Fischer carbene complexes acidities

Due to the high a-C,H acidity in the alkoxyethylidene complexes 6 (e.g.,piCa=8 (R=Me)) [ 16], transformations via an enolate analog are possible and have been used to introduce additional functionality into the carbene side chain to access various Fischer carbene complexes [3]. The a,/J-unsaturated complex 8 could be obtained from 6 (R=Et) by an aldol-type condensation with benzaldehyde 7 in the presence of triethylamine and trimethylsilyl chloride (Scheme 2) [17]. This reaction proceeds completely diastereoselectively to yield only the trans-isomer. Analogously, binuclear complexes have been prepared from 6 and 1,3-and 1,4-phthaldialdehyde in good yields [17]. This type of condensation has... 

A somewhat similar situation has been observed in the deprotonation of the Fischer carbene complexes 20-24 summarized in Table 7.72,73 There is an increase in acidity in the order 20 < 21 < 22 and 23 < 24 which has been... 

Carbon acids activated by strong ji-acceptors that also contain a jt-donor capable of interacting with the ji-acceptor in a push-pull fashion pose an interesting problem. Fischer carbene complexes such as 20,94 23,97 36,96 37,96 38,98 and 3998 fall into this category. Thermodynamic... 

Table 8 Acidities of Fischer carbene complexes and intrinsic rate constants for their deprotonation by secondary alicyclic amines, primary aliphatic amines and hydroxide ion in 50% MeCN-50% water (v/v) at 25°C... 

Thermal cyclization reaction of Fischer carbene complexes with a, 3-unsaturated ketones and aldehydes led to 2,3-dihydrofurans, which were converted to the corresponding furans under various conditions, including treatment with silica gel, use of non-aqueous acid (HBF4 or CF3CO2H) or simply by heating <07AGE4136>. 

Anions formed from group 6 and manganese Fischer carbene complexes undergo aldol condensations with aldehydes and ketones. Allylic carbenes exclusively react in the y position with aldehydes affording dienyl-substituted carbenes. For alkoxy-substituted carbenes, the presence of an excess Lewis acid see Lewis Acids Bases), such as boron trifluoride etherate, titanium tetrachloride, or tin tetrachloride is required for the reaction to proceed in reasonable yield. The initial aldol product can be isolated without elimination (Scheme 12). ... 

Irradiation of Fischer carbene complexes generates, by insertion of carbon monoxide, a metal-bound ketene intermediate. Photolytic reactions of carbene complexes are synthetically attractive, in that the reaction conditions are mild and the reactions of ketene intermediates with a variety of reagents is of significant scope. A low concentration of metal-bound ketene is probably obtained and in the absence of a nucleophile, the starting material can usually be recovered even after prolonged irradiation. The ketene intermediates are readily trapped with nucleophiles for example, dipeptides are formed in excellent yield and with very high diastereoselectivity upon irradiation of optically active carbenes in the presence of natural or urmatural a-amino acids (Scheme 28). Dipeptides and PEG-supported amino acids and dipeptides can also be used as nucleophiles. 

As pointed out earlier, nucleophilic addition to Fischer carbene complexes is closely related to addition to carboxylic acid esters. The ester analog of reaction (56) is equation (57). 

These results may be understood in the context of soft-hard acid-base theory.As mentioned earlier, the Fischer carbene complexes can be regarded as soft electrophiles, especially the alkylthio complexes. Hence, the adducts 99 formed by the reaction of 98b with a thiolate ion nucleophile enjoy enhanced stability due to the symbiotic effect of adding a soft nucleophile. This stabilization apparently reduces the need for additional stabilization by the phenyl substituent, which translates to a reduced p(Ki) value. 

As pointed out earlier, most data on pK values and rate constants for proton transfer were obtained in 50% MeCN-50% water (v/v), a solvent that is essentially aqueous but which provides better solubility for some sparingly soluble Fischer carbene complexes. Some acidity measurements were reported in other solvents as... 

As discussed in the section Alcohols and alkoxide ion nucleophiles, the most useful measure of reactivity of a reaction system is its intrinsic barrier or intrinsic rate constant because, in comparing different systems, these quantities correct for potential differences in the thermodynamics of the reactions. A comparison of intrinsic rate constants for the deprotonation of Fischer carbene complexes by buffer bases with those for the deprotonation of other carbon acids is revealing. A representative hst of such values is given in Table 26. They show the well-known... 

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