Alkylation with arene-chromium

Alkyl radical addition reactions to styrene chromium tricarbonyl can be accomplished using alkyl halides (10 equiv) and (TMSlsSiH (5 equiv) in the presence of AIBN in refluxing benzene, for 18 h (Reaction 66). " These reactions are believed to proceed through intermediates in which the unpaired electron is interacting with the adjacent arene chromium tricarbonyl moiety since the analogous reaction with styrene affords only traces of addition products. 

The same chiral auxiliary has also been used for the stereoselective synthesis of arene-chromium complexes treatment of an aromatic aminal with chromium hexacarbonyl gives the corresponding complex with high diastereomeric excess. This protocol was recently applied in a total synthesis of (—)-lasubine (eq 4). A successful application of 1,2-diaminocyclohexane (as its IR,2R enantiomer) as a chiral auxiliary is illustrated by the di-astereoselective alkylation of the potassium enolate of bis-amide (3) with electrophiles such as benzyl bromide to give bis-alkylated products with excellent diastereoselectivity (eq 5). Lower levels... 

Generally, arene(alkoxy)carbene chromium complexes react with aryl-, alkyl-, terminal or internal alkynes in ethers or acetonitrile to yield 4-alkoxy-l-naphthols, with the more hindered substituent ortho to the hydroxyl group . Upon treatment with alkynes, aryl(dialkylamino)carbene chromium complexes do not yield aminonaphthols, but they form indene derivatives . Vinyl(dialkylamino)carbene complexes, however, react with alkynes to yield aminophenols as the main products The solvent is one of the many factors that affects this type of reaction, for which the most important is the polarity and/or coordinating ability of the solvent. The Dotz benzannulation reaction yields either arene chromium tricarbonyl complexes or the decomplexed phenols, depending on the work-up conditions. Oxidative work-up yields either decomplexed phenols or the corresponding quinones. 

In methanol/benzene solutions, bis- 7r-benzene chromium undergoes a reversible 1-electron oxidation (the half-wave reduction potential = —0-8 volts [76]). There is little change in the potential for a number of alkyl-substituted bis-TT-arene chromium complexes, except in the case of bis-Tt-diphenylchromium for which the reduction potential = —0-66 volts [77]. The ability of bis- r-benzene chromium to act as an electron donor is shown by the ease with which it forms 1 1 molecular complexes with acceptor molecules such as tetracyanoethylene [78]. It seems probable that these complexes are best formulated as salts, e.g. [( r-C H )2Cr]+TCNE. In contrast, arene chromium tricarbonyls do not readily oxidize giving the cations [areneCr(CO)3l, and they form correspondingly weaker charge-transfer complexes, for example with 1,3,5-trinitrobenzene [78a, 78h]. 

The preparations of several (arene)(thiocarbonyl)chromium(0) complexes bearing electron-donating and/or electron-withdrawing substituents on the ring are described here (A-E). This type of compound is useful in organometallic chemistry for problems related to stereochemistry around a chromium atom6 and in organic chemistry in the activation of arene substituents with respect to alkylation.7... 

Methyl benzoate, anisole, and diphenyl ether each give sandwich compounds with chromium vapor, although in rather low yield (32, 55, 110). Chromium appears to attack alkyl ethers and this deoxygenation probably competes with complexation with the aromatic oxygen compounds. No simple product has been isolated from chromium atoms and aniline, but bis(7V,7V-dimethylaniline)chromium has been prepared (32). The behavior of molybdenum and tungsten vapors closely resembles that of chromium in reactions with oxygen- and nitrogen-substituted arenes (113). 

Three types of reaction systems have been designed and applied for the enantioposition-selective asymmetric cross-coupling reactions so far. First example is asymmetric induction of planar chirality on chromium-arene complexes [7,8]. T vo chloro-suhstituents in a tricarhonyl("n6-o-dichlorobenzene)chromium are prochiral with respect to the planar chirality of the 7t-arene-metal moiety, thus an enantioposition-selective substitution at one of the two chloro substituents takes place to give a planar chiral monosubstitution product with a minor amount of the disubstitution product. A similar methodology of monosuhstitution can be applicable to the synthesis of axially chiral biaryl molecules from an achiral ditriflate in which the two tri-fluoromethanesulfonyloxy groups are enantiotopic [9-11]. The last example is intramolecular alkylation of alkenyl triflate with one of the enantiotopic alkylboranes, which leads to a chiral cyclic system [12], The structures of the three representative substrates are illustrated in Figure 8F.1. 

The reactions of the phosphabenzene system [124] confirm these conclusions. Phosphabenzenes have low basicity towards hard acids. They are not protonated by CF3CO2H nor alkylated by trialkyloxonium salts. However, soft acids attack at phosphorus. For instance, 2,4,6-triphenyl-phosphabenzene forms compounds 4 with the hexacarbonyl derivatives of Cr, W and Mo in which the phosphorus coordinates to the metal, possibly with metal-P back-donation. The complexes 4 rearrange photochemically or thermally affording the 67i-heteroarene complexes 5. Although 2,4,6-triphenyl-pyridine is protonated on nitrogen, it undergoes complex formation with chromium hexacarbonyl exclusively on the phenyl moieties yielding the ri -arene complexes 6 [125]. 

Asymmetric reaction of the sulfides bearing a tricarbonyl(ri -arene)chromi-um complex was shown to be successful by Gibson and Simpkins [48,49]. The benzyhc methylene groups in tricarbonyl(ri -phenylmethyl alkyl sulfide)chro-mium(O) and tricarbonyl(ri -l,3-dihydroisobenzothiophene)chromium(0) were highly asymmetrically functionahzed by deprotonation with a chiral bis-Uthium amide and subsequent electrophihc reactions (Tables 4 and 5). 

Enantiomeric separation of nonpharmaceutical compounds include IV-alkyl-Af-methylaniline W-oxides (ethyl to butyl plus isomers) on a Chiralcel OD column. (A = 210 nm) using 1% to 3% ethanol in hexane [143]. Carrea et al. [144] separated the enantiomers of various substituted chromium and magnesium tricarbonyl metallocenes ( / -benzene and -cyclopentadiene) on a Chiralcel OD column (A = 315 run) with an isocratic mobile phase that varied from 1% to 10% ethanol in hexane depending on the enantiomeric pair involved. Chromium tricarbonyl compounds complexed with a variety of ij -arenes were separated on a Whelk-O column (A = 315 nm) using a 20/80 IPA/hexane as the mobile phase [145]. 

Whereas nucleophilic addition of alkyl-lithium compounds to the optically pure arene(tricarbonyl)chromium complex (8) proceeds without asymmetric induction, the chelates (9) react to give amines (10), after hydrolysis, with optical purity of up to 94%." Replacement of the phenyl groups on the azomethine function by alkyl groups should provide an efficient route to a large number of chiral amines. 

Theoretical analyses indicate that there is a general correlation between the site of nucleophilic addition to [Cr(CO)3(Tj -arene)] complexes and the magnitude of the coefficients in the lowest arene-centered unoccupied molecular orbital in the complex.Other important factors are charge polarization induced by the conformation adopted by the Cr(CO)3 group, the reactivity of the nucleophile, and the steric demands of arene substituents and the nucleophile. For example, with [Cr(CO)3(i7 -alkylbenzene)] substrates and carbon nucleophiles, the generally unfavored para addition becomes more important with large alkyl groups (e.g., Bu ) and more stabilized carbanions. ° Extension of these studies to (1,1 -dimethylindane)-tricarbonyl and (l,4-dimethoxynaphthalene)-tricarbonyl chromium complexes has been reported. ... 

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