions involving carbenes are believed to involve the initial formation of weak, highly reactive complexes. For example, several reactions of electrophilic carbenes with various nucleophiles are thought to involve n complexes.49-60-64 However, while kinetic and product studies often suggest their existence, their direct detection is often quite difficult. Recently,... 

Cyclodditions to Carbon-Heteroatom Triple Bonds. Transient electrophilic carbenes are known to react with nitriles to give transient46 or even stable nitrile ylides 30.47 No reaction of transient nucleophilic carbenes with nitriles has been reported. 

MO small energy-difference between metal nd and carbene 2p nucleophilic carbene complex large energy-difference between metal nd and carbene 2p electrophilic carbene complex... 

Fig. 1.5. Orbital interaction in nucleophilic and electrophilic carbene complexes.

The structure of rhodium(II) carboxylate-derived carbene complexes has been assessed both by quantum mechanical calculations [19,20] and by the study of rhodium(II) carboxylate isonitrile complexes [20,21]. Recent investigations [20] suggest, that also in these highly electrophilic carbene complexes there is a significant n backbonding from rhodium to carbon. 

Fig. 1.9. Possible mechanism of the cyclopropanation of alkenes with electrophilic carbene complexes [28].

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

Protonation of alkenyl complexes has been used [56,534,544,545] for generating cationic, electrophilic carbene complexes similar to those obtained by a-abstraction of alkoxide or other leaving groups from alkyl complexes (Section 3.1.2). Some representative examples are sketched in Figure 3.27. Similarly, electron-rich alkynyl complexes can react with electrophiles at the P-position to yield vinylidene complexes [144,546-551]. This approach is one of the most appropriate for the preparation of vinylidene complexes [128]. Figure 3.27 shows illustrative examples of such reactions. 

In addition to catalytically active transition metal complexes, several stable, electrophilic carbene complexes have been prepared, which can be used to cyclopropanate alkenes (Figure 3.32). These complexes have to be used in stoichiometric quantities to achieve complete conversion of the substrate. Not surprisingly, this type of carbene complex has not attained such broad acceptance by organic chemists as have catalytic cyclopropanations. However, for certain applications the use of stoichiometric amounts of a transition metal carbene complex offers practical advantages such as mild reaction conditions or safer handling. 

Because electrophilic carbene complexes can cyclopropanate alkenes under mild reaction conditions (Table 3.1) [438,618-620], these complexes can serve as stoichiometric reagents for the cyclopropanation of organic compounds. Thoroughly investigated carbene complexes for this purpose are neutral complexes of the type (C0)5M=CR2 (M Cr, Mo, W) and cationic iron(IV) carbene complexes. The mechanism of cyclopropanation by electrophilic carbene complexes has been discussed in Section 1.3. 

Some transition metal complexes readily react with ylides to yield electrophilic carbene complexes. If these complexes can transfer the carbene to a given substrate in such a way that the original transition metal complex is regenerated then this complex can be used as a catalyst for the transformation of the ylide (carbene precursor) into carbene-derived products (Figure 3.35). 

In cyclopropanations with electrophilic carbene complexes, yields of cyclopropanes tend to improve with increasing electron density of the alkene. As illustrated by the examples in Table 3.5, cyclopropanations of enol ethers with aryldiazomethanes often proceed in high yields. Simple alkyl-substituted olefins are, however, more difficult to cyclopropanate with diazoalkanes. A few examples of the cyclopropanation of enamines with diazoalkanes have been reported [650]. 

Most electrophilic carbene complexes with hydrogen at Cjj will undergo fast 1,2-proton migration with subsequent elimination of the metal and formation of an alkene. For this reason, transition metal-catalyzed cyclopropanations with non-acceptor-substituted diazoalkanes have mainly been limited to the use of diazomethane, aryl-, and diaryldiazomethanes (Tables 3.4 and 3.5). 

Carbene C-H (and Si-H, [695]) insertion is characteristic of electrophilic carbene complexes. In particular the insertion reactions of acceptor-substituted carbene complexes (Section 4.2) have become a valuable tool for organic synthesis. 

Electrophilic carbene complexes generated from diazoalkanes and rhodium or copper salts can undergo 0-H insertion reactions and S-alkylations. These highly electrophilic carbene complexes can, moreover, also undergo intramolecular rearrangements. These reactions are characteristic of acceptor-substituted carbene complexes and will be treated in Section 4.2. 

Fig. 4.3. Possible mechanisms for the formation of vinylcarbene complexes from alkynes and electrophilic carbene complexes.

The intramolecular addition of acylcarbene complexes to alkynes is a general method for the generation of electrophilic vinylcarbene complexes. These reactive intermediates can undergo inter- or intramolecular cyclopropanation reactions [1066 -1068], C-H bond insertions [1061,1068-1070], sulfonium and oxonium ylide formation [1071], carbonyl ylide formation [1067,1069,1071], carbene dimerization [1066], and other reactions characteristic of electrophilic carbene complexes. 

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