Cyclopropane carbene-mediated

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

A catalytic tandem cyclopropanation-ring-closing metathesis of dienyne 80 led to derivative 81 in good yield (Scheme 30 <2004JA9524>). For internal alkynes, carbene-mediated ring-closing enyne metathesis was observed. Less favorable alkyne binding leads to preferential reactions of the metal carbene with the 1-alkene moiety. 

Korkowski, P. F., Hoye, T. R., Rydberg, D. B. Fischer carbene-mediated conversions of enynes to bi- and tricyclic cyclopropane-containing carbon skeletons. J. Am. Chem. Soc. 1988, 110, 2676-2678. 

The factors that direct a metallacyclobutane intermediate along one of these pathways are only partially understood. For example, in the case shown in Fig. 4.10, both metathesis and cyclopropanation are mediated by the same tungsten-carbene complex when the reaction is performed in a non-coordinating solvent [31]. These conditions are consistent with reaction via a metallacyclobutane because they allow the olefin to coordinate to the metal center, a prerequisite for [2 -I- 2] cycloaddition. In contrast, only cyclopropanation occurs when the reaction is performed in a coordinating solvent, presumably because formation of a metal-solvent adduct prevents olefin coordination and leaves only a direct carbene transfer mechanism available. 

The reaction of a metal-carbene complex with an olefin may lead to either cyclopropane or metathesis products, depending on the metal center and its ancillary ligands. In the case of olefin metathesis, the reaction may occur in variations that have enormous numbers of synthetic applications. Although these products are diverse in structure, they are all related by the same basic metal-carbene-mediated mechanism of formation. Because we provide only an overview of applications in this section and do not specify the particular catalyst used in each case, we direct the reader to the extensive reviews that are available for more information [32]. 

The molybdenum complex 1, a typical high-valent Schrock-type carbene, efficiently catalyzes the self-metathesis of styrene. On the other hand, the cationic iron complex 3 does not induce metathesis but stoichiometrically cyclopropanates styrene. The tungsten complex 2, again a Fischer-type carbene complex, mediates... 

These observations indicate that there is no sharp borderline between cyclopro-panating and metathesis-catalyzing carbene complexes. Fortunately the number of carbene complexes which mediate both cyclopropanation and alkene metathesis is rather small, and in the detailed overview given in the following sections it will become apparent that most carbene complexes are highly selective and thus valuable reagents for organic synthesis. 

Krief has applied selenium chemistry to some anionic cascade cyclisations.128 For example, 293 can be cyclised in two successive 5-exo reactions to give a mixture of the stereoisomers of 297. If 294 is warmed to 0 °C, an alternative sort of tandem process occurs after cyclisation onto the alkene, the organolithium 295 undergoes an intramolecular displacement, stereoselectively generating the 5,3-fused system of 296. Similar intramolecular cyclopropanations (of a-bromo organolithiums) have been described by Hoffmann151 but are probably mediated by carbenes rather than a sequential cyclisation-substitution sequence. 

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]. 

Metal aUcylidene complexes (see Schrock-type Carbene Complexes) have been proposed as intermediates in many catalytic reactions, including alkene metathesis (see Organic Synthesis Using Metal-mediated Metathesis Reactions), alkene and aUcyne polymerization, methylenation of carbonyl compounds, and cyclopropanation of alkenes. ... 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

Styrene cyclopropanation continues to attract much interest. Cationic complex CpFe(CO)2(THF) BF4" mediates carbene transfer from ethyl diazoacetate with high cis selectivity cis trans = 85 15) [38]. On the other hand, Tp Cu(C2H4), where Tp is hydrotris(3,5-dimethyl-l-pyrazolyl)borate, is one of the rare catalysts to promote carbene transfer from ethyl diazoacetate to alkenes and also to alkynes. While cyclopropanes are formed in high yield, cyclopropenes are obtained only in moderate yield [39]. The same complex also catalyzes nitrene transfer from PhI=NTs to alkenes to produce aziridines in high yields. 

Synthesis and structure of ruthenium and osmium porphyrin carbene complexes and their role in the metal-mediated cyclopropanation of alkenes 02CCR(231)151. 

Formation of the fused cyclopropane 96 from 95 by carbene cycloaddition, and subsequent TFA-mediated ring expansion provided access to the 1-benzoxepines 97 in low to moderate... 

Fig. 4.10. A tungsten-carbene complex that mediates both olefin cyclopropanation and metathesis.

Dirhodium compounds have proved to be highly efficient and effective catalysts for diverse reactions, which has led to their reputation as being important players in synthetic organic chemistry. A wide range of synthetically useful transformations, such as cyclopropanation, cyclopropenation, insertion into C-H and heteroatom-H bonds, cydoadditions, ylide formation and rearrangement, and other processes are mediated by the catalytic formation of dirhodium(II) carbenes via diazocarbonyl compounds [77],... 

There has been a summary of computational and experimental studies of the use of palladium complexes with A -heterocyclic carbenes (NHCs) in the asymmetric coupling of -hybridized carbon-hydrogen bonds with aryl halides. It has been shown that the electronic and catalytic properties of NHCs fused to porphyrins may be modified by varying the inner metal in the porphyrin. A DPT study of the use of palladium-NHC complexes in the asymmetric intramolecular a-arylation of 2-bromoaryl amides to give 3,3-disubstituted oxindoles (101) has been reported. The likely pathway involves insertion of the palladium into the arene-bromine bond to form a palladacycle which deprotonates to give an (9-enolate. Conversion into the C-enolate followed by reductive elimination gives the product. The intramolecular reaction of 0 a cyclopropane carbon-hydrogen bond in a 2-bromoanilide derivative has been used to form cyclopropyloxindoles, (102), in a palladium-catalysed, silver-mediated reaction. 

The use of diazo compounds has also attracted some attention. NHC-Au catalysts, and especially those bearing the IPr and IMes ligands, mediated the decomposition of diazo species, leading to organogold carbenes, which could be observed in the gas phase. Once formed, the NHC-Au carbene could participate in a variety of reactions that include insertions into X-H bonds (X = C, N, Buchner reactions, ° and olefin cyclopropanation. ... 

The absolute configuration of 1 was set by the Rh-mediated cyclopropanation of 4 with the diazo ester 5. Though closely related to the a-diazo P-keto ester 6, the alkene of 5 donates election density to the intermediate Rh carbene, making it more susceptible to the influence of the chiral ligands. The alkene of the enol ether then participated in the Cope rearrangement, dehvering 8. Routine functional group transformation then converted 8 to 1, that cyclized smoothly to 2. 

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