Total Synthesis of Aleutianamine

Yu, Hao; Sercel, Zachary P.; Rezgui, Samir P.; Farhi, Jonathan; Virgil, Scott C.; Stoltz, Brian M.

doi:10.1021/jacs.3c10212

Cited by 6 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Catalytic asymmetric dearomatization (CADA) has attracted extensive attention over the past decade and has enabled readily available planar aromatics to rapidly transform into intricate chiral three-dimensional molecular structures. , Despite these significant achievements, most of the methodologies have been extremely limited to functionalized arenes. The CADA reaction of nonfunctionalized arenes is largely underdeveloped.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4 + 1] Spiroannulation

Li,

Guo,

Zhang

et al. 2024

ACS Catal.

View full text Add to dashboard Cite

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of complex chiral three-dimensional cyclic molecules featuring quaternary carbon centers from readily available arenes. However, the asymmetric dearomatization of ubiquitous nonfunctionalized 1-naphthols to afford chiral quaternary centers remains challenging and undeveloped. This study reports the asymmetric dearomative [4 + 1] spiroannulation of nonfunctionalized 1-naphthols via copper catalysis. This reaction features a highly chemo-, regio-, and stereoselective nucleophilic addition and intramolecular annulation cascade of a reactive π-extended copper-allenylidene, thus enabling the practical synthesis of a range of valuable spirocyclic enones bearing a chiral quaternary stereocenter with high efficiency. Furthermore, this protocol is applicable to phenols. Control experiments supported the substitution-annulation cascade mechanism by excluding a process involving a 1,3-sigmatropic shift. Preliminary biological activity studies indicated that the synthesized spirocyclic enones hold significant promise as anticancer agents by inducing tumor cell apoptosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4 + 1] Spiroannulation

Li,

Guo,

Zhang

et al. 2024

ACS Catal.

View full text Add to dashboard Cite

show abstract

“…N -aryl amines are among the most important structural features found in pharmaceuticals, − natural products, − agrochemicals, − and organic materials. − In recent years, Cu-catalyzed approaches to C–N bond formation have emerged as promising alternatives to well-established Pd-catalyzed methods by offering the use of a metal catalyst with diminished cost and toxicity, − along with, in some cases, orthogonal reactivity. , Central to these advances has been the development of new ligands to support the Cu-centered catalyst. Early ligand designs involved charge-neutral molecules, such as trans -cyclohexane-1,2-diamine , and phenanthroline derivatives, to facilitate amidation or N -heterocycle arylation.…”

Section: Introductionmentioning

confidence: 99%

Cu-Catalyzed Amination of Base-Sensitive Aryl Bromides and the Chemoselective N- and O-Arylation of Amino Alcohols

Strauss,

Liu,

Greaves

et al. 2024

J. Am. Chem. Soc.

View full text Add to dashboard Cite

We report a general and functional-group-tolerant method for the Cu-catalyzed amination of base-sensitive aryl bromides including substrates possessing acidic functional groups and small five-membered heteroarenes. The results presented herein substantially expand the scope of Cu-catalyzed C−N coupling reactions. The combination of L8, an anionic N 1 ,N 2diarylbenzene-1,2-diamine ligand, along with the mild base NaOTMS leads to the formation of a stable yet reactive catalyst that resists deactivation from coordination to heterocycles or charged intermediates. This system enables the use of low catalyst and ligand loadings. Exploiting the differences in nucleophile deprotonation in C−O and C−N coupling reactions catalyzed by Cu•L8 we developed a method to chemoselectively N-and Oarylate a variety of amino alcohol substrates. Employing NaOt-Bu as the base resulted exclusively in C−O coupling when the amino alcohols featured primary alcohols and more hindered amines or aniline groups. Utilizing NaOTMS enabled the ability to override the steric-based selectivity of these reactions completely and exclusively promoted C−N coupling regardless of the structure of the amino alcohol. The ability to invert the observed chemoselectivity is distinct from previously described methods that require protecting group manipulations or rely entirely on steric effects to control reactivity. These results substantially improve the scope of Cu-catalyzed C−N coupling reactions using N 1 ,N 2 -diarylbenzene-1,2-diamine ligands and introduce a new chemoselective method to arylate amino alcohols.

show abstract

“…Alkene difunctionalization allows selective construction of sp 3 -hybridized carbon centers, emerging as a simple and efficient method with enormous applications in pharmaceutical, material sciences, and natural products . Compared to the incorporation of heteroelements, increasing the percentage of sp 3 -hybridized carbon of organic molecules becomes particularly appealing, not only because it enables challenging CC bond formation, but it also opens avenues for improved clinical success in drug candidates .…”

mentioning

confidence: 99%

Palladium-Catalyzed 1,2-Alkynylarylation of Vinyl Arenes with Haloalkynes and Arylboronic Acids

Ma,

Fang,

Jiang

et al. 2024

Org. Lett.

View full text Add to dashboard Cite

We herein disclose a novel palladium-catalyzed 1,2-alkynylarylation of vinyl arenes using haloalkynes and arylboronic acids as coupling partners. This reaction is characterized by broad substrate scope, controllable reaction sequence, and excellent chemo-and regioselectivities. Mechanistic investigations suggest that the reaction is initiated by regioselective insertion of vinyl arenes into the alkynyl-Pd(II) species, and the silver salt is crucial for this transformation, serving as both the Lewis acid and halide scavenger. This protocol provides efficient access to new carbon skeletons, which are embedded in the key biologically active motifs.

show abstract

Total Synthesis of Aleutianamine

Cited by 6 publications

References 35 publications

Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4 + 1] Spiroannulation

Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4 + 1] Spiroannulation

Cu-Catalyzed Amination of Base-Sensitive Aryl Bromides and the Chemoselective N- and O-Arylation of Amino Alcohols

Palladium-Catalyzed 1,2-Alkynylarylation of Vinyl Arenes with Haloalkynes and Arylboronic Acids

Contact Info

Product

Resources

About