A copper‐catalyzed dearomative alkynylation of pyridines is reported with excellent regio‐ and enantioselectivities. The synthetically valuable enantioenriched 2‐alkynyl‐1,2‐dihydropyridine products afforded are generated from the readily available feedstock, pyridine, and commercially available terminal alkynes. The three‐component reaction between a pyridine, a terminal alkyne, and methyl chloroformate employs copper chloride and StackPhos, a chiral biaryl
- Award ID(s):
- 1401998
- NSF-PAR ID:
- 10016235
- Date Published:
- Journal Name:
- Tetrahedron. Asymmetry
- Volume:
- 27
- Issue:
- 2
- ISSN:
- 1362-511X
- Page Range / eLocation ID:
- 91-100
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract A copper‐catalyzed dearomative alkynylation of pyridines is reported with excellent regio‐ and enantioselectivities. The synthetically valuable enantioenriched 2‐alkynyl‐1,2‐dihydropyridine products afforded are generated from the readily available feedstock, pyridine, and commercially available terminal alkynes. The three‐component reaction between a pyridine, a terminal alkyne, and methyl chloroformate employs copper chloride and StackPhos, a chiral biaryl
P ,N‐ ligand, as the catalytic system. Under mild reaction conditions, the desired 1,2‐addition products are delivered in up to 99 % yield with regioselectivity ratios up to 25 : 1 and enantioselectivities values of up to 99 % ee. Activated and non‐activated terminal alkynes containing a wide range of functional groups are well tolerated. Even acetylene gas delivered mono‐alkynylated products in high yield and ee. Application of the methodology in an efficient enantioselective synthesis of the chiral piperidine indolizidine, coniceine, is reported. -
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/http://dx.doi.org/10.1016/j.tetasy.2015.12.002
