Catalytic Asymmetric 1,4‐Addition Reactions of Simple Alkylnitriles

Abstract

The development of catalytic asymmetric carbon-carbon bond-forming reactions of alkylnitriles that do not have an activating group at the α-position, under proton-transfer conditions, is a challenging research topic. Here, we report catalytic asymmetric direct-type 1,4-addition reactions of alkylnitriles with α,β-unsaturated amides by using a catalytic amount of potassium hexamethyldisilazide (KHMDS) with a chiral macro crown ether. The desired reactions proceeded in high yields with good diastereo- and enantioselectivities. To our knowledge, this is the first example of catalytic asymmetric direct-type 1,4-addition reaction of alkylnitriles without any activating group at the α-position.

Catalytic Carbon–Carbon Bond‐Forming Reactions of Weakly Acidic Carbon Pronucleophiles Using Strong Brønsted Bases as Catalysts

“…Propionitrile could be employed,and the desired adducts were obtainedi nh ighy ields and good diastereo-and enantioselectivities. [26] An alkanesulfonamide was also as uitable substrate, with N,N-dimethyle thanesulfonamider eactingt oa fford the desired adducts in high yields and good diastereo-and enantioselectivities. [27] For activation of the latter substrates, normally more than one equivalent of strong base was employed.…”

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

“…The main issue relates to the difficulty of completing the turnover of strong Brønsted base catalysts because of the weak acidity of the α‐hydrogen atoms of alkylazaarenes. We have recently developed an efficient method of catalytic deprotonation for such weakly acidic substrates by using strong Brønsted base catalysts through the generation of strongly basic reaction intermediates ,,. Herein, we expand this methodology and describe the first example of Brønsted base catalyzed 1,4‐addition reactions of a range of alkylazaarenes under mild reaction conditions.…”

Nucleophilic and Electrophilic Activation of Non‐Heteroaromatic Amides in Atom‐Economical Asymmetric Catalysis

“…Kobayashi and co‐workers developed a catalytic enantioselective conjugate addition of alkylnitriles 61 to simple α,β‐unsaturated amides 62 by taking advantage of the product base mechanism described in Section 2.3 (Scheme ), where a strongly basic intermediate was responsible for the generation of the carbanion for the next catalytic cycle. This catalytic system was specifically designed for low‐acidicity pronucleophiles, such as 61 , the deprotonation of which was fulfilled by strongly basic KHMDS decorated with chiral crown ether 29 .…”