Bischler-Napieralski ring closure

A second direct route to an extended 3,4-dihydro-j8-carbolinium system (120) using the Bischler-Napieralski ring closure is based on the cyclization of intermediates of general structure 118. Three approaches to intermediates of this type have been developed in connection with stereospecific syntheses in the indole alkaloid field. The first approach, introduced independently by Stork and Hill and by van Tamelen and co-workers and often used... 

A synthetic approach to the same tetracyclic y-carboline nucleus (235) is the consecutive Fischer indole and Bischler-Napieralski ring closure of o-acetamidoacetophenone methylphenyUiydrazone (234). The Bischler-Napieralski reaction has also been used in the synthesis of 3,4-benz-j8-carbolines (236) and 3,4-benz-3-carbolines, e.g. 237... 

An analogous acylation reaction has been described in another 3,4-dihydro-j8-carboline derivative. The amide 315, on Bischler-Napieralski ring closure with phosphorus oxychloride, yields an... 

A new route has been developed for the efficient formation of the variably substituted indolo[2,3-a]quinolizine ring system, starting from a properly substituted 2-piperidone (103, 104). For the preparation of octahydroindolo-quinolizine (1), the unsubstituted 2-piperidone 139 was treated with triethox-onium tetrafluoroborate. Then the corresponding lactim ether 140 was alkylated with 3-chloroacetylindole followed by a subsequent two-step reduction process and Bischler-Napieralski ring closure. Finally, reduction of the C=N bond afforded ( )-l (104). 

A simple synthesis of ( )-71 was carried out from tryptamine and iso-chroman-3-one 353 through the formation of amide 354, followed by Bischler-Napieralski ring closure and reduction, in an overall yield of 45% (193). 

Secologanin has been converted (by stages) into the hydrazone (110), which, on Bischler-Napieralsky ring-closure, reduction, and hydrolysis, yields protoemetine this was converted into cephaeline and deoxytubulosine by its reaction with (3-hydroxy-4- methoxyphenyl)ethylamine and with tryptamine respectively.138 The dithioacetal (111), prepared from norcamphor (see Volume... 

Bischler -Napieralski ring closure of 5 (R = CHO) with phosphorus oxychloride6,8 9 and of 5 (R = COCH3) with phosphorus oxychloride6, 8 or polyphosphate ester10 gave 8 (R = H and R = CH3, respectively). Reduction of 8 (R = H) with lithium aluminum hydride... 

A synthesis of sevanine (16) by Bischler-Napieralski ring-closure of the amide (17) followed by hydrogenolysis and dehydrogenation has been reported.27 The alkaloid has also been prepared from papaverine by demethylation and methyl-enation with dichloromethane.27... 

Methods of synthesis of bisbenzylisoquinoline alkaloids have been reviewed83 and the use of electrochemical methods for the reduction of the dihydro-isoquinolinium salts that result from Bischler-Napieralsky ring-closures in the synthesis of, for example, espinidine has been studied.84... 

A completely different route devised by Prelog and co-workers (14) not only afforded a new synthesis of the erythrinane skeleton but also achieved a method of introducing an oxygen function at C-3, the site of the aliphatic methoxyl in the alkaloids. The synthesis is outlined in Fig. 5. The dihydroisoquinolinium salt XXXIV was prepared by Bischler-Napieralski ring closure of the lactam XXXIII. Hydrolysis of the vinyl chloride of XXXIV gave the methyl ketone XXXV. When this salt was made alkaline, addition of the carbanion from the acidic methyl to the C=N double bond created the spiro link. Sodium borohydride reduction of XXXVI gave a mixture of epimeric alcohols. One of them had an IR-spectrum identical with that of a transformation product (XXXVII) of erysonine (If) and on resolution w ith tartaric acid its (— )-enantiomer proved to be identical with XXXVII. 

Cyclodehydration. Attempts to cyclize the imide (1) with phosphoryl chloride, the usual reagent for Bischler-Napieralski ring closure, gave back only starting material, but the lactam (2) was obtained by refluxing (1) with P2O., in xylene. ... 

A novel syrTEhesis of the aporphine system has been achieved from the diphenylethylamine (149) by condensation with diethyl oxalate followed by Bischler-Napieralski ring closure to the dihydroisoquinoline (150) and further cyclisation with polyph-osphoric acid to the oxoaporphine (151). A -methylation and reduction of this gave the trimethoxyaporphine 0,iV-dimethyl-tuduranine (M. Grecke and A. Brossi, Helv., 1979, 62. 1549). 

An improved synthesis of polyhydroxybenzylisoquinolines without protection of the hydroxy-groups has been reported, in which Bischler-Napieralsky ring closure of the appropriate amide is achieved with phosphorus oxychloride in acetonitrile coclaurine, isococlaurine, and reticuline, as well as a key intermediate in the synthesis of multifloramine, have been prepared in this way. 

The alcohol 119 derived from the minor product of the biaryl coupling was then converted into (+)-0-methylhamatine (92) (ref. 71) as well as the enantiomer 140 of O-methylancistrocladine (2). Hydrolysis of the butanamide 137 gives the amine 141 which was converted into methylhamatine. This successful intermolecular approach was next applied in first total synthesis of the 5,l -linked (-)-ancistrocladinine (143) (ref. 21, 72). It was envisaged that deprotection and Bischler-Napieralski ring closure of the amide 144 would yield the dihydroisoquinoline 143, and the amide 144 was available from a coupling between the oxazoline 105 and the Grignard reagent 145 (Scheme 19). 

Attempts to synthesize isothebaine 0-methyl ether by routes which have been so successful with other aporphines have thus far failed. Gulland and coworkers (83) failed in the Bischler-Napieralski ring closure to yield a... 

Bischler-Napieralski ring closure 24, 930 ring expansion 24, 861 -, H-labeled... 

Bischler-Napieralski ring closure with cycloalkane methylene groups... 

Phosphorus oxide chloride 1,2,3,4-Tetrahydroisoquinolines via Bischler-Napieralski ring closure... 

Bisboric acid esters 16, 157 Bischler-Napieralski ring closure 17, 942 G-Bis(hydroxymethylation)... 

Bischler s. a. Mdhlau Bischler-Napieralski ring closure 10,665 23,914 suppl. 26 ... 

---