Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

Ding, Jinyue; Rybak, Taras; Hall, Dennis G.

doi:10.1038/ncomms6474

Cited by 52 publications

(44 citation statements)

References 54 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Asymmetric Suzuki-Miyaura cross-coupling to provide dehydropiperidine products are scarce, with the most relevant method being enantiospecific coupling of enantiomerically enriched allylic boronates42. With phenylboronic acid the conditions above gave lower ee’s (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

et al. 2017

View full text Add to dashboard Cite

Using asymmetric catalysis to simultaneously form carbon–carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib—an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery.

show abstract

Section: Resultsmentioning

confidence: 99%

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

et al. 2017

View full text Add to dashboard Cite

show abstract

“…2d-i, 4, 5 α-Stereogenic γ-substituted allylic boronates can also be elaborated to a range of arylated products via stereospecific palladium-catalyzed cross couplings that occur with allylic transposition. 2d, 6 These powerful allylic transposition reactions make such allylic boronates highly valuable intermediates.…”

Section: Introductionmentioning

confidence: 99%

Accessing Both Retention and Inversion Pathways in Stereospecific, Nickel-Catalyzed Miyaura Borylations of Allylic Pivalates

et al. 2016

View full text Add to dashboard Cite

We have developed a stereospecific, nickel-catalyzed Miyaura borylation of allylic pivalates, which delivers highly enantioenriched α-stereogenic γ-aryl allylboronates with good yields and regioselectivities. Our complementary sets of conditions enable access to either enantiomer of allylboronate product from a single enantiomer of readily prepared allylic pivalate substrate. Excellent functional group tolerance, yields, regioselectivities, and stereochemical fidelities are observed. The stereochemical switch from stereoretention to stereoinversion largely depends upon solvent, and can be explained by competitive pathways for the oxidative addition step. Our mechanistic investigations support a stereoretentive pathway stemming from a directed oxidative addition and a stereoinvertive pathway that is dominant when MeCN blocks coordination of the directing group by binding the nickel catalyst.

show abstract

“…With the optimized protocol developed, we attempted to generate enantioenriched α -aryl piperidines 9,28,29 , which have thus far proven to be much more challenging substrates for α- lithiation when compared to pyrrolidine substrates 9,29 . Under the standard reaction conditions, the piperidine substrate gave only 24% conversion with 93:7 er.…”

mentioning

confidence: 99%

Enantioselective amine α-functionalization via palladium-catalysed C–H arylation of thioamides

et al. 2016

View full text Add to dashboard Cite

Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, development of methods to functionalize the α-methylene C–H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (–)-sparteine followed by Pd(0) catalyzed cross coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalyzed enantioselective α-C–H coupling of a wide range of amines, including ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines, and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C–H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

show abstract

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

Cited by 52 publications

References 54 publications

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

Accessing Both Retention and Inversion Pathways in Stereospecific, Nickel-Catalyzed Miyaura Borylations of Allylic Pivalates

Enantioselective amine α-functionalization via palladium-catalysed C–H arylation of thioamides

Contact Info

Product

Resources

About