Synthesis of polysubstituted bicyclo[2.1.1]hexanes enabling access to new chemical space

Chemical Science, Год журнала: 2023, Номер 14(36), С. 9885 - 9891

Опубликована: Янв. 1, 2023

Crossed [2 + 2] cycloaddition yields bicyclo[2.1.1]hexanes with 11 different substitution patterns. ortho -, meta - and polysubstituted benzene bioisosteres, structures substituent patterns that go beyond aromatic chemical space can be prepared.

Язык: Английский

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Three-dimensional saturated C(sp3)-rich bioisosteres for benzene

Nature Reviews Chemistry, Год журнала: 2024, Номер 8(8), С. 605 - 627

Опубликована: Июль 9, 2024

Язык: Английский

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Light‐Driven Synthesis and Functionalization of Bicycloalkanes, Cubanes and Related Bioisosteres

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Янв. 5, 2024

Bicycloalkanes, cubanes and their structural analogues have emerged as bioisosteres of (hetero)arenes. To meet increasing demand, the chemical community has developed a plethora novel synthetic methods. In this review, we assess progress made in field light-driven construction functionalization such relevant molecules. We focused on diverse targets, well reaction processes giving access to: (i) [1.1.1]-bicyclopentanes (BCPs); (ii) [2.2.1]-bicyclohexanes (BCHs); (iii) [3.1.1]-bicycloheptanes (BCHeps); (iv) cubanes; other structurally related scaffolds. Finally, future perspectives dealing with identification manifolds to new functionalized bioisosteric units are discussed.

Язык: Английский

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C–H functionalization of pyridines

Organic & Biomolecular Chemistry, Год журнала: 2023, Номер 21(28), С. 5671 - 5690

Опубликована: Янв. 1, 2023

This review discusses known approaches for selective pyridine C–H editing, focusing on recent discoveries uniquely suited to pyridines.

Язык: Английский

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2‐Oxabicyclo[2.1.1]hexanes: Synthesis, Properties, and Validation as Bioisosteres of ortho‐ and meta‐Benzenes

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(19)

Опубликована: Март 11, 2024

Abstract We have developed a general and practical approach towards 2‐oxabicyclo[2.1.1]hexanes with two three exit vectors via an iodocyclization reaction. The obtained compounds been easily converted into the corresponding building blocks for use in medicinal chemistry. 2‐Oxabicyclo[2.1.1]hexanes incorporated structure of five drugs agrochemicals, validated biologically as bioisosteres ortho ‐ meta ‐benzenes.

Язык: Английский

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(Bio)isosteres of ortho- and meta-substituted benzenes

Beilstein Journal of Organic Chemistry, Год журнала: 2024, Номер 20, С. 859 - 890

Опубликована: Апрель 19, 2024

Saturated bioisosteres of substituted benzenes offer opportunities to fine-tune the properties drug candidates in development. Bioisosteres

Язык: Английский

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Selective P450_BM3 Hydroxylation of Cyclobutylamine and Bicyclo[1.1.1]pentylamine Derivatives: Underpinning Synthetic Chemistry for Drug Discovery

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(50), С. 27767 - 27773

Опубликована: Дек. 5, 2023

Achieving single-step syntheses of a set related compounds divergently and selectively from common starting material affords substantial efficiency gains when compared with preparing those same by multiple individual syntheses. In order for this approach to be realized, complementary reagent systems must available; here, panel engineered P450BM3 enzymes is shown fulfill remit in the selective C–H hydroxylation cyclobutylamine derivatives at chemically unactivated sites. The oxidations can proceed high regioselectivity stereoselectivity, producing valuable bifunctional intermediates synthesis applications fragment-based drug discovery. process also applies bicyclo[1.1.1]pentyl (BCP) amine achieve first direct enantioselective functionalization bridging methylenes open short efficient route chiral BCP bioisosteres medicinal chemistry. combination substrate, enzyme, reaction engineering provides powerful general platform small-molecule elaboration diversification.

Язык: Английский

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Recent Progress in Accessing Multi-functionalized Caged Hydrocarbons: En Route to Highly Functionalized Saturated (Bio)isosteres of Benzene Rings

Synthesis, Год журнала: 2024, Номер unknown

Опубликована: Июль 4, 2024

Abstract Recently, many saturated bioisosteres of the benzene ring have been developed, and their applications in drug development evaluated. Most these are caged hydrocarbons, which rigid skeletons three-dimensional spaces. Recent efforts to synthesize hydrocarbons enabled access multi-functionalized congeners that expected be (bio)isosteres benzenes. This short review summarizes recently reported methods for obtaining (typically more than disubstituted) hydrocarbons. 1 Introduction 2 Proposed Structures Caged Hydrocarbons as Saturated (Bio)isosteres Benzene Ring: A Brief Summary 3 Access Multi-functionalized Hydrocarbons: De Novo Synthetic Approaches 3.1 Bicyclo[1.1.1]pentanes (BCPs) 3.2 Bicyclo[2.1.1]hexanes (BCHs) 3.3 Bicyclo[3.1.1]heptanes (BCHeps) 3.4 Others 4 C–H Functionalization 5 Conclusion

Язык: Английский

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Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations

Nature Synthesis, Год журнала: 2024, Номер 3(12), С. 1538 - 1549

Опубликована: Сен. 5, 2024

Язык: Английский

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One-Pot Synthesis of Difluorobicyclo[1.1.1]pentanes from α-Allyldiazoacetates

Organic Letters, Год журнала: 2023, Номер 25(28), С. 5214 - 5219

Опубликована: Июль 10, 2023

Rapid access to 2,2-difluorobicylco[1.1.1]pentanes is enabled from an α-allyldiazoacetate precursor in a one-pot process through cyclopropanation afford 3-aryl bicyclo[1.1.0]butane, followed by reaction with difluorocarbene the same flask. The modular synthesis of these diazo compounds affords novel 2,2-difluorobicyclo[1.1.1]pentanes that were inaccessible previously reported methods. reactions chiral 2-arylbicyclo[1.1.0]butanes manner generate altogether different products high asymmetric induction, methylene-difluorocyclobutanes. Larger ring systems including bicyclo[3.1.0]hexanes are also rapidly furnished due nature starting material.

Язык: Английский

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