1.2- Dihydroisoquinolines, 1-allyl

Methyl-1,2-dihydropapaverine (175, R = OMe) rearranges to the 2-methyl-3-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinolin-ium salt (176, R = OMe) under very mild conditions (treatment with 2% hydrochloric acid). A similar rearrangement of l-(3,4-methyl-enedioxybenzyl) - 2 - methyl - 6,7 - dimethoxyisoquinoline (175, R, R = —O—CHj—O—) affords 3-(3,4-methylenedioxybenzyl)-2-methyl-6,7-di-methoxy-3,4-dihydroisoquinolinium chloride (176, R, R = O—CHj—O—) (256). The reaction was shown to be an allylic rearrangement with internal return (275,275). 

Nucleophilic addition reactions of allylic tin reagents to chiral 3-substituted 3,4-dihydroisoquinolines 89 activated by acyl chlorides afford trans 1,3-disubstituted 1,2,3,4-tetrahydroisoquinolines 90 stereoselectively <95CL1003>. 

Isoquinoline alkaloids. The regioselective allylation of N-acyl heterocycles (13, 10) can be used for synthesis of isoquinoline alkaloids. Thus simultaneous reaction of the dihydroisoquinoline (1) with a diunsaturated acyl chloride (2) and allyltributyltin affords the 1,2-adduct (3), which undergoes a Diels-Alder cyclization... 

Rozwadowska and coworkers carried out the asymmetric alkylation of isoquino-line Reissert compounds under phase-transfer conditions using cinchonine-derived quaternary ammonium salts as catalysts. The best enantioselectivity was achieved in the benzylation and allylation of 1 -cyano-2-phenoxy carbonyl-1,2-dihydroisoquinoline (17) catalyzed by 2a (Scheme 2.14) [34]. 

When l-allyl-2-methyl-l,2-dihydroisoquinoline [(149) R = H] is treated with dilute mineral acids under the conditions of the benzyl... 

AP831). Product 74 was obtained in only 10% yield, and a considerable part of the starting material (22a) was found to be resinified under the acidic conditions. The iminium salts 75 and 76 form in 23 and 49% yields, respectively. In both cases, disproportionation products could be isolated from 23a the compounds 77 and 78 in low yields and from 24a the compounds 79 and 80 in yields of about 15%. These findings demonstrate that the furo-(22a) and thienodihydropyridines (23a and 24a) under the rearrangement conditions behave similarly to the corresponding l-allyl-1,2-dihydroisoquinolines. 

In Section III,C it was shown that various 1-substituted 1,2-dihydroiso-quinolines can be cyclized intramolecularly to give pavinanes, isopavinanes, homopavinanes, and homoisopavinanes. Section III,D deals with the formation of 3-substituted isoquinoline derivatives from 1-allyl-, 1-benzyl-1,2-dihydroisoquinolines, and related compounds. In this section some synthetic reactions of 1,2-dihydroisoquinolines are reported. 

The reaction of 3,4-dihydroisoquinoline-/V-oxide (22) with olefins such as allyl alcohol,39 styrene,45 methyl acrylate,36,100 and ethyl acrylate36 gives stereospeciflcally isoxazolidine of type It. 

Pseudocyanides. 6,7-Dimethoxy-2-methyl-l-allyl-l,2-dihydroisoquinoline dissolved in N H(5i, heated 0.5 hr. at 80° bath temp., cooled, made alkaline with NaHCOj, and treated with coned. NaCN-soln. pseudocyanide. Y 92%. F. rearrangements s. J. Knabe and H.-D. Holtje, Ardi. Pharm. 303, 404 (1970) Pharmazie 25, 313 (1970). 

When l-allyl-2-methyl-l,2-dihydroisoquinoline is heated with dilute mineral acid, a rearrangement occurs rapidly and in high yield to the 2-methyl-3-allyl-3,4-dihydroisoquinoline salt (14). This is an intramolecular suprafacial sigma-tropic [3,3] shift analogous to the Claisen and Cope rearrangements, with a transition state as denoted below. " ... 

Takemoto et al reported that ln(OTf)3 catalyzed the tandem allylation and cyclization of O-alkynylarylaldimines to form 1,2-dihydroisoquinolines, with a proton source to accelerate the rate of the reactions [233] (Figure 8.110). The authors proposed two pathways for the reaction, with the ln(OTf)3 functions either to activate the imine for an initial allylation followed by cyclization, or to activate the alkyne for cyclization followed by allylation. The authors also reported that nucleophiles other than allyltributyl stannane, notably silyl enol ethers, could also be used. 

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