Organocatalysis articles within Nature Chemistry

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  • Article |

    The redox properties of visible-light-absorbing photosensitizers are limited by the energy of visible photons, but methods using sensitization-initiated electron transfer have recently been developed to address these challenges. Now a multiphoton dual-catalyst strategy has been used to enable the enantioselective de Mayo reaction for the synthesis of enantioenriched 1,5-diketones.

    • Xin Sun
    • , Yilin Liu
    •  & Zhiyong Jiang

  • Article |

    The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Now, an alternative strategy exploiting chiral phosphoric acid catalytic aromatization has been developed, affording structures possessing a central chirality or a stereogenic C–N axis with high efficiency and enantiocontrol.

    • Ye-Hui Chen
    • , Meng Duan
    •  & Bin Tan

  • News & Views |

    Stereoselective decarboxylative protonation can produce diverse chiral molecules from widely available carboxylic acids. However, general and practical strategies are lacking. Now, a chiral spirocyclic phosphoric acid-catalysed decarboxylation of aminomalonic acids has enabled the modular synthesis of α-amino acids.

    • Xufeng Lin
    •  & Alemayehu Gashaw Woldegiorgis

  • News & Views |

    Fluorination strategies are important in assisting the synthesis of pharmaceuticals. Iodine(I/III) catalysis has become particularly useful for installing gem-difluoro groups but is limited to styrenes. Now, the hypervalent iodane-catalysed difluorination of enynes has enabled access to diverse homopropargylic difluorides.

    • Rachel C. Epplin
    •  & Tanja Gulder

  • Article
    | Open Access

    Hypervalent iodine catalysis remains a powerful method to enable geminal difluoromethylenation of alkenes. However, the scope is mainly limited to styrene derivatives. Now, enynes have been validated as competent substrates where a formal 1,2-shift of the alkyne occurs, thereby enabling highly versatile homopropargylic difluorides to be generated.

    • Zi-Xuan Wang
    • , Keith Livingstone
    •  & Ryan Gilmour

  • Article |

    Stabilization of RNAs for storage, transport and biological application remains a profound challenge. Now, it has been shown that reversible 2′-OH acylation with easily accessible acylimidazoles unlocks efficient protection of RNA. RNA can be deprotected by non-basic nucleophiles or spontaneously in cells to restore RNA functions.

    • Linglan Fang
    • , Lu Xiao
    •  & Eric T. Kool

  • Article
    | Open Access

    Catalytic enantioselective approaches to access chiral organophosphorus compounds are rare. A two-stage catalytic strategy for the synthesis of diverse enantioenriched P(V) compounds has now been developed: a bifunctional iminophosphorane superbase enables enantioselective nucleophilic desymmetrization, followed by downstream enantiospecific diversification of the resulting intermediate by substitution with medicinally relevant O-, N- and S-based nucleophiles.

    • Michele Formica
    • , Tatiana Rogova
    •  & Darren J. Dixon

  • News & Views |

    Enantioenriched β-amino acid derivatives are attractive synthetic targets, considering the significance of these motifs in medicinal and material chemistry. Now, using ambiphilic ynamides as two-carbon synthons in a four-component reaction, three classes of β-amino amides with well-defined stereocentres can be accessed.

    • Sunliang Cui
    •  & Linwei Zeng

  • Article |

    β-Amino acids are broadly found in biomimetic drugs and therapeutics, but the general synthesis of chiral β-amino amides remains limited. An organocatalytic four-component reaction has now been developed for their asymmetric synthesis with notable efficiency, chemoselectivity and stereoselectivity. This protocol shows broad product scope and provides a shortcut to other important structures.

    • Jun Wei
    • , Jian Zhang
    •  & Bin Tan

  • Article |

    The direct conversion of sulfones to chiral sulfinyl compounds is one of the major challenges in the fields of asymmetric synthesis and organosulfur chemistry. Now, through incorporation of a cyano group into the sulfone, an organocatalytic asymmetric deoxygenation strategy has been developed that enables the synthesis of chiral sulfinyl compounds.

    • Shengli Huang
    • , Zhen Zeng
    •  & Hailong Yan

  • News & Views |

    The direct carbon isotope exchange reaction on α-amino acids is highly desirable, as existing labelling methods require several synthetic steps and harsh conditions. Now, an aldehyde-catalysed carboxylate exchange with isotopically labelled *CO2 has enabled the direct formation of 11C, 13C and 14C-labelled α-amino acids.

    • Karoline T. Neumann
    •  & Troels Skrydstrup

  • Article |

    Carbon-labelled α-amino acids are valuable compounds in drug development and nuclear medicine, but are difficult and time consuming to prepare. Now, an aldehyde-catalysed method has been developed for the direct C1-labelling of α-amino acids using *CO2 (* = 14, 13, 11), providing access to many proteinogenic and non-natural labelled α-amino acids.

    • Odey Bsharat
    • , Michael G. J. Doyle
    •  & Rylan J. Lundgren

  • Article |

    The direct copolymerization of carbon dioxide and commodity olefins has been a long-standing challenge in polymer science. Now, an indirect approach has been developed in which hydrogenated disubstituted valerolactones derived from telomerization of CO2 and butadiene can undergo ring-opening polymerization, yielding chemically recyclable and degradable aliphatic polyesters with high CO2 content.

    • Rachel M. Rapagnani
    • , Rachel J. Dunscomb
    •  & Ian A. Tonks

  • News & Views |

    Plastics that are developed from renewable resources and can be recycled are highly environmentally desirable alternatives to current petroleum-based non-degradable polymers. Now, an effective and robust industrially relevant strategy towards high-performance biomass-derived degradable poly(γ-thiobutyrolactone)s has been developed.

    • Sophie M. Guillaume

  • Article |

    Although organocatalysis has emerged as a powerful catalysis platform, its application for the selective transformation of inactive arenes remains challenging. Now, an organocatalyst-controlled site-selective C–H functionalization of arenes has been developed, with wide substrate generality and applicability, offering a general strategy for arene transformation.

    • Jian-Hui Mao
    • , Yong-Bin Wang
    •  & Bin Tan

  • Article |

    In 1949, Winstein and Trifan proposed that the 2-norbornyl cation adopts a bridged, non-classical structure. Now, the generation of an asymmetric environment around the three-centre two-electron bond of such an ion has been reported, enabling highly enantioselective catalytic addition reactions to a simple, non-functionalized non-classical cation.

    • Roberta Properzi
    • , Philip S. J. Kaib
    •  & Benjamin List

  • News & Views |

    The widespread application of quinone methides — reactive intermediates in a variety of reactions — is limited by their tedious synthesis. Now, hypoiodite catalysis allows the efficient generation and use of these species in a plethora of tandem processes for the functionalization and synthesis of biologically active compounds.

    • Boris J. Nachtsheim

  • Article |

    ortho-Quinone methides are highly reactive transient intermediates found in some organic syntheses and biological processes. The generation of these species often requires pre-functionalized substrates and/or metal oxidants, but now the chemoselective oxidative generation of ortho-quinone methides from ortho-alkylarenols has been achieved using hypoiodite catalysis under nearly neutral conditions.

    • Muhammet Uyanik
    • , Kohei Nishioka
    •  & Kazuaki Ishihara

  • News & Views |

    Nucleophiles directly substitute alcohols in the Mitsunobu reaction, but the process uses hazardous materials and generates an excessive amount of toxic waste. More than 50 years on from its initial discovery, chemists report a new catalytic version of the reaction, with water as the only by-product.

    • Andy McNally

  • Article |

    Secondary-sphere interactions serve a fundamental role in controlling the reactivity and selectivity of organometallic and enzyme catalysts, but their study in organocatalytic systems is scarce. Now, it has been shown that the in situ secondary-sphere modification of organocatalysts combined with machine-learning techniques can uncover reaction mechanisms and streamline catalyst optimization.

    • Vasudevan Dhayalan
    • , Santosh C. Gadekar
    •  & Anat Milo

  • Meeting Report |

    Two recent back-to-back meetings conveyed a common set of ongoing challenges for the fields of organocatalysis, photoredox catalysis and photochemistry.

    • Craig P. Johnston

  • Article |

    Chiral tertiary aldols are encountered in a variety of biologically relevant molecules. Making these valuable compounds directly from unbiased ketones has proven to be extremely challenging. Now it has been shown that sub-ppm levels of in situ generated silylium-based organic Lewis acid catalysts can give quantitative product formation in very high enantiopurity through a Mukaiyama aldol reaction.

    • Han Yong Bae
    • , Denis Höfler
    •  & Benjamin List

  • Article |

    The catalytic asymmetric α-alkylation of aldehydes has historically been a significant challenge within organic synthesis. Now, this elusive transformation has been achieved through the merger of organocatalysis, photoredox catalysis and hydrogen-atom transfer catalysis to enable the coupling of simple olefins and aldehydes.

    • Andrew G. Capacci
    • , Justin T. Malinowski
    •  & David W. C. MacMillan

  • Article |

    Chiral iminium ions generated from an amine catalyst and enals are key organocatalytic intermediates in thermal asymmetric processes. Now, visible-light excitation of these iminium ions can turn these compounds into strong oxidants to enable enantioselective photochemical β-alkylations of enals with silanes, which are unachievable via conventional ground state pathways.

    • Mattia Silvi
    • , Charlie Verrier
    •  & Paolo Melchiorre

  • Article |

    Amidation is one of the most widely utilized organic reactions for the synthesis of pharmaceuticals and functional materials. DATB, characterized by the B3NO2 heterocycle, proved to act as a superb catalyst for the direct amidation with a distinct mechanistic pathway, displaying broadened applicability to a wide range of substrates.

    • Hidetoshi Noda
    • , Makoto Furutachi
    •  & Naoya Kumagai

  • Article |

    Higher-order cycloadditions — cycloadditions involving more than six π electrons — provide easy access to complex molecules containing heterocyclic or carbocyclic scaffolds. Now, it has been shown that aminocatalytic activation of 2-cycloalkenones affords mixtures of dienamines that can undergo [6 + 4] cycloadditions with heptafulvenes through a cross dienamine, or [8 + 2] cycloadditions through a linear dienamine.

    • Rasmus Mose
    • , Gert Preegel
    •  & Karl Anker Jørgensen

  • Article |

    By simply deprotonating a neutral hydrogen-bond donor thiourea it is possible to generate a class of highly efficient and tunable thioimidates that can simultaneously activate a pro-nucleophile and an electrophile. These bifunctional thioimidates exhibit fast kinetics and high selectivity for ring-opening polymerizations of cyclic lactones and carbonates.

    • Xiangyi Zhang
    • , Gavin O. Jones
    •  & Robert M. Waymouth

  • News & Views |

    Catalytic methods are among the most valuable tools for sustainable synthesis. Domino catalysis enables multiple reactions to be combined so that synthetic efficiency may begin to approach that of nature, but significant challenges remain before this promising approach can fulfil the needs of pharmaceutical and materials chemistry.

    • Thomas Broja
    • , Patrick J. W. Fuchs
    •  & Kirsten Zeitler

  • Article |

    Formaldehyde is universally employed in the fixation of tissue specimens, where it forms adducts with biomolecules, but this hinders the analysis of nucleic acids in the specimen. Bifunctional organocatalysts that speed the reversal of formaldehyde adducts of RNA and DNA are now reported, and show promise for general use in clinical specimens.

    • Saswata Karmakar
    • , Emily M. Harcourt
    •  & Eric T. Kool

  • News & Views |

    Preparing powerful reactive intermediates such as enolates and homoenolates for C–C bond formation used to require strong bases and stoichiometric reagents. They can now be catalytically generated from α-functionalized aldehydes or even from saturated esters under mild conditions using N-heterocyclic carbene catalysts.

    • Jeffrey W. Bode

  • Article |

    Spirooxindoles are important structural motifs found in an array of bioactive compounds. Here a Michael–aldol domino reaction for the construction of bispirooxindoles is presented, creating four stereocentres, including three quaternary carbon centres. Novel multifunctional organocatalysts have been developed for this transformation.

    • Bin Tan
    • , Nuno R. Candeias
    •  & Carlos F. Barbas III

  • Article |

    Chiral thiols and organosulfur compounds are important in many areas of chemistry but there are relatively few methods available for their efficient enantioselective synthesis. Here, a kinetic resolution of chiral thiols is reported along with a demonstration that a concomitant desymmetrization of the acylating agent is beneficial for the selectivity of both processes.

    • Aldo Peschiulli
    • , Barbara Procuranti
    •  & Stephen J. Connon

  • Review Article |

    The field of organocatalysis has grown rapidly in the past decade to become, along with metal catalysis and biocatalysis, a third pillar of asymmetric catalysis. Here, progress in the use of organocatalytic cascade reactions for total synthesis is reviewed. The elegance and efficiency of such cascades mean that they have emerged as a powerful tool in synthetic organic chemistry.

    • Christoph Grondal
    • , Matthieu Jeanty
    •  & Dieter Enders

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