C═N-Containing Azaarenes as Activating Groups in Enantioselective Catalysis

Abstract

Nitrogen-containing aromatic heterocycles (azaarenes) are of widespread chemical significance, and chiral compounds containing azaarenes feature prominently in pharmaceuticals, agrochemicals, and natural products. ThisPerspective highlights the use of a relatively underdeveloped strategy to prepare chiral azaarene-containing compounds: exploitation of the C=N bond embedded within certain azaarenes to activate adjacent functionality in catalytic asymmetric reactions. Work in this area has resulted in the development of several different types of catalytic enantioselective processes, including reductions, nucleophilic additions, and reductive couplings. It is hoped that this Perspective will encourage more researchers to work in this promising area.

A second-generation ligand for the enantioselective rhodium-catalyzed addition of arylboronic acids to alkenylazaarenes

“…[2][3][4] In this context, we have reported 1b the enantioselective rhodium-catalyzed 1,4-arylation [5][6][7][8] of β-substituted alkenylazaarenes with arylboronic acids using a secondary amide-containing chiral diene 9-11 ligand L1 (see Table 1, entry 1), which builds upon early studies by the groups of Lautens 12a and Genet 12b using vinylazaarenes. Although L1 was highly effective, it was of interest to determine whether a ligand of this complexity, possessing stereochemical elements additional to those of the chiral diene component, was actually necessary for optimal results.…”

Catalytic Direct‐type 1,4‐Addition Reactions of Alkylazaarenes

“…[15] We have already reported that ac hiral macrocyclic crown ether, binaphtho-34-crown-10 (34-C-10), could be used to form an effective asymmetric environment around the potassium cation of KHMDS.W eh ave also shown that catalytic asymmetric direct-type 1,4-addition reactions of simple amides,p romoted by K/34-C-10, can be achieved with high enantioselectivities. [15] We have already reported that ac hiral macrocyclic crown ether, binaphtho-34-crown-10 (34-C-10), could be used to form an effective asymmetric environment around the potassium cation of KHMDS.W eh ave also shown that catalytic asymmetric direct-type 1,4-addition reactions of simple amides,p romoted by K/34-C-10, can be achieved with high enantioselectivities.…”

Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition

“…Vinyl azines are isostructural with respect to α,β-unsaturated carbonyl compounds and, as described in the review literature (53), display analogous reactivity. However, their use as pronucleophiles in catalytic reductive coupling has only recently begun to be explored.…”