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

Abstract

1,4-addition reactions of alkylazaarenes catalyzed by strong Brønsted bases have been developed for the first time. The desired reactions with α,β-unsaturated amides proceeded under mild reaction conditions to give the 1,4-adducts in high yields. Both ortho- and para-substituted azaarenes afforded the desired adducts in high yields. Regioselective reactions of di- or trimethylpyridine were found to be possible depending on the acidity of the α-hydrogen atoms. Furthermore, a candidate of allosteric protein kinase modulators was synthesized in two steps. An asymmetric variant of this reaction was also found to be feasible.

Potassium‐Zincate‐Catalyzed Benzylic C−H Bond Addition of Diarylmethanes to Styrenes

“…[7] Kobayashi and Schneider and their co-workers reported catalytic additions of simple esters,a mides,a lkylnitriles,a lkylazaarenes,a lkanesulfonamides, and allylbenzenes to imines and a,b-unsaturated carbonyl compounds by using astrong Brønsted base such as KH, KHMDS,and NaHMDS as acatalyst. [8] Recently,weachieved the KHMDS-catalyzed benzylic CÀHa ddition of alkylpyridines to styrenes. [9] To our knowledge,d iphenylmethane,t he benzylic CÀH bond of which has an acidity [pK a (C 6 H 6 ) = 35] similar to that of alkylpyridines and allylbenzenes, [10] has never been utilized in similar transformations.Herein, we report the first catalytic addition of the benzylic C À Hb ond of diarylmethanes to alkenes [Scheme 1, Eq.…”

Activating Pronucleophiles with High pKa Values: Chiral Organo‐Superbases

“…From the viewpoint of ideal synthesis, direct activation of pronucleophiles with high p K a values using a Brønsted base would always be more attractive. The groups of Kobayashi and Terada successfully applied an efficient, in situ generated catalyst from a chiral chelator and a potassium base to deprotonate simple amides, alkylazaarenes, and α‐oxoesters for asymmetric addition reactions. Another effective way of deprotonation is through cooperative activation .…”

Enantioselective Synthesis of Alkyl Azaarenes

“…Kobayashi studied the 1,4-addition of alkyl azaarenes to α,βunsaturated amides 99, employing strong Brønsted bases in the presence of crown ethers to deprotonate the heterocyclic alkyl group. [20] Most of the report is based on the use of 18-crown-6 leading to achiral compounds. The asymmetric variant of this reaction was performed with 1-methylisoquinoline 98, in a limited number of entry, using the chiral macrocyclic crown ether (R,R)-binaphtho-34-crown-10 (34-C-10) IX as illustrated in Scheme 24.…”