Cyclopropanation carbene synthesis, diazo compounds

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 control of carbene reactions from diazo compounds as precursors is classically mediated by copper catalysts and all the carbene reactions discussed in Section 8 are, in fact, improved by such catalysts. Moreover, the use of ligands on the metal allows some control of the stereochemistry of the products, the most striking example being the asymmetric synthesis of cyclopropanes with an excellent optical yield (>90S ce) [35]. 

For comprehensive reviews that provide numerous examples of cyclopropanation based on Rh- and Cu-carbene catalysis, see M. P. Doyle, M. A. McKervey, and T. Ye, Modem Catalytic Methods for Organic Synthesis with Diazo Compounds, Wiley New York, 1998 M. P. Doyle and D. C. Forbes, Chem. Rev., 1998, 98, 911 and M. P. Doyle, J. Org. Chem., 2006, 71, 9254. 

Monoaryldiazomethanes, readily prepared by a number of methods, are the carbene precursors most frequently used for the synthesis of arylcyclopropanes. When such diazo compounds are decomposed photochemically, thermally, or by using various transition-metal salts in the presence of an alkene, arylcyclopropanes are formed. The yield is often quite high, but in a number of cases cyclopropane formation has been hampered by competing reactions, of which, disregarding intramolecular reactions, azine formation, stilbene formation, and hydrogen abstraction followed by dimerization are the most predominant. Many aspects related to the use of diazomethane derivatives as carbene precursors have been thoroughly discussed by Wentrup. ... 

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. 

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. 

Fluorodiazirines have also been used extensively as carbene photoprecursors for cryogenic matrix isolation " and laser flash photolysis studies. Photolysis of fluorophenoxydiazirine has made observation of the corresponding carbene directly observable in yet another fashion encapsulated in a hemicarcer-and. Diazirines have been used for studies in solution of carbene philicities as well as for synthesis of cyclopropanes and cyclopropenes.Of course, diazo compounds can also serve as carbene photoprecursors, but for carbenes such as difluorocarbene, the diazo precursor is either nonexistent or extremely unstable. 

Intramolecular reactions of carbenes with alkenes have been exploited in synthesis. The sesquiterpene cycloeudesmol was prepared using, as a key step, the intramolecular cyclopropanation of the diazoketone 122 (4.97). The cyclopropana-tion reaction occurs stereoselectively to give the tricyclic product 123, which was subsequently converted into the natural product. A synthesis of sesquicarene was achieved using the copper(I)-catalysed decomposition of the diazo compound 125, itself prepared by oxidation of the hydrazone 124 (4.98). 

Cyclopropanes and their derivatives are versatile building blocks in organic synthesis. They are also present in many natural products and frequently included as substituents in the structure of new biologically active substances. While cydopropylbo-ranes have long been described [34], it is only since an efficient access to the boronic esters was reported that they really attracted chemist s interest. In 1989, the first additions of carbenes, generated from diazo compounds and palladium acetate, to pina-col alkenylboronic esters were reported to give racemic mixtures of cyclopropyl-boronates (Scheme 9.15) [35]. 

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]. 

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