Komblum reaction

The Komblum reactions at the tertiary carbon atoms also proceed as the dark Sr I substitutions. Let ns compare the reactions of a-cnmyl chloride and 4-nitro-a-cnmyl chloride with phenyl-thiolate ion (Komblnm 1975 Scheme 7.70). 

The Komblum reactions at the tertiary carbon atoms also belong to the dark SrnI substitutions. Let us compare the reactions of a-cumyl chloride and 4-nitro-a-cumyl chloride with the phenylthiolate ion (Komblum 1975) (Scheme 8-8). As seen, the substitution of the arylthio moiety for chlorine at the former position of the chlorine is observed only for the 4-nitroderivative. The optically active substrate gives the racemic substitution product upon reaction with the phenylthiolate ion (Scheme 8-9). 

Tributyltin hydride replaces the nitro group of tertiary (and some secondary) nitroalkanes with hydrogen in a variation of the Komblum reaction, "- and in the case of vicinal dinitro-compounds or /3-nitrosulphones produces olefins. The reagent also deoxygenates primary alcohols via several thiocarbonyl derivatives). ... 

The ability of a nltro group in the substrate to bring about electron-transfer free radical chain nucleophilic subsdnidon fSpj li at a saniratedcarbon atom is well documented. Such electron transfer reacdons are one of the characterisdc feanires of nltro compounds. Komblum and Russell have established ihe Spj l reaction independently the details of the early history have been well reviewed by them. The reacdon of -nitrobenzyl chloride v/ith a salt of nitro ilkane is in sharp contrast to the general behavior of the ilkyladon of the carbanions derived from nitro ilkanes here, carbon ilkyladon is predominant. The carbon ilkyladon process proceeds via a chain reacdon involving anion radicals and free radicals, as shovmin Eq. 5.24 and Scheme 5.4 fSpj l reacdoni. 

From the foregoing it can be seen that the nitro group can be activated for C-C bond formation in various ways. Classically the nitro group facilitates the Henry reaction, Michael addition, and Diels-Alder reaction. Komblum and Russell have introduced a new substitution reaction, which proceeds via a one electron-transfer process The Spj l reactions have... 

This principle, sometimes called Komblum s rule, was first stated by Komblum, N. Smiley, R.A. Blackwood, R.K. Iffland, D.C. J. Am. Chem. Soc., 1955, 77, 6269. Actually, this reaction is more complicated than it seems on the surface see Austad, T. Songstad, J. Stangeland, L.J. Acta Chem. Scand, 1971,25, 2327 Carretero, J.C. Garcia Ruano, J.L. Tetrahedron Lett., 1985, 26, 3381. 

SRN I reactions using related p-nitrophenyl or p-nitrocumyl systems41 as reductive alkylating agents have been studied by Komblum and co-workers these are well summarized in the reviews.39 At the same time, Russell discovered the S l reaction of geminal halonitroalkanes with stabilized carbanions (see Eq. 5.25).42 The products are readily converted into alkenes via elimination of nitro groups (see Section 7.3). 

Arylations of nitro compounds can be achieved by aromatic nucleophilic substitution using aromatic nitro compounds, as discussed in Chapter 9.100 Komblum and coworkers reported displacement of the nitro group of nitrobenzenes by the anion of nitroalkanes. The reactions are usually carried out in dipolar aprotic solvents such as DMSO or HMPA, and nitroaromatic rings are substituted by a variety of electron-withdrawing groups (see Eq. 5.63).101... 

Conversion of ketone 80 to the enol silane followed by addition of lithium aluminum hydride to the reaction mixture directly provides the allylic alcohol 81 [70]. Treatment of crude allylic alcohol 81 with tert-butyldimethylsilyl chloride followed by N-b ro m o s u cc i n i m i de furnishes the a-bromoketone 82 in 84 % yield over the two-step sequence from a.p-unsaturated ester 80. Finally, a one-pot Komblum oxidation [71] of a-bromoketone 82 is achieved by way of the nitrate ester to deliver the glyoxal 71. It is worth noting that the sequence to glyoxal 71 requires only a single chromatographic purification at the second to last step (Scheme 5.10). 

In a series of recent papers, Komblum et at. have systematically investigated various factors of the reaction at saturated carbon, namely, the stereochemistry (Kornblum and Wade, 1987), the effect of light (Wade et ai, 1987), the effect of leaving groups (Kornblum et al., 1988) and the particular reactivity of the p-nitrocumyl system (Kornblum et al, 1987) as well as the conditions under which the cyano-group may replace the nitro-substituent in reactions involving a benzylic carbon (Kornblum and Fifold, 1989). 

This nuance of the original Sr I mechanism may thus occur in quite a number of cases. Nomenclature purists may consider it necessary to find other symbols to name this mechanism and, presumably, to question the adequacy of the 1 in this case. Beyond symbols, if the Sr I mechanism is viewed as an outer sphere electron-transfer-induced nucleophilic substitution , a possible designation of the mechanism under discussion might be dissociative electron-transfer-induced nucleophilic substitution . The original designation of these reactions as nucleophilic reactions proceeding via anion radical intermediates (Komblum, 1975) would still apply to both nuances of the mechanism since, in the present case, RNu is an essential intermediate in the reaction, even if RX is not. 

The reaction of o,p-dicyano-a-phenylsulphonyl cumene with sodium thiophenolate in DMF produces o,p-dicyano-a-phenylthiocumene. A product of similar substitution is obtained with the potassium salt of diethyl malonate as a reactant (Komblum and Fifolt 1980 Scheme 4.1). 

Let us follow the role of steric hindrance in a forming product during the course of process according to Komblum and Erickson (1981) as well as Akbulut et al. (1982). Scheme 6.5 clearly demonstrates the effect here, all of the constituent reactions were performed in equal conditions (HMPA as a solvent, at 25°C). The nature was proven for all the cases. The intermediary cumyl radical reacts with the nitroalkane anion, but this reaction is retarded with an increase in the size of an alkyl anion. The significance of the cumyl radical dimerization grows accordingly. 

Replacement of the aromatic primary amino group by hydrogen. Komblum, N., Org. Reactions 1, 262 (1944). 

With alkali cyanides, a reaction via a SN2-mechanism takes place the aUcyl halide is attacked by cyanide with the more nucleophilic carbon center rather than the nitrogen center, and the alkylnitrile is formed. In contrast, with silver cyanide the reaction proceeds by a SnI-mechanism, and an isonitrile is formed, since the carbenium intermediate reacts preferentially with the more electronegative center of the cyanide—i.e. the nitrogen (Komblum s rule, HSAB concept) ... 

Pross and Shaik, 1983). The conventional view which describes an SN2 reaction as a two-electron process in contrast to the electron-transfer SRN1 pathway (Bunnett, 1978 Komblum, 1975) is, at best, misleading. The traditional curly arrow picture for an SN2 reaction (78) implies that the nucleophile attacks with two electrons and that the leaving group leaves with two... 

Some chemical additives can induce ion radical formation and direct the reaction along the ion radical route. The effect was discovered and studied in cases of nucleophilic substitutions of cumene derivatives (Komblum 1975,1982). Cumyl radicals are formed at the first step of substitution irrespective of whether a dissociative or homolytic cleavage takes place as a result of electron transfer to the cumene derivatives (Zheng et al. 1999). 

Thus, sodium azide and a,p-dinitrocumene do not react unless subjected to the action of light (48-hr control period). In contrast to sodium azide, the lithium salt of 2-nitro-propane reacts with a,p-dinitrocumene in the dark for 3 hr, giving the product of a-substi-tution in 87% yield. When a,p-dinitrocumene (1 mole) is treated with sodium azide (2 moles) in the presence of the lithium salt of 2-nitropropane (only 0.1 mole), the initial a,p-dinitrocumene quantitatively converts into p-nitrocumyl azide for 3 hours. The product is extremely pure, and the reaction requires no UV irradiation (Kornblum et al. 1970) (Scheme 5-3). Typical one-electron donors, e.g., sodium naphthalene, also induced the reaction of p-nitrocumyl chloride with sodium nitrite (Komblum et al. 1970). 

If the oxidation proceeds more slowly than the decomposition, oxygen may affect the nature of the reaction products. Thus, treating p-nitrocumyl chloride with sodium malonate ester in a flow of pure dry nitrogen yields a product of C-alkylation (route a in Scheme 5-7) the yield is 90%. Oxygen completely inhibits the C-alkylation, and the reaction gives p-nitrocumyl alcohol in the same yield (Komblum et al. 1968). 

When the malonate is absent, oxygen is incapable of converting p-nitrocumyl chloride into the alcohol (Komblum et al. 1968). In the presence of oxygen, the reaction devel-... 

At this point a common method of conversion of tertiary aliphatic nitro compounds into nitromethyl derivatives and, further, into aldehydes deserves mention (Komblum Erickson 1981). According to this method, the reagent NaCH2N02 is used. To prepare this reagent, sodium hydride reacts with nitromethane. Then a tertiary aliphatic nitro compound is introduced into the solution formed. Several organic solvents were probed. The reaction considered proceeds most effectively in DMSO. Komblum and Erickson (1981) attributed this feature to small amounts of NaCH2SOCH3 (sodium dimsyl) produced in DMSO at the expense of its reaction with sodium hydride. Sodium dimsyl acts as a powerful one-electron reducer that induces the following chain anion radical process ... 

They carried this reaction out under pseudo-first-order conditions (excess of 2-nitro-propanate ions) in acetonitrile at 25°C, under argon atmosphere in a light-protecting vessel. The 2-nitropropanate ion was introduced as the tetramethylammonium salt. Two products were formed (Scheme 8-10). One of the products was the expected C-substituted compound. The other was an unstable species, which decomposed into the 4-nitrocumyl alcohol during workup and was ascribed to O-substitution. In 1975, Komblum had obtained the same products. He considered the C-substitution as an SRN1 reaction and the O-substi-... 

The solution of the riddle posed by Komblum s dark SrnI reaction is as follows. The nucleophile does work as a single electron-transfer initiator of the chain process. However, the mechanism of initiation does not consist of a mere outer-sphere electron transfer from the nucleophile to form the anion radical of the substrate. Rather, it involves a dissociative process in which electron transfer and bond breaking are connected (Costentin Saveant 2000). Scheme b at the beginning of Section 8.2 (p. 387) illustrates this mechanism. 

Komblum, N. Substitution reactions which proceed via radical anion intermediates. 

Komblum, N. Stuchal, F. W. New and fatile substitution reactions at tertiary carbon. The reactions of amines with p-nitrocumyl chloride and a,p-dinitrocumene. J. Am. Chem. Soc. 

In experimental work indirect methods of introducing nitro groups find wide application as, for example, the substitution of a halogen (iodine or bromine in an alkyl iodide or bromide) by the Nitro group, by means of silver nitrite (the Victor Meyer reaction), and the new modification of this method described recently by Komblum et al. [4, 4a], in which alkyl halides are reacted with sodium nitrite. 

Komblum, in his investigations of the factors that control the course of ambident anion alkylation reactions [64, 65], found a new type of radical chain substitution reaction that involves anion-radicals and free radical intermediates. When... 

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