Aminocarbene complex

Alkylideneaminocarbene complexes 76, which are aza analogs of alkenyl-carbene complexes, upon reaction with alkynes primarily give formal [3+2] cycloadducts analogous to the 1-aminocarbene complexes (Scheme 16) [74,75]. Aumann et al. proposed that this should be considered as a formal 1,3-dipo-... 

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]. 

The insertion reaction between alkenylcarbene complexes and electron-rich alkynes such as 1-alkynylamines (ynamines) leads to mixtures of two regioi-someric cyclopentyl derivatives [78]. Thus, if the insertion occurs on the carbon-metal bond a new aminocarbene complex is produced which evolves to a cyclopentenylmetal derivative. On the other hand, if the insertion reaction occurs on the carbon=carbon double bond of the alkenyl complex, the reaction gives a l-metala-4-amino-l,3,5-triene complex which finally generates a different regioisomer of the cyclopentenylmetal derivative (Scheme 31). 

The superior donor properties of amino groups over alkoxy substituents causes a higher electron density at the metal centre resulting in an increased M-CO bond strength in aminocarbene complexes. Therefore, the primary decarbo-nylation step requires harsher conditions moreover, the CO insertion generating the ketene intermediate cannot compete successfully with a direct electro-cyclisation of the alkyne insertion product, as shown in Scheme 9 for the formation of indenes. Due to that experience amino(aryl)carbene complexes are prone to undergo cyclopentannulation. If, however, the donor capacity of the aminocarbene ligand is reduced by N-acylation, benzannulation becomes feasible [22]. 

Wulff et al. examined the necessary reaction conditions for a,fi-unsaturated aminocarbene complexes to react in a benzannulation reaction [23]. The reaction of dimethylamino(alkenyl)carbene complexes 18 with terminal alkynes in non-coordinating and non-polar solvents afforded phenol products in acceptable yields (Scheme 12). 

With optically active formamide-derived aminocarbene complexes high enantioselectivity was observed in most cases (Table 5). This chemistry was used in the synthesis of 1-carbacephalathin and 3-ANA precursors (Eq. 9) [48], as well as the synthesis of a,a -disubstituted amino acids (Scheme 1) [49]. 

In contrast to alkoxycarbene complexes, most aminocarbene complexes appear too electron-rich to undergo photodriven reaction with olefins. By replacing aliphatic amino groups with the substantially less basic aryl amino groups, modest yields of cyclobutanones were achieved (Table 10) [63], (Table 11) [64]. Both reacted with dihydropyran to give modest yields of cyclobutanone. Thio-carbene complexes appeared to enjoy reactivity similar to that of alkoxycar-benes (Eq. 15) [59]. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

The second Had synthesis provided a route to 2,3,4-trisubstituted pyrroles <06CC2271>. Mixing cinnamaldehyde 27 with aminocarbene complex 28 in the presence of molecular sieves (MS) gave pyrrole 29. The authors proposed a mechanism that included a cyclopropane intermediate and subsequent fragmentation and intramolecular condensation. 

Generally phenol formation is the major reaction path however, relatively minor modifications to the structure of the carbene complex, the alkyne, or the reaction conditions can dramatically alter the outcome of the reaction [7]. Depending on reaction conditions and starting reactants roughly a dozen different products have been so far isolated, in addition to phenol derivatives [7-12], In particular, there is an important difference between the products of alkyne insertion into amino or alkoxycarbene complexes. The electron richer aminocarbene complexes give indanones 8 as the major product due to failure to incorporate a carbon monoxide ligand from the metal, while the latter tend to favor phenol products 7 (see Figure 2). 

Fig. 2.6. Preparation of aminocarbene complexes from isonitrile complexes (Z electron withdrawing group X=Y dipolarophile).

Multicomponent condensations have also been described in these an isonitrile, a carbonyl compound and a suitable transition metal complex are combined in one step to afford heterocycloalkylidene complexes. Examples of the use of isolated or intermediate isonitrile complexes for the preparation of aminocarbene complexes are given in Table 2.4. 

Fig. 2.7. Conversion of a-haloiminium salts into aminocarbene complexes [120].

Fig, 2.8. Generation of aminocarbene complexes from metallates and carboxamides. 

Depending on the types of substituents and the precise reaction conditions (l,3-butadien-l-yl)carbene complexes can undergo direct cyclization to yield cyclo-pentadienes [337,350]. As mentioned in Section 2.2.5.1, cyclopentadiene formation occurs particularly easily with aminocarbene complexes [351]. Alternatively, in particular at higher reaction temperatures, CO-insertion can lead to the formation of a vinylketene complex, which, again depending on the electronic properties of the substituents and the reaction conditions, can cyclize to yield cyclobutenones, furans [91,352], cyclopentenones, furanones [91], or phenols (Dotz benzannulation) [207,251,353]. 

The Dotz benzannulation reaction, based on the alkyne cycloaddition to chromium carbene complexes, is the most important application of Fischer carbene complexes. Among the various Fischer carbene complexes, alkoxy and aminocarbene complexes of chromium undergo a novel inter- and intramolecular tandem alkyne insertion/ carbene annotation sequence to give 9H-carbazoles and nf/-benzo[fl]carbazoles. 

Chatani s proposed mechanism bears some similarity to that of Jun s reaction (Scheme 9.12). They both begin with hydroamination of the C=C 7t-bond of a rhodium vinylidene. The resultant aminocarbene complexes (71 and 62) are each in equilibrium with two tautomers. The conversion of 71 to imidoyl-alkyne complex 74 involves an intramolecular olefin hydroalkynylation. Intramolecular syn-carbome-tallation of intermediate 74 is thought to be responsible for ring closure and the apparent stereospecificity of the overall reaction. In the light of the complexity of Chatani and coworkers mechanism, the levels of chemoselectivity that they achieved should be considered remarkable. For example, 5 -endo-cyclization of intermediate 72 was not observed, though it has been for more stabilized rhodium aminocarbenes bearing pendant olefins [27]. 

Aminocarbene complexes usually are less sensitive towards oxygen than the corresponding alkoxycarbene complexes, but nevertheless should be handled in an inert atmosphere. Their preparation is carried out under nitrogen free from oxygen and moisture, using dry, nitrogen-saturated solvents. 

The methoxyketene 297, coordinated to Cr carbonyl, is formed from methoxy-carbene easily by insertion of CO under irradiation [90]. An ester is formed by the reaction of ketene with alcohol. The aminocarbene complex 298 was prepared from benzamide and converted to phenylalanine ester 300 under irradiation of sunlight in alcohol via ketene 299 [91]. The eight-membered lactone 304 was prepared in high yield by the reaction of the alkyne 301 having the OH group in a tether with Cr carbene without irradiation. The vinylcarbene 302 is formed at first and converted to the vinylketene intermediate 303 as expected. The keto lactone 304 is formed from 303 by intramolecular reaction with the OH group and hydrolysis [92],... 

The alkoxy substituent in 12 may be replaced by thio or amino groups upon treatment with thiols and amines to give thiocarbene 13 and aminocarbene complexes 14, respectively. 

A complementary access to alkoxy- and aminocarbene complexes ( Semmelhack-Hegedus route ) involves the addition of the pentacarbonylchromate dianion 18 (obtained from the reduction of hexacarbonylchromium with C8K) to carboxylic acid chlorides and amides [27] (Scheme 10). While alkylation of acyl chromate 19 leads to alkoxycarbene complexes 12, addition of chromate dianion 18 to carboxylic amides generates the tetrahedral intermediates 20, which are deoxygenated by trimethylsilyl chloride to give amino carbene complexes 14. 

Aminocarbene complexes of chromium, such as 25 (or tungsten) have been transformed into 3-aza-l-metallahexatrienes 26, which in turn underwent cyclization into the 2-aminopyrroles 27 in good yields upon heating <02OM1819>. 

For example, photocyclization61,78 of compound 49, derived from the phenyl complex la by addition of cyclopentadiene, was shown to afford the 1,2-dioxy naphthalene 50 (Scheme 18).79 Thus, the regiochemistry of this type of ring annulation is complementary to that of the Dotz reaction, which yields 1,4-dioxy compounds. Photocyclization of aminocarbene complex 5180 involves insertion of carbon monoxide and leads to production of an 2-amino-l-oxy naphthalene derivative 52. Regio isomers, e.g., l-amino-2-oxy compounds 54, can be generated thermally by intermediate formation of a ketene imine 53 by addition of an isocyanide to compound 49 79,81,82 (Amino)alkynylcarbene complexes also give [4+2] cycloadducts, but they prove to be much less reactive than the corresponding alkoxycar-bene compounds (Scheme 18).42,83... 

Acylmetallates lp,q generated by addition of lithio prop-2-ynylic ethers to hexacarbonyl chromium or tungsten afford oxacyclopenten-2-ylidene complexes 173 on contact with wet silica gel (Scheme 73).194 The chromium complex 173 (M = Cr) undergoes a condensation with tolane to give a 1,4-dioxy aromatic compound 174. Addition of cyclopentadiene to 173 (M = W) affords a Diels-Alder adduct 176 in a 1 3 exo/endo ratio,195 while addition of dimethylamine quite unexpectedly does not lead to production of an aminocarbene complex but to formation of 5,5 -diphenyl-2,2 -bifuran 175 (Scheme 73).196... 

Electrocyclization of the precursor 148, which was prepared by condensation of a chromium aminocarbene complex with a suitable amide, provided the pyrrole 149 (Equation 44) <20020M1819>. 

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