Oxidative Coupling and Reductive Cleavage

Formation of an alkane a-bond complex then would lead to loss of alkane. For late metals, where both pathways a and h are formally allowed in Eq. 6.43 and 6.44, it is hard to tell which pathway is followed pathway a is normally assumed to operate in the absence of specific evidence to the contrary. 

Alkynes undergo the reaction more easily than do alkenes. Alkenes can be activated by electron-withdrawing sub.stituents or by strain. Simple alkenes will 

Still undeigo the reaction if the metal is sufficiently n basic. Some examples 

Intermediates with one coordinated alkene are often seen (e.g., Eq. 6.49), but the bis-alkcne species is probably the immediate precursor of the coupled product. The products from alkynes are often stable and are known as metalloles (Eq. 6.51) but they can also reductively eliminate to give cyclobutadiene complexes (Eq. 6.47). 

Coupling is not limited to alkenes and alkynes. A particularly inqmrtant. case involves carbenes and alkenes going to metalacyclobutancs (1. 6.52), the key step of the alkene metathesis reaction (Section 11..3). Hie reverse reaction constitutes another example of a C—C bond cleavage reacticm, as we also saw in Eq. 6.45. 

Oxidative coupling is a reaction like that shown in Eq. 6.4S in which the metal induces a coupling reaction between two alkene ligands to give a me-talacycle. The formal oxidation state of the metal increases by two units  

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Oxidative coupling and reductive cleavage are yet two additional reaction types in which the names reflect metal-based redox changes.In this regard, the metal-catalyzed reactions of carbon monoxide with other donor molecules such as isonitriles (RNC), carbynes (CR), alkenes, and alkynes, often referred to in the literature as reductive couplings to reflect the transformations affecting the ligands, frequently involve metal-based oxidations and should... 

Scheme 20. The interrelationship of some alkaloids of the papaveraceae (the C atoms of reticuline, I, marked by dots and arrows, show the possible linkage during the formation of the derivatives II-XV). a = Oxidative coupling b = reductive cleavage R = H or CH3.

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

Oxidative coupling and its reverse, reductive cleavage, are relatively common reactions in organometallic chemistry that illustrate what is essentially a double /1-alkyl elimination (Eq. 2.70). 

EIEs provide invaluable information concerning both molecular structure and the determination of reaction mechanisms. EIEs are traditionally defined as the ratio of equilibrium constants for unlabeled and labeled reactants and products (EIE = A h/A d Figure 2). For oxidative addition and reductive elimination reactions, the presence of intermediates along the reaction coordinate, such as alkane cr-complexes and agostic interactions, make these reactions multistep processes and hence, additional terms are necessary in order to more fully describe the overall mechanism. Thus, reductive elimination may consist of a reductive coupling (rc) step followed by dissociation (d), whereas the microscopic reverse, oxidative addition, could consist of ligand association (a) followed by oxidative cleavage (oc), as illustrated in Scheme 6. 

Early examples of such branched polysulphides, e.g. Thiokol FA, are believed to possess hydroxyl end groups and are coupled by means of zinc compounds such as the oxide, hydroxide, borate and stearate by a mechanism which is not understood. Later elastomers, e.g. Thiokol ST, have been modified by a restricted reductive cleavage (see below) and this generates thiol (mercaptan) end groups. These may be vulcanised by oxidative coupling as illustrated below with lead peroxide ... 

Oxidative coupling of o-nitrotoluene gives 4,4 -dinitrodibenzyl which is reduced with hydrogen to the diamine. The diamine is pyrolyzed to give dihydrobenzazepine. This is reacted with N-(3-chloropropvl)-N-methylbenzamine to give N-benzyldesipramine. This is debenzylated by reductive cleavage and then reacted with HCI. 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

Besides dissociation of ligands, photoexcitation of transition metal complexes can facilitate (1) - oxidative addition to metal atoms of C-C, C-H, H-H, C-Hal, H-Si, C-0 and C-P moieties (2) - reductive elimination reactions, forming C-C, C-H, H-H, C-Hal, Hal-Hal and H-Hal moieties (3) - various rearrangements of atoms and chemical bonds in the coordination sphere of metal atoms, such as migratory insertion to C=C bonds, carbonyl and carbenes, ot- and P-elimination, a- and P-cleavage of C-C bonds, coupling of various moieties and bonds, isomerizations, etc. (see [11, 12] and refs, therein). 

There is ample evidence that the reductive elimination of alkanes (and the reverse) is a not single-step process, but involves a o-alkane complex as the intermediate. Thus, looking at the kinetics, reductive elimination and oxidative addition do not correspond to the elementary steps. These terms were introduced at a point in time when o-alkane complexes were unknown, and therefore new terms have been introduced by Jones to describe the mechanism and the kinetics of the reaction [5], The reaction of the o-alkane complex to the hydride-alkyl metal complex is called reductive cleavage and its reverse is called oxidative coupling. The second part of the scheme involves the association of alkane and metal and the dissociation of the o-alkane complex to unsaturated metal and free alkane. The intermediacy of o-alkane complexes can be seen for instance from the intramolecular exchange of isotopes in D-M-CH3 to the more stable H-M-CH2D prior to loss of CH3D. 

Other derivatives were prepared by modifications of the original Ellman route. Thus, a second cyclopentene precursor 18 containing the C5 6 cis double bond was carried through to give the resin-bound intermediate 19 via a Stille coupling and an oxidation. Subsequent cuprate addition, reduction, and cleavage give 20 and 21 (the F and E series) with the C56 double bond intact. This type of approach was used to synthesize 11 more compounds in this series. 

Fatty acid chains are taken apart two carbon atoms at a time by (3 oxidation. Biosynthesis of fatty acids reverses this process by using the two-carbon acetyl unit of acetyl-CoA as a starting material. The coupling of ATP cleavage to this process by a carboxylation-decarboxylation sequence, the role of acyl carrier protein (Section H,4), and the use of NADPH as a reductant (Section I) have been discussed and are summarized in Fig. 17-12, which gives the complete sequence of... 

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