Oxidative coupling intermolecular

Examples of catalytic formation of C-C bonds from sp C-H bonds are even more scarce than from sp C-H bonds and, in general, are limited to C-H bonds adjacent to heteroatoms. A remarkable iridium-catalyzed example was reported by the group of Lin [116] the intermolecular oxidative coupling of methyl ethers with TBE to form olefin complexes in the presence of (P Pr3)2lrH5 (29). In their proposed mechanism, the reactive 14e species 38 undergoes oxidative addition of the methyl C-H bond in methyl ethers followed by olefin insertion to generate the intermediate 39. p-hydride elimination affords 35, which can isomerize to products 36 and 37 (Scheme 10). The reaction proceeds under mild condition (50°C) but suffers from poor selectivity as well as low yield (TON of 12 after 24 h). 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

Many cyclization reactions via formation of metallacycles from alkynes and alkenes are known. Formally these reactions can be considered as oxidative cyclization (coupling) involving oxidation of the central metals. Although confusing, they are also called the reductive cyclization, because alkynes and alkenes are reduced to alkenes and alkanes by the metallacycle formation. Three basic patterns for the intermolecular oxidative coupling to give the metallacyclopentane 94, metallacyclopentene 95 and metallacyclopentadiene 96 are known. (For simplicity only ethylene and acetylene are used. The reaction can be extended to substituted alkenes and alkynes too). Formation of these metallacycles is not a one-step process, and is understood by initial formation of an tj2 complex, or metallacyclopropene 99, followed by insertion of the alkyne or alkene to generate the metallacycles 94-96, 100 and 101-103 (Scheme 7.1). 

A marked difference exists between the ozonolysis of C=C or C=N double bonds and C=C triple bonds as indicated in the formulas in the latter case, the fragments remain attached, and the carbonyl oxide couples intra- or intermolecularly with another partner. 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

Some natural products have been synthesized by means of oxidative coupling promoted by iron reagents. In 1995, Herbert and co-workers reported the formation of the alkaloid kreysigine (84) by intermolecular oxidative coupling of diaryl substrates 83a/b with iron(III) chloride followed by methanol work-up [67]. The yield for the free phenolic compound 83a was 53 %, whereas the benzyl-protected analogue 83b presumably cydizes and then de-benzylates, in an overall yield of 71 % (Scheme 19). 

A serendipitous use of a chiral auxiliary in atrop-selective biaryl bond formation has recently been published by Kita and co-workers [39, 137]. With diaryl substrate 201, which is related to precursors of the ellagitannins (see Section 14.6.1), PIFA-mediated oxidative coupling did not lead to the expected ellagitannin structure 202 (Scheme 50). Rather surprisingly, this reaction proceeds with intermolecular Ar-Ar bond formation. The chiral glucose framework efficiently transfers stereochemical information, but not in a intramolecular closure. 

Tertiary and cyclic alkyl halides (cyclohexyl iodide), secondary alkyl chlorides and primary and secondary tosylates cannot be used in these intermolecular alkylations. This is also the case with dibro-moethane and 2-bromo-2-nitropropane, which both lead instead to a,3-dithianylalkanes resulting from the oxidative coupling of the carbanion. 

An example of intermolecular oxidative coupling with the new complex is the oxidation of p-cresol (3) to Pummerer s ketone (4) in 28% yield. 

Reaction of electron-rich aromatic compounds with TTFA leads to intermolecular oxidative coupling to form the corresponding biaryls without aromatic thallation. The reaction proceeds through one-electron transfer from aromatic compounds to Tl(III) to give an aromatic radical cation which leads to biaryls (Schemes 9.52 and 9.53 [52]). Intramolecular aryl coupling also occurs (Schemes 9.54 [53] and 9.55 [54]) and, further, when the carboxylic acid moiety is present, intramolecular as well as intermolecular lactonization occurs (Schemes 9.56 [55] and 9.57 [56]). 

Phenolic or non-phenolic oxidative coupling methods have been extensively used since the 1970 s to synthesize polyoxygenated bridged biaryl compounds, as will be illustrated later in the case of steganes. Remarkably enough, the use of transition metal oxidants is particularly suited to perform intramolecular biaryl coupling whereas most other methods are better suited to intermolecular coupling. 

Since the intermolecular oxidative coupling of benzene to biphenyl using stoichiometric amounts of PdCl2 was first described by van Helden and Verberg in 1965 [41], the intramolecular oxidative coupling of two arenes mediated by a palladium catalyst to synthesize cyclic compounds has also attracted great attention. 

Intermolecular dehydrogenative oxidative homocouplings of (hetero)arenes turned out to be among the most important methods for the synthesis of symmetrically substituted biaryls [122]. A recent illustrative example is oxidative coupling reactions of 2-naphthols, which were accomplished in an asymmetric fashion employing an inexpensive iron catalyst (Scheme 9.47) [123]. 

The benzyl radical presumably participates ala) in an intermolecular oxidative coupling of another antioxidant, 4,4.-isopropylidenebis(2-methyl-6-tert-butyl-phenol). The resulting phenolic oligomer is further oxidized and forms the more complex product XLVIII via intramolecular C—0 bonding50. ... 

Intermolecular oxidative coupling of phenols. Italian chemists have reported a synthesis of the unusual neolignan ( )-eusiderin (4) patterned on a... 

In a related study, intramolecular oxidative coupling of enolate derivatives has been investigated by Schmittel and co-workers [167]. The intermolecular version of this reaction provides a useful route to 1,4-dicarbonyl compounds but typically suffers from low levels of stereoselectivity. Furthermore, in mixed systems, the desired heterocoupling products are often accompanied by appreciable amounts of homocoupling products. It was hoped that the use of a single metal for both enolate precursors with concomitant intramolecularization of the bond-forming event might overcome some of these problems. 

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