Manganese mediation

Boyes and Wild reported the manganese-mediated regioselective chlorination of allenes [14]. For the dichlorination of cyclo-l,2-nonadiene, the dichloride was obtained as the major product whereas the reaction of monosubstituted allene afforded a mixture of regiosomers of the dichlorination products with 2,3-dichloro-1-alkene 12 being the major one. The yield with oxalyl chloride is better than that with TMSC1. 

Carbohydrates such as 6-deoxyhexoses [210] and aldopentose [211] have been oxidized electrochemically by using manganese mediators. Manganese mediators are also useful for the oxidation of a-amino acids [212]. Sorbic acid precursors... 

Tab. 10 Indirect electrooxidation of alcohols, ethers and aromatics with manganese mediators... 

Scheme 143 Manganese-mediated pinacolization and hydrogenation of aryl ketones.

The photo-oxidation of n-butane has been modelled by ab initio and DFT computational methods, in which the key role of 1- and 2-butoxyl radicals was confirmed.52 These radicals, formed from the reaction of the corresponding butyl radicals with molecular oxygen, account for the formation of the major oxidation products including hydrocarbons, peroxides, aldehydes, and peroxyaldehydes. The differing behaviour of n-pentane and cyclopentane towards autoignition at 873 K has been found to depend on the relative concentrations of resonance-stabilized radicals in the reaction medium.53 The manganese-mediated oxidation of dihydroanthracene to anthracene has been reported via hydrogen atom abstraction.54 The oxidation reactions of hydrocarbon radicals and their OH adducts are reported.55... 

The simple piperidine alkaloid coniine (for selected asymmetric syntheses of coniine see [22, 81-85]) offered a preliminary test case for hybrid radical-ionic annulation in alkaloid synthesis. From butyraldehyde hydrazone and 4-chloro-iodobutane (Scheme 4), manganese-mediated photolysis afforded the acyclic adduct in 66% yield (dr 95 5) the cyclization did not occur in situ [69, 70]. Nevertheless, Finkelstein conditions afforded the piperidine, and reductive removal of the auxiliary afforded coniine in 34% overall yield for four steps. This reaction sequence enables a direct comparison between radical- and carbanion-based syntheses using the same retrosynthetic disconnection an alternative carbanion approach required nine to ten steps [81, 85]. The potential for improved efficiency through novel radical addition strategies becomes quite evident in such comparisons where multifunctional precursors are employed. 

Our approach to the antimalarial alkaloid quinine focuses on strategic application of the manganese-mediated hybrid radical-ionic annulation. Retrosyntheti-cally, this is illustrated (Scheme 5) by disconnection of either of two C-C bonds... 

Because disconnection of a-alkoxy-y-amino acid 28 calls for (3-alkoxyhydra-zone 30, the potential for (3-elimination of the alkoxy group from the hydrazone precursor 30 (Scheme 7) makes non-basic conditions critical. In fact, treatment of 30 with TBAF in THF led to just such a (3-elimination (Marie, University of Iowa, unpublished). However, the manganese-mediated radical addition of isopropyl iodide proceeded in 77% yield, without any evidence of (3-elimination, to afford 31 as a single diastereomer. Reductive removal of the chiral auxiliary and oxidation to the carboxylic acid gave 28 in good overall yield [103]. 

Phenylacetaldehyde /V-acylhydrazone 32 served as the radical acceptor for assembly of y-amino acid 29 (Scheme 8), employing difunctional iodide 33 in the manganese-mediated radical addition (56% yield, single diastereomer) [103]. As with 31 (shown above), this radical adduct 34 was converted through the same four-step sequence to y-amino acid 29. 

Although the aforementioned routes provided the desired y-amino acids, it was desirable to develop a synthesis which incorporates the carboxylic acid oxidation state prior to coupling. We hypothesized that manganese-mediated radical addition would accomplish this objective, and therefore initiated a study of manganese-mediated coupling of alkyl iodides with y-hydrazonoesters [104]. We had already shown that the manganese-mediated radical addition conditions offer excellent chemoselectivity, but it remained to be seen whether the stereocontrol model would be disrupted would an additional Lewis basic ester function in the hydra-zone interfere with the role of In(III) in two-point binding and rotamer control ... 

Prototypical radical additions were examined under manganese-mediated photolysis conditions with InCp as the Lewis acid, coupling isopropyl iodide with a variety of y-hydrazonoesters 35a-35d (Table 6) bearing varied substitution at the position a to the ester. The a-methyl, a,a-dimethyl, and a-benzyloxy substituents appeared to have little effect on reaction efficiency and selectivity, as all provided the isopropyl adducts with consistently high diastereoselectivities and excellent yields (91-98%). Surprisingly, the selectivity was only slightly... 

Despite the development of various intermolecular radical addition methods, those studies have rarely accommodated additional functionality, our discovery of the manganese-mediated photolysis conditions notwithstanding. Prior to that discovery, we began to elaborate an alternative strategy which employs temporary tethers ([115, 116] reviews of silicon-tethered reactions [117-120]) (silyl ether or acetal linkages) linking radical and acceptor. In this scenario the C-C bond is constructed via cyclization, in which internal conformational constraints can control diaster-eoselectivity. The tether itself would be converted to useful functionality upon cleavage, and once the tether is cleaved the net result may be considered as formal acyclic stereocontrol. ... 

A final component of the sediment N cycle that warrants mention is manganese-mediated conversion of NHa to NOx or N2. The reduction of Mn-oxides can be... 

These manganese-mediated pinacol processes are believed to proceed via single-electron transfer. 

Figure 3-3. Possible pathway for chromium-catalyzed, manganese-mediated pinacol couplings.

Liccione, J.J., and Maines, M.D. Manganese-mediated increase in the rat brain mitochondrial cytochrome-P-450 and drug metabolism activity. Susceptibility of the striatum. J Pharmacol Exp Ther 248 222-228, 1989. 

A. Murphy, G. Dubois, T. D. P. Stack, Ligand and pH influence on manganese-mediated peracetic acid epoxidation of terminal olefins, Org. Lett. 6 (2004) 3119. 

Manganese-Mediated Coupling with Multifunctional Precursors... 

Ito K, Yamamoto K, Kawanishi S. 1992. Manganese-mediated oxidative damage of cellular and isolated DNA by isoniazid and related hydrazines Non-Fenton-type hydroxyl radical formation. Biochemistry 31 11606-11613. 

Wetlands exhibit distinct redox gradients between the soil and overlying water column and in the root zone (Chapter 4), resulting in aerobic interfaces. For example, the aerobic layer at the soil-floodwater interface is created by a slow diffusion of oxygen and the rapid consumption at the interface. The thin aerobic layer at the soil-floodwater interface and around roots functions as an effective zone for aerobic oxidation of Fe(ll) and Mn(II). Below this aerobic layer there exists the zone of anaerobic oxidation of Fe(ll) and Mn(ll) and reduction of Fe(III) and Mn(IV). The juxtaposition of aerobic and anaerobic zones creates conditions of intense cycling of iron and manganese mediated by both biotic and abiotic reactions. 

Another interesting stereoselectivity was observed in our group druing the manganese mediated pinacol coupling in water. An intramolecular pinacol coupling produced a single tram diastereomer was observed in this reaction (eq. 5). 

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