Indolyl diol

Antilla and coworkers [64] reported in 2010 the first Bronsted acid-catalyzed true pinacol rearrangement, in which the chiral phosphoric acid diester 34 was the best catalyst for the rearrangement of a series of indolyl diols (Scheme 40.54). A plausible mechanistic pathway for this transformation begins with the acid-induced dehydration of the starting indolyl diol to an intermediate iminium ion, followed by a 1,2-aryl shift (Scheme 40.55). 

Liang et al. demonstrated that the phosphoric acid catalysis was also applicable to pinacol rearrangement reaction. In the presence of 2.5 mol% phosphoric acid 6e, indolyl diols 85 dehydrated to form iminium intermediate XIO, which then underwent a [l,2]-aryl shift to furnish chiral a-indolyl ketone products 86 with high levels of stereoselectivity (up to 96% ee, Scheme 2.25) [36]. 

Gribble and Saulnier (79) have extended their ellipticine synthesis 43) to the synthesis of 9-methoxyellipticine (2) (Scheme 24). One of the key features of this approach is the regioselective nucleophilic addition to the C-4 carbonyl group of pyridine anhydride 28. The other noteworthy transformation is the conversion of keto lactam 142 to the diol 143 with methyllithium, a process that presumably involves cleavage of the initial adduct to a methyl ketone which undergoes cyclization at the C-3 position of the indolyl anion. Reduction of 143 with sodium borohydride completes the synthesis of 2, in 47% overall yield from 5-methoxyindole (139). Gribble and students 80) have also used this method to synthesize 8-methoxyellipticine (134), 9-fluoroellipticine (144), and the previously unknown 7,8,9,10-tetrafluorellipticine (145), each from the appropriate indole. 

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