Bischler-Napieralski reaction Subject

Bischler-Napieralski reaction of 139 to a 3,4-dihydroisoquinoline, oxidation, dehydrogenation and reduction of the nitro to the amino function gave 140 which was subjected to a Pschorr reaction (Scheme 49). Quaternization was accomplished by methyl iodide to furnish the isoquinolininium salt 141 which underwent an ether cleavage on heating a solid sample or benzene or DMF solution to Corunnine (127) (73TL3617). 

The transformations are acid-catalyzed. It is suggested66 that the previously64 prepared compounds 83 (R1 = H, Me, Ph R2 = R3 = OMe) also exist as dimers. Variously substituted 2-benzazepines, which are the subject of patents,68-68 were prepared by the Bischler-Napieralski reaction of JV-acylated 3-phenylpropylamines using phosphorus pentoxide66 67 and phosphorus oxychloride-phosphorus pentoxide.68 The cyclization of N-formylated phenylalkylamines (82, Rl = Me R2 = H R3 = R4 = 0— CH2—0) with phosphorus oxychloride, designated as the Vilsmeyer intramolecular reaction,69 gave an 82% yield of 19 (R1 = OH R2 = Me R3 = R4 = R7 = H R6 = R8 = O—CH2—0). 

The allylic carbamate 193 formed as shown in Scheme 17 can be exploited in the synthesis of a pancratistatin analogue. Thus, Suzuki-Miyaura cross-coupling of this carbamate with aryl boronic acid 61 (Scheme 18) afforded the expected arylated cyclohexene 200 (87%) that upon sequential treatment with diborane, alkaline hydrogen peroxide, aqueous acid then acetic anhydride gave the triacetate 201 (42%). Subjecting this last compound to the Bischler-Napieralski reaction... 

Electrophilic cyclodimerization (to 26) also results when (25) is subjected to Bischler-Napieralski conditions (POCI3, reflux), presumably through reaction of pyrazole with the imino chloride intermediate (78JHC1339). 

Catalytic hydrogenation of alkene 62 proceeded in a completely facially selective manner to give the C7-arylated perhydroindole 63 (quant.) that was then subjected to treatment with phosphoms oxytrichloride and so effecting a Bischler-Napieralski cyclisation reaction to give the lactam 64 (81%). Upon reduction with lithium aluminium hydride this lactam provided ( )-y-lycorane [( )-54] in 84% yield. 

The synthesis began with the silver ion catalyzed reaction between diazoketone 453 and tryptamine which afforded amide 454. When 454 was subjected to Bischler-Napieralski cyclization conditions, tetracyclic ester 455 formed along with the pentacyclic lactam 456 containing a trans DE-ring fusion. Treatment of 455 with mild base effected cyclization to produce the cis-fused pentacyclic lactam 457 which was reduced to provide alloyohim-bane (82). Alternatively, lactam 456 was reduced to provide 458, a substance which Ninomiya had previously converted to yohimbane (120) (61). 

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