Late-Stage Functionalization

Börgel, Jonas; Ritter, Tobias

doi:10.1016/j.chempr.2020.07.007

Cited by 236 publications

(147 citation statements)

References 64 publications

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“…Of course, C–H functionalization can be an excellent example of late-stage functionalization, provided it meets specified requirements. Last year, Ritter made an attempt to define late-stage functionalization based on the analysis of representative examples (Börgel and Ritter, 2020 ). Two main factors should characterize the process: (1) chemoselectivity and (2) absence of directing or activating group previously incorporated to the molecule for this purpose.…”

Section: Late-stage Functionalizationmentioning

confidence: 99%

“…Two main factors should characterize the process: (1) chemoselectivity and (2) absence of directing or activating group previously incorporated to the molecule for this purpose. These specifications result in the definition of late-stage functionalization being “a desired chemoselective transformation on a complex molecule to provide at least one analog in sufficient quantity and purity for a given purpose without the necessity for the installation of a functional group that exclusively serves the purpose to enable said transformation” (Börgel and Ritter, 2020 ). Of course, the “complexity” is still hard to determine and often remains intuitive.…”

Section: Late-stage Functionalizationmentioning

confidence: 99%

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Reductive Functionalization of Amides in Synthesis and for Modification of Bioactive Compounds

Czerwiński

Furman

2021

Front. Chem.

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In this review, applications of the amide reductive functionalization methodology for the synthesis and modification of bioactive compounds are covered. A brief summary of the different protocols is presented in the introduction, followed by the synthetic application of these in late-stage functionalization, leading to known pharmaceuticals or to their derivatives, including bioisosteres, with potential higher activity as the main axis of the article. The synthetic approach to natural products based on amide reduction is also discussed; however, this is given in a condensed form focusing on recent or as yet unexplored applications due to a number of recently published excellent reviews covering this topic. The aim of this review is to illustrate the potential of reductive functionalization of amides as an elegant and useful tool in the synthesis of bioactive compounds and inspire further work in this field.

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Section: Late-stage Functionalizationmentioning

confidence: 99%

Section: Late-stage Functionalizationmentioning

confidence: 99%

Reductive Functionalization of Amides in Synthesis and for Modification of Bioactive Compounds

Czerwiński

Furman

2021

Front. Chem.

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“…However, available thermal energy to promote the reaction is su ciently high to perturb the regio-selection as multiple C-H bonds of arenes are prone to undergo activation, which results in multiple unwanted products formations. This genre of non-directed C-H functionalization chemistry could herald the next phase of modern organic synthesis particularly in expanding the chemical space through late-stage functionalization; provided there is no compromise on the regioselectivity [5][6][7][8] .…”

Section: Main Textmentioning

confidence: 99%

Photoinduced regioselective olefination of arenes at proximal and distal sites

Saha¹,

Guin²,

Ali³

et al. 2020

Preprint

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The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had rendered it redundant. The revival of this exemplary reaction requires the development of a mechanistic paradigm that would have simultaneous control on both the reactivity and regioselectivity. Often high thermal energy required to promote olefination leads to multiple site functionalization. To this aim we established a photoredoxcatalytic system constituting a merger of palladium/organo-photocatalyst that forges oxidative olefination in an explicit regioselective fashion of diverse arenes and heteroarenes. Visible light plays a significant role in executing ‘regio-resolved’ Fuijiwara-Moritani reaction without the requirement of silver salts and thermal energy. The catalytic system is also amenable towards proximal and distal olefination aided by respective directing groups (DGs), which entails the versatility of the protocol in engaging the entire spectrum of C(sp2)-H olefination. Furthermore, streamlining the synthesis of natural products, chiral molecules, drugs and diversification through late-stage functionalizations underscore the importance of this sustainable protocol. The photoinduced attainment of this regioselective transformation is mechanistically established through control reactions, kinetic studies and theoretical calculations.

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“…The direct transformation of such a frequently appearing motif is challenging, but highly advantageous, as it allows rapid access to molecular diversity in a single step. In the late-stage functionalization (LSF) context, this would allow to surpass the need of de novo synthesis of new analogues (Blakemore et al, 2018;Cernak et al, 2016;Bö rgel and Ritter 2020). This is beneficial with respect to time, overall step count, and atom economy and thus highly advantageous for the drug discovery process.…”

Section: Introductionmentioning

confidence: 99%