Alkenes as Substrates

The first experiments in this area were carried out by Thomas et al. in 1974 [52], inspired by their earlier work on similar reactions from alkynes and cydopro-panes [53]. However, in the case of alkenes a stoichiometric amount of gold was indeed needed for the process gold was an oxidant and not a catalyst. 

Using in situ prepared [AuOTfPPh3] as catalyst and relatively mild conditions, He and Yang obtained the first intramolecular addition to terminal alkenes [54]. Phenols and carboxylates were the nucleophiles chosen and several types of olefins, even unactivated ones, worked well in the reaction. In this study, the aforementioned authors also discovered gold s capacity for the constitutional isomerization of olefins, as demonstrated by the obtainment of the two isomers shown in Equation 8.16. 

Moreover, intramolecular addition of alcohol to olefin was shown to give comparable yields to the platinum-based system [55]. 

A tandem reaction was also tried by Floreancig et al., who reported an example of intramolecular addition of alcohol to olefin [57]. In this case, reaction started with the 

Research in this area was developed further by Li et at. using 1,3-dienes 64 for the gold-catalyzed annulation of phenols and naphtols [58, 59]. These generated various dihydrobenzofuran derivatives. The best yields were achieved when the catalytic system included enough AuCl3 and silver salt to remove halogen atoms and deliver cationic gold. 

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Fluorescent pseudomonads are capable of synthesizing poly(3HAMCL)s from a large number of substrates. Work on the biotechnological production of poly(3HAMCL) has focused mainly on two model systems - Pseudomonas oleo-vorans and P. putida. P. oleovorans is able to use alkanes and alkenes as substrate due to the presence of the OCT-plasmid while P. putida, which does not have this plasmid, cannot. In contrast to P. oleovorans, however, P. putida can use carbohydrates such as glucose and fructose for the production of poly(3HAMCL). 

The use of cyclic alkenes as substrates or the preparation of cyclic structures in the Heck reaction allows an asymmetric variation of the Heck reaction. An example of an intermolecular process is the addition of arenes to 1,2-dihydro furan using BINAP as the ligand, reported by Hayashi [23], Since the addition of palladium-aryl occurs in a syn fashion to a cyclic compound, the 13-hydride elimination cannot take place at the carbon that carries the phenyl group just added (carbon 1), and therefore it takes place at the carbon atom at the other side of palladium (carbon 3). The normal Heck products would not be chiral because an alkene is formed at the position where the aryl group is added. A side-reaction that occurs is the isomerisation of the alkene. Figure 13.20 illustrates this, omitting catalyst details and isomerisation products. 

A large number of reports have concerned transfer hydrogenation using isopropanol as donor, with imines, carbonyls-and occasionally alkenes-as substrate (Scheme 3.17). In some early studies conducted by Nolan and coworkers [36], NHC analogues of Crabtree catalysts, [Ir(cod)(py)(L)]PF,5 (L= Imes, Ipr, Icy) all proved to be active. The series of chelating iridium(III) carbene complexes shown in Scheme 3.5 (upper structure) proved to be accessible via a simple synthesis and catalytically active for hydrogen transfer from alcohols to ketones and imines. Unexpectedly, iridium was more active than the corresponding Rh complexes, but... 

The effect of structural variation and the use of different caboxylate salts as cocatalysts was investigated by Pietikainen . The epoxidation reactions were performed with the chiral Mn(III)-salen complexes 173 depicted in Scheme 93 using H2O2 or urea hydrogen peroxide as oxidants and unfunctionalized alkenes as substrates. With several soluble carboxylate salts as additives, like ammonium acetate, ammonium formate, sodium acetate and sodium benzoate, good yields (62-73%) and moderate enantioselectivities (ee 61-69%) were obtained in the asymmetric epoxidation of 1,2-dihydronaphthalene. The results were better than with Ai-heterocycles like Ai-methylimidazole, ferf-butylpyridine. 

The reactions are normally limited to the use of electron deficient alkenes as substrates. However, there have been some reports of copper-catalyzed reactions of sulfur ylides with simple alkenes, as exemplified in equation (16).147... 

Cyclopropanations are known for several other carbanionic intermediates of the general type (7), in which the substituent G is ultimately lost as an anionic leaving group in the last step of the ring-forming pathway (see Scheme 3 above). The substituent G is most often a functional group based upon sulfur, selenium or nitrogen. Halide-substituted derivatives probably react via the a-elimination pathway in most cases (see Section 4.6.3.1), but in some reactions with electron deficient alkenes as substrates, the normal order of steps may be altered (e.g. Table 10, ref. 162). 

The ability of diazonium salts to act as radical scavengers for nucleophilic alkyl radicals was first discovered in mechanistic studies on the Meerwein arylation [96]. Shortly after, this concept was applied for the functionalization of a limited group of activated alkenes [97-99]. The much greater synthetic potential of this functionalization type, which arises from the successful use of non-activated alkenes as substrates, has recently been investigated. In a typical reaction, as illustrated in Scheme 19, the diazonium salt 48 acts as source for aryl radicals 49 and as radical scavenger [100]. 

Other reoxidants which minimize overoxidation are f-butyl hydroperoxide in the presence of Et4NOH [4], tertiary amine oxides, and most importantly N-methylmorpholine A -oxide (NMO) (Upjohn process) [14], although for tri- and particularly tetrasubstituted alkenes as substrates, trimethylaminoxide is superior to NMO [14 c], The introduction of potassium hexacyanoferrate(III) in the presence of potassium carbonate [15] substantially improved the selectivities in chiral dihydroxylations [16], although it was first reported as a co-oxidant in 1975 [17]. Industrial efforts led to an electrochemical oxidation of potassium ferrocyanide to ferricyanide in order to use electricity as the actual co-oxidant [18]. 

Within the context of ketones and alkenes as substrates one must do either of the following ... 

The Rh/TPPTS catalyst system is only applicable to the hydroformylation of terminal linear alkenes. With branched or internal alkenes as substrates only very low conversion rates are achieved. Exceptions include strained cyclic alkenes such as cyclopentene and norbornene, which are hydroformylated at moderate rates under Ruhrchemie/Rhone-Poulenc conditions. 

Since the discovery of the Wilkinson catalyst, most of the work on hydrogenation has been carried out with functionalised alkenes as substrates and Rh(I) complexes as catalytic precursors. These hydrogenations are discussed in the next sections. There are also a few results on hydrogenation of ketones and imines, described in Section 7.2.3. 

Alternatively, a ruthenium catalyst could be applied in phthalide preparation. In 2011, Ackermann s group developed a ruthenium-catalyzed cross-dehydrogenative C-H bond alkenylation reaction. The methodology used water as a solvent, benzoic acids and terminal alkenes as substrates good yields of the desired phthalides were isolated (Scheme 2.164). The reaction sequence consisted of cross-dehydrogenative alkenylation and a subsequent intramolecular oxa-Michael reaction. Mechanistic studies provided strong evidence that the oxidative alkenylation proceeds by an irreversible C-H bond metalation via acetate assistance. 

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