Cyclization reactions base- catalyzed

Regio-isomeric naphthofurans and benzodifurans were made by a base-catalyzed cyclization reaction from their corresponding o-alkoxybenzoylarenes as shown below <05T545>. An innovative synthesis of dibenzofurans through a carbanion-induced ring transformation reaction was so described <05TL491>. 

The first building block, the commercially available 11, is synthesized by a base-catalyzed cyclization reaction of N-cyano-dimethyldithioimidocarbonate (10a, CIDT) [65, 66] or N-cyano-dimethyl-imidocarbonate (10b, DCC) [67] with cyste-amine hydrochloride. From the technical process for 1, several attractive synthetic routes are described for the preparation of 5 (Table 29.2.2.3). Finally, the technical process is readily available by N-alkylation of 11 with 5. 

Shanmugham and White used an intramolecular base-catalyzed cyclization reaction to construct the tricyclic framework of 6-P-hydroxyeuryopsin, a compound with strong antifeedant activity against insects of the genera Leptinotarsa and Myzus Treatment of a chiral aldehyde precursor with TMSOTf in the presence of 2,6-lutidine gave the desired tetrasubstituted furan in quantitative yield. Two additional steps were required to access the target compound, 6p-hydroxyeuryopsin. 

The [Co(NH3)s(NH2CH2COCH3)] ion undergoes an intramolecular base-catalyzed cyclization reaction to give a coordinated carbinolamine, which undergoes a slower base-catalyzed dehydration to give a chelated imine. The synthesis, characterization and kinetics of formation of various reaction products are described. Several reactions of the imine product have been carried out, including BH4 reduction and condensation with methyl vinyl ketone. 

Another approach uses the reaction of 6-chloro-5-nitropyrimidines with a-phenyl-substituted amidines followed by base-catalyzed cyclization to pteridine 5-oxides, which can be reduced further by sodium dithionite to the heteroaromatic analogues (equation 97) (79JOC1700). Acylation of 6-amino-5-nitropyrimidines with cyanoacetyl chloride yields 6-(2-cyanoacetamino)-5-nitropyrimidines (276), which can be cyclized by base to 5-hydroxypteridine-6,7-diones (27S) or 6-cyano-7-oxo-7,8-dihydropteridine 5-oxides (277), precursors of pteridine-6,7-diones (278 equation 98) (75CC819). 

AB-Dinorsteroids have been prepared by Dauben et al from B-nor-A" -3-ketones by reactions analogous to the sequence (4) - (7). Pyrolysis of the B-nor-2,3-seco diacid anhydride gives the AB-dinor-A -2-ketone in 5 % yield. However, refluxing the diacid with acetic anhydride containing potassium cyanide for 2 days gives the ketone in 50-60% yield, apparently by base-catalyzed cyclization of an intermediate bis-acylcyanide. 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

In this example, the /3-diketone 2-methyJ-l,3-cyclopentanedione is used to generate the enolate ion required for Michael reaction and an aryl-substituted a,/3-unsaturated ketone is used as the acceptor. Base-catalyzed Michael reaction between the two partners yields an intermediate triketone, which then cyclizes in an intramolecular aldol condensation to give a Robinson annulation product. Several further transformations are required to complete the synthesis of estrone. 

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

Chukhadzyan et al. made N-junction fused tricyclic systems such as 123 via a base-catalyzed cyclization onto the tetrazole 122 (Equation 29). The exothermic reaction proceeds at room temperature <1999CHE343>. 

The related syn diol epoxide isomers were synthesized from the 1,2- and 7,8-dihydrodiols of 5-MC by reaction with N-bromoacetamide in moist DMSO followed by base-catalyzed cyclization by the usual Method I procedures (60). 

Dioxane solutions of 4(5)-aminoimidazole (64) have been treated with several reagents [92JCS(P1)2789], Imidazo[l,5-a]-l,3,5-triazines (65 R = Ph, Me SMe) were obtained by reaction with methyl N-cyanobenzimidate (57 R = Ph), ethyl N-cyanoacetimidate (58 R = Me), and dimethyl yV-cyanodithioiminocarbonate (59 R = SMe). The uncy-clized product (68 R = H) (73%), obtained by condensation with ethyl N-cyanoformimidate (58 R = H), underwent facile cyclization to give the imidazo[l,5-a]-l,3,5-triazine (65 R = H). Likewise, the condensation adduct (69 R = H) (78%) was obtained using ethoxy methyleneurethane (60 R = H) and this underwent base-catalyzed cyclization to give the imidazo[ 1,5-a]-1,3,5-triazinone (67). Imidazo[l, 5-a]pyrimidines (66 R = H, Me) were obtained from the condensation of 4(5)-aminoimidazole... 

Several syntheses of l,3-dioxoperhydropyrrolo[l,2-c]imidazoles have been developed using different strategies. a-Substituted bicyclic proline hydantoins were prepared by alkylation of aldimines 135 of resin-bound amino acids with a,tu-dihaloalkanes and intramolecular displacement of the halide to generate cr-substituted prolines 136 and homologs (Scheme 18). After formation of resin-bound ureas 137 by reaction of these sterically hindered secondary amines with isocyanates, base-catalyzed cyclization/cleavage yielded the desired hydantoin products <2005TL3131>. 

Fig. 8.12. Activation of hemiester prodrugs of phenols by acid-catalyzed hydrolysis (Reaction a), base-catalyzed hydrolysis (Reaction b), and cyclization-elimination (Reaction c). Enzymatic hydrolysis not shown (adapted from [174]). 

In a base-catalyzed substitution reaction with benzamide, ethyl 2-cyano-3,3-bis(methylsulfanyl)acrylate 280 gave the 3-aminoacrylate derivative 281, which on thermal cyclization yielded the functionalized 6-imino-l,3-oxazine 282 (Scheme 52) <1995BML695>. 

Reaction of 232 with 4-substituted l,3-oxazol-5(4/7)-one 247 led to diacylhydrazines 248 or to imidazole derivatives 249 depending on the reaction temperature (Scheme 24). l,2,4-Triazole-3-thione 250 was obtained by a two-step sequence from 232 with phenyl isothiocyanate and subsequent base-catalyzed cyclization of thiosemicarbazide 251. The effects of hydrazones 241-246 on inhibition of photosynthetic electron transport in spinach chloroplasts and chlorophyll content in the antialgal suspensions of Chlorella vulgaris were investigated <2005CEC622>. 

A reported example (115) of this ring system was prepared by the reaction of two molar equivalents of 2-cyanocyclohexanone with hydrazine to give the azine 114, which underwent base-catalyzed cyclization to 115 [63CI(M)709]. 

A remarkably simple and efficient method for preparing oxazolo[2,3- >]quinazoline (208) is the reaction of anthranilic acids or their esters with /3-haloisocyanates, followed by base-catalyzed cyclization of the intermediate urea derivatives (207) [74GEP(0)2252122 76S469 80JHC1553]. 

The stereochemistry of the C-glycosidic products, obtained with the above-mentioned procedure, depends on the structure of the starting sugar and on the experimental conditions. In general, base catalyzed cyclizations afford a mixture of anomers, which on prolonged reaction time is converted into the thermodynamic product. For example, in the case of 4,6-O-isopropylidene-D-glucose,... 

Benzoxathiin 2,2-dioxides (245) are prepared from 2-acylphenols by reaction with a sulfonyl chloride, followed by base-catalyzed cyclization of the sulfonate ester (244) (66HC(21-2)792). 

CB585). In addition to the reductive cyclization included in Table 11, 1-hydroxyindole-2-carboxylate can also be prepared by base-catalyzed cyclization of dimethyl o-nitrobenzyl-malonate, a reaction which is formulated as involving a nucleophilic attack on the nitro group 72CRV627). 

Thieno[3,2-fc]pyridines are obtained in 49-87% yield (74JPR169). Application of the Friedlander reaction to 3-amino-2-formylthiophene gives (261) in reasonable yield (Scheme 78) (75ACS(B)224,75 ACS(B)233). As in the case of the synthesis of furo[3,2- >]pyridines (Section 3.17.2.1.1(i)(d), Scheme 17), it was unnecessary to isolate the o-aminocarbonyl compounds. 6-Substituted 7-hydroxythieno[3,2-6]pyridin-5(4/7)-ones (e.g. 295) can be prepared by base-catalyzed cyclization of the amides (294), which were obtained in high yields from readily available 3-amino-2-alkoxycarbonylthiophenes (293 Scheme 79) (80JCR(S)6) for... 

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