Metal-carbene complexes protecting group

B. Transition Metal-Carbene Complex Residues as Amino-Protective Groups for Amino Acids and Peptides. . . . 11... 

The cyclic variety of MACs are called cyclic alkyl amino carbenes (CAACs) and have an excellent steric element [198]. With a cyclohexyl wingtip group on the carbon end of the carbene - known as a wall of protection - they can sterically block one side of the transition metal centre in a transition metal carbene complex effectively introducing outstanding regioselectivity and stereoselectivity in catalytic processes [198] (see Figure 3.70). 

Systems 4 and 5 provide an interesting contrast. The thermodynamic stability of the cyclohepten-5-one derivative produced in system 4 effectively prevents any units of M2 from being incorporated in the polymer of Mi. The carbonyl group is evidently sufficiently protected to prevent it from undergoing a Wittig-like reaction with the metal carbene complex. 

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. 

Aminolysis of methoxy carbene metal pentacarbonyl complexes of the chromium group yields amino carbene compounds. If the aminolysis is performed with amino acid esters, amino carbene derivatives of amino acids are obtained [162,163]. The metal carbene is relatively stable under a variety of conditions but can be removed with TFA. It may therefore be regarded as an amino protecting group in peptide synthesis. The metal amino carbene amino acid may be activated and coupled to other amino acid esters. Following this idea, Weiss and Fischer prepared various dipeptides, the tripeptide (OC)5Cr(Ph)-Ala-Ala-Ala-OMe 69 [162] and the tetrapeptide (OC)5Cr(Ph)-Gly-Gly-Pro-Gly-OMe 70 (Scheme 5.35) [163]. Treatment with cone. TFA at 20 °C for 10 min. removes the metal carbene group and furnishes the free peptide esters along with Cr(CO)g. Removal of the metal carbene is also possible with 80% acetic acid (80 °C, 30 min.), which leaves Boc... 

Oxidative addition provided an alternative method towards the synthesis of non-classical carbene complexes (Scheme 5.3), and also avoided protection protocols in order to specifically inhibit normal carbene formation. This methodology was developed for the metalation of non-classical imidazolyli-dene, pyrazolylidene, and pyridylidene ligand precursors as well as for CAACs and allowed for installing various metals including molybdenum and the metals of the group 10. ... 

Isolation of novel free carbenes is not always trivial, mainly due to difficulties with decomposition and the need to handle free NHCs under inert atmosphere conditions. In this context, the use of protected forms of free NHC carbenes has appeared as a useful alternative to the preparation of NHC complexes. N-Heterocyclic rings containing alkoxide or trichloromethyl groups, such as shown in Scheme 7, can be considered as NHC-adducts in the sense that they can readily eliminate alcohol or chloroform to unmask the carbene, which would then coordinate to the metal. 

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