Asymmetric synthesis: From transition metals to organocatalysis

Abstract

Umpolung in the allylation reaction is discussed with examples drawn from transition-metal-catalyzed allylic substitution (with the allylic unit acting as an electrophile) and Lewis base-catalyzed allylation of aldehydes with allyltrichlorosilane (with the allyl acting as a nucleophile). Iridium-catalyzed electrophilic allylation of O-nucleophiles has been employed in our new approach to C-nucleoside analogs, where the C-O bond (rather than C-C) was constructed stereospecifically. Variation of the absolute configuration in the starting segments allowed the synthesis of all four combinations of D/L-α/β-ribosides. In the nucleophilic allylation of aldehydes, chiral pyridine-type N-oxide catalysts are presented, in particular QUINOX and METHOX, and the intriguing behavior of QUINOX is discussed. Here, the π-π interactions between the substrate aldehyde and the catalyst are suggested to rationalize the experimental observations. Good correlation between the calculated energies for the transition states and the experimentally observed enantioselectivities has been obtained.

Heteroaromatic N-Oxides in Asymmetric Catalysis: A Review

“…Enantioselective organocatalysis is one of the more rapidly growing fields of research in modern organic chemistry. It provides the ability to effectively replace the enantioselective metal-containing catalysts with wholly organic molecules, while maintaining a high level of chemical efficiency and stereo control [1][2][3]. A key for success is the structural simplicity of the organocatalyst, which should be much more readily available than their organometallic equivalents.…”

Synergistic–cooperative combination of enamine catalysis with transition metal catalysis

“…The rapid growth in organocatalysis, in which a small organic molecule serves as the catalyst, over the last decade has dramatically changed the profile of asymmetric catalysis. [1][2][3][4][5][6][7][8][9] Transition metal catalysis, on the other hand, has long been established as one of the most powerful tools in organic synthesis. 10 In recent years, a new research area, the combination of organocatalysis with metal catalysis, has emerged, aiming to achieve organic transformations that cannot be accessed by organocatalysis or metal catalysis independently.…”

Mechanistic Dichotomy in the Asymmetric Allylation of Aldehydes with Allyltrichlorosilanes Catalyzed by Chiral Pyridine N‐Oxides

“…14, 18–21 Nakajima then demonstrated a similar catalytic effect for the axially chiral biquinoline N,N′ ‐dioxide,22 which inspired Hayashi,23 Kotora,24, 25 Kwong,26 and others to develop a diverse range of bipyridine N,N′ ‐dioxides23–25, 27 and N,N′,N′′ ‐trioxides,26 the enantioselectivities of which were thoroughly studied in the past few years. In parallel, we have developed novel pyridine‐derived N ‐monooxides12d, 28–31 and demonstrated their superior enantio‐ and diastereoselectivity in the allylation and crotylation of various aldehydes. Hoveyda then reported on the first “non‐pyridine‐type” N ‐monooxide derived from proline,32 and Govender made use of the N ‐oxides derived from tetrahydroisoquinolines 27d.…”