Carbene Experimental Procedures

Of course the structural changes represented in Table 1 are much more complex than the simple bond angle plus electronic effect analysis reveals. For example, solvation of the carbene may depend on the details of its structure, and solvation undoubtedly influences chemical and physical properties (Langan et al., 1984). Nonetheless, it is possible to develop a good grasp of the most important properties of aromatic carbenes from the simple considerations described above. Before we proceed to examine these relationships in more detail, the carbene properties of interest must be identified, and the experimental procedures available for measurement of these properties must be critically considered. 

Experimental Procedure 2.1.1. Preparation of a Chromium Carbene Complex from Chromium Hexaearbonyl [Methoxy(methyl)carbene]pentacarbonylchro-mium [37, p 130]... 

Experimental Procedure 2.1.3. Preparation of an Iron Carbene Complex by a-Abstraction of Hydride Dicarbonyl(T 5-cyclopentadienyl)(phenylthiocarbene) iron hexafluorophosphate [179]... 

Experimental Procedure 2.2.1. Photolysis of a Chromium Carbene Complex 2-Benzyl-4-benzyloxy-4-methyl-2,3,4,4a,7,7a-hexahydro-li/-cyclopenta[c]pyri-din-3-one [294]... 

Experimental Procedure 2.2.2. Cyclopropanation with a Chromium Carbene Complex Diethyl n-a/i5-3-Methoxy-3-phenylcyclopropane-l,2-dicart>oxylate [325]. 

Experimental Procedure 2.2.5. Gyclopentannulation with a Tungsten Alkynyl-carbene Complex l-(l-Ethoxy-3-phenyl-5,9b-dihydro-4H-cycldpenta a]naph-thalen-9 yl)pyrrolidine [353]... 

Experimental Procedure 2.2.6. Cyclopentannulation with a Molybdenum Aryl-carbene Complex 3-Hexyl-5-methyl-l-indanone 346]... 

Photolysis or thermolysis of heteroatom-substituted chromium carbene complexes can lead to the formation of ketene-like intermediates (cf. Sections 2.2.3 and 2.2.5). The reaction of these intermediates with tertiary amines can yield ammonium ylides, which can undergo Stevens rearrangement [294,365,366] (see also Entry 6, Table 2.14 and Experimental Procedure 2.2.1). This reaction sequence has been used to prepare pyrrolidones and other nitrogen-containing heterocycles. Examples of such reactions are given in Figure 2.31 and Table 2.21. 

Experimental Procedure 2.2.9. [4 + 3] Cycloaddition of a Chromium Carbene Complex to a 2-Aminodiene 6-(2-Furyl)bicyclo[5.4.0]undecan-2,4-dione [264]... 

Experimental Procedure 3.1.1. Preparation of a Molybdenum Carbene Complex by Nucleophilic Abstraction (2,6-Piisopropylphenylimido)bis[ 1,1 -bis(trifluoro-methyl)ethoxy](2-methyl-2-phenyH-propylidene)molybdenum [37,416,417]... 

Experimental Procedure 3.2.1. Cyclopropanation with an Iron Carbene Conqjlex 1,1-Diphenylcyclopropane [468]... 

Experimental Procedure 3.2.2. Cyclopropanation with a Titanium Carbene Complex (E)-l-Hexyl-2-(2-phenylethenyl)cyclopropane [33]... 

Table 3.7. Intramolecular C-H insertion reaction of cationic iron carbene complexes generated in situ by S-alkylation of 1-(phenylthio)alkyl complexes (see Experimental Procedure 3.2.3).

Apart from the tandem metathesis/carbonyl o[efination reaction mediated by the Tebbe reagent (Section 3.2.4.2), few examples of the use of stoichiometric amounts of Schrock-type carbene complexes have been reported. A stoichiometric variant of cross metathesis has been described by Takeda in 1998 [634]. Titanium carbene complexes, generated in situ from dithioacetals, Cp2TiCl2, magnesium, and triethylphosphite (see Experimental Procedures 3.2.2 and 3.2.6), were found to undergo stoichiometric cross-metathesis reactions with allylsilanes [634]. The scope of this reaction remains to be explored. 

Enantiomerically pure copper and rhodium complexes enable enantioselective catalysis of carbene-mediated reactions. Such reactions will be discussed more thoroughly in Section 4.2. Experimental Procedure 4.1.1 describes the preparation of an enantiomerically pure rhodium(II) complex which has proven efficient for catalysis of different types of carbene complex-mediated C-C-bond-forming reactions with high asymmetric induction. 

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. 

Since the first experiments with chiral copper complexes reported by Nozaki [650] and Aratani [1027] many different catalysts have been examined, both for intermolecular and intramolecular cyclopropanations (for a review, see [1369]). Syntheses of natural products [955,1370] and drugs [1371] using asymmetric cyclopropanation with chiral electrophilic carbene complexes have been reported. A selection of useful catalysts is given in Figure 4.20 (see also Experimental Procedure 4.1.1). 

The subject of this book has been organized in three main sections preparation and applications of heteroatom-substituted carbene complexes (Fischer-type carbenes), non-heteroatom-substituted carbene complexes, and acceptor-substituted carbene complexes. In each section the different types of reaction have been ordered either according to the mechanism or according to the type of product. In addition to a selection of illustrative examples, several experimental procedures have been included. These were chosen taking into account safety, availability of starting materials, relevance of the products, and general interest. 

Experimental Procedure 2.2.5. Cyclopentannulation with a Tungsten Alkynyl-carbene Complex I-(I-Ethoxy-3-phenyI-5,9b-dihydro-4f/-cyclopenta[a]naph-thaIen-9-yl)pyrroIidine... 

Experimental Procedure 3.1.3. Preparation of a Ruthenium Carbene Complex from a Diazoalkane Dichloro-bis(tricyclohexylphosphine)benzylideneruthenium... 

Experimental Procedure 3.2.3. Intramolecular C-H Insertion of an Iron Carbene Complex 8-Phenylbicyclo[4.3.0]nonan-2-one... 

It should be pointed out that despite their high reactivity carbenes are selective, and while they will react with hydrocarbons in the absence of nucleophiles, a nucleophilic group exposed within the bilayer will preferentially be attacked. Some properties of the three most thoroughly tested reagents iodonaphthyl azide, adamantane diazirine, and 3-trifluoromethyl-3-(m-iodophenyl)diazirine are summarized in Table 6.1. There follows a brief description of a typical experimental procedure, a discussion of control experiments, and several caveats, followed by some examples of the applications of hydrophobic reagents. 

The present overview deals with the application of Fischer chromium carbene complexes in the benzannulation reaction for the preparation of highly substituted aromatic compounds. Before focussing on specific arenes (Section 8.5), details of the mechanism are given (Section 8.2), and the scope and limitations of the reaction are defined (Section 8.3). A short description of the experimental procedure is given thereafter (Section 8.4). Finally, the contribution deals with the application of the chromium carbene benzannulation to natural compounds and molecules with biological activity (Section 8.6). 

Enders D, Balensiefer T, Niemeier O, Christmann M (2007c) Nucleophilic N-heterocyclic carbenes om asymmetric organocatalysis. In Dalko PI (ed) Enantioselective organocatalysis—reactions and experimental procedures. Wiley-VCII, Weinheim, p 331... 

Thermal decomposition of 2-diazohexafluoropropane, or 2-diazo-3,3,3-trifluoro-propanenitrile in excess benzene (150-200 "C, autoclave) resulted in efficient cyclopropanation of an aromatic C-C double bond. In solution, the 7-trifluoromethylnorcaradiene 9 (-bicyclo[4.1.0]hepta-2,4-diene) so formed is in rapid valence equilibrium with the corresponding cycloheptatriene 10 however, this equilibrium is shifted predominantly or completely to the cycloheptatriene side. As a byproduct in the synthesis, the product of carbene insertion into an aromatic C-H bond is obtained. An experimental procedure for the synthesis of 10b can be found in Houben-Weyl, Vol. 19 b, p 1031. 

Carbenoid addition of diazocarbonyl compounds to pyrrole, A -alkylpyrroles, indole, N-alkylindoles, imidazole, and benzimidazole does not result in cyclopropanation, but leads to the formal products of carbene insertion into a heterocyclic C-H bond (see Houben-Weyl, Vol.E19b, ppll58 and 1334). However, Af-acylpyrroles, and Af-acylindoles - " have successfully been converted into 2-azabicyclo[3.1.0]hex-3-ene-exo-6-carboxylates and alkyl-1,la,2,6b-tetrahydrocyclopropa[ ]indole-exo-l-carboxylate, respectively (for an experimental procedure, see Houben-Weyl, Vol.E19b, pll60). 

This experimental procedure involves a three-step synthesis of a carbene transfer agent, imidazo-2-yildene-silver(I) chloride (6) (Fig. 2). In the first step glyoxal-fcz.v (2,4,6-trimethylphenyl)unine (7) is produced, which is converted into l,3-d/5(2,4,... 

In order to facilitate the search for the stereoselective synthesis of a cyclopropane derivative with a particular substitution pattern, this section is organized according to the carbene (carbenoid) substituents. The sequence of carbenes therefore parallels that in the Houben-Weyl Volume E 19 b on Carbene (Carbenoidc)/Carbine which deals with all aspects of carbene chemistry including scope and limitations of various [2 + 1] cycloadditions. For many classes of carbenes. and. in particular, for typical experimental procedures, cross references are made to the corresponding pages in that volume. 

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