Cyclopropanation, Fischer carbene

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

One of the earliest reported thermal reactions of Fischer carbene complexes was the reaction with olefins to give cyclopropanes [127]. More recently it has been shown that photolysis accelerates inter molecular cydopropanation of electron-poor alkenes [128]. Photolysis of Group 6 imine carbenes with alkenes... 

Carbenes are both reactive intermediates and ligands in catalysis. They occur as intermediates in the alkene metathesis reaction (Chapter 16) and the cyclopropanation of alkenes. As intermediates they carry hydrogen and carbon substituents and belong therefore to the class of Schrock carbenes. As ligands they contain nitrogen substituents and are clearly Fischer carbenes. They have received a great deal of attention in the last decade as ligands in catalytic metal complexes [58], but the structural motive was already explored in the early seventies [59],... 

The major direction taken with Fischer carbenes, however, has been annulation reactions (e.g., Eqs. 11-13) rather than cyclopropanation and insertion. Here, the dissociation of carbon monoxide initiates the sequence of events that lead to product (e.g., Eq. 42). °° Alternatively, an unsaturated unit conjugated with the carbene... 

So what is left to be accomplished During the current decade one can expect further asymmetric applications and catalyst designs for metathesis reactions, a maturing of chiral catalyst development for cyclopropanation and insertion with increasing synthetic applications, and decreased reliance on traditional Fischer carbenes in synthesis. Major changes remain for ylide applications, especially those that can be enantioselective, in catalytic carbene chemistry, and advances in nitrene chemistry that are comparable to those achieved over the years in carbene chemistry are in their infancy. 

Table 1. Synthesis of Donor-Acceptor-Substituted Cyclopropanes with Fischer-Carbene-Complexes...

Alkynyl Fischer carbene complexes 64 (R = H) in the presence of a nitrone undergo a cascade cycloaddition/cyclopropanation process to afford 4-isoxazolines such as 65 in good yields. Under the same conditions, substituted complexes 64 (R = Me, Ph) gave naphthalenes 66 through a cycloaddition/metathesis process <07OL4143>. 

An enantiopure Fischer carbene complex was able to react with 2-methoxyfuran in an intriguing manner that led to the formation of trisubstituted cyclopropane molecules in excellent diastereoselectivities. The relevant mechanism for the formation of a cyclopropane is depicted in Scheme 88 <2007CEJ1326>. 

Several useful inter- and intramolecular reactions of chromium, molybdenum, tungsten, iron, or manganese Fischer carbenes with aUcenes to form cyclopropanated products have... 

Diastereoselective and enantioselective (see Enantio-selectivity) cyclopropanations of chiral alkenes can be achieved (Scheme 57). Unactivated alkenes usually do not participate in cyclopropanation reactions of Fischer carbenes. However, alkenyl- and heteroaryl-substituted group 6 alkoxy carbene complexes cyclopropanate unactivated alkenes in good yield (Scheme 58). ... 

Intramolecular cyclopropanations of pendant alkenes are more favorable. Heteroatom-substituted 2-aza- and 2-oxabicyclo[3.1.0]hexanes, together with 2-oxabicyclo[4.1.0] heptanes, can be prepared from chromium and tungsten Fischer carbenes having a tethered alkene chain. An interesting carbene formation via a cationic alkylidene intermediate, nucleophilic addition (see Nucleophilic Addition Rules for Predicting Direction), and intramolecular cyclopropanation is shown in Scheme 59. An intramolecular cyclopropanation via reaction of alkenyl Fischer carbene complex (28) andpropyne was used in a formal synthesis of carabrone (Scheme 60). 

Cyclopropanation reactions of nonheteroatom-stabilized carbenes have also been developed. The most versatile are the cationic iron carbenes that cyclopropanate alkenes with high stereospecificity under very mild reaction conditions. The cyclopropanation reagents are available from a number of iron complexes, for example, (9-alkylation of cyclopentadienyl dicarbonyliron alkyl or acyl complexes using Meerwein salts affords cationic Fischer carbenes. Cationic iron carbene intermediates can also be prepared by reaction of CpFe(CO)2 with aldehydes followed by treatment with TMS-chloride. Chiral intermolecular cyclopropanation using a chiral iron carbene having a complexed chromium tricarbonyl unit is observed (Scheme 61). 

Interestingly, thermal reactions of olefins with Fischer carbenes give rise to cyclopropanation products. Although relatively rare, photochemical cyclopropanations have been reported. 

The reaction of alkenes with Fischer carbene complexes most typically leads to cyclopropane products however, the formation of a three-membered ring product from a reaction with an alkyne has been observed on only one occasion. The reaction of the cationic iron-carbene complex (199) with 2-butyne presumably leads to the formation of the cyclopropene (200), which was unstable with respect to hydride abstraction by the starting carbene complex and the ultimate product isolated from this reaction was the cyclopropenium salt (201) and the benzyl-iron complex (202). Cyclopropene products have never been observed from Group 6 carbene complexes despite the extensive investigations of these complexes with alkynes that have been carried out since the mid 1970s. 

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. 

Equations 10.47 to 10.51 demonstrate several examples of cyclopropanation reactions. As shown in equation 10.47, reaction of Group 6 Fischer carbene complexes with an electron-poor alkene—at a temperature high enough to promote CO dissociation—gives diastereomeric mixtures of cyclopropanes.71 Path a (Scheme 10.6) is the likely mechanism for this reaction, and the first of the two diastereomeric products tends to be favored. 

Although the use of Fischer carbene complexes for cyclopropanation is somewhat limited, there are other procedures that are more general. One such method is the use of cationic alkylidene complexes, with Fe complexes being perhaps the most thoroughly studied. These react at low temperature with a variety of alk-enes bearing alkyl and aryl substituents equation 10.50 shows a typical example with the cationic alkylidene precursor usually generated in situ.74 Path b (Scheme 10.6) has been shown to be the operative mechanism for these reactions.75... 

Coupling of a Fischer carbene complex with an alkene can generate a vinylcarbene intermediate 12 via an insertion-rearrangement reaction, which can then further react with a double bond. For intramolecular reactions of tethered enynes 10, the products formed are bicyclic cyclopropanes 14 intermolecular reactions lead to cycloalkenylcyclopropanes. 

The results of a series of reactions of Fischer carbene complexes with enynes are summarized in Tables 1 and 2. Cyclopropane synthesis is accomplished in the alkoxy series (Y = OMe) by the generation of a mixture of geometric isomers of enol ethers, whereas in the dialkyl-amino series, ketones are directly obtained after hydrolysis of the enamines. Higher yields have been obtained using the amino analog pentacarbonyl(l-pyrrolidinoethylidene)chromium [Y = N(CH2)J. - ... 

Electrophilic transition-metal-carbene complexes (Fischer carbene complexes) serve as formal carbene transfer reagents in reactions with alkenes to give functionalized cyclopropanes. This reaction behavior is well documented for alkoxycarbene complexes of elements of group In contrast, aminocarbene complexes exhibit a different reactivity over a wide range of conditions and [2 + 1] cycloadditions to alkenes represent exception. 

Interestingly, cobalt porphyrin catalysts tend to prevent carbene dimerization reactions, and allow cyclopropanation reactions with electron-deficient alkenes. This feature illustrates the more nucleophilic behavior of the carbenoid species formed as compared to typical electrophilic Fischer carbenes. The enhanced nucleophilic character of the carbene reduces its tendency to dimerize and allows reactions with more electron-deficient olefins. 

On the other hand, there have been hardly any kinetic investigations of the many reactions that have proven to be among the most useful or unique applications of Fischer carbene complex chemistry. Hence they are not part of this chapter although a few of the most prominent ones need to be mentioned. They include cyclopropanation of electrophilic olefins (e.g., equation 5), metathesis (e.g., equation 6) and reactions of a,j8-unsaturated carbene complexes such as 6 (see equation 3) that lead to what de Meijere et al have called an... 

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