Anisoles, complexation

Diazocinediones react with some secondary amines, with the aid of the titanium(IV) chlor-ide-anisole complex, to give 1,4-diazocine systems containing two amidine moieties.8... 

Detailed NMR and theoretical studies have identified and characterized a number of the complexes along the proposed reaction pathways for anisole, 1,2-dimethoxybenzene and Al,Al-dimethylaniline ° . For example, anisole deaggregates the BuLi hexamer to form a tetrameric BuLi-anisole complex 4. Adding TMEDA displaces the anisole from the tetramer and breaks it down further to give a BuLi-TMEDA dimer 5, which deprotonates anisole at >0°C yielding 6 (Scheme 4). 

It has usually been assumed that the lithiation step involves loss of TMEDA and reformation of a BuLi-anisole complex prior to the deprotonation itself. However, the kinetics of the deprotonation step are inconsistent with this proposition both TMEDA molecules remain part of the complex during the deprotonation, which may therefore involve no 0-Li coordination and be directed purely by the acidifying effect on nearby protons of the a-electron-withdrawing MeO substituent. ... 

By careful optimization, Widdowson and coworkers were able to show that methoxy-methyl ethers of phenols are better substrates for alkyllithium-diamine controlled enan-tioselective deprotonation, and (—)-sparteine 362 is then also the best ligand among those surveyed the BuLi-(—)-sparteine complex deprotonates 447 to give, after electrophilic quench, compounds such as 449 in 58% yield and 92% ee (Scheme 180) . Deprotonation of the anisole complex 410 (see Scheme 169) under these conditions gave products of opposite absolute stereochemistry with poor ee. 

Scheme 18. Preparation of a 2-cyclohexene-l-one complex from a 2,3-i)2-anisole complex.

Substituted arene Cr(CO)3 complexes show little further fragmentation of the (P — 3CO)+ ion (117). Loss of 2 H from the anisole complex gave stable C7H6OCr+, possibly (XVIII), and the analogous isopropoxy complex... 

The chiral anisole derivative 37 has been used in the synthesis of several asymmetric functionalized cyclohexenes (Table 9) [22]. In a reaction sequence similar to that employed with racemic anisole complexes, 37 adds an electrophile and a nucleophile across C4 and C3, respectively, to form the cyclohexadiene complex 38. The vinyl ether group of 38 can then be reduced by the tandem addition of a proton and hydride to C2 and Cl, respectively, affording the alkene complex 39. Direct oxidation of 39 liberates cydohexenes 40 and 41, in which the initial asymmetric auxiliary is still intact. Alternatively, the auxiliary may be cleaved under acidic conditions to afford /y3 -allyl complexes, which can be regioselectively attacked by another nucleophile at Cl. Oxidative decomplexation liberates the cyclohexenes 42-44. HPLC analysis revealed high ee values for the organic products isolated both with and without the initial asymmetric group. 

One of the most versatile applications of [Os]-anisole chemistry is the efficient generation of complex polycyclic systems. Through the application of a variety of methodologies, anisole complexes have been used to generate a number of cyclic arrangements, including a bi-cyclo[2.2.2]octadiene, decalins, tetralins, and tricyclic arrays. 

In the presence of Lewis acids, N-substituted aniline complexes of [Os] also add electrophiles at C4, again at the arene face opposite to that involved in metal coordination. This reaction has been shown to be general for a broader range of Michael acceptors than may be utilized with anisole complexes of [Os]. The N-ethyl aniline complex, for example, adds Michael acceptors and acetals in yields ranging from 53-95 % (Table 13, entries 1-6) [27]. The N,N-dimethyl aniline complex (entries 7-9) also adds Michael acceptors to C4 in moderate to high yields (Table 13) and adds to the <5-carbon of an a,/ ,y,<5-un saturated ester (entry 3). 

Another early success of the (TpRe(CO)(MeIm) fragment was the promotion of Diels-Alder cycloaddition reactions with benzene and anisole. Complex 101 [TpRe(CO)(MeIm)( 2-benzene)] undergoes an endo-selective Diels-Alder reaction with N-methylmaleimide to afford the bound bicyclo[2.2.2]octadiene complex 102 in 65 % yield (Scheme 12) [40]. Oxidation of 102 yields the bicyclo[2.2.2]octadiene 103 and/or the bicyclo[2.2.2]octenone 104 depending upon the choice of oxidation conditions. 

The more activated TpRe(CO)(MeIm)(r/2-anisole) complex has demonstrated a slightly broader range of reactivity by undergoing cycloadditions with both N-methylmaleimide (Scheme 13) and dimethylacetylene dicarboxylate (DMAD) (Scheme 14). Analysis of these reactions is complicated by the fact that the initial anisole complex exists as a 3 1 mixture of... 

Deuterio-dealkoxylation also occurs on treating 4-tert-butyl-anisoletricarbonylchromium complex 83c with LiEt3BD, giving p-tert-butyl-deuteriobenzene complex 84c. Carbon-nitrogen bonds can be similarly cleaved by hydride p-dimethylamino anisole complex 83d affords, under the same experimental conditions, complex 84d in 24 % yield (Scheme 37)... 

An adamantane-fused 1,4-diazocine 114 was formed by reacting 1,2-diaminoadamantane with o-dibenzoylbenzene (87UP1). The diazocinedione 57 and substituted 57 were converted into the bisamidines 73 by reaction with secondary amines in the presence of titanium tetrachloride/anisole complex (85H1425). (See Section II,C,1 and IV,B). 

The anodic oxidation of benzene produces a mixture of polyphenylene compounds. This oligomerization can be performed in acetonitrile [21] or in liquid sulfur dioxide [22]. Mixed coupling between naphthalene and alkyl benzenes has also been demonstrated (Table 1, numbers 12-16). The relative yield of mixed coupling products increases with the basicity of the alkyl benzene with mesitylene 19%, with tetramethylbenzene 42%, and with pentamethylbenzene 64% of mixed coupling products are obtained. This suggests an electrophilic reaction between naphthalene cation radicals and alkylbenzenes. The mixed coupling reaction of phenanthrene with anisole has been studied kinetically. The results indicate that initially a complex PA is formed between the phenanthrene radical cation and anisole, followed by an electron transfer from the complex. The resulting PA" -anisole complex then decomposes to the product [23]. 

Scheme 6-10 Selective para-chlorination of anisole complexed by a-cyclodextrin.

One interesting feature of this work is that the enzyme chlorinase also can chlorinate anisole in water solution, but it gives a random mixture of ortho and para products [65]. Apparently the enzyme merely makes a chlorinating reagent, probably HOCl, and this then acts on the unbound anisole in free solution. However, the selectivity seen in our anisole complex chlorination is typical of that seen in other enzymes that do indeed direct reactions by geometric control within an enzyme-substrate complex. 

The product of hydrogenation for the anisole complex of pentaammineos-mium(II) depends on the reaction medium [43]. In the presence of dry methanol, bound anisole of 17 is converted cleanly to 3-methoxycyclohexene (i.e., 18),... 

Table 3 Electrophilic addition reactions with r -anisole complexes...

Fig. 15 [4+2] Cycloaddition reactions of r -anisole complexes via a 4H-anisolium intermediate and the formation of various bicyclo[2.2.2]octadiene and bicyclo[2.2.2.]octatriene complexes...

Fig. 16 The formation of functionalized cfs-decalins from an r -anisole complex and an enone via a Michael-type cyclization...

The more activated TpRe(CO)(MeIm)(q -anisole) complex has demonstrated a slightly broader range of cycloaddition reactivity. The anisole complex 110 cychzes with DM AD to give the diastereomeric bound bicyclo [2.2.2] octatriene 111 isolated as a 1 1 ratio of coordination diastereomers (Fig. 23). Oxidation of these complexes liberates the corresponding triene 112 as well as the disubstitut-ed anisole 113, which presumably is generated with acetylene from the cycloreversion of 112. 

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