Small-molecule H-bond donors in asymmetric catalysis.

Hydrogen bonding is responsible for the structure of much of the world around us. The unusual and complex properties of bulk water, the ability of proteins to fold into stable three-dimensional structures, the fidelity of DNA base pairing, and the binding of ligands to receptors are among the manifestations of this ubiquitous noncovalent interaction. In addition to its primacy as a structural determinant, hydrogen bonding plays a crucial functional role in catalysis. Hydrogen bonding to an electrophile serves to decrease the electron density of this species, activating it toward nucleophilic attack. This principle is employed frequently by Nature's catalysts, enzymes, for the acceleration of a wide range of chemical processes. Recently, organic chemists have begun to appreciate the tremendous potential offered by hydrogen bonding as a mechanism for electrophile activation in small-molecule, synthetic catalyst systems. In particular, chiral hydrogen-bond donors have emerged as a broadly applicable class of catalysts for enantioselective synthesis. This review documents these advances, emphasizing the structural and mechanistic features that contribute to high enantioselectivity in hydrogen-bond-mediated catalytic processes.

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Asymmetric catalysis by chiral hydrogen-bond donors.

The legacy of Gilbert Newton Lewis (1875-1946) pervades the lexicon of chemical bonding and reactivity. The power of his concept of donor-acceptor bonding is evident in the eponymous foundations of electron-pair acceptors (Lewis acids) and donors (Lewis bases). Lewis recognized that acids are not restricted to those substances that contain hydrogen (Bronsted acids), and helped overthrow the "modern cult of the proton". His discovery ushered in the use of Lewis acids as reagents and catalysts for organic reactions. However, in recent years, the recognition that Lewis bases can also serve in this capacity has grown enormously. Most importantly, it has become increasingly apparent that the behavior of Lewis bases as agents for promoting chemical reactions is not merely as an electronic complement of the cognate Lewis acids: in fact Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound. This diversity of behavior leads to a remarkable versatility for the catalysis of reactions by Lewis bases.

Lewis Base Catalysis in Organic Synthesis

Catalytic Enantioselective Formation of C−C Bonds by Addition to Imines and Hydrazones: A Ten-Year Update

2. Essential Components: Earlier Developments 5449 2.1. Activated alkenes/alkynes 5450 2.1.1. Acyclic activated alkenes/ alkynes 5450 2.1.2. Cyclic activated alkenes 5451 2.2. Electrophiles 5451 2.3. Catalysts 5452 3. Essential Components: Recent Developments 5452 3.1. Activated Alkenes/Alkynes 5452 3.2. Electrophiles 5460 3.3. Catalysts 5477 4. Asymmetric Baylis-Hillman Reaction: Earlier Developments 5495

Recent contributions from the Baylis-Hillman reaction to organic chemistry.

β-Isocupreidine-Catalyzed Asymmetric Baylis−Hillman Reaction of Imines

β-Isocupreidine–hexafluoroisopropyl acrylate method for asymmetric Baylis–Hillman reactions

Beta-isocupreidine-catalyzed Baylis-Hillman reaction of chiral N-boc-alpha-amino aldehydes.

Compound 20, a pseudoenantiomer of β-isocupreidine (β-ICD), was synthesized from quinine employing a Barton reaction of nitrosyl ester 13 and acid-catalyzed cyclization of carbinol 18 as key steps. The Baylis-Hillman reaction of benzaldehyde, p-nitrobenzaldehyde, and hydrocinnamaldehyde with 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) using 20 as a chiral amine catalyst was found to give the corresponding S-enriched adducts in high optical purity (>91% ee) in contrast to the β-ICD-catalyzed reaction which affords R-enriched adducts. This result suggests that compound 20 can serve as an enantiocomplementary catalyst of β-ICD in the asymmetric Baylis-Hillman reaction of aldehydes with HFIPA.

Ayako Nakano

Papers

β-Isocupreidine-Catalyzed Asymmetric Baylis−Hillman Reaction of Imines

β-Isocupreidine–hexafluoroisopropyl acrylate method for asymmetric Baylis–Hillman reactions

Beta-isocupreidine-catalyzed Baylis-Hillman reaction of chiral N-boc-alpha-amino aldehydes.

Synthesis of an enantiocomplementary catalyst of β-isocupreidine (β-ICD) from quinine

Organocatalytic asymmetric synthesis of quinine and quinidine