Multifunctional Asymmetric Catalysis.

Abstract

Two types of general and practical enantioselective catalysts, namely, bimetallic complexes and Lewis acid-Lewis base bifunctional catalysts were developed based on the concept of multifunctional catalysis. In the first part of this review, the first example of a catalytic enatioselective nitro-Mannich reaction as well as a direct catalytic enantioselective aldol reaction of 2-hydroxyacetophenone using bimetallic complexes is discussed. The new complex, composed of ytterbium, potassium, and BINOL in a ratio of 1 : 1 : 3, promoted the nitro-Mannich reaction of nitromethane with up to 91% ee. On the other hand, second generation ALB catalyzed an enantioselective and diastereoselective nitro-Mannich reaction of nitroalkanes in up to 83% ee with a diastereomeric ratio up to 7 : 1. Moreover, the reaction of aldehydes with 2-hydroxyacetophenone in the presence of LLB, KHMDS, and H 2 O selectively gave the corresponding anti-a a,b b-dihydroxy ketones in up to 95% ee and, in the presence of the catalyst prepared from linked-BINOL and 2 eq of Et 2 Zn, selectively afforded the syn-a a,b b-dihydroxy ketones in up to 86% ee. In the second part, the development of new catalysts displaying a Lewis acidity and a Lewis basicity is described. The Lewis acid of the catalyst activates aldehydes, imines, acyl quinoliniums, and ketones. At the same time, the Lewis base activates the nucleophile (TMSCN). Catalysts of this type produced a highly enantioselective cyanation of these electrophiles. Application of the catalytic enantioselective cyanosilylation of aldehydes to a total synthesis of epothilones is also described.

Recent Advances in Catalytic Asymmetric Addition to Imines and Related C=N Systems

“…Transfer hydrogenation using stable organic hydrogen donors such as 2-propanol or formic acid is an attractive solution to the above demand. Some recent examples include tetrahydroisoquinolines (13) [47,48] and indole alkaloids (14)(15)(16) [49]. The methodology has been applied to a numerous synthesis of optically active amines.…”

Asymmetric Henry reaction catalyzed by bifunctional copper‐based catalysts

“…[46][47][48]. For example, Hoveyda and coworkers reported asymmetric addition of TMSCN (trimethylsilyl cyanide) to aromatic and aliphatic ketones catalyzed by bifunctional aluminum-complex 1 (Fig.…”

Synthesis, Characterization, and Metal Complexes of a Salen Ligand Containing a Quinoline Base

“…Investigation into the mechanism of carboxypeptidase A and aldolase has revealed that a Lewis acid acting in concert with a Brønsted base will effect the intramolecular enolization of ketones as shown in 1 . An exciting area of research is the design of bifunctional ligands , with noncoordinating basic groups. When these ligands are bound to a metal, the complexes behave like enzymes, combining molecular recognition with catalysis.…”

“…While enolization of acetone was accomplished under mild, neutral conditions to generate the carbon-bound Rh enolate, the presumed lack of reactivity of the Rh enolate has prevented the development of a general catalytic system with this complex. Shibasaki and co-workers have recently described heterobimetallic lithium−lanthanum BINOL complexes which catalyze the direct aldol, nitro-aldol, and Michael reactions with good yields and enantioselectivities …”