Bischler-Napieralski isoquinoline synthesis

In the laboratory of J. Bonjoch the first total syntheses of the pentacyclic (+)-strychnoxanthine and (+)-melinonine-E alkaloids were accomplished using a radical carbocyclization via a-carbamoyidichloromethyl radical followed by the Bischler-Napieralski cyclization, as the two key cyclization steps. 

The first total synthesis of annoretine, an alkaioid containing the 1,2,3,4-tetrahydronaphtho [2,1-f]isoquinoline moiety was achieved by J.C. Estevez and co-workers. The total synthesis had two key steps first a Bischler-Napieralski reaction to form the 5-styrylisoquinoline unit followed by a photocyclization to provide the desired naphthoisoquinoline skeleton. 

The asymmetric total synthesis of rauwolfia alkaloids (-)-yohimbane and (-)-alloyohimbane was carried out by S.C. Bergmeier et al. by utilizing a novei aziridine-allylsilane cyclization and the Bischler-Napieralski isoquinoline synthesis as key steps.These alkaloids have a characteristic pentacyclic ring framework and exhibit a wide range of interesting biological activities such as antihypertensive and antipsychotic properties. 

The first enantioselective total synthesis of the 7,3 -linked naphthylisoquinoline alkaloid (-)-ancistrocladidine was accomplished by J.C. Morris and co-workers. The key steps of the synthesis were the Pinhey-Barton ortho-arylation and the Bischier-Napieralski cyclization. The natural product was isolated from the 1 1 mixture of atropisomers by recrystallization from toluene/petroleum ether. 

Retro-Brook Rearrangement Retro-Brook Rearrangement  

---

BISCHLER NAPIERALSKI Isoquinoline synthesis Isoqutnoline synthesis Irom amides of phenethylamines... 

BERNTHSEN Acndine synthesis 32 BIGINELLI Pynmidone synthesis 33 BIRCH - HUCKEL - BENKESER Reduction 34 BISCHLER Benzomarine synthesis 35 BISCHLER - MOHLAU Indole synthesis 35 BISCHLER - NAPIERALSKI Isoquinoline synthesis 36... 

Bischler-Napieralski isoquinoline synthesis Preparation of isoguinolines from acylated phenviethvlamines. 62... 

BISCHLER-NAPIERALSKI Isoquinoline Synthesis Isoquinoline synthesis from amides or phenethylamines (see 1st edition). 

BISCHLER NAPIERALSKI Isoquinoline synthesis Isoquinoiine synthesis from amides of phenethylammes... 

Many biologically active derivatives are based on the dihydrobenzodiazepine structure. The tranquilizer medazepam is of this type its synthesis (Scheme 9.56) is of interest because of its close resemblance to the Bischler-Napieralski isoquinoline synthesis, in that an amide is subjected to cyclodehydration with PPA. Here, a second nitrogen atom must be present in the side chain, as in the starting amide 9.114. This product is the tranquilizer medazepam (9.115). 

Other references related to the Bischler-Napieralski isoquinoline synthesis are cited in the literature. 

The Vilsmeier reaction is used to this day in largely the same way as it was originally conceived, though its substrate scope continues to expand. One important variation, known as the Bischler-Napieralski isoquinoline synthesis, involves an intramolecular Fiedel-Crafts acylation reaction where the acylating agent resembles a Vilsmeier electrophile. If the acylated phenethylamine substrate contains an a-hydroxyl group, a subsequent dehydration yields an isoquinoline. ... 

---