Building C(sp3)-rich complexity by combining cycloaddition and C-C cross-coupling reactions.

Abstract:

:Prized for their ability to rapidly generate chemical complexity by building new ring systems and stereocentres1, cycloaddition reactions have featured in numerous total syntheses2 and are a key component in the education of chemistry students3. Similarly, carbon-carbon (C-C) cross-coupling methods are integral to synthesis because of their programmability, modularity and reliability4. Within the area of drug discovery, an overreliance on cross-coupling has led to a disproportionate representation of flat architectures that are rich in carbon atoms with orbitals hybridized in an sp2 manner5. Despite the ability of cycloadditions to introduce multiple carbon sp3 centres in a single step, they are less used6. This is probably because of their lack of modularity, stemming from the idiosyncratic steric and electronic rules for each specific type of cycloaddition. Here we demonstrate a strategy for combining the optimal features of these two chemical transformations into one simple sequence, to enable the modular, enantioselective, scalable and programmable preparation of useful building blocks, natural products and lead scaffolds for drug discovery.

journal_name

Nature

journal_title

Nature

authors

Chen TG,Barton LM,Lin Y,Tsien J,Kossler D,Bastida I,Asai S,Bi C,Chen JS,Shan M,Fang H,Fang FG,Choi HW,Hawkins L,Qin T,Baran PS

doi

10.1038/s41586-018-0391-9

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

350-354

issue

7718

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-018-0391-9

journal_volume

560

pub_type

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