New Developments in the Chemistry of Low‐Valent Titanium

Abstract

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

Allene formation by gold catalyzed cross-coupling of masked carbenes and vinylidenes

“…The residue was extracted with methylene chloride (10 ml), and the solvent was removed under vacuum, affording complex 2 as a white solid (850 mg, 86% yield). Crystals suitable for an x-ray diffraction study were obtained by slow evaporation of a CH 2 …”

“…Among them are reactions that directly couple two different sp 2 -hybridized carbon centers to form an olefin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Conceptually, the simplest process would be the dimerization and cross-coupling of two free carbenes (Fig.…”

“…1), but because of the very high reactivity of these species, this route is not selective and is plagued by carbene insertion, cyclopropanation, and other side reactions (14). In marked contrast, when ''masked'' carbene reagents are used, this synthetic approach is highly effective stoichiometrically and catalytically as exemplified by the Wittig (1), McMurry (2) (Fig. 1, Eqs.…”

Mechanistic Study of Half-titanocene-based Reductive Pinacol Coupling Reaction

“…[8][9][10][11][12][13] Recently, catalytic systems giving diols with stereoselectivity have attracted much interest. Accordingly, precise understanding of the reaction mechanism is essential to obtain highly stereoselective products and to control the catalytic behaviors.…”

The McMurry Coupling and Related Reactions

“…In view of the leading role played by McMurry in establishing its reputation, the reductive coupling of carbonyls to give pinacols and alkenes by means of low-valent titanium compounds was called the McMurry reaction. The very broad scope of the McMurry reaction, which has been outlined in several reviews [4][5][6][7][8][9][10][11], will be summarized in the first part of this chapter, focusing on the most recent aspects. Today, a large array of ketones, aldehydes, acylsilanes, keto esters, and oxoamides can be efficiently coupled, in an inter-or intramolecular fashion, to produce a variety of products, including strained or sterically hindered olefins, macrocycles, polymers, and heterocycles.…”