Lewis Acid‐Catalyzed CH Functionalization for Synthesis of Isoindolinones and Isoindolines

Abstract

The Lewis acid-catalyzed C À H functionalization of 2-substituted azaarenes with N-sulfonyl-A C H T U N G T R E N N U N G aldimines has been developed, which provides a rapid and efficient approach for synthesis of heterocycle-containing isoindolinones and isoindolines.

Lewis Acid Promoted Benzylic Cross‐Couplings of Pyridines with Aryl Bromides

“…The beneficial effect of Lewis acids in the additions of 2-picoline to imines and enones has already been demonstrated. [10,11] Thus, we directed our attention toward the use of bases (Met-base) bearing a Lewis acidic metal center for the metalation. Recently, we have reported a kinetically highly active LiCl-solubilized TMP base (TMP = 2,2,6,6-tetramethylpiperidyl): TMPZnCl·LiCl (7) displays high chemoselectivity in various directed zincations of arenes and heterocycles.…”

Lewis‐Acid‐Catalyzed Benzylic Reactions of 2‐Methylazaarenes with Aldehydes

“…[3] In addition, 2-alkenylyridine derivatives are not only ubiquitous structural motifs in biologically relevant molecules -for example, CGS23114 (4)but also serve as valuable precursors for a wide range of 2-alkylpyridines and piperidines, themselves of significant biological importance, [4] whereas 2-alkenylquinolines, especially those containing the (7-chloroquinolin-2-yl)vinylphenyl moiety, are always present in the leukotriene receptor antagonists (LTRAs), such as montelukast (5), L-660,711 (6), and LY290154 (7), used for the treatment of asthma. Next, a series of catalysts including inorganic acid and base (Entries 9 and 10), traditional Lewis acids (Entries [10][11][12][13][14], and other rare earth triflates (Entries [15][16][17] were tried in order to improve the yields of the product, but none was better than Sc(OTf) 3 . Next, a series of catalysts including inorganic acid and base (Entries 9 and 10), traditional Lewis acids (Entries [10][11][12][13][14], and other rare earth triflates (Entries [15][16][17] were tried in order to improve the yields of the product, but none was better than Sc(OTf) 3 .…”

“…2-(Pyridin-2yl)ethanols with common substituents were formed through the LiNTf 2 -promoted aldol reaction for the first time. [9c] As we can see from the literature reports, [9][10][11][12][13] the reactivity of 2-alkylazarenes varied with the structures of the azarenes. In the presence of La(Pfb) 3 as catalysis, 2-alkenylquinolines were obtained in high yields through the reactions between 2-methylquinolines and aldehydes under air.…”

“…Series of azaarene derivatives were afforded by this reaction. [8] However, additional steps were needed to introduce the activation groups in these reactions.Recently, direct C(sp 3 )-H bond functionalization of 2alkyl-substituted azaarenes catalyzed by palladium, [9] Lewis acids, [10] Brønsted acids, [11] or iodine, [12] or even without catalyst, [13] has been widely used to synthesize azaarene derivatives. 2-Alk-…”

“…Recently, direct C(sp 3 )-H bond functionalization of 2alkyl-substituted azaarenes catalyzed by palladium, [9] Lewis acids, [10] Brønsted acids, [11] or iodine, [12] or even without catalyst, [13] has been widely used to synthesize azaarene derivatives. The electrophilic reagents included C=N double bonds of N-sulfonyl aldimines [9a,10b-10d,13a] and C=C double bonds of methylenemalononitriles, [10a] maleimides, [13b] and enones, [10e] as well as N=N double bonds of azodicarboxylates.…”