Reaction discovery using
N
-heterocyclic carbene organocatalysis has been dominated by the chemistry of acyl anion equivalents. Recent studies demonstrate that NHCs are far more diverse catalysts, ...with a variety of reactions discovered that proceed without acyl anion equivalent formation. In this tutorial review selected examples of acyl anion free NHC catalysis using carbonyl compounds are presented.
N
-Heterocyclic carbenes are powerful nucleophilic catalysts that catalyse a range of reactions that occur
without
acyl anion equivalent formation.
First reported less than a decade ago, the α,β-unsaturated acyl azolium has emerged as a central reactive intermediate for reaction discovery using N-heterocyclic carbene catalysis. In this ...Perspective, an introduction to the four main reactivity patterns accessible from this intermediate is provided. The Perspective is handled in a largely chronological fashion, with an emphasis on alternate approaches to the key intermediate and first-in-class reaction cascades. Finally, a brief discussion of emerging trends in this field of catalysis is presented. Although not exhaustive, the Perspective provides an overview of this active area of research and serves as a guide for future investigations.
N-Heterocyclic carbene-catalyzed formation of beta-anionic intermediates from enones has been employed in the enantioselective synthesis of 2-aryl propionates. The reaction was achievable using a ...homochiral 4-MeOC6H4 morpholinone catalyst allowing the first example of enantioselective catalysis by umpolung of alpha,beta-unsaturated ketones. The reaction is high yielding, and shows robustness with reasonable generality. A mechanism is proposed in which the enantiodetermining protonation is achieved using either hexafluoroisopropanol or the formed naphthol product.
The N-heterocyclic carbene (NHC)-catalyzed Claisen rearrangement of hybrid Ireland–Coates structures has been achieved, allowing the stereoselective synthesis of highly functionalized β-lactones. The ...reaction proceeds with high diastereoselectivity (>20:1) and affords a diverse range of β-lactone fused cyclopentanes. Mechanistic studies are detailed.
N‐Heterocyclic carbene‐catalyzed formation of β‐anionic intermediates from enones has been employed in the enantioselective synthesis of 2‐aryl propionates. The reaction was achievable using a ...homochiral 4‐MeOC6H4 morpholinone catalyst allowing the first example of enantioselective catalysis by umpolung of α,β‐unsaturated ketones. The reaction is high yielding, and shows robustness with reasonable generality. A mechanism is proposed in which the enantiodetermining protonation is achieved using either hexafluoroisopropanol or the formed naphthol product.
One for addition: The 1,4‐addition of N‐heterocyclic carbenes (NHCs) into conjugate acceptors followed by tautomerization provides the β‐azolium ylide. This intermediate provides access to a range of enantioenriched 2‐aryl propionates. The reaction was possible using electron‐rich N‐substituted triazolium catalysts in the presence of hexafluoroisopropanol (HFIP).
Alkyne CC bond breaking, outside of alkyne metathesis, remains an underdeveloped area in reaction discovery. Recently, nitrogenation has been reported to allow nitrile formation from alkynes. A new ...protocol for the metal-free CC bond cleavage of terminal alkynes to produce nitriles is reported. This method provides an opportunity to synthesize a vast range of nitriles containing aryl, heteroaryl, and natural product derivatives (38 examples). In addition, the potential of t BuONO to act as a powerful nitrogenating agent for terminal aryl alkynes is demonstrated.
One carbon-four new bonds Nakano, Yuji; Lupton, David W
Science (American Association for the Advancement of Science),
2023-Feb-03, 2023-02-03, 20230203, Letnik:
379, Številka:
6631
Journal Article
Recenzirano
Stable carbenes deliver a carbon atom to simple amides, producing a range of cyclic compounds.
Herein we report the enantioselective (4+2) annulation of donor–acceptor cyclobutanes and unsaturated acyl fluorides using N‐heterocyclic carbene catalysis. The reaction allows a 3‐step synthesis of ...cyclohexyl β‐lactones (25 examples) in excellent chemical yield (most ≥90 %) and stereochemical integrity (all >20:1 d.r., most ≥97:3 e.r.). Mechanistic studies support ester enolate Claisen rearrangement, while derivatizations provide functionalized cyclohexenes and dihydroquinolinones.
Feeling a little strained? The enantioselective (4+2) annulation of donor–acceptor cyclobutanes with unsaturated acyl fluorides using N‐heterocyclic carbene (NHC) catalysis has been discovered. The reaction provides a 3‐step entry to cyclohexyl β‐lactones (25 examples) in excellent chemical yield (most ≥90 %) and stereochemical integrity (all >20:1 d.r., most ≥97:3 e.r.).
β-Substituted acrylamides have low electrophilicity and are yet to be exploited in the enantioselective Rauhut–Currier reaction. By exploiting electron-withdrawing protection of the amide and ...moderate nucleophilicity N-heterocyclic carbenes, such substrates have been converted to enantioenriched quinolones. The reaction proceeds with complete diastereoselectivity, good yield, and modest enantioselectivity. Derivatizations are reported, as are computational studies, supporting decreased amide bond character with electron-withdrawing protection of the nitrogen.
-Heterocyclic carbene catalysed redox isomerisation with reduction about the carbonyl has been developed in the transformation of trienyl esters to tetrasubstituted benzaldehydes. The reaction ...proceeds in good to excellent yield, and in cases that provide 2,2'-biaryls, enantioselectivity is observed. Mechanistic studies demonstrate the intermediacy of a cyclohexenyl β-lactone, while implicating formation of the homoenolate as turnover limiting.
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