Quinone imine cyclization

For the quinone imine cyclization of iron complexes to carbazoles the arylamine is chemoselectively oxidized to a quinone imine before the cyclodehydrogenation [99]. The basic strategy of this approach is demonstrated for the total synthesis of the 3-oxygenated tricyclic carbazole alkaloids 4-deoxycarbazomycin B, hyellazole, carazostatin, and 0-methylcarazostatin (Scheme 17). 

Over the past 15 years, we developed three procedures for the iron-mediated carbazole synthesis, which differ in the mode of oxidative cyclization arylamine cyclization, quinone imine cyclization, and oxidative cyclization by air (8,10,557,558). The one-pot transformation of the arylamine-substituted tricarbonyl(ri -cyclohexadiene) iron complexes 571 to the 9H-carbazoles 573 proceeds via a sequence of cyclization, aromatization, and demetalation. This iron-mediated arylamine cyclization has been widely applied to the total synthesis of a broad range of 1-oxygenated, 3-oxygenated, and 3,4-dioxygenated carbazole alkaloids (Scheme 5.24). 

Electrophilic aromatic substitution of 708 with the iron-coordinated cation 602 afforded the iron-complex 714 quantitatively. The iron-mediated quinone imine cyclization of complex 714, by sequential application of two, differently activated, manganese dioxide reagents, provided the iron-coordinated 4b,8a-dihydrocarbazole-3-one 716. Demetalation of the iron complex 716 with concomitant... 

The total synthesis of carbazomycin D (263) was completed using the quinone imine cyclization route as described for the total synthesis of carbazomycin A (261) (see Scheme 5.86). Electrophilic substitution of the arylamine 780a by reaction with the complex salt 779 provided the iron complex 800. Using different grades of manganese dioxide, the oxidative cyclization of complex 800 was achieved in a two-step sequence to afford the tricarbonyliron complexes 801 (38%) and 802 (4%). By a subsequent proton-catalyzed isomerization, the 8-methoxy isomer 802 could be quantitatively transformed to the 6-methoxy isomer 801 due to the regio-directing effect of the 2-methoxy substituent of the intermediate cyclohexadienyl cation. Demetalation of complex 801 with trimethylamine N-oxide, followed by O-methylation of the intermediate 3-hydroxycarbazole derivative, provided carbazomycin D (263) (five steps and 23% overall yield based on 779) (611) (Scheme 5.91). 

Arylamine cyclization Oxidative cyclization by air Quinone imine cyclization... 

A direct synthesis of cyclic quinone imine acetals has been accomplished by the treatment of substituted phenol ethers bearing an alkyl azido side chain with IBTA (Eq. 39) [96JCS(CC)1491]. The cyclization reaction proceeds smoothly in polar and low nucleophilic solvents such as CF3CH2OH and (CF3)2CH0H in the presence of 10% MeOH. 

Electrophilic substitution at the arylamine 709 using the complex salt 602, provided the iron complex 725 quantitatively. Sequential, highly chemoselective oxidation of the iron complex 725 with two, differently activated, manganese dioxide reagents provided the tricarbonyliron-complexed 4b,8a-dihydrocarbazol-3-one (727) via the non-cyclized quinone imine 726. Demetalation of the tricarbonyliron-complexed 4b,8a-dihydrocarbazol-3-one (727), followed by selective O-methylation, provided hyellazole (245) (599,600) (Scheme 5.70). 

Electrophilic aromatic substitution of the arylamine 780a using the iron-complex salt 602 afforded the iron-complex 785. Oxidative cyclization of complex 785 in toluene at room temperature with very active manganese dioxide afforded carbazomycin A (260) in 25% yield, along with the tricarbonyliron-complexed 4b,8a-dihydro-3H-carbazol-3-one (786) (17% yield). The quinone imine 786 was also converted to carbazomycin A (260) by a sequence of demetalation and O-methylation (Scheme 5.86). The synthesis via the iron-mediated arylamine cyclization provides carbazomycin A (260) in two steps and 21% overall yield based on 602 (607-609) (Scheme 5.86). 

An interesting new method to cyclize phenylalkylazides to the quinone imine 29 by oxidative cyclization with phenyliodine (III) bis(trifluoroacetate) (PIFA) was reported <99CPB241>. 

An interesting report on the synthesis of quinone imines was the oxidative cyclization of phenylalkylazides with phenyliodine(m) bis(trifluoroacetate) (PIFA) (Equation 20) <1999CPB241>. 

In this reaction, DA-o-quinone is initially attacked by CySH to give 5-5 -CyS-DA, which is appreciably more easily oxidized than DA to give o-quinone 15. This intermediate very rapidly cyclizes to give the bicyclic o-quinone imine 16. In the presence of free CySH 16 can either be reduced to DHBT 17 or nucleophilic addition of a second CySH molecule occurs to give DHBTs 18 and 19. The latter compounds are even more easily oxidized than DA and 5-5 -CyS-DA to o-quinone imines 20 and 21, respectively, which can be either reduced by CySH or further... 

Cyclizations. Annulation accompanies oxidation of A-sulfonyl-4-methoxyanilines with Phl(OCOCp3)2 in the presence of 1-alkenes. 5-Methoxyindoles or indolines are produced in this one-pot reaction. Cyclization of 3-arylpropyl azides where the aromatic ring is activated (e.g., 3-methoxylated) to fused quinone imines is observed. ... 

Kita Y, Egi M, Ohtsubo M, Saiki T, Okajima A, Takada T, Tohma H (1999) Hypervalent iodine(III)-induced intramolecular cyclization reaction of substituted phenol ethers with an alkyl azido side-chain a novel and efficient synthesis of quinone imine derivatives. Chem Pharm Bull 47 241-245... 

A third pathway leads via the quinone imine intermediates 38 to 3-hydro-xycarbazoles 41 (mode C in Scheme 12) [97, 98, 108, 109]. Oxidation of the complexes 36 with manganese dioxide afforded the quinone imines 38, which on treatment with very active manganese dioxide undergo oxidative cyclization to the tricarbonyl(ri" -4b,8a-dihydrocarbazol-3-one)iron complexes 39. Demetalation of 39 with trimethylamine iV-oxide and subsequent aromatization lead to the 3-hydro-xycarbazoles 41. The isomerization providing the aromatic carbazole system is a... 

Anilides with pendant double bonds 898 undergo DMP-induced stereoselective oxidative cyclization to give complex and diverse natural product-like polycycles 899 (Scheme 3.361) [1176,1277]. This oxidative cyclization is proposed to occur by the initial ortho directed oxidation of anilide 898 to give an ort/io-hydroxylated benzene ring that is further oxidized to the quinone imine intramolecular Diels-Alder cyclization of the... 

Nicolaides observed that the reflux of oxime 19 in PhMe formed oxazole 4 in 37% yield, and proposed its formation by a sequence of reactions as follows. A homolytic reaction between oxime 19 and PhMe led originally to the formation of radicals 20 and 21 from oxime 19 and PhMe, respectively then the combination of the two radicals formed intermediate 22. After loss of one molecule of MeOH from 22, o-quinone-imine 23 was formed. o-Quinone-imine 23 tautomerized to hydroxyl-imine 24, which after cyclization and loss of of one molecule of H2 formed oxazole 4 in 37% yield. Oxime 19 could also react with other methyl containing aromatics and heteroaromatics to form oxazoles (19 25). 

When the aniline moiety of iron complex 57 has a p-anisidine structure, the iron complex can be oxidized selectively to quinone imine 59 using commercial manganese oxide. Thus, oxidative cyclization of the quinone imines 59 using highly active manganese dioxide and demetallation provides 3-hydroxycarbazoles 60 directly (Scheme 23.23) [30]. 

Quinone imine-substituted ( n -cyclohexa-l,3-diene)iron complexes are obtained by oxidation of the corresponding p-anisidine precursors with manganese dioxide (Scheme 4—133). Treatment of the former species with very active manganese dioxide triggers an oxidative cyclization to afford iron-coordinated 4b,8a-dihydrocarbazol-3-Demetalation with trimethylamine N-oxide leads via concomitant... 

Scheme 4-133. Oxidative cyclization of (ri -cyclohexadiene)iron complexes with pendent quinone imine moieties.

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