6,7,3',4'-Alkoxy-substituted 1-(2'-bromobenzoyl)-3,4-dihydroisoquinoline methiodides 17 were treated with sodium borohydride in methanol or acetic acid to give erythro-1-(2'-bromo-alpha-hydroxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines 19. Treatment of 17 with lithium aluminum hydride in tetrahydrofuran gave the threo-isomer 20 in preference to the erythro 19. On the basis of studies on palladium(0)-catalyzed carbonylation of 2-bromo-3,4-dimethoxybenzyl alcohol to 6,7-dimethoxyphthalide, amino alcohol 19 or 20 was treated with a catalytic amount of palladium(II) acetate and triphenylphosphine in an atmosphere of carbon monoxide in the presence of chlorotrimethylsilane and potassium carbonate in boiling toluene to give the corresponding erythro- or threo-types of phthalideisoquinoline alkaloids 1 or 2, respectively. One-pot cyclization of the erythro-amino alcohols 19 was achieved by heating in N,N-dimethylformamide containing potassium carbonate to give 2,3,8,9- or 2,3,9,10-alkoxy-substituted 5,6-dihydroindolo[2,1-a]isoquinolines 3, which have a unique tetracyclic skeleton characteristic of dibenzopyrrocoline alkaloids. Similarly, palladium(0)-catalyzed carbonylation of 1-(2'-bromobenzyl)tetrahydroisoquinolines 21 in the presence of excess potassium carbonate was found to give 8-oxoberbines 22, which on reduction with lithium aluminum hydride can be converted to protoberberine alkaloids 4.

Treatment of 1-(2'-bromo-3',4'-dialkoxybenzyl)-1,2,3, 4-tetrahydroisoquinoline carbamates, 1a,c, with excess alkyllithium gave 8-oxoberbines, 2a,c, which were successively attacked in situ with another molecule of alkyllithium to give 1,2 and/or 1,4 addition products. A primary alkyllithium, such as MeLi or BuLi, gave a 1,2 addition product, 8-methyleneberbine 9a or 8-butylideneberbine 3a. t-BuLi preferred 1,4 addition, followed by elimination of the alkoxy group, to give 9-tert-butyl-8-oxoberbine 6a or 7c. s-BuLi gave a mixture of 1,2 and 1,4 addition products, 1-[2'-(2' '-methylbutyryl)benzyl]-1,2,3,4-tetrahydroisoquinoline 4a and 9-s-butyl-8-oxoberbine 5a. Similar treatments of carbamate 1b having no alkoxy group at its 3' position gave 1,2 addition products, 8-butylideneberbine 3b, 1-[2'-(2' '-methylbutyryl)benzyl]-1,2,3, 4-tetrahydroisoquinoline 4b, and 1-(2'-pivaloylbenzyl)-1,2,3, 4-tetrahydroisoquinoline 6b, in all cases. Reactions of 1a with s-BuMgCl and isoPrMgCl also gave the 1,4 adduct, 5a, and its 9-isoPr analogue, 12a. Treatment of 9a with excess NaBH(4) in AcOH gave (+/-)-coralydine (10b).

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