Synthesis and stereochemistry of 1,2,3,4-tetrahydro-6-methoxy-2-methyl-1-phenylisoquinoline and related compounds

Kametani, Tetsuji; Sugi, Hideo; Yagi, H.; Fukumoto, Keiichiro; Shibuya, S.

doi:10.1039/j39700002213

Cited by 6 publications

(9 citation statements)

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“…spectroscopy suggesting that (9) was being produced with complete control over both the regioand stereo-chemistry. Treatment of complex (6) with butyllithium, followed by methyl iodide, however, gave a 2: 1 mixture of (6) and (9) indicating incomplete C-1 deprotonation with the weaker base. Deprotonation of (6) with t-butyl-lithium gave, on addition of ethyl iodide or benzyl bromide, the complexes (10) and ( A common side product formed in the preparation and reactions of complex (15) was identified as the ring-opened complex (16) which could be oxidatively decomplexed to the styrene (17) (Scheme 5).…”

Section: Base: Buli 100mentioning

confidence: 94%

“…6~ solution in hexane and t-butyl-lithium as a 2~ solution in pentane. Tricarbonyl(q6-2-methyl-1 ,2,3,4-tetrahydroisoquinoline)chromium(o) (4), tricarbonyl(q6-2,4-dimethyl-1,2,3,4-tetrahydroisoquinoline)chromium(o) (6), and tricarbonyl(q6-4-ethyl-2-methyl-1,2,3,4-tetrahydroisoquinoline)chromium(o) (7) were prepared as previously described. '…”

Section: Methodsmentioning

confidence: 99%

“…2 790 (N-CH,), 1 960, and 1 880 cm-' ( C a ) ;6,m,ArH) C,54.2;H,6.1;N,3.9. C,6H,,CrNO,requires C,54.1;H,6.0;N,3.9%).…”

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confidence: 98%

“…The first fraction (SiO,, Et,O, R, = 0.72) was recrystallised from diethyl ether-hexane to give the title compound as yellow needles (680 mg, 4773, m.p. 113-115 "C; v, , , . 2 795 (N-Me), 1 965, and 1 890 cm-' ( C a ) ; 6,m,ArH),3.33 (1 H, t, J3. 6 (3 H,t,J 7.5 Hz,CH,CH,), 0.75 (3 H,t,J 7.4 Hz,CH,CH,); m/z 339 ( M + ) (Found: C,60.1;H,6.5;N,4.1.…”

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confidence: 99%

“…113-115 "C; v, , , . 2 795 (N-Me), 1 965, and 1 890 cm-' ( C a ) ; 6,m,ArH),3.33 (1 H, t, J3. 6 (3 H,t,J 7.5 Hz,CH,CH,), 0.75 (3 H,t,J 7.4 Hz,CH,CH,); m/z 339 ( M + ) (Found: C,60.1;H,6.5;N,4.1. C,,HzlCrN03 requires C,60.2;H,6.2;N,4.1%).…”

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confidence: 99%

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Tetrahydroisoquinolines. Part 3. Stereoselective synthesis of cis- and trans-1,4-disubstituted N-methyl-1,2,3,4-tetrahydroisoquinolines as their tricarbonylchromium complexes

Blagg¹,

Coote²,

Davies³

et al. 1987

J. Chem. Soc., Perkin Trans. 1

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The 1 -exo proton of tricarbon y 1-4 -ex0 -methyl -or tr icar bony1 -4-exo -et h y I -2 -methyl -1,2,3,4-tetra hydroisoquinolinechromium (6) and (7) can be regio-and stereo-selectively removed by t-butyl-lithium and replaced with a variety of electrophiles to give cis-I ,4-disubstituted 2-methyl-l,2,3,4-tetrahydroisoquinoline complexes. Oxidative decomplexation generates the corresponding cis-1,4-disubstituted tetrahydroisoquinolines. Similar methodology applied to tricarbonyl (4-exo-trimethylsilyl-2-methyl-l,2,3,4-tetrahydroisoquinoline)chromium (1 5) gives, after desilylation, 1 -exo-su bstituted tetrahydroisoquinoline complexes.Among the tetrahydroisoquinoline alkaloids * a number have been isolated which contain substituents in the 1-and 4-positions. These include the 4-hydroxyaporphines, e.g. cataline (1),2 the pyrroloisoquinolines, e.g. (2),3 which exhibit potent antidepressant activity and the 4-hydroxy-1-methyltetrahydroisoquinolines (3) which are believed alcohol a d d i~t i o n .~ OH 1 Me0 u Me0 (1) OH HO \ to be involved in Ph I I ( 3 )Although syntheses of simple polysubstituted tetrahydroisoquinolines, including the elaboration of 4-oxotetrahydroisoquinolines and the cyclisation of aldehydes with 1-hydroxy-2-phenylethyIamine~,~ are available, the stereoselective introduction of substituents into the 1-and 4-positions is generally difficult. Recently a general synthetic route to optically active 1-substituted tetrahydroisoquinolines has been developed by Meyers et al.,' and we have previously described the application of arene tricarbonylchromium methodology to the introduction of substituents into the 4-po~ition.'~'It has been established that benzylic carbanions co-ordinated to tricarbonylchromium are ~tabilised.~ Thus, 2-methyl-tetrahydroisoquinoline (4) undergoes regio-and stereo-selective 4-exo-deprotonation to generate the anion (5) (Scheme 1). * For clarity the descriptors 1,2,3,4-are omitted. (5) generates the 4-exoderivatives (6) and (7) which, after decomplexation, yield the corresponding 4-alkyl-2-met hyltetrahydroisoquinolines. Exclusive removal of the 4-exo-proton of complex (4) presumably occurs because co-ordination of the butyl-lithium to the nitrogen directs the base to the 4-position whilst the bulk of the tricarbonylchromium moiety prevents approach to the 4-endo-proton. ' ** R N\ =,pp N\ -dN , Cr(Co)3 / CrKO), C r (CO), ( 5 ) (6) R = M e ( 7 ) R = E t &erne I. Subsequent addition of alkyl halides toWe describe here the extension of this methodology to the stereoselective synthesis of 1,4-disubstituted-2-methyltetrahydroisoquinolines. Results and DiscussionTreatment of complex (4) with t-butyl-lithium at -78 "C followed by the addition of methyl iodide gave, after work-up, a 2 : l mixture of complexes (6) and (8) which were readily separable by column chromatography. Complex (6) was identical with an authentic sample of tricarbonyl-2,4,-exodimethy1tetrahydroisoquinoIine)chromium.' The structure of complex (8) followed from its 'H n.m.r. spectrum; the AB system, 6 3.50,3.27 (JAB 15 H...

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Section: Base: Buli 100mentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

“…2 790 (N-CH,), 1 960, and 1 880 cm-' ( C a ) ;6,m,ArH) C,54.2;H,6.1;N,3.9. C,6H,,CrNO,requires C,54.1;H,6.0;N,3.9%).…”

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confidence: 98%

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confidence: 99%

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confidence: 99%