Cyclopropanation, Fischer carbene complexes

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). 

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... 

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>. 

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). 

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. 

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. 

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... 

Electron-deficient 1,3-dienes yield vinylsubstituted cyclopropanes upon [2+l]-cycloaddition with Fischer carbene complexes. [36] In particular cases, however, the three-membered cycloadducts are rather unstable and susceptible to a Cope rearrangement as outlined in Scheme 19 for an electron-rich diene ... 

Scheme 31.12 Polymer-bound Fischer carbene complexes for cyclopropanation.

Alternatively, Barluenga and coworkers have described the construction of related polycyclic systems 96 and 97 incorporating a cyclopropane, based on various cascade processes involving alkynyl Fischer carbene complexes of type 95 and nitrones or dihydrofurane, as illustrated in Scheme 5.34. 

Barluenga and coworkers [32] reported on [2+1]- and [4+3]cyclization reactions of alkyl-, aryl-, and acetoxyfulvenes with Fischer carbene complexes (Scheme 7.31). Unlike the previous cyclopropanation reactions of dienes with Fischer carbene complexes, the cyclopropanation reactions of fulvenes therein... 

Fischer carbene complexes have proven to be useful in a number of selective syntheses, although the major drawback of these systems is the need for a stoichiometric amount of metal. One way to circiunvent this problem is to employ polymer-boimd complexes that can be recycled. Barluenga et aL [34] prepared polymer-bound Fischer timgsten carbene complexes from the corresponding pentacarbonyl metal compounds The reactivity and reusabihty of the polymer-supported complexes was exemplified by a cyclopropana-tion reaction (Scheme 9). Carbene 11 was heated with methyl acrylate in dichloroethane, and after cooling, saturation with CO, filtration and washing, the polymer 12 could be re-converted to a carbene and recycled. The product of the reaction was a mixture of cyclopropane 13 and C - H inser-... 

Scheme 9 Cyclopropanation on solid phase using polymer-bound Fischer carbene complexes...

---