Indole 5-bromo-2- -, ring

In an alternate mode of radical cyclization, indolyl-2-radicals generated from the corresponding 2-bromo derivatives 152 (n=l-3) undergo intramolecular reactions with appended aromatic rings to afford fused [ 1,2-a]indoles 153 <00TL4209>. 

Hegedus also described an efficient synthesis of 4-bromoindoIe (10) and 4-bromo-l-(4-toluenesulfonyl)indole (11) starting from 2-amino-6-nitrotoluene (9) [20]. The synthesis is lengthy but yields are good, and the method involves the Hegedus indole ring synthesis discussed later in this chapter. 

Reaction of the radical derived from substituted 2-bromo indole 78 leads in moderate (37%) yield to benzo[d]pyrrolo[l,2- ]azepinone 79 along with 32% of the reduction product 80. The process occurs via radical addition to the benzene ring followed by rearomatization (Equation (9) (2000TL4209)). 

Because Pd(II) salts, like Hg(Il) salts, can effect electrophilic metallation of the indole ring at C3, it is also possible to carry out vinylation on indoles without 3-substituents. These reactions usually require the use of an equiv. of the Pd(ll) salt and also a Cu(II) or Ag(I) salt to effect reoxidation of the Pd. As in the standard Heck conditions, an EW substitution on the indole nitrogen is usually necessary. Entry 8 of Table 11.3 is an interesting example. The oxidative vinylation was achieved in 87% yield by using one equiv. of Pd(OAc)2 and one equiv. of chloranil as a co-oxidant. This example is also noteworthy in that the 4-bromo substituent was unreactive under these conditions. Part B of Table 11.3 lists some other representative procedures. 

Carbanions derived from side chain tertiary amides have also been cyclized to provide isoquinolones and isoindoles (equation 36).125 126 While benzyne intermediacy in the formation of the former is likely, the latter seems to arise through a SrnI reaction pathway. Synthesis of indole from the meta bromo compound (87), on the other hand, clearly involves an aryne cyclization. 27 A more versatile route to indoles is based on intramolecular addition of aminyl anions to arynes (equation 38).128 A somewhat similar dihydroindole preparation constitutes the first step in a synthesis of lycoranes (equation 39).129 The synthesis of (88) also falls in the same category of reactions, but it is noteworthy because only a few examples of ring closure of heteroarynes are mentioned in literature.27 28... 

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