Synlett

Catalytic ring-opening/functionalization of unactive cyclopropanes has proven to be a significant but challenging task in organic synthesis. Herein, we disclose the photoredox and cobalt cocatalyzed ring-opening/acceptorless dehydrogenative functionalization of monodonor cyclopropanes, which provides a promising platform to achieve a sustainable and atom-economic approach to assemble allylic N-acyl-acetal derivatives. The reaction features mild conditions, broad substrate scopes, and excellent functional group compatibilities. The optimized conditions accommodate various cycloalkylamides and primary, secondary, and tertiary alcohols, with applications in late-stage functionalization of pharmaceutically relevant compounds, stimulating the further utility in medicinal chemistry. Selective nucleophilic substitutions and further transformations of desired products with various carbon nucleophiles were succeed in a one-pot fashion, thus offering diverse acyclic or cyclic derivatives.1 Introduction2 Cooperative Photoredox and Cobalt-Catalyzed Dehydrogenative Functionalization of Allylic N-Acyl-acetal Derivatives3 Mechanistic Study4 Preliminary Studies of Asymmetric Transformation5 Conclusion and Perspectives

α-Boryl carbenes, which are hybrid structures combining elements of carbenes and boryl groups, represent promising intermediates for constructing organoboron compounds. However, these carbenes are challenging to synthesize and exhibit limited structural diversity. Moreover, their applications in asymmetric transformations remain largely unexplored. In this study, we utilized boryl cyclopropenes as precursors to rapidly synthesize α-Bpin metal carbenes, a novel category of intermediates critical for the synthesis of chiral organoboron molecules. Facilitated by a copper complex modified by a chiral bisoxazoline ligand, these α-boryl carbenes participate in a range of highly enantioselective transfer reactions, including B–H and Si–H insertions, as well as cyclopropanation and cyclopropanation/Cope rearrangement processes. This methodology provides access to previously inaccessible, yet highly useful, chiral organoborons, thereby significantly advancing both carbene and organoboron chemistry.1 Introduction2 Previous Discovery and Our Design3 Copper Catalyzed Enantioselective α-Boryl Carbene Transfer Reactions4 Mechanistic Studies5 Conclusions

A highly regioselective synthesis of allylic amines based on a tungsten-catalyzed allylic amination has been developed. This protocol, which is catalyzed by commercially available W(CO)3(MeCN)3 and 4,4′-di-tert-butyl-2,2′-bipyridine, permits the formation of synthetically useful branched allylic N-aryl- and N-alkylamines in moderate to good yields with a >20:1 branched/linear ratio under mild conditions. The noble-metal-free catalytic system complements conventional allylic aminations catalyzed by an Ir or Rh complex.

We report the first example of an acid- and oxidant-free one-pot conversion of benzylic or primary alkyl halides into aldehydes by using simple ruthenium chloride as the catalyst. The developed synthetic strategy is pot-economical and is also cheap as it uses hexamethylenetetramine as a reagent, employs as little as 0.5 mol% of ruthenium chloride, and efficiently converts the benzylic or primary alkyl halides into aldehydes in aqueous medium. The methodology was also found to be highly selective, as it forms the aldehyde product exclusively without forming possible byproducts, namely amines or carboxylic acids. The methodology is also superior in comparison with the conventional Sommelet and Kornblum oxidation reactions as it avoids the use of excess acid or DMSO, and uses very cheap and ecofriendly hexamethylenetetramine as both the formylating agent and base. The recyclability of the developed catalyst system was also tested, and showed excellent activities for up to three cycles.

A new method for the preparation of 3-hydroxy-4-methoxypicolinic acid, the acid moiety of the fungicidally active natural product UK-2A is reported. In contrast to the two previously reported routes to UK-2A acid, which start from 3-hydroxypyridine and furfural, this novel synthesis applies maltol as inexpensive starting material and proceeds via a unique modification of the Pummerer reaction.

We recently achieved an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins through the utilization of a new Gluconobacter ene-reductase mutant (GluER-W100F-W342F). Our method simplifies the reaction system by eliminating the need for a cofactor regeneration mixture and, in contrast with previous photoenzymatic systems, does not depend on the formation of an electron donor–acceptor (EDA) complex between the substrates and enzyme cofactor. Moreover, the GluER variant exhibits good substrate compatibility and excellent enantioselectivity. Mechanistic investigations indicate that a tyrosine-mediated HAT process is involved and support the proposed oxidation-initiated mechanism. In this Synpacts article, we discuss the conceptual framework that led to the discovery of this reaction and reflect on the key aspects of its development.1 Introduction2 Conceptual Background2.1 Intramolecular Photoenzymatic Reactions via Single-Electron Reduction2.2 Intermolecular Photoenzymatic Reactions via Single-Electron Reduction3 The Development of the Process4 Conclusion

An efficient Michael addition of 4-hydroxycoumarins to α,β-unsaturated 2-acyl imidazoles catalyzed by Ni(OTf)2 as a Lewis acid has been developed. A series of 4-hydroxycoumarin derivatives were obtained in excellent yields (up to 96%) with a 2 mol% catalyst loading under mild conditions. Additionally, when a chiral-at-metal rhodium complex was used as the catalyst, moderate enantioselectivity was observed (74% ee).

In this study, we proposed a novel electrochemical dehydrogenative synthetic method for preparing 2-substituted quinoxalines by intermolecular cyclization of aryl alkyl ketones and o-phenylenediamines. This method gave various quinoxalines in yields ranging from 35% to 71%. This novel protocol employs mild reaction conditions and offers moderate to excellent yields, a wide substrate scope, and broad functional-group compatibility. Furthermore, a late-stage functionalization and the wide substrate scope demonstrated the synthetic utility of this protocol.

Catalytic transformations of alkenes via the metal-hydride hydrogen atom transfer (MHAT) mechanism have notably advanced synthetic organic chemistry. This Account focuses on MHAT/radical-polar crossover (MHAT/RPC) conditions, offering a novel perspective on generating electrophilic intermediates and facilitating various intramolecular reactions. On using cobalt hydrides, the MHAT mechanism displays exceptional chemoselectivity and functional group tolerance, making it invaluable for the construction of complex biologically relevant molecules under mild conditions. Recent developments have enhanced regioselectivity and expanded the scope of MHAT-type reactions, enabling the formation of cyclic molecules via hydroalkoxylation, hydroacyloxylation, and hydroamination. Notably, the addition of an oxidant to traditional MHAT systems enables the synthesis of rare cationic alkylcobalt(IV) complexes, bridging radical mechanisms to ionic reaction systems. This Account culminates with examples of natural product syntheses and an exploration of asymmetric intramolecular hydroalkoxylations, highlighting the ongoing challenges and opportunities for future research to achieve higher enantioselectivity. This comprehensive study revisits the historical evolution of the MHAT mechanism and provides a groundwork for further innovations on the synthesis of structurally diverse and complex natural products.1 Introduction2 Intramolecular Hydroalkoxylation and Hydroacyloxylation Reactions3 Intramolecular Hydroamination Reactions4 Intramolecular Hydroarylation Reactions5 Deprotective Cyclization6 Asymmetric Intramolecular Hydroalkoxylation7 Conclusion

Synlett 2024; 35: V-DOI: 10.1055/s-0043-1774929Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents