Enantioselective access to tricyclic tetrahydropyran derivatives by a remote hydrogen bonding mediated intramolecular IEDHDA reaction.
Nat Commun
; 12(1): 7188, 2021 12 10.
Article
in En
| MEDLINE
| ID: mdl-34893616
ABSTRACT
Inverse-electron-demand-hetero-Diels-Alder reactions of alkenes with α,ß-unsaturated keto compounds allow rapid access to the tetrahydropyran ring found in numerous natural products and bioactive molecules. Despite its synthetic interest, catalytic asymmetric versions of this process remain underdeveloped, especially regarding the use of non-activated alkenes reacting with α,ß-unsaturated ketone or aldehyde, for which no report can be found in the literature. Herein, we describe the catalytic inverse-electron-demand-hetero-Diels-Alder reactions between neutral alkenes and an α,ß-unsaturated ketones or aldehydes to produce a variety of trans-fused [5,6,8] tricyclic structures containing a central, chiral tetrahydropyran ring. This complex transformation, which is achieved using a chiral phosphoric acid, allows for the formation of four stereogenic centers in a single step with high regio-, diastereo- and enantioselectivity (up to 99% ee). Such level of stereocontrol could be achieved by a key remote double hydrogen atom bonding interaction between the linear substrate and the catalyst.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biological Products
/
Aldehydes
/
Alkenes
/
Ketones
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Document type:
Article