Regioselective oxidative cyclization

The intermolecular coupling of allenes 123 and enones 124 selectively afforded dienones 125 in 53-81% yields (Scheme 4.45) [93]. As a catalyst precursor, [CpRuCl(cod)] was employed with CeCl3 7H20 and an alkynol 126 as activators. The proposed reaction mechanism involves the regioselective oxidative cyclization of the two components on a cationic ruthenium center, leading to the ruthenacyclopentane intermediate 127. When allenyl alcohols 128 were employed under otherwise identical conditions, the final products were cyclic ethers 129 (Scheme 4.46) [94]. As a catalyst precursor, the cationic ruthenium complex 68 can be used in the absence of the alkynol 126. The ether ring was considered to be formed directly via the ruthenacyclopentane 130 or alternatively through its Jt-allyl form 131. 

Isoprene also underwent the intermolecular coupling with vinyl acetate (Scheme 4.47) [95[. In the presence of 0.7 mol% 17, isoprene and vinyl acetate were heated at 100 °C in MeOH for 14 h to give dienes 132 and 133 with a ratio of 96 4. The present selectivity was attributed to the regioselective oxidative cyclization of the more substituted alkene moiety of isoprene and vinyl acetate giving rise to the ruthenacyclopentane intermediate 134. 

Less common is the use of nbd, but it has been utilized to obtain crystals for the determination of the absolute configuration of chiral palladium(ll) complexes of the type palladatricycloheptane produced by regioselective oxidative cyclization of Ca-symmetrical chiral alkenes. The structures of 26 and 27 were determined.Previously, complexes of the racemic equivalent with E = C02Me with nbd and with COD were crystallized, and their X-ray structures solved. 

Retrosynthetic path e in Scheme 2.2 requires a regioselective oxidation of an o-nitrostyrene to the corresponding phenylacetaldehyde. This transformation has been accomplished hy Wacker oxidation carried out in such a way as to ensure the desired regioselectivity. The required o-nitrostyrenes can be prepared by Heck vinylation. One procedure for oxidation uses 1,3-propaiiediol to trap the product as a l,3-dioxane[15]. These can then be hydrogenated over Rh/C and cyclized by treatment with dilute HCl,... 

The total synthesis of the carbazomycins emphasizes the utility of the iron-mediated synthesis for the construction of highly substituted carbazole derivatives. The reaction of the complex salts 6a and 6b with the arylamine 20 leads to the iron complexes 21, which prior to oxidative cyclization have to be protected by chemoselective 0-acetylation to 22 (Scheme 13). Oxidation with very active manganese dioxide followed by ester cleavage provides carbazomycin B 23a [93] and carbazomycin C 23b [94]. The regioselectivity of the cyclization of complex 22b to a 6-methoxycarbazole is rationalized by previous results from deuterium labeling studies [87] and the regiodirecting effect of the 2-methoxy substituent of the intermediate tricarbonyliron-coordinated cyclo-hexadienylium ion [79c, 79d]. Starting from the appropriate arylamine, the same sequence of reactions has been applied to the total synthesis of carbazomycin E (carbazomycinal) [95]. 

Addition of the arylamines 117 to 2-methoxy-3-methyl-l,4-benzoquinone 118 affords regioselectively the 5-arylamino-2-methoxy-3-methyl-l,4-benzo-quinones 119 (Scheme 37). Palladium(II)-catalyzed oxidative cyclization leads to the carbazole-l,4-quinones 28 [135,136],previously obtained by the iron-mediated approach (cf. Scheme 14). Regioselective addition of methyllithium to the quinones 28 provides carbazomycin G 29a and carbazomycin H 29b [96,135]. Reduction of 29a with lithium aluminum hydride followed by elimination of water on workup generates carbazomycin B 23a [135]. Addition of heptylmag-... 

The bicyclic ethers 277 and 278 are obtained by a transannular oxidative cyclization using HTIB. Although this reaction shows poor regioselectivity, the addition to the double bond proceeds with high trans stereoselectivity (87TL5229) (Scheme 70). 

Wu et al. reported the total synthesis of clausenaquinone A (112) using a palladium(ll)-mediated oxidative cyclization of the 2-arylamino-5-methoxy-l,4-benzoquinone 874 (107). This total synthesis was undertaken to establish the structure of natural clausenaquinone A (112). The key intermediate, 2-(3-hydroxy-4-methylanilino)-5-methoxy-l,4-benzoquinone (874), required for this synthesis, was obtained by the reaction of 5-amino-o-cresol (873) with 2-methoxy-l,4-benzoquinone (872) which was readily obtained by oxidation of methoxyhydroquinone (871). The palladium(ll)-mediated oxidative cyclization is non-regioselective. Thus, the cyclization of the 2-arylamino-5-methoxy-l,4-benzoquinone 874 with palladium(Il)... 

Construction of the carbazole framework was achieved by slightly modifying the reaction conditions previously reported for the racemic synthesis (641,642). The reaction of the (R)-arylamine 928 with the iron complex salt 602 in air provided by concomitant oxidative cyclization the tricarbonyliron-complexed 4b,8a-dihydro-9H-carbazole (931). Demetalation of the complex 931, followed by aromatization and regioselective electrophilic bromination, afforded the 6-bromocarbazole 927, which represents a crucial precursor for the synthesis of the 6-substituted carbazole... 

The intramolecular oxidative cyclization of the anilinobenzoquinone 940 with a catalytic amount of palladium(II) acetate in the presence of copper(II) acetate in air afforded the carbazole-l,4-quinone 941 in almost quantitative yield. The regioselective introduction of the heptyl side chain at C-1 of the carbazole-l,4-quinone 941 was achieved by a 1,2-addition of the corresponding Grignard reagent to give the carbazole-l,4-quinol 942 in 55% yield. However, 1,4-addition at C-3 and 1,2-addition at C-4 led to the regioisomeric products 943 and 944 as well. Finally, under acidic reaction conditions, the carbazole-l,4-quinol 942 was smoothly transformed to... 

N-Oxide Azaheterocycle Azole Pyrazole Imidazole Triazole Tetrazole N-Oxidation Cyclization Functionalization Activation Regioselectivity One pot... 

Hintz, S. Frolich, R. and Mattay, J. (1996) PET-oxidative cyclization of unsaturated silyl enol ethers. Regioselective control by solvent effects. Tetrahedron Letters, 37, 7349-7352. 

The regioselective nudeophUic attack of the arylamine at the 2-methoxy-substituted iron complex salt is controlled by the methoxy group, which directs the arylamine to the para-position. Moreover, electrophilic attack takes place at the sterically less-hindered orfho-amino position. Iron-mediated oxidative cyclization of the resulting iron complex to the carbazole followed by proton-catalyzed aimulation of the furan ring provides 8-methoxyfurostifoline. Oxidation with 2,3-dich]oro-5,6-dicyano-l,4-benzoquinone (DDQ) to O-methylfurodausine-A followed by deavage of the methyl ether provides furoclausine-A (five steps, 9 % overall yidd). 

Addition of aniline to 2-methoxy-3-methyl-l,4-benzoquinone affords the anilino-substituted benzoquinone with complete regioselectivity. Optimization of the palladium(II)-catalyzed oxidative cyclization to 3-methoxy-2-methylcarbazol-l,4-quinone was achieved by varying the different reaction parameters. The best yield of the product was obtained using 30 mol% of the palladium(II) catalyst. Using 5 mol%... 

It is well known that ir-allylpalladium complexes (86) are easily formed by the reaction of PdCb with P. y-unsaturated esters or ketones (85). An attempted oxidation of. y-unsaturated esters and ketones with the PdCl2/CuCl/02 catalyst system in aqueous DMF led to ir-allylpalladium complex formation as the main reaction, and the oxidation of the alkenic bond was hardly observed to a significant extent. However, in aqueous dioxane or THF, the oxidation became the main reaction, giving y-keto esters and 1,4-diketones (87), respectively, with high regioselectivity (Scheme 26).Some results are shown in Table 2. In all cases, no P-keto ester or 1,3-diketone was detected. At the end of the reaction, formation of a considerable amount of the ir-allylpalladium complex (86) was observed. y-Keto esters and 1,4-diketones are useful intermediates for Ae preparation of cyclopentanedione and cyclopentenone, respectively, by base-catalyzed cyclization. Tliis regioselective oxidation provides a unique and efficient synthetic method for y-keto ester and 1,4-diketone synthesis. 

Since no evidence was provided in support of the above mechanistic proposals there is a priori no reason to exclude mechanism C as an alternative route to the observed products (see also Scheme 5). Interestingly, route C would also readily explain the observed regioselectivity in the oxidative cyclization reaction of enol acetates [221]. Some years later, however, Laurent and coworkers [226,227] demonstrated that in the presence of fluoride (CHjCN/EtsN, 3HF) enol acetate radical cations partially afforded rearrangement products (e.g. 141) not compatible with mechanism C. Rather, the products found suggest that fluoride adds directly to enol acetate radical cations providing the most stable radical intermediate (e.g. 140). 

After exploring intermolecular reactions, White and coworkers utilized complex Ll/Pd11 to catalyze the intramolecular oxidative cyclization of 4 to synthesize the macrolide 5 with moderate yield and good regioselectivity (Scheme 7) [23]. Further studies on substrate scope demonstrated that this catalytic system was compatible with various carboxylic acids as nucleophiles, such as aryl acids, vinylic and alkyl acids, leading to the generation of 14- to 19-membered macrolides with remarkable levels of selectivity. 

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