Dienes reactions with carbon electrophiles

This chapter illustrates that electron-rich transition metal-diene complexes can couple with carbon electrophiles and, thereby, provide unusual methods for carbon-carbon bond formation. These procedures are of interest from a synthetic viewpoint since normally uncomplexed dienes or polyenes are not reactive toward weak carbon electrophiles or, with strong electrophiles, undesirable reactions such as polymerization occur. Furthermore, the metal-mediated route often results in desirable regio- and/or stereo-selectivity. Important to the utility of these methods is the ability to free the organic ligand from the metal. In most instances efficient oxidative procedures have been developed for such cleavage reactions. 

The reactions of alkenes with carbon electrophiles have already been mentioned in the cyclization of 1,5-dienes. However, carbon electrophiles may be generated in other ways. Protonation of formaldehyde (methanal) leads to a carbocation that may be stabilized by the oxygen lone pair (Scheme 3.12a). This may react with alkenes with the formation of 1,3-glycols or unsaturated alcohols, depending upon the way in which the intermediate carbocation is discharged (the Prins reaction, Scheme 3.12b). 

With electrophiles such as hydrogen halides, perfluoropropadiene affords products with the central carbon atom of the allene moiety being protonated [57]. Although HX are normally considered as electrophiles, these reactions with tetrafluoropropa-diene may be nucleophilic in nature [57]. 

As in the case of addition reactions of carbon nucleophiles to activated dienes (Section HA), organocopper compounds are the reagents of choice for regio- and stereoselective Michael additions to acceptor-substituted enynes. Substrates bearing an acceptor-substituted triple bond besides one or more conjugated double bonds react with organocuprates under 1,4-addition exclusively (equation 51)138-140 1,6-addition reactions which would provide allenes after electrophilic capture were not observed (cf. Section IV). 

From the investigation of all these data it is clear that the aromaticity of phosphinine is nearly equal to that of benzene. Their chemical reactivity, however, is different. Most important is the effect of the in-plane phosphorus lone pair, which (i) is able to form a complex and (ii) can be attacked by electrophiles to form A -phosphinines. Thus, electrophilic substitution reaction on the ring carbon is impossible. In Diels—Alder reactions, phosphinines behave as dienes, providing similar products to benzene but under less forcing condition (the reaction with bis(trifluoromethyl) acetylene takes place at 100 °C with 3, while for benzene 200 °C is required). 

The same transition metal systems which activate alkenes, alkadienes and alkynes to undergo nucleophilic attack by heteroatom nucleophiles also promote the reaction of carbon nucleophiles with these unsaturated compounds, and most of the chemistry in Scheme 1 in Section 3.1.2 of this volume is also applicable in these systems. However two additional problems which seriously limit the synthetic utility of these reactions are encountered with carbon nucleophiles. Most carbanions arc strong reducing agents, while many electrophilic metals such as palladium(II) are readily reduced. Thus, oxidative coupling of the carbanion, with concomitant reduction of the metal, is often encountered when carbon nucleophiles arc studied. In addition, catalytic cycles invariably require reoxidation of the metal used to activate the alkene [usually palladium(II)]. Since carbanions are more readily oxidized than are the metals used, catalysis of alkene, diene and alkyne alkylation has rarely been achieved. Thus, virtually all of the reactions discussed below require stoichiometric quantities of the transition metal, and are practical only when the ease of the transformation or the value of the product overcomes the inherent cost of using large amounts of often expensive transition metals. 

As noted in the introduction, in contrast to attack by nucleophiles, attack of electrophiles on saturated alkene-, polyene- or polyenyl-metal complexes creates special problems in that normally unstable 16-electron, unsaturated species are formed. To be isolated, these species must be stabilized by intramolecular coordination or via intermolecular addition of a ligand. Nevertheless, as illustrated in this chapter, reactions of significant synthetic utility can be developed with attention to these points. It is likely that this area will see considerable development in the future. In addition to refinement of electrophilic reactions of metal-diene complexes, synthetic applications may evolve from the coupling of carbon electrophiles with electron-rich transition metal complexes of alkenes, alkynes and polyenes, as well as allyl- and dienyl-metal complexes. Sequential addition of electrophiles followed by nucleophiles is also viable to rapidly assemble complex structures. 

Once single zirconacyclopentadienes 20 are formed, only the regiospecific reaction of one carbon-zirconium bond with an electrophile could lead to the stereoselective preparation of metalated dienes 26 (Scheme 13). 

A palladium-based method has been developed for the alkylation of the phenolic oxygen of tyrosine residues. Fig. 5f (61). In this reaction, allylic carbonates, esters, and carbamates are activated by palladium(O) complexes in aqueous solution to form electrophilic pi-allyl complexes. These species react at pH 8-10 with the phenolate anions of tyrosine residues, which results in the formation of an aryl ether and the regeneration of the Pd(0) catalyst. The reaction requires P(m-C6H4S03 )3 as a water-soluble phosphine ligand. Activated pi-allyl complexes that do not react with tyrosine residues undergo P-hydride elimination under the basic conditions to yield diene by-products. A particularly attractive feature of this method is its ability to use substrates with charged groups in the allylic positions. This ability allows hydrophobic substrates, such as lipids, to be solubilized to facilitate protein modification. 

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. 

Figure 9 displays the Af(r) density maps for two reactions - in the left panel the diene and the dienophile are monosubsituted in position 1 by OCH3 and CN and in right panel the diene and the dienophile are monosubsituted in position 1 by CN and OCH3. In both cases, the carbon Cj of the diene and the C t of the dienophile have opposite behaviour. When the former is electrophile/nucleophile, the latter is nucle-ophile/electrophile. Similarly carbons C4 of the diene and carbon C2 of the dienophile present opposite behaviour, then when the nucleophilic part of one molecule reacts with the electrophilic part of the other molecule, it can be observed that the Af(r) descriptor match perfectly to produce in both cases the ortho adduct. 

---