Transition metal-lead double bond synthesis

One of the first enantioselective transition metal-catalyzed domino reactions in natural product synthesis leading to vitamin E (0-23) was developed by Tietze and coworkers (Scheme 0.7) [18]. This transformation is based on a Pdn-catalyzed addition of a phenolic hydroxyl group to a C-C-double bond in 0-20 in the presence of the chiral ligand 0-24, followed by an intermolecular addition of the formed Pd-spe-cies to another double bond. 

Another rapidly progressing field is that of multistep reactions which occur in ordered sequences chemo-, regio- and stereo-selectively on a transition metal species. To this end, it is necessary to delay release of the desired product until the whole series of steps has been completed competitive terminations (such as hydride elimination) must be prevented or must only occur at low rates compared to the main sequence. An example, reported by Chiusoli in the late 50s, is offered by the nickel-catalyzed synthesis of methyl 2,5-heptadienoate from 2-butenyl chloride, acetylene, CO and methanol. The reaction is chemo-, regio- and stereo-selective the four molecules react in the order shown in Equation A3.4 (chemoselectivity) the butenyl group attacks the terminal allylic carbon rather than the internal one (regioselectivity) and acetylene insertion leads to a Z double bond (stereoselectivity). 

Additions to nonactivated olefins and dienes are important reactions in organic synthesis [1]. Although cycloadditions may be used for additions to double bonds, the most common way to achieve such reactions is to activate the olefins with an electrophilic reagent. Electrophilic activation of the olefin or diene followed by a nucleophilic attack at one of the sp carbon atoms leads to a 1,2- or 1,4-addition. More recently, transition metals have been employed for the electrophilic activation of the double bond [2]. In particular, palladium(II) salts are known to activate carbon-carbon double bonds toward nucleophilic attack [3] and this is the basis for the Wacker process for industrial oxidation of ethylene to acetaldehyde [41. In this process, the key step is the nucleophilic attack by water on a (jt-ethylene)palladium complex. 

Carbohalogenation of double and triple bonds can be achieved in various ways one method is a two-step version via carbometalation, followed by oxidative cleavage of the newly formed metal carbon bond (see Section 1.5.8.4.4.). Several examples using this methodology in stereoselective organic synthesis have employed catalytic (see Section I.5.8.4.4.) or stoichiometric use of transition metals. An example of the latter case is the zirconium-mediated cyclization of 1,6-hep-tadienes which leads to tram- or (is-1,2-bis(haIomethyI)cydopentane (1), depending on the metal reagent1. 

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