Cyclopropanation metal carbene synthesis

The carbene derived by metal-catalysed decomposition of ethyl diazoacetate attacks alkenes to introduce a two-carbon fragment into a cyclopropane—an industrial synthesis of ethyl chrysanthe-mate, a precursor to the pyrethrin insecticides (see p. 000), uses this reaction. The diene in the starting material is more nucleophilic (higher-energy HOMO see Chapter 20) than the single alkene in the product, so the reaction can be stopped after one carbene addition. 

For discussions on pathways available for cyclopropanation, see (a) C. P. Casey, Metal-Carbene Complexes in Organic Synthesis, in Transition Metal Organometallics in Organic Synthesis, H. Alper, Ed, Academic Press New York, 1976, Vol. 1, pp. 189-233 (b) M. Brookhart and W. B. Studabaker, Chem. Rev., 1987, 87, 411 and (c) R. H. Grubbs, T. M. Trnka, and M. S. Sanford, Transition Metal-Carbene Complexes in Olefin Metathesis and Related Reactions, in Fundamentals of Molecular Catalysis, H. Kurosawa and A. Yamamoto, Eds, Elsevier Amsterdam, 2003, pp. 187-231. 

Stoichiometric use of transition-metal-carbene complexes in organic synthesis has been thoroughly reviewed.Various examples using carbene complexes containing cyclopropane subunits have been reported.Here, the cyclopropyl moiety is either attached directly to the carbene carbon or is placed in a more remote position. This section only discusses isolated carbene complexes. Related transition-metal-catalyzed conversions of diazo compounds containing cyclopropane subunits, which are interpreted to proceed via carbene intermediates (e.g. ref 130), are not discussed here. 

Cyclopropyl-substituted transition-metal carbene and carbyne complexes, especially as cyclo-propylidene- or as cyclopropylcarbene complexes, have been used as synthetic building blocks with or without ring opening. Examples of cyclopropane synthesis via decomplexation are described in Section 1.A.5.2.6. 

There has been no comprehensive monograph on carbenes since the books of Kirmse, Jones, and Maas were published in the early 1970 s. Does this development indicate a decrease in interest in carbene chemistry Not at all One might even say that it seems that the enormous increase in the number of investigations on carbene reactions, particularly with the help of complex rhodium and related metal catalysts, makes it difficult to write a book on all aspects of carbene chemistry. The catalytic procedures for metal-carbene transformations from aliphatic diazo compounds are now the most important tool for cyclopropanations and related processes in organic synthesis. We shall mention reviews on that subject in Sections 8.7 and 8.8. 

The ligand substitution reactions of carbene complexes such as (CO)s-CrC(OCH3)CHj allow the synthesis of many phosphine- and phosphite-substituted carbene complexes. It is expected that these complexes will have modified reactivity and will provide a means of fine tuning reactions of carbene complexes. More importantly, the substitution reactions of carbene complexes proceed by a dissociative mechanism involving coordinatively unsaturated intermediates. Study of the ligand substitution reactions can give valuable information about these coordinatively unsaturated intermediates which are also involved in the important cyclopropanation, alkene scission, and thermolysis reactions of metal-carbene complexes. 

The metal-carbenoid intermediate has been widely applied in organic synthesis for cycloaddition, cyclopropanation, and selective C-H bond insertion [245, 246]. The traditional methods to prepare metal carbenoids are from diazo compounds, and the recent reports have shown the feasibility to generate metal carbenes or carbenoids in situ from some precursors, such as alkynes [247] and cyclopropenes [248]. With great efforts, the metal-carbenoid chemistry was esteemed as one efiftcient redox-neutral C(sp )-H bond functionalization protocol (Scheme 2.42). Herein, we list several key reviews in this topic to readers for extending reading [249-254]. 

The metal-carbene complexes are nowadays extensively used as reagents in organic synthesis. Fischer carbene complexes have become valuable building blocks in various stoichiometric reactions such as the aldol reaction, benzannu-lation, cycloaddition, cyclopropanation, and Michael reaction. In particular, Fischer alkenyl carbene complexes have been widely used in cycloadditions [2c,2f,5]. On the other hand, a typical reaction of Schrock carbene complexes is olefin metathesis (Figure 5.2) [6]. Schrock s olefin metathesis catalyst is a high reactivity, but air- and moisture-sensitive reagent. 

These complexes can be isolated in some cases in others they are generated in situ from appropriate precursers, of which diazo compounds are among the most important. These compounds, including CH2N2 and others, react with metals or metal salts (copper, palladium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds.1063 Optically active complexes have been used for enantioselective cyclopropane synthesis.1064... 

The addition of transition metal fragments ML (L = two-electron donor ligand) across formally unsaturated metal-metal or metal-carbon bonds is a well-developed synthetic route to heteronuclear clusters (1,2,11,12,27) and has received theoretical justification from Hoffmann s isolobal principle (46). The addition of a PtL2 fragment across an M=M double bond may be considered as analogous to the reaction of a carbene with an olefin, resulting in a cyclopropane. The use of isolobal analogies in the directed synthesis of heteronuclear clusters has been reviewed (11,12,27). 

Another broad class of compounds are the bridged carbene complexes. These compounds contain two identical or two different metal centers with the carbene centers bonded to both of the metal atoms in a bridging relationship. However, these binuclear complexes generally do not show classical carbene reactivity and will therefore not be discussed further, except to mention briefly the special case of the titanium-aluminum complex (3) developed by Tebbe and Grubbs and their coworkers.101 This, and related complexes, has proven to be particularly useful in organic synthesis, although its principal importance is in reactions other than cyclopropanations. 

It is abundantly clear from the preceding discussion that dihalocyclopropanes are versatile intermediates in organic synthesis. Although a wealth of chemistry has already been uncovered, prospects remain bright for interesting developments in the future. Areas such as the application of dihalocyclopropanes in heterocyclic synthesis via carbene insertion into C—H bonds adjacent to heteroatoms, reactions of dihalocyclopropanes with organometallics and the synthetic applications of metallated derivatives deserve further exploration. The chemistry of difluoro-, diiodo- and mixed dihalo-cyclopropanes can be expected to attract some attention. Finally, other heteroatom-substituted cyclopropanes derived ftom dihalocyclopropanes will also invoke further investigation. 

Carbenes, as synthetic species, are fascinating chemicals, and the synthesis of cyclopropanes by a [2 +1] cycloaddition of alkenes with carbenes represents an extremely fruitful approach. Recently, highly effective intramolecular [2 + 1] cycloadditions, novel triplet sensitizers, metal-catalyzed cyclopropanations, and novel precursors of carbenes have been developed. 

---