1.2- Dihydroisoquinolines, rearrangement

The cyclopropylcarbinyl isoquinoline (882) does not rearrange on treatment with acid, excluding a cationic mechanism for the dihydroisoquinoline rearrangement, but disproportionates to (883) and (884). 

Knabe et al. (271-274) later observed that 6,7-dimethoxy-2-methyl-1,2-dihydroisoquinolines (175), possessing either a free or a substituted benzyl group in position 1, readily rearrange to 3,4-dihydroisoquinoline salts (176) on treatment with dilute acids. 

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). 

The, g 7M-dibroniodihydrocyclopropa[r]isoqiiinolines 8 (R = H, Cl), prepared by addition of dibromocarbene to the corresponding 2-acctyl-l-phcnyl-l,2-dihydroisoquinolines, in the presence of silvcr(I) trifluoioacetate, undergo rearrangement to the 5/f-2-bcnzazepines 9, albeit in poor yields.3... 

The l,3,4-oxadiazin-6-one (240) undergoes cycloaddition followed by a remarkable rearrangement to give the triazole A(-imine 241 and an open-chain product (136). Cycloadditions have also been carried out with the following ring systems 1,2-dihydroisoquinoline (242) (137) dihydro-1,3-oxazine (243) (138,139), 2H-, 3-benzothiazine (244) (140,141), and 27/-l-pyran-2-thione (245) (142). 

The best catalyst for this transformation was AgSbFg (10 mol%), and (3-ketoesters, malonates, and silyl enol ethers have been used for the nucleophilic addition on the pyridinium intermediate DD. The dihydroisoquinolines 48 have been further used in several reactions in order to assemble the framework of various alkaloids. One example is given in the formation of dihydroisoquinoline 49, bearing a pendent a, 3-unsaturated ketone. Compound 49 can rearrange to the tetracycle 50 (related to the core structure of karachine, Scheme 5.23), using TMSOTf, via a tandem Michael addition-Mannich reaction process (intermediates EE and FF). 

In an effort to define the scope of the benzyl migration reaction, and to elucidate its mechanism, Knabe et al.1 have treated a series of 1-substituted 1,2-dihydroisoquinolines with acids. The following reactions have been observed (a) rearrangement, (b) elimination of the C-l substituent, (c) disproportionation without rearrangement, (d) disproportionation after rearrangement, and (e) recovery of starting material (Scheme VIII). The results are summarized in... 

The l-benzyl-l,2-dihydroisoquinoline [(138) R = OH, R = OMe] has been rearranged,116 and the structure of the product (140) proved by synthesis.147 The threshold for pavine formation versus migration... 

Thermal [l,3]-sigmatropic rearrangements of enamines have also been reported75. Compound 78 obtained from the reaction of dihydroisoquinoline and phenyl isocyanate,... 

The related photocyclizations of divinylamines to pyrroles and of diarylamines to dihydrocarbazoles are well established in the literature. A further example of this type of behaviour has been reported in the N-unsubstituted divinylamine (23) which is converted on irradiation in diethyl ether into the hexahydroindolone (24). In contrast, xanthone-sensitized excitation of 1 -(1-phenylvinyl)-3,4-dihydroisoquinoline (25) yields the spirobenzylisoquinoline (26), but in only 6% yield. The presence of vitamin C during the photo-induced rearrangement of... 

The Beckmann rearrangement-cyclization sequence terminated by aromatic moieties is fairly general. Recent examples of isoquinoline and dihydroisoquinoline synthesis exhibit two-step sequences using phosphorus pentachloride and phosphorus pentoxide via the cyclization of the intermediate imidoyl chlorides (equation 34). ... 

A further reaction of 1,2-dihydroisoquinolines with acids is the elimination of the C-1 substituent. An isoquinolinium salt (29) and a toluene derivative (30) are formed from (28) (70AP255). The reaction can occur if the C-1 substituent is a benzyl or a heteroanalogous benzyl group. In 1,2-dihydroisoquinolines that are able to rearrange, the elimination reaction only is... 

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 order to study the stereochemical course of the rearrangement of 1-benzyl-l,2-dihydroisoquinolines, the optically active acetal (-f-)-106 was synthesized, starting with the amine (-i-)-105. Compound (-f-)-106 is a precursor of an optically active l-benzyl-l,2-dihydroisoquinoline possessing an asymmetric center in the 1 position. The ring closure of the acetal (-f- )-106, performed with 6 N HCl, leads to 1,2-dihydroisoquinolines or, in compounds that can be rearranged under acidic conditions, via 107 to the 3-substituted... 

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