New Developments in the Chemistry of Low-Valent Titanium

Among the applications of low-valent titanium in organic synthesis, the reductive coupling of carbonyl compounds to produce alkenes (the McMurry reaction) is particularly prominent. Discovered at the beginning of the 1970s, it has been developed and tested repeatedly, for example in numerous syntheses of natural products. This alkene synthesis has become a standard reaction in the repertoire of preparative chemists. However, the possibilities of low-valent titanium are by no means limited to this process: the last few years have brought some spectacular applications of the conventional McMurry reaction (for example the synthesis of taxol) along with a considerable extension of the scope of reductive carbonyl couplings. Thus, diverse heterocycles are now accessible following novel and efficient pathways based on intramolecular cross-coupling of functional groups—some of which were hitherto considered to be inert to titanium. The use of this method for the synthesis of indole and pyrrole alkaloids illustrates the new possibilities. At the same time, considerably simplified methods for conducting McMurrytype reactions have been developed. Examples include the particularly convenient “instant” method, the first ketone–amide coupling reactions requiring only catalytic amounts of titanium salts, and the first application of commercially available titanium powder as a coupling agent. Last but not least, the detailed investigation of diverse classical McMurry reagents has afforded a deeper understanding of the nature and mode of action of low-valent titanium. Revision of some of the current conceptions of the process of reductive carbonyl coupling is thus indispensable.     

Recent Advances in the Synthesis of Indole and Quinoline Derivatives through Cascade Reactions

One right after the other : Cascade reactions represent an efficient method for accessing highly functionalized final products from simple starting materials in a single synthetic operation. This Focus Review surveys the most representative and interesting recent reports on the synthesis of indoles and quinolines through cascade reactions.

     

Three-Component Reactions of 3-Arylidene-3H-Indolium Salts,Isocyanides and Amines

A multicomponent reaction of isocyanides with aryl(indol-3-yl)methylium salts and amines has been found. A series of aryl(indol-3-yl)acetimidamides was obtained in up to 96% yields. In the case of ethyl isocyanoacetate, the reaction is followed by cyclization to form 3,5-dihydro-4H-imidazol-4-one derivatives.     

Reactions of methoxycarbonylcarbene with 3-ethyl-2-phenyl- and 2,3-diphenyloxazolidines

The reactions of methoxycarbonylcarbene, which was generated by catalytic thermal decomposition of methyl diazoacetate, with 3-ethyl-2-phenyl- or 2,3-diphenyloxazolidines resulted in the insertion of the former predominantly at the C—N bond of the oxazolidine ring to produce substituted esters of morpholine-3-carboxylic acid.     

Reductive Umpolung Reactions with Low‐Valent Titanium Catalysts

The coupling of similarly polarized carbon fragments can be achieved by a reductive umpolung strategy. This gives access to compounds with functional groups in even bond distances, which are difficult to synthesize by other means. Low‐valent titanium catalysts enable such couplings under mild conditions. This account covers the recent progress on this topic with a focus on the development of cross‐selective coupling reactions and stereoselective examples.