Benzyltetrahydroisoquinolines, oxidative

An interesting variation on the above theme for the biosynthesis of the pavines and isopavines has been proposed by Dyke (169). This proceeds via a quinone methine intermediate. The precursor, a l-benzyltetrahydroisoquinoline-3-car-boxylic acid 165 oxidizes to a quinone methide 166, which then decarboxylates to afford a reactive enamine 167. Cyclization then readily furnishes a pavine. Alternatively, hydration of the enamine 167 at C-4 would ultimately result in formation of an isopavine (Scheme 36). 

The solvent may influence the course of such coupling reactions. Thus N-trifluoracetyl-l-benzyltetrahydroisoquinolines (82) cyclize on anodic oxidation in acetonitrile to neospirodienones (83), whereas morphinandienones (84) are formed in methanol-acetonitrile [Eq. (70)].147... 

Oxidation of the 1-benzyltetrahydroisoquinoline (195) with VOCl3 (145) yielded the dienone (196) in 34% yield reaction of this with boron trifluoride etherate provided 197, and this was converted, as shown in Scheme 41, to 14-methoxyerysodienone (199). Oxidation of the secondary amine (200) gave (146) the methoxyerysodienone (201) in only 6% yield. The alternative mode of oxidation, leading to 202, was not observed. 

The oxidative coupling of aromatic nuclei activated by alkoxy groups has been explored for the formation of natural products. Thus, laudanosine (VII), Y = NCH3, Z = CH2, has been oxidized [18-22] at a platinum anode in MeCN-TMABF4 to O-methylflavinantine (VIII), and other benzyltetrahydroisoquinolines react similarly on anodic oxidation in good to excellent yield ... 

In early studies, we reported that LTA oxidation in CH2CI2 of the ( )-l-benzyltetrahydroisoquinolin-6-ols 77 and 78 affords a diaster-eomeric mixture of the ( )-4-acetoxy compounds 222 and 223, treatment of which with concentrated hydrochloric acid in ethanol gives ( )-2,3,8-trimethoxy- and ( )-8-methoxy-2,3-methylenedioxy-7-hydroxyisopa-vines (224 and 225) in 70 and 54% overall yield, respectively (69) (Scheme 24). Later, we confirmed that the oxidation of 77 and 78 gives the reactive... 

Although it is only one example, Blasko et al. (79) reported the formation of 10-hydroxy-2,3,9-trimethoxydibenzopyrrocoline by LTA oxidation of N-nor-l-benzyltetrahydroisoquinoline. LTA oxidation in CH2CI2 of ( )-A-norlaudanine (242) in the presence of TFA and trifluoroacetic anhyride (TFAA) (9 1 by volume) gave ( )-10-hydroxy-2,3,9-trimethoxydibenzopyrrocoline (243) in 16.5% yield (Scheme 27). 

Thalfine (102), a benzyltetrahydroisoquinoline-benzylisoquinolinc alkaloid, is the ring B oxidized derivative of thalfinine (103). Thalfine (102) has also only been isolated from Thalictrum foetidum and Thalictrum minus. 

Oxidative phenol coupling (4, 499-500). Schwartz and Mami have effected oxidative para-ortho coupling of the benzyltetrahydroisoquinoline alkaloid (1) to (2) with TTFA in CH2CI2 ("78 to 20°, overnight) in 23% yield. This oxidative coupling is involved in the biosynthesis of morphine alkaloids, but it has... 

Oxidative coupling of benzyltetrahydrohoqumolines. Application of this coupling reaction to benzyltetrahydroisoquinolines such as (1) leads to aporphines (2) also in remarkably high yields. ... 

BiosynthesisBy oxidative phenol coupling from benzyltetrahydroisoquinolines. 

Additional examples of intramolecular oxidative coupling of phenolic ethers include the oxidative biaryl coupling of various N-substituted 1-benzyltetrahydroisoquinolines 313 to the corresponding aporphines 314 [374], the oxidative cyclization of 3,4-dimethoxyphenyl 3,4-dimethoxyphenylacetate (315) leading to the seven-membered lactone 316 [375] and the conversion of phenol ether derivatives 317 into the products of... 

Barton DHR, Potter CJ, Widdowson DA (1974) Phenol Oxidation and Biosynthesis. Part XXIII. On the Benzyltetrahydroisoquinoline Origins of the Erythrina Alkaloids. I Chem Soc Perkin Trans 1 346... 

Barton, D.H.R. Potter, C.J. Widdowson, D.A. Phenol oxidation and biosynthesis Part XXIII. On the benzyltetrahydroisoquinoline origins of the Erytrina alkaloids. J. Chem. 

The intramolecular oxidative coupling reaction of benzyltetrahydroisoquinolines, like... 

The mass spectrum gave a base peak at m/e 121, which was considered to be due to the ion CXXV in agreement with the isolation of anisic acid by Manske by oxidation of the original corpaverine. The two pairs of aromatic protons derive from this moiety of the molecule. The other main peaks were due to the m/e 150 and 178 ions. The last peak was assigned to ion CXXVI which is transformed into the ion m/e 150 (CXXVII). That the peak m/e 178 was due mainly to ion CXXVI and not to CXXIX received support when the mass spectrum of sendaverine was compared with that of the 1-benzyltetrahydroisoquinoline (CXXVIII) (195). In this case the base peak is the ion m/e 178, to which structure CXXIX is assigned and which is transformed into the radical ion m/e 163 (CXXX), of low abundance in the case of sendaverine. On the other hand, the ion m/e 150 (CXXVII) is not detectable in the spectrum of CXXVIII. 

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