Fischer carbene complexes nucleophilic substitution

S+3C] Heterocyclisations have been successfully effected starting from 4-amino-l-azadiene derivatives. The cycloaddition of reactive 4-amino-1-aza-1,3-butadienes towards alkenylcarbene complexes goes to completion in THF at a temperature as low as -40 °C to produce substituted 4,5-dihydro-3H-azepines in 52-91% yield [115] (Scheme 66). Monitoring the reaction by NMR allowed various intermediates to be determined and the reaction course outlined in Scheme 66 to be established. This mechanism features the following points in the chemistry of Fischer carbene complexes (i) the reaction is initiated at -78 °C by nucleophilic 1,2-addition and (ii) the key step cyclisation is triggered by a [l,2]-W(CO)5 shift. 

Nucleophilic additions to alkenes 293 Nucleophilic vinylic substitution (SNV) Reactions 298 Nucleophilic substitution of Fischer carbene complexes 303 Reactions involving carbocations 309 Miscellaneous reactions 312... 

Other reactions for which a discussion of their structure-reactivity behavior in terms of the PNS has provided valuable insights include nucleophilic addition and substitution reactions on electrophilic alkenes, vinylic compounds, and Fischer carbene complexes reactions involving carbocations and some radical reactions. 

NUCLEOPHILIC SUBSTITUTION OF FISCHER CARBENE COMPLEXES Intrinsic rate constants... 

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 most prominent systems studied thus far are the Fischer carbene complexes of the Group 6 metals, i.e., Cr, Mo and W, e.g., 4. One important process that will be discussed at some length in this chapter is nucleophilic substitution, e.g., the replacement of the MeO group by a group with a different heteroatom such as an amino or thioalkyl group. This reaction proceeds via a tetrahedral intermediate (equation 1) and is similar to nucleophilic substitutions on carboxylic esters. 

The bonding interactions of a carb)me ligand are essentially those of a metal carbene complex, but with an additional ir-bond (Figure 2.16). One orbital of cr-symmetry and two of iT-symmetry overlap with three metal orbitals of appropriate symmetry. When considered trianionic, all three orbitals of the ligand fragment contain two electrons. Theoretical studies of heteroatom-substituted or "Fischer-type" carbyne complexes - indicate that the HOMO predominantly consists of the metal fragment, and the LUMO consists of one of the TT -orbitals of the metal-carbon bond. This result explains the tendency of nucleophiles to attack the carbyne carbon in carbyne complexes, just as they attack the carbene carbon in Fischer carbene complexes. 

The electrophilic nature of Fischer carbene complex of Cr and W featuring an alkoxy or a thiomethyl substituent has been assessed in the nucleophilic substitution of the carbene heteroelement by the cyanamide anion.Alkoxy carbene complexes were found to be expectedly more reactive. Tungsten carbene were found to exhibit higher kinetic constants as a consequence of the higher electronegativity of W compared to Cr. 

OrganometaUic nucleophiles are also useful for MIRC cyclopropanation. The treatment of chloroalkyl oxazoline with LDA generated an oxazoline anion, which underwent cyclopropanation with alkenes through conjugate addition followed by intramolecular substitution [14]. The unsaturated Fischer carbene complex was also useful (Scheme 1.10) [15]. MIRC reactions to heterocyclic compounds have also been reported [16]. 

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

Indeed, nucleophilic attack at Ca is the most widely observed single reaction of Fischer carbenes. Substituent substitution is favored when one of the substituents on the carbene carbon is a good leaving group, e.g., halide, alkoxide, etc. Aminolysis of complex 41 typifies this mode of reaction (17),... 

The reactivity displayed by the heteroatom-substituted Ru, Os, and Ir carbene complexes discussed in this section toward nucleophilic reagents contrasts sharply with that described for the Fischer compounds. The reactions of these Group 8 complexes are almost exclusively restricted to the metal-ligand framework, with only two related substituent substitution reactions being reported (44) ... 

As in carboxylic esters it is possible to substitute alkoxy groups of Fischer-type carbene complexes by non-carbon nucleophiles, such as other alcohols [73,214,218], enols [219], aliphatic amines [43,64,66,220-224], aniline [79], imines [225], or pyrroles [226]. Strong nucleophiles can also lead to a dealkylation of methoxy-substituted carbene complexes (5 2 at the methyl group, [227]), in the same way as methyl esters can be cleaved by nucleophiles such as iodide. Carbon... 

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

Reaction of crowded chromium alkenyl Fischer carbene (50) with bulky ketene acetals provides an interesting entry to 3-substituted pent-l-ynoate (53)45 Formation of the alkyne can be rationalized by a 1,4-nucleophilic addition of the ketene on the unsaturated carbene complex (crowded complexes will not undergo potential 1,2-addition), following by oxonium (51) formation and fragmentation to a vinylidene carbene complex (52), which undergoes a 1,3-shift to the alkynylchromium complex leading the alkyne after reductive elimination. 

Alkylidenes have been prepared by reduction of alkyli-dynes, by C H oxidative addition from alkyls, and by treatment of unsaturated metal clusters with diazoalkanes. In most instances, the alkylidene adopts a /r2-h coordination mode. However, alkylidenes with heteroatom substituents may also be found in terminal coordination modes. The latter are typically prepared by the Fischer-type carbene route (see Fischer-type Carbene Complexes) (sequential addition of nucleophilic and electrophilic alkylating agents to carbonyl or isocyanide ligands), by condensation of metal fragments with mono- or dimetallic carbene complexes, or by C-H activation of alkylamines. These heteroatom substituted carbenes may also bind in a p3-ri mode, as in (12). 

Other interesting reactions of nucleophiles with metal-carbene complexes include the reaction of 1-aminoethanol which leads to imino-substituted carbene complexes (Fischer and Knauss, 1971a) and the reaction of isonitriles which leads to the unusual complex XV (Aumann and Fischer, 1968a). 

Main routes to 71-donor-substituted allenylidene complexes include (1) the nucleophilic addition of secondary amines to Fischer-type carbenes [M =C(OR ) C=CR (C0)5] (M = Cr, W) [9], (2) the Lewis-acid induced abstraction of NR2 groups from anionic complexes [M C=CC(NMe2)3](CO)5] (M = Cr, W) [9], and (3) the regioselective addition of protic nucleophiles to metallacumulenylidenes with more extended unsaturated carbon chains, such as butatrienylidenes or penta-tetraenylidenes [10]. In the following sections updated syntheses are presented by Periodic Group. 

Fischer-type carbenes can also be modified via transition metal catalyzed reactions. Fischer chromium aminocarbene complexes can be used as nucleophiles in palladium-catalyzed allyUc substitution reactions with aUylic acetates and carbonates, alFording the corresponding allyl-substituted aminocarbenes. For example, reaction of the Uthiated carbene (15) gives (16) in good yield (Scheme 25). ... 

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