Tandem reactions oxidative steps

An exciting addition to the armoury of asymmetric phase transfer catalysed reactions has been the oxidative cyclisation of 1,5-dienes (Scheme 13) [21]. This tandem reaction process leads to the formation of tetrahydrofurans such as 35 in a single step from the open chain dienes 34. The step which determines the sense of asymmetry is the initial attack of permanganate anion, and this chiral information is efficiently relayed in the cyclisation to give products with three new stereogenic centres. For example, oxidation of the di-enone 34 with potassium permanganate, catalysed by the salt 36, gave the tetrahydrofuran 35 in 72% ee. 

This C - H activation event is reversible, and is required to achieve catalytic turnover [62], A series of alcohols, mostly secondary benzylic examples, have been oxidized using this catalyst. The catalytic activity does not match that of the Ir examples described above, but it has been used in several tandem reactions that feature both dehydrogenation and hydrogenation steps to achieve interesting transformations. One example is a tandem alcohol oxidation/Wittig reaction/alkene hydrogenation sequence (Scheme 9) [61,62],... 

At this point one could reach the nearly trivial conclusion that a synthesis is better, the shorter it is (the least number of bonds in the bond-set) the fewer the number of refunctionalization steps involved (oxidations, reductions) the fewer the number of protecting group steps and the more it relies on reactions that form two or more skeletal bonds at a time. This accounts for the significant attention that is presently being given to tandem reactions [10] and reaction cascades. 

Special hydroformylation protocols allow the one-step production of alcohols (hydroformylation-hydrogenation tandem reaction, see also Section 5.2), which are also of crucial importance as aroma compounds. Acetals, which have similar odors like their aldehydic precursors, maybe produced in the hydroformylation in alcohols as solvent under acidic conditions (hydroformylation-acetalization tandem reaction, see also Section 5.3) [15]. The acetal formed protects the aldehyde toward oxidations, reactions with amines, or aldol condensations. Especially in demanding fragrances, these modifications that may affect the scent impression are not desired. 

C S cross-coupling reactions, where benzothiazole intermediates were further transformed to arylsulfides 139 under intermolecular C—S cross-coupling reaction conditions. In 2010, Pan et al. selectively synthesized 2-(phenylihio)phe-nols 142 via a tandem C S coupling and C H functionalization employing a copper catalyst system. The reaction mechanism, based on an isotope labeled strategy, revealed that dimethyl sulfoxide served as a main oxidant in the C H oxidation step 143. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Although nitrile oxide cycloadditions have been extensively investigated, cycloadditions of silyl nitronates, synthetic equivalent of nitrile oxides in their reactions with olefins, have not received similar attention. Since we found that the initial cycloadducts, hl-silyloxyisoxazolidines, are formed with high degree of stereoselectivity and can be easily transformed into isoxazolines upon treatment with acid or TBAF, intramolecular silylnitronate-olefin cycloadditions (ISOC) have emerged as a superior alternative to their corresponding INOC reactions [43]. Furthermore, adaptability of ISOC reactions to one-pot tandem sequences involving 1,4-addition and ISOC as the key steps has recently been demonstrated [44]. 

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

For the first time, application of sequential Diels-Alder reactions to an in situ-generated 2,3-dimethylenepyrrole was shown with various dienophiles 548 to afford 2,3,6,7-tetrasubstituted carbazoles (549). This novel tandem Diels-Alder reaction leads to carbazole derivatives in two steps, starting from pyrrole 547 and 2 equivalents of a dienophile, and is followed by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) oxidation of the intermediate octahydrocarbazole. Mechanistically, the formation of the intermediate octahydrocarbazole appears to involve two sequential [4+2] cycloadditions between the exocyclic diene generated by the thermal elimination of acetic acid and a dienophile (529) (Scheme 5.17). 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

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