1.2.3.4- Tetrahydroisoquinoline, oxidation

The Pictet-Spengler synthesis is usually used when the tetrahydroisoquinoline oxidation level is required. 

Tetrahydroisoquinoline Oxidation. Papaveraldine could be produced by Fremy s salt oxidation over 7 days in 30% yield (eq 12). The corresponding A( alkyl tetrahydroisoquinolines give cleavage products (eq 13). ... 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

Ahl and Reichstein have pointed out that though it is certain that the structure of emetine includes one, and possibly two, 6 7-dimethoxy-tetrahydroisoquinoline nuclei, the suggestions so far made as to the nature of the rest of the molecule are speculative. They investigated the Hofmann degradation of A-acetylemetine, m.p. 97-9°. This forms a monomethiodide, m.p. 2ia-6°, from which, by the action of silver oxide and potassium hydroxide, followed by eautious tbermal deeomposition and reacetylation,... 

Treatment of (11 aS)-3-isopropyl-11 a-methyl-4-phenyl-1,6,11,11 a-tetrahy-dro[l,4]oxazino[4,3-6]isoquinolin-l-one (243) with 6N HCl in a pressure tube, then the reaction of the work-up residue with propylene oxide gave (3S)-3-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (244) (99S704). 

A new strategy for the syntheas of oxide-containing fragments of morphine has been developed. Thus, the tricyclic (ANO) morphine fragment 45 was obtained as the sole product via an intramolecular radical cyclization. The tetracyclic (ACNO) fragment 46 was synthesized in a similar fashion starting from 5,6,7,8-tetrahydroisoquinoline <96T10935>. 

Two molecules with comparable geometry in an asymmetric unit were found for 3,4-bis(4-fluorophenyl)-l,2,5-oxadiazole 2-oxide. The bond length of the dipolar N-O bond is 1.107 (7) A <2006AXEo4827>. In the molecule of 5-(6,7-dimethoxy-l,2,3,4-tetrahydroisoquinolin-2-yl)-4-phenyl-l,2,5-oxadiazole Ar-oxide, the six-membered heterocyclic ring has a flattened boat form. Intermolecular C-H- O hydrogen bonds link the molecules into dimers, which may be effective in the stabilization of the crystal structure <2006AXEo3130>. 

Diels-AIder reactions were utilized to prepare isoquinoline derivatives. Various tetrahydroisoquinoline-3-carboxylic acid derivatives were prepared by an enyne metathesis followed by a Diels-AIder reaction. For example the enyne 71 was treated with Grubb s catalyst to afford diene 72 in 65% yield. Subsequent Diels-AIder reaction and oxidation gave tetrahydroisoquinoline 73 in 93% yield <0OCC5O3>. Dihydrosoquinoline 75 was prepared... 

The /V -hydroxylamino compounds (404) and (405), obtained from the reaction of tert-butyl acetate with 3,4-dihydroisoquinoline-A-oxide or 5,5-dimethyl-pyrroline-/V-oxide, when boiled in methylene chloride in the presence of triphenylphosphine, carbon tetrachloride and triethylamine, are transformed to (1,2,3,4- tetrahydroisoquinolin-l-ilidene) acetate (406) or (pyrrolidin-2-ilidene) acetate (407) (Scheme 2.181) (645). 

Scheme 29. Oxidative decarboxylation of tetrahydroisoquinoline-1-carboxylic acids by fungal laccase and horseradish peroxidase.

Oxidative coupling of aryl tetrahydroisoquinolines. This reagent is superior to thallium(III) trifluoroacetate or vanadium oxyfluoride for nonphenolic oxidative coupling of substrates such as 2 to provide aporphines and homoaporphines (3). 

The power and utility of the anode as a selective oxidant is highlighted beautifully by the electrooxidative cyclization of 1-benzyl-tetrahydroisoquinolines (Scheme 18) [42]. 

A silyl group a to the nitrogen atom in tetrahydroisoquinolines and piperidines governs the regiochemistry, leads to an exclusive cyanation at this position, and additionally lowers the oxidation potential compared to the nonsilylated analogs [47]. Anodic cyanation of A-2,2,2-trifluoroethyl... 

IsoquinoUne was converted to 1,2,3,4-tetrahydroisoquinoline in 89% yield by reduction with sodium in liquid ammonia and ethanol [473], and to a mixture of 70-80% cis- and 10% trans-decahydroisoquinoline by catalytic hydrogenation over platinum oxide in acetic and sulfuric acid [474]. Without sulfuric acid the hydrogenation stopped at the tetrahydro stage. Catalytic hydrogenation of isoquinoline and its derivatives is the topic of a review in Advances in Catalysis [439]. 

Oxidation of cyclic secondary amines such as pyrrolidine (351) and piperidine (353) with iodosobenzene in water leads to lactams 352 and 354, respectively (88TL6913, 88TL6917) (Scheme 90). Similar oxidation of 2-piperidinecarboxylic acid and 2-pyrrolidinecarboxylic acid is accompanied by decarboxylation. Cyclic tertiary amines 355, 357, and 359 (Eq. 48) are likewise oxidized to the corresponding lactams. Other examples include phencyclidine (360) to A-(l-phenylcyclohexyl)piperidone (361), N-(cyanocyclohexyl)piperidine (362) to A-(l-cyanocyclohexyl)piperidone (363) (Scheme 91), and 1,2,3,4-tetrahydroisoquinoline to 1,2,3,4-tetrahy-droisoquinolinone (Eq. 49). 

A third method is exemplified by the cyclization of N-oxide intermediate 162 to give isomers 163 and 164 they are analogs of couple 160/161 and can just like these be independently obtained from a 1-phenylethyl tetrahydroisoquinoline (80H(14)817). 

The system Ru2(OAc) Cl/O2/toluene/50°C oxidisedR CH NHR to imines R CH=NR converted 1,2,3,4-tetrahydroisoquinoline to the 3,4-dihydroisoquinoline with isoquinoline, and 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline to 6,7-dimethoxy-3,4-dihydro-iso-qninoline (cf. mech. Ch. 1) [18], Such oxidations were also catalysed by TPAP/NMO/PMS/CH3CN, e.g. the conversion of indoline to indole (in which indoline nndergoes a donble-bond shift and aromatisation), and the oxidation of 1,2,3,4-tetrahydroqninoline to 3,4-dihydroquinoline (Fig. 5.1, Table 5.1) [19]. 

Isoquinoline can be hydrogenated in high yield to 5,6,7,8-tetrahydroisoquinoline (47) by use of platinum oxide and concentrated hydrochloric acid at 50 psi (Scheme 33). The method employs a relatively large amount of catalyst (1 g of Pt02 for 8.6 g of isoquinoline) (75JOC2729). 

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