Benzynes alkaloid synthesis using

This methodology has since been applied to constructing [6]-an-nelated carbazoles, and benz[/]indole, and the tetracyclic skeleton of the benzophenanthridine alkaloids. Arynes used in this type of reaction include 3,4-didehydropyridine in the synthesis of ellipticine 8 and isoellipticine 9," 3,4-(methylenedioxy)benzyne, and 2,3-naphthalyne. ... 

The benzyne route to 1-cyanobenzocyclobutenes has been employed for the synthesis of a myriad of complex natural products. The cyano group in (74) was used to attach the dienophile as well as for building die imino bridge of (75), an important precursor for some diterpene alkaloids (Scheme 15).110... 

An interesting synthesis of the lycorine-type alkaloids (46) and (47) using the photocyclization of an enamido-ketone (44) as the key step has been reported (Scheme 5). Benzyne reaction of the phenethylamine (41) provided the indoline... 

The benzyne reaction of the bromoisoquinoline 140 was examined by using sodium methylsulfinylmethanide, and dibenz[6,g]azecine 141 was obtained (80,81). An attractive modification appeared to be the expansion of the central ring of ( )-homoargemonine (143), since it seemed possible that 143 could be a representative of a new, as yet undiscovered alkaloid class originating from a 1-phenethyltetrahydroisoquinoline precursor. The synthesis of 143 was accomplished by reaction of the 1,2-dihydroisoquinoline 142 and formic acid-phosphoric acid (82). 

More recently, the preparative value of VOCl3 and VOF3-TFA in chemical oxidation has been demonstrated (see Section III, on the pro-aporphine and promorphinane alkaloids) (415,462). Some other authors used the purified enzyme horseradish peroxidase (463). By this method the aporphine base (besides the quaternary dibenzopyrrocoline) is readily obtained from (S)-( + )-laudanosoline hydrobromide or from (/ )-(—)-laudanosoline methiodide with retention of the absolute configuration. The synthesis of 6a,7-dehydroaporphine bases was also carried out by making use of the benzyne reaction (439). Reduction of these substances affords the corresponding aporphine bases (439). The synthesis of isoquinoline alkaloids by lead tetraacetate oxidation was reviewed by Umezawa and Hoshino (343). 

Furthermore, the following compounds were synthetically prepared racemic cheilanthifoline (58c) (47), kikemanine (58d) (129), canadine (58e), berberine (59a) (590, 614), tetrahydropalmatine (58g) (475), sinac-tine (58h), cavidine (68d) (616,617), nandinine (58i) (590, 614, 615), capaurine (58p) (618), capaurimine (58o) (128, 618a), xylopinine (60c) (610, 615, 619), O-methylcaseanadine (62b) (70, 620), thalictricavine (68b), and corydaline (68h) (615). Xylopinine (60c) and some other alkaloids were synthesized by benzoylation of 1-alkyl-3,4-dihydroisoquinolines followed by photocyclization. This method provides a useful route to the synthesis of other protoberberine alkaloids (619). It is also applicable to the synthesis of cularine (51) and spirobenzyltetrahydroisoquinoline alkaloids (188). Xylopinine was also synthesized from the corresponding enamide under benzyne reaction conditions (615). Kametani etal. summarized their findings on the synthesis of these alkaloids and described the formation of protoberberines by debenzylation and photolysis of tetrahydroisoquinolines (622, 623). The total stereospecific synthesis of racemic ophiocarpine (70a) from the 3,4-dihydroisoquinoline derivative by Mannich cyclization was also described (624). 

Nucleophilic aromatic substitution, based on an intramolecular attack of the phenoxide ion in the benzyne intermediate 87 (generated by dimsyl sodium treatment of 86), has been used by Castedo et al. (66) in a versatile synthesis of cularine alkaloids. However, N-attack competes with 0-attack in all instances to give dibenzopyrrocoline derivates (88), together with tetradehydrocularines (89). The main value of this approach is the easy conversion of 89 to norcularines, by catalitic hydrogenation to cularines, by quatemization with methyl iodide fol-... 

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