Chemistry 1.2- dihydroisoquinolines

A wide variety of other functional groups can be employed in these annulations. For example, this chemistry has been extended to the synthesis of 1,2-dihydroisoquinolines, benzofurans and benzopyrans (Scheme 3).3 One can also employ vinylic halides and triflates in this process.4... 

Chemistry. Nicotinamide (NAm), a product of PARP-1 enzymatic action on NAD and a weak inhibitor of PARP-1 activity (Curtin, 2006), was used as a model for the first PARP-1 inhibitors, including benzamide and 3-aminobenzamide (3AB) (Shall, 1975) (Fig. 7a). Benzamide and 3AB inhibit PARP-1 activity in the mM range and may also inhibit other PARP family members e.g., PARP-2 and tankyrase Smith et al, 1998 Ame et al, 1999), thus lacking the potency and specificity required for therapeutic purposes. Banasik et al developed 1,5-dihydroisoquinoline (Fig. 7c) and a variety of other inhibitors (Banasik et al, 1992), which were used in turn to develop even more inhibitors with greater specificity. 

Various heterocyclic compounds contain an a,)3-unsaturated amine moiety in their structure, for example, indoles, 1,2,3,4-tetrahydro-pyridines, 1,4-dihydroquinolines, and 1,2-dihydroisoquinolines. It is the purpose of this review to summarize our knowledge of the chemistry of 1,2-dihydroisoquinolines and to evaluate those reactions that may be interpreted in terms of enamine character. 

Volume 14 of this serial publication comprises six chapters of which four deal with general accounts of ring systems benzisothiazoles (M. Davis), 1,2-dihydroisoquinolines (S. F. Dyke), benzo[c]thiophenes (B. Iddon), and pyrazines (G. W. H. Cheeseman and E. S. G. Werstiuk). One chapter updates a previous review in this series and is concerned with the rapidly expanding chemistry of mononuclear isothiazoles (K. R. H. Wooldridge). The remaining chapter (O. Meth-Cohn and H. Suschitzky) deals with the cyclizations of ortho-substituted f-anilines. 

Volume 40 also contains three more conventional chapters. Knabe reviews 1,2-dihydroisoquinolines in a chapter which updates the review by S. F. Dyke in Volume 14 of our series that appeared in 1972. Albert covers the chemistry of... 

The indolizidinedione derivatives (322), easily available from l-alkyl-3,4-dihydroisoquinolines and oxalyl chloride, react with arynes to give 13-substituted 8-oxo-protoberberines (323), probably through the mechanism outlined in Scheme 73. This chemistry has been exploited in the total synthesis of the alkaloid (+ )-corydaline <86JOC278i>. 

On the other hand, nitriles are widely used as intermediates in the synthesis of many types of heterocycles [7] and other compounds of interest in medicinal chemistry, for example, 3,4-dihydroisoquinolines [8], imidazoles [9], indoles [10], lactim ethers [11], napthyridines [12], pyridones [13], pyridopyrimidi-nes [14], pyrimidines [15], quinazolines [16], quinazolones [17], quinolines [18], sydnones [19], 1,2,4,5-tetrazines [20], tetrazoles [21,22], 1,2,4-triazoles [20], N-substituted amides [23], amidines [24] and basic esters [25]. 

In similar Heck-type reactions, commercially available palladium acetate is used as a catalyst, providing a new route for synthesizing indoles, benzofurans, 1,2-dihydroisoquinolines and other interesting derivatives, quite gratifyingly with regioselectivities often matching those reported in our chemistry. ... 

In 2010, a methodology for the synthesis of 1,2,3-triazole-fused iso-indolines and dihydroisoquinolines was reported. Starting from easily available terminal allgmes and (2-haloaryl)allq7lazides, the desired products were formed in good to exeellent yields. This method is based on a cycloaddition reaction, via Click chemistry, followed by a transition-metal-catalyzed functionalization of a C-H bond. Later on, a one-pot procedure was reported as well. °... 

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