Low-Valent Titanium Induced Carbonyl Coupling Reactions

60
C
H 3
NH
O
O
O
Ti/Graphite in DME
CH 3
Several aspects of this chemoselective transformation are worth mentioning:
• The observation, that a keto-amide coupling completely overcomes both inter- as well
as intra-molecular diketone coupling is in sharp contrast to earlier reports[24,34] on
low-valent titanium coupling reactions;
• This reaction pathway is even more surprising given the fact that an intramolecular
diketone coupling would have provided a well known and stable 3,4-dimethyl-2(1H)quinolone;
• High dilution are unnecessary for the formation of indoles[65,67];
• Owing to the short reaction times the remaining ketone in (61) perfectly resists subsequent
intermolecular coupling although an excess of the low-valent titanium reagent is present
in the reaction system;
In accordance with this result, the trifunctional substrate (62) and (63), obtained from
commercially available 5-chloro-2-aminobenzophenone and ethyl oxalyl chloride, formed
indoles (64) and (65) in 93 and 94% isolated yield, respectively[71].
61
N
H
CH 3
CH 3
N
H
O
CH 3
61 %
CH 3
O
29