Benzolactams. 4. Reaction of 3‘,4‘- or 4‘,5‘-Dialkoxy-Substituted 1-(2‘-Bromobenzyl)-2-ethoxycarbonyl-1,2,3,4-tetrahydroisoquinolines with Alkyllithium. 1,2 and 1,4 Additions of Alkyllithium to Benzolactams

Abstract

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).

Recent Strategies for the Synthesis of Protoberberines and Protoberberine Type Compounds

“…treatment of 2'-brominated benzyltetrahydroisoquinoline carbamates (45) with excess methyllithium provides the 8-methyleneprotoberberines (46) in good yield via the corresponding not obtainable berberinones I. Reduction with NaBH 4 give the B/C trans-8-methylprotoberberines 47a and 47b exclusively [26] (Scheme 4). It is well known, that the intramolecular Mannich reaction performed with 3',4'-oygenated 1-benzyltetrahydroisoquinolines predominantly or exclusively yields the 10,11-disubstituted protoberberines rather than the 9,10-disubstitution products, which in turn represent the majority of the naturally occurring alkaloids.…”

β-Phenylethylamines and the isoquinoline alkaloids

“…In a similar manner (±)-coralydine 110b has been prepared from 105b. 99 The 3-methoxytetrahydroisoquinoline 111 reacts with Omethyleugenol 112 and boron trifluoride to give 113, which may be oxidised by osmium tetroxide to the diol 114 and then further by periodic acid to the aldehyde 115a. Reduction of this to the alcohol 115b, followed by hydrolysis and debenzylation affords the amino-alcohol 116, which is cyclised to (±)-schefferine 117 by the Mitsunobu reaction.…”

Total Synthesis of New 8‐(Arylmethyl)berbines

“…The C-8 substituent may also be incorporated once the berbine skeleton has been formed. In one method, protoberberinium salts [11] or 8-oxoprotoberberine alkaloids, [12] which are readily available compounds, are treated with organometallic reagents to yield the corresponding 8-substituted berbines. A second method to insert the substituent at C-8 is based on the stereoselective Stevens rearrangement.…”