Indoles 1-TIPS-indole, 3-lithiation

Widdowson expanded his hexacarbonylchromium chemistry to the synthesis and lithiation of Cr(CO)3-Af-TIPS indole (29), leading to 4-iodoindole 30 after oxidative decomplexation [37]. Stannylation at C-4 could also be achieved using this method (62% yield), and comparable chemistry with 3-methoxymethylindole leading to C-4 substitution was described. 

Iwao also observed direct lithiation at C3 with A-(2,2-diethylbutanoyl)indole 9b (Table 13, entries 5-8) [18]. The yields obtained with the DEB-protecting group were somewhat lower than those obtained with the TIPS-protecting group. The optimal reaction conditions included hexane as the solvent much lower yields were obtained when the reactions were run in ether. When superbase was used (sec-BuLi - - t-BuOK), lithiation of 9b occurred preferentially at C2. 

TIPS groups have been used in different ways to prevent undesired C-2 lithiation of indoles and benzothiophenes. The introduction of a TIPS group onto 4-bromo-l/f-pyrrolo[2,3b]pyridine permitted metalation to occur exclusively at C-4, affording the 4-fluoro product (eq 16). The TIPS group was removed with TEAR Without TIPS, transmetalation at C-2 was observed. 

---