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
Naturejournal_title
Natureauthors
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 PSdoi
10.1038/s41586-018-0391-9subject
Has Abstractpub_date
2018-08-01 00:00:00pages
350-354issue
7718eissn
0028-0836issn
1476-4687pii
10.1038/s41586-018-0391-9journal_volume
560pub_type
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