Benzoimidazole–pyrrolidine (BIP), a highly reactive chiral organocatalyst for aldol process

Benzo[d]imidazole and Aliphatic α-Amino Acid Derived Primary Amines in Asymmetric Aldol Reactions

“…In general, all organocatalysts having (S)-configuration provided (R)-aldol, whereas amine (R)-1 provided the opposite enantiomer (S)-17. This is consistent with the results reported by Vincent et al 10 Interestingly, the attained enantiomeric excesses increased with increasing steric bulk of the R-substituent. The highest ee values of 59 and 65% were achieved for the aldol reaction catalyzed with leucine-and isoleucinederived amines (S)-3 and (S)-4, bearing isobutyl and secbutyl R-substituents ( Table 2, entries 5 and 6).…”

Benzimidazole‐pyrrolidine/H+ (BIP/H+), a Highly Reactive Organocatalyst for Asymmetric Processes

“…It is also worth noting that the methyl groups probably enhance the nucleophilicity of the aromatic amino groups and also improve the solubility of the catalyst in organic solvents. X‐ray structure determination confirmed the structure of 1 and provided useful information 7. For instance, it was observed that two molecules of 1 crystallize in the presence of one molecule of water with the electron lone pairs of the oxygen atom linked to 1 through two hydrogen bonds involving pyrrolidine and benzimidazole N–H bonds with bond lengths of 1.87 Å and 2.71 Å, respectively.…”

“…In order to rule out the possibility of formation of the enamine on the benzimidazole ring, we carried out the condensation between acetone and 1 in the presence of NaBH 3 CN to trap the iminium intermediate 14. This led exclusively to the formation of the N ‐isopropylpyrrolidine 5 in 65 % isolated yield (Scheme ),7 indicating that iminium II is an intermediate in the process and that the benzimidazole moiety is not nucleophilic enough to generate an iminium 15…”

“…We recently reported on the design, synthesis and application of a new and simple proline surrogate, the benzimidazole‐pyrrolidine (= BIP) ( 1 ) in asymmetric, organocatalyzed, aldol reactions (Scheme ) 7. Preliminary results showed that 1 , when activated by one equiv.…”

Towards a Series of Chiral Primary Amines Bearing α-Amino Acid and Benzo[d]imidazole Pendants, and Their Application in Asymmetric Aldol Reactions

“…This is in agreement with the observations of Vincent and co-workers. 26 In the series of amines bearing aliphatic residues (5bf), the attained enantiomeric excess steadily increased with increasing bulkiness of the R substituent (Table 1, entries 2-6). Hence, the highest enantiomeric excess of 65% was achieved with amine 5f derived from isoleucine (Table 1, entry 6).…”