Chem. Pharm. Bull. 54(2) 209—212 (2006)

heterocycles. Substitution reactions of 1(2H)-isoquinolone derivatives have been reported, however, little attention has been focused on addition reactions. Dyke et al. reported a Diels–Alder (DA) reaction of 2-methyl-1(2H)-isoquinolone derivatives as the diene. To the best of our knowledge, however, there have been no reports of a DA reaction of 1(2H)isoquinolones acting as dienophiles. DA reaction of 1(2H)isoquinolone derivatives with dienes afforded phenanthridones. A number of Amaryllidaceae alkaloids contain phenanthridine skeletons, and are thought to be potentially valuable synthetic intermediates. Moreover, these alkaloids may possess novel pharmacological activities. Recently, Weltin et al. verified the ability of 5(6H)-phenanthridones to inhibit PARP [poly(ADP-ribose)polymerase] activity in lymphoma cells. Herein, we report a novel Diels–Alder reaction of 4-nitro-1(2H)-isoquinolones acting as the dienophile. This Diels–Alder reaction is a novel synthetic methodology employing the phenanthridine skeleton. Examination of the regioselectivity of 4-nitro-1(2H)-isoquinolones with 1methoxy-3-silyloxy-1,3-butadienes using molecular orbital (MO) calculations is also discussed in the current work. DA Reaction of 4-Nitro-1(2H)-isoquinolones First, DA reactions of 2-methyl(1a) and 2-unsubstituted-1(2H)-isoquinolones (1b) bearing a nitro group at the 4-position with 1-methoxy-1,3-butadienes (2a—c) were examined under atmospheric pressure conditions, as shown in Table 1 (entries 1—8) and Chart 1. Reaction of 1a with 1-methoxy-1,3-butadiene (2a) gave the 6-methyl-5(6H)-phenanthridone (4a: 59%; entry 1 and 26%; entry 2) at 180 °C for 3 d in 1,2dimethoxyethane (DME) and o-xylene (pathway A). Reaction of 1b with 2a gave 5(6H)-phenanthridone (4b: 82%; entry 3) at 160 °C for 3 d in DME in high yield. Reaction of 1a with 1-methoxy-3-trimethylsilyloxy-1,3-butadiene (2b: TMS) was carried out in o-xylene and reaction mixture was treated with trifluoroacetic acid (TFA) to give 8-hydroxy-6methyl-5(6H)-phenanthridone (5a: 72%; entry 4) as a single product (pathway B). However, in DME, reaction of 1a with 2b (entry 5) gave 5a (63%) and 8-methoxy-6-methyl5(6H)-phenanthridone (7a: 7%). Further, reaction of 1a with 1-methoxy-3-t-butyldimethyl-silyloxy-1,3-butadiene (2c: TBS) in DME (entry 6) gave 5a (52%), 7a (2%) and 8-tbutyldimethylsilyloxy-6-methyl-5(6H)-phenanthridone (6a: 29%) in total 83% yield. Moreover, reaction of 1b with 2b gave 8-hydroxy-5(6H)-phenanthridone (5b: 75%; entry 7), whereas reaction of 1b with 2c gave 5b (37%) and 6b (6%) in DME (entry 8). Next, reaction of 1a, b with symmetric dienes (2d, e) were subsequently investigated as shown in Table 1 (entries 9—12) and Chart 1. The reaction of 1a with 2,3-dimethyl-1,3-butadiene (2d) afforded 6,8,9-trimethyl-5(6H)phenanthridone (8a: 18%; entry 9 and 36%; entry 10) at 180 °C for 3 d in o-xylene and DME (pathway C). But, the reaction of 1a with 2d did not give 8,9-dimethyl-5(6H)phenanthridone (8b), and 1b was recovered. Further, the reFebruary 2006 Chem. Pharm. Bull. 54(2) 209—212 (2006) 209