Amino-alkoxy carbene

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]. 

Alkoxy(carbene)iron(0) and amino(carbene)iron(0) complexes usually react with alkynes to give rj4-pyrone iron complexes and furans, respectively [54]. Nevertheless the chemoselective formation of naphthols was reported for alkoxy(carbene)iron(0) complexes with the electron-poor alkyne dimethyl... 

Replacing the alkoxy carbene substituent by a better electron-donating amino group stabilizes the metal carbonyl bond. As a result, CO insertion in vinyl carbene D is hampered instead, cyclopentannulation via the chromacyclohexadiene I leads to aminoindenes K, which are readily hydrolyzed to indanones L (Scheme 6) [20]. 

Aminomethylenation of [2-(AT/-amino)ethenyI]carbene complexes affords alkoxy(l-alkynyl)carbene complexes (22-30% yield) by /3-elimination, together with [2-amino-l-(iminoacyl)ethenyl]carbene complexes (61-83% yield),37 e.g., (CO)5M=C(OEt)-CH = CPh(NHPh) + HCONR2 + POCl3/Et3N - (CO)5M = C(OEt) — C=CPh (M = Cr, W R = pyrrolidine, morpholine). 

The competition of benzannulation and pentannulation significantly depends on the donor ability of the carbene ligand. Substitution of alkoxy for amino groups in the carbene ligand increases the thermal stability of the metal-carbonyl bond which hampers both the primary decarbonylation and the CO incorporation into the final product. As a consequence, annulation of chromium amino(aryl)carbenes requires elevated temperatures (> 90°C) and affords cyclopentannulation products (indenes). A-Acylation e.g. by Boc) reduces the donor properties of the amino substituent and thus favours again the... 

A more general approach concentrates on the chiral modification of the carbene ligand. Some examples based on a chiral carbene carbon side chain are depicted in Figure 4. [68] The reaction of alkoxy- and amino(cyclohexenyl)carbene complexes with 1 -pentyne afforded diastereomeric tetralin complexes in moderate yields. [69] The sense of stereoselection was found to depend on the substitution pattern of the cyclohexenyl substituent. Whereas 5-methyltetralin derivatives were obtained in low preference for the syn complex, a higher preference for the anti diastereomer was observed synthesizing the 8-methyltetralin complexes 50 (Scheme 27). [69]... 

For R = para-substituted phenyl, the C(4) carbons (most sensitive to n distribution) are shifted slightly downfield for the alkoxy carbenes and slightly upheld for the amino carbenes. This was interpreted to mean that n electron release is relatively unimportant in these systems. 

Amino-substituted Fischer carbene complexes can also be prepared from isocyanide complexes. This synthesis is less common than the synthesis of alkoxy-substituted carbenes because there are fewer appropriate isocyanide complexes to use as reactants than there are carbonyl complexes, and isocyanide ligands are less electrophilic. Thus, this reaction sequence has often been conducted intramolecularly to promote attack on the isocyanide ligand instead of an ancillary carbonyl group. An intramolecular example of the synthesis of an amino-substituted carbene by attack of an isocyanide ligand is shown in Equation 13.3, ... 

The mechanisms are also parallel. The reaction between an alkoxy carbene and an amine to give an amino carbene is equivalent to the exchange reaction between an ester and an amine to give an amide (Scheme 8.5). 

The use of metal-carbene complexes as an amino-protecting group in peptide synthesis has been reported by Fischer and Weiss (1973). The free amino group of an amino acid ester readily displaces the alkoxy group of an alkoxy-substituted carbene complex. The nitrogen atom of the resulting N-substituted carbene complex is nonbasic and nonnucleophilic because it bears a partial positive charge. The low reactivity of the amino-substituted carbene complex allows a series of reactions to be carried out to construct a peptide chain. Finally, the completed peptide chain can be removed from the carbene complex by treatment with trifluoroacetic acid at 20°. Scheme 16 illustrates the variety of reactions that can be carried out in the presence of the metal-carbene functionality. 

H-Pyran, 2-alkoxy-4-methyl-2,3-dihydro-conformation, 3, 630 4H-Pyran, 2-amino-IR spectra, 3, 593 synthesis, 3, 758 4H-Pyran, 4-benzylidene-synthesis, 3, 762 4H-Pyran, 2,3-dihydro-halogenation, 3, 723 hydroboration, 3, 723 oxepines from, 3, 725 oxidation, 3, 724 reactions, with acids, 3, 723 with carbenes, 3, 725 4H-Pyran, 5,6-dihydro-synthesis, 2, 91 4H-Pyran, 2,6-diphenyl-hydrogenation, 3, 777 4H-Pyran, 6-ethyl-3-vinyl-2,3-dihydro-reactions, with acids, 3, 723 4H-Pyran, 2-methoxy-synthesis, 3, 762 4H-Pyran, 2,4,4,6-tetramethyl-IR spectra, 3, 593 4H-Pyran, 2,4,6-triphenyl-IR spectra, 3, 593... 

The electrophilic carbene carbon atom of Fischer carbene complexes is usually stabilised through 7i-donation of an alkoxy or amino substituent. This type of electronic stabilisation renders carbene complexes thermostable nevertheless, they have to be stored and handled under inert gas in order to avoid oxidative decomposition. In a typical benzannulation protocol, the carbene complex is reacted with a 10% excess of the alkyne at a temperature between 45 and 60 °C in an ethereal solvent. On the other hand, the non-stabilised and highly electrophilic diphenylcarbene pentacarbonylchromium complex needs to be stored and handled at temperatures below -20 °C, which allows one to carry out benzannulation reactions at room temperature [34]. Recently, the first syntheses of tricyclic carbene complexes derived from diazo precursors have been performed and applied to benzannulation [35a,b]. The reaction of the non-planar dibenzocycloheptenylidene complex 28 with 1-hexyne afforded the Cr(CO)3-coordinated tetracyclic benzannulation product 29 in a completely regio- and diastereoselective way [35c] (Scheme 18). 

The 1,3,4-oxadiazole 113 is formed from the azo compound 112 by the action of triphenylphosphine <96SL652>. A general synthesis of 1,3.4-oxadiazolines consists in boiling an acylhydrazone with an acid anhydride (e.g., Scheme 18) <95JHC1647>. 2-Alkoxy-2-amino-l,3,4-oxadiazolines are sources of alkoxy(amino)carbenes the spiro compound 114, for instance, decomposes in boiling benzene to nitrogen, acetone and the carbene 115, which was trapped as the phenyl ether 116 in the presence of phenol <96JA4214>. 

A combination of a Diels-Alder and a Fisher carbene-cyclopentannulation is described as the last example in this subgroup. Thus, Barluenga and coworkers used a [4+2] cycloaddition of 2-amino-l,3-butadienes 4-115 with a Fischer alkoxy-arylalky-nylcarbene complex 4-116 this is followed by a cyclopenta-annulation reaction with the aromatic ring in 4-116 to give 4-117 (Scheme 4.25) [36]. An extension of this domino process is the reaction of 4-118 with 2equiv. of the alkynyl carbene 4-119 containing an additional C-C-double bond (Table 4.2) [37]. The final product 4-120, which was obtained in high yield, is formed by a second [4+2] cycloaddition of the primarily obtained cyclopenta-annulated intermediate. 

In Figure 2.2 the most important synthetic approaches to alkoxy- or (acy-loxy)carbene complexes from non-carbene precursors are sketched. Some of these strategies can also be used to prepare amino- and thiocarbene complexes. These procedures will be discussed in detail in the following sections. In addition to the methods sketched in Figure 2.2, many complexes of this type have been prepared by chemical transformation of other heteroatom-substituted carbene complexes. Because of the high stability of most of these compounds, many different reactions can be used to modify the substituents at C without degrading the carbon-metal double bond. The generation of heteroatom-substituted carbene complexes from other carbene complexes will be discussed in Section 2.2. 

SiMe3) in the presence of ethanol, i-propanol, or diphenylamine to account for the formation of alkoxy- and amino (alkenyl) allenylidene complexes [25] or of a buta-trienyl(methoxy)carbene complex in the presence of methanol [26]. Two representative examples are depicted in Scheme 3.12. 

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