Oxidative cyclization phenols

Phenol, Oms-2-(2-butenyl)-asymmetric intramolecular oxidative cyclization, 6,365 Phenol, 4-cyano-hydrolysis... 

Oxidative cyclization of the 2-(morpholinomethyl)phenol 394 by use of Pb02 resulted in the 1,3,4,11 -tetrahydro-6/7-[l,4]oxazino[3,4+][l,3]benzoxazine 388 along with a dimeric minor product 395 (Equation 45). The structure of 388 was supported by X-ray crystallography <1997RCB1272>. 

In this route a dihydroisoquinoline (58) is N alkylated with a highly functionalized o -bromoacetophenone (59) to give a quaternary salt (60), which is treated with base and cyclizes to a pyrroloisoquinoline (60). The pyrrole nucleus is then formylated under Vilsmeier-Haack conditions at position 5 and a proximate mesylated phenolic group is deprotected with base to yield a pen-tasubstituted pyrrole (61). Subsequent oxidative cyclization of this formylpyr-role produces the 5-lactone portion of lamellarin G trimethyl ether (36). This sequence allows for rapid and efficient analog synthesis as well as the synthesis of the natural product. 

The phenolic oxygen on 2-allyl-4-bromophenol (7) readily underwent oxypalladation using a catalytic amount of PdCl2 and three equivalents of Cu(OAc)2, to give the corresponding benzofuran 8. This process, akin to the Wacker oxidation, was catalytic in terms of palladium, and Cu(OAc)2 served as oxidant [17]. Benzofuran 10, a key intermediate in Kishi s total synthesis of aklavinone [18], was synthesized via the oxidative cyclization of phenol 9 using stoichiometric amounts of a Pd(II) salt. 

Oxidative polymerization of phenol derivatives is also important pathway in vivo, and one example is the formation of melanin from tyrosine catalyzed by the Cu enzyme, tyrosinase. The pathway from tyrosine to melanin is described by Raper (7) and Mason (8) as Scheme 8 the oxygenation of tyrosine to 4-(3,4-dihydro-xyphenyl)-L-alanin (dopa), its subsequent oxidation to dopaqui-none, its oxidative cyclization to dopachrome and succeeding decarboxylation to 5,6-dihydroxyindole, and the oxidative coupling of the products leads to the melanin polymer. The oxidation of dopa to melanin was attempted here by using Cu as the catalyst. 

N-Acyl-3-(3,4-dihydroxyphenyl)-L-alanines (224) on oxidative cycliza-tion provide a one-step synthesis of 3,4-dihydrocouumarins 225 (70HCA1708). This example, in fact, is based on oxidative cyclization of phenols. 

VO(acac)2/TBHP CATALYZED EPOXIDATION OF 2-(2-ALKENYL)PHENOLS. HIGHLY REGIO- AND DIASTEREOSELECTIVE OXIDATIVE CYCLIZATION TO 2,3-DIHYDROBENZOFURANOLS AND 3-CHROMANOLS... 

Table 6.6 VO(acac)2/TBHP/TFA oxidative cyclization of 2-(2-aIkenyl) phenols 1.

VO(acac)2/TBHP/TFA CATALYZED OXIDATIVE CYCLIZATION OF 2-(3,7-DIMETHYL-OCTA-2,6-DIENYL)-PHENOL... 

The procedures are very easy to reproduce and the mild and catalytic conditions are far superior to previously employed m-CPBA ", to perform, respectively, the epoxidation and the oxidative cyclization of 2-(2-alkenyl)phenols. 

Benzylideneamino)-phenols (49) can be oxidatively cyclized to form 2-phenyloxa-zols (50) (Eq. (13)) by direct anodic oxidation 2, by Pb(OAc)4AgjO " and nickel peroxide The oxidation of 49 proceeded disappointingly in t-butanoT. water at the nickel hydroxide electrode. 50 was isolated only in traces, benzaldehyde was the major product, which indicated that 49 hydrolysed under the reaction conditions. The hydrolysis could effectively be suppressed by electrolysis in an emulsion of water and cyclohexane, where the portion of water was kept low. The temperature was around 70 °C to secure a fast oxidation. With these reaction conditions good yields of 50 were obtained (Table 16). 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

Oxidative Cyclization of Substituted Phenols and Phenol Ethers. . 103... 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

Ag20. Protection of the basic nitrogen as an amide moiety was also found to decrease the side reactions involving oxidation at nitrogen. By combining these various tactics, it is now possible to obtain good yields of compounds related to 306 via oxidative cyclizations of phenols and their derivatives. 

By phenolic oxidation of the amide 183 using K3[I e(CN)6] the two coupling products 184 and 185 in 5 and 10% yields, respectively, were obtained. Conversion of 184 into 147 and 148 proceeded in the usual manner (<3S). The important intermediate 184 was also prepared from the bromoamide 186 by photochemical cyclization (39). 

The manganese(UI) acetate mediated oxidative cyclization of fl-ketoesters has been utilized to construct a pentacyclic compound in low yield [95CC403]. The intermediate radical 107 formed from an initial 6-endo-trig reaction undergoes further lactonization in the presence of copper(II) acetate. The compound 108 has the basic skeleton found in fungal metabolite sesquiterpene phenols. 

DAIB and BTIB oxidations of phenols proceed through aryloxyiodane 129 and/or aryloxenium ion 130 intermediates and are quite useful for the preparation of quinones, quinol ethers, and quinone acetals (e.g., Scheme 39) (88TL677, 92MI2, 93JCS(P1)1891, 01OR327). When phenols bearing nucleophilic side chains are used as substrates, such oxidations provide fertile ground for the assembly of heterocyclic structures. This can be accomplished by oxidative-cyclization reactions of different types. 

An oxidative spiroannulation reaction was carried out for simple phenols and as a result good yields of spiro-compounds containing tetrahydrofuran rings were obtained <02TL3597>. In the stereospecific and enantiospecific total synthesis of the sarpagine indole alkaloid dehydro-16-epinormacusine B, an oxidative cyclization of the alcohol shown below was the key and final step <02OL4681>. 

---