Imines cyclization

Besides the domino Michael/SN processes, domino Michael/Knoevenagel reactions have also been used. Thus, Obrecht, Filippone and Santeusanio employed this type of process for the assembly of highly substituted thiophenes [102] and pyrroles [103]. Marinelli and colleagues have reported on the synthesis of various 2,4-disubstituted quinolines [104] and [l,8]naphthyridines [105] by means of a domino Michael addition/imine cyclization. Related di- and tetrahydroquinolines were prepared by a domino Michael addition/aldol condensation described by the Hamada group [106]. A recent example of a domino Michael/aldol condensation process has been reported by Brase and coworkers [107], by which substituted tetrahydroxan-thenes 2-186 were prepared from salicylic aldehydes 2-184 and cycloenones 2-185 (Scheme 2.43). 

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). 

Carbacephalosporins The ketene-imine cyclization described above has been extended to a synthesis of a chiral carbacepham (4). This synthesis uses a dihy-droanisole group as the equivalent of a p-keto ester. Thus the azetidinone 1, obtained in 80% yield by the above route, was reduced and acylated in situ to provide 2. Ozonization followed by a rhodium-catalyzed cyclization of an a-diazo-P-keto ester provides 3, which is a useful intermediate to various substituted car-bacephams such as 4. 

The azomethine imine (155), containing a cyclic dipolarophile, cyclized to a tetracyclic pyrazolidine in 48% yield.78 Aldehyde (156), containing a furan ring, reacted with A/-methyl-A/ -(phenylacetyl)hydra-zine to afford an azomethine imine the imine cyclized to one product, probably with the two new rings cis fused.80... 

Katritzky and coworkers have developed two new methods of pyrrole synthesis involving condensation of C3-C4-C5 synthons with Schiff bases to obtain 1,2-diaryl pyrroles. The synthon 2a is obtained by condensation of acrolein, morpholine and benzotriazole, followed by a base-catalyzed elimination. Lithiation gives an anion which adds to the imine. Cyclization occurs on acid treatment. <95TL343> An alternative synthon is obtained by lithiation of 2b. <95S1315>... 

An interesting example of a system where both amino-carbonyl and amino-imine cyclizations occur involves the biisoxazolyl (103), which on catalytic hydrogenation followed by cyclization gives the pyridones (104) and (105).238... 

Preparative Methods the imine from (5)-alanine iV-methylamide and pivalaldehyde is cyclized by heating with benzoic anhydride to give mainly cis-(l) [(2/f,5S)-(l)] in modest yields alternatively, the imine cyclizes to the trans-substituted heterocycle by treatment with HCl in MeOH, and subsequent benzoylation produces trans-(l) [(25,55)-(l)] in high yield (eq 1). ... 

Aminobenzimidazoles, quaternized with l-bromoprop-2-yne and converted with ammonia into the 2-imines, cyclize on heating with a strong base the quaternary salt behaves similarly. The enzyme catalase promotes the cyclization of the amino-alkene (12.5) to a benzimidazole under comparatively mild conditions (review [B-53]). 

A method for the synthesis of c/s-lV-aiylaziridines involves sequential condensation of a substituted chloro p-tolyl sulfoxide and an aromatic imine, cyclization with Bu OK and desulfinylation with ethylmagnesium bromide (Scheme 20). Treatment of 1-chloroundecanyl p-tolyl sulfoxide with LDA (-40 C) followed by benzalaniline (89 Ar = Ar = Ph) affords the corresponding crystalline adduct (90) as a single diastereomer (94% yield). Cyclization provides the sulfinylaziridine (91) in 87% yield desul-fmylation (-55 to -35 C, 2 h) provides stereospecifically (retention) the c -aziridine (92) in 95% yield. Several related examples are provided in which products are obtained stereospecifically in similar yields. 

Cyclic conjugated imines. Cyclization of A-alkenyl amides in which the double bonds are properly distanced to the carbonyl group is effected by this reagent. It is prepared by heating P4O10 (O.I mol) and (Me3Si)20 (30 mL) in CCI4 (70 mL) for 1.5 h. 

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

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