1337927-63-5Relevant articles and documents
Synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones utilizing pyrrole weinreb amides
Greger, Jessica G.,Yoon-Miller, Sarah J. P.,Bechtold, Nathan R.,Flewelling, Scott A.,MacDonald, Jacob P.,Downey, Catherine R.,Cohen, Eric A.,Pelkey, Erin T.
, p. 8203 - 8214 (2011/12/04)
A regiocontrolled synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones has been achieved in three steps from 1,2-diaryl-1-nitroethenes with pyrrole-2-carboxamides (pyrrole Weinreb amides) serving as the key linchpin intermediates. Two different methods for the preparation of the requisite nitroalkenes were investigated: (1) modified Henry reaction between arylnitromethanes and arylimines; and (2) Suzuki-Miyaura cross-coupling reaction of 2-aryl-1-bromo-1-nitroethenes with arylboronic acids. Some difficulty was encountered in the preparation of arylnitromethanes, thus leading to the exploration of a cross-coupling strategy that proved more useful. A Barton-Zard pyrrole cyclocondensation reaction between 1,2-diaryl-1-nitroethenes and N-methoxy-N-methyl-2-isocyanoacetamide gave the corresponding pyrrole Weinreb amides, which were then converted into the desired 3-pyrrolin-2-ones in two steps. Overall, this method allowed for the construction of 3,4-diaryl-3- pyrrolin-2-ones with complete regiocontrol of the substituents with respect to the lactam carbonyl. The utility of this synthetic methodology was demonstrated by the preparation of eight unsymmetrical and symmetrical 3,4-diaryl-3-pyrrolin- 2-ones including the N-H lactam analogue of the selective COX-II inhibitor, rofecoxib.
