Metal-Catalyzed Methods

In lieu of the traditional acid catalysts that we saw in the previous section, several groups have explored the use of metals (Rh, Ti, Ru, Au, Zn, Al) to achieve Fischer indoUza-tion or to access phenylhydrazines. 

Titanium-crafted catalysts have been employed by several groups to effect hydroamination of alkynes with hydrazines to afford hydrazones en route to indoles via 

Ackennann used TiCl with f-BuNH as a catalyst for the hydroamination of alkynes with hydrazines, leading to indoles. Three examples of this nice Fischer indolization are shown in equations 4 to 6 [103], 

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Non-metal catalyzed aziridinations have also been reported. These methods are often more broadly applicable than the metal-catalyzed methods. The use of iV-methylpyrrolidine-2-one hydrotribromide (MPHT) and chloramine-T is an effective route for the synthesis of iV-tosyl aziridines <06MI16>. The aziridination of olefins using i-BuOI and sulfonamides appears to be a general method for aziridination <06CC3337>. The i-BuOI is prepared in situ from t-BuOCl and Nal. This is a broadly applicable method in that a wide variety of sulfonamides (tosyl, nosyl, SES) can be used with roughly equivalent yields. 

Traditional methods for the halogenation of Ge-H bonds are still widely used.1 116 A versatile palladium-metal-catalyzed method has been reported (Equation (93), Table 14).125... 

Besides stoichiometric epoxidation and subsequent hydrolysis to diols, metal-catalyzed methods for converting olefins to glycols are also known in the literature. The classical method utilizes hydrogen peroxide in the presence of catalytic amounts of acidic metal oxides (Milas reagents) [2]. Typically, strong oxidants such as osmium [3] and ruthenium tetroxides [4], permanganate [5], and chro-... 

The reaction scheme shown is a nice application of the use of several important transition metal-catalyzed methods for producing C-C and C=C bonds.215... 

Most substrates for enzyme-catalyzed kinetic resolution reactions do not undergo spontaneous racemization under conditions that are suitable for enzyme activity. One solution to this problem has been to design mild transition metal-catalyzed methods for in situ racemization 17. In order to achieve this goal, the racemisation method must be able to function without an adverse effect on the enzyme. Additionally, the enzyme must not inhibit the racemization method. 

Abstract The oxidative functionalization of olefins is an important reaction for organic synthesis as well as for the industrial production of bulk chemicals. Various processes have been explored, among them also metal-catalyzed methods using strong oxidants like osmium tetroxide. Especially, the asymmetric dihydroxylation of olefins by osmium(Vlll) complexes has proven to be a valuable reaction for the synthetic chemist. A large number of experimental studies had been conducted, but the mechanisms of the various osmium-catalyzed reactions remained a controversial issue. This changed when density functional theory calculations became available and computational studies helped to unravel the open mechanistic questions. This mini review will focus on recent mechanistic studies on osmium-mediated oxidation reactions of alkenes. 

Transition-metal-catalyzed methods were utilized in the preparation of 2-substituted benzimidazoles. Oxidative C-H amination of arylamidines 64 provided access to 1,2-disubstituted benzimidazoles 65 in the presence of MCPBA as a terminal oxidant (130L1334). 1,2-Disubstituted benzimidazoles were synthesized using microwave-assisted solid phase with a phos-phonium linker (13JHC720). 

Formation of C-N bond has raised of interest in the scientific community in the last 10 years. In this context, the formation of enamides is a valuable protocol. In addition to conventional approaches that include condensation of amides and aldehydes, addition of amides to alkynes, acylation of imines, Curtius rearrangement of a,jS-unsaturated acyl azides, amide Peterson olefination, and Wittig and Horner-Wadsworth-Emmons reactions, several transition metal-catalyzed methods have been developed that allow the synthesis of enamides.Inspired by the analogous arylation of amines catalyzed by palladium or copper complexes (Buchwald-Hartwig reaction), a new approach for the synthesis of enamides has been published recently, which allows to prepare enamides from readily available starting materials (amides and vinyl halides) proceeding under very mild conditions. Thus, we decided to test the Porco-Buchwald amidation of vinyl halides in our synthesis [144-146]. 

As we will see in the following, different groups have been interested in developing stereoselective metal-catalyzed methods to reach this framework. 

Figure 10.4 Common strategies for the synthesis of spirocycles. (a) Alkylation methods, (b) metal-catalyzed methods, (c) rearrangement strategies, (d) radical strategies, (e) cycloaddition strategies, (f) ring-closure methods.

Antos JM, Francis MB (2006) Transition metal catalyzed methods for site-selective protein modification. Curr Opin Chem Biol 10 253-262... 

Liittenberg, S., Ta, T.D., von der Heyden, J., and Scherkenbeck, J. (2013) Enantioselective reduction of 3-aryl-2-oxo-propanoic acids a comparison of enzymatic and transition-metal-catalyzed methods. Ear. J. Org. Chem., 2013, 1824-1830. 

Lautens has spearheaded the study of a range of metal-catalyzed methods for the desymmetrization of various meso-oxabicyclooctanes [40]. In initial work, enantioselective nickel-catalyzed hydroalumination reactions of substrates such as 148 proved effective for the generation of cycloheptene 150 (95% ee, Scheme 14.24) [118], as also described in Section 7.5. The related desymmetrization reactions could be effected with carbon nucleophiles as well [119, 120], Thus, asymmetric ring-opening of 145 with Me2Zn mediated by a palladium catalyst prepared in situ with ligand 146 [121] led to the C3-C9 fragment (147) of the polyether antibiotic ionomycin (151) [120]. 

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