10.1021/ja4126565.s001
Fang Gao
Fang
Gao
James L. Carr
James L.
Carr
Amir H. Hoveyda
Amir H.
Hoveyda
A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site‑, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis
American Chemical Society
2015
heterocyclic trisubstituted alkenyl groups
carbon stereogenic site
santolina alcohol
enantioselective synthesis
carboxylic ester
trisubstituted alkene
enantioselective allylic substitution
allylic electrophiles
terminal alkynes
alkenyl units
aldehyde group
alkenylmetal reagent
Allylic Phosphates
alternative approach
SN
carbon center
NHC
Natural Product SynthesisA
EAS
heliannuol E
2015-12-17 00:24:49
Dataset
https://acs.figshare.com/articles/dataset/A_Broadly_Applicable_NHC_Cu_Catalyzed_Approach_for_Efficient_Site_and_Enantioselective_Coupling_of_Readily_Accessible_Pinacolato_alkenylboron_Compounds_to_Allylic_Phosphates_and_Applications_to_Natural_Product_Synthesis/2028195
A set
of protocols for catalytic enantioselective allylic substitution
(EAS) reactions that allow for additions of alkenyl units to readily
accessible allylic electrophiles is disclosed. Transformations afford
1,4-dienes that contain a tertiary carbon stereogenic site and are
promoted by 1.0–5.0 mol % of a copper complex of an <i>N</i>-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted
electrophiles bearing a di- or trisubstituted alkene may be employed.
Reactions can involve a variety of robust alkenyl–(pinacolatoboron)
[alkenyl–B(pin)] compounds that can be either purchased or
prepared by various efficient, site-, and/or stereoselective catalytic
reactions, such as cross-metathesis or proto-boryl additions to terminal
alkynes. Vinyl-, <i>E</i>-, or <i>Z</i>-disubstituted
alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted
alkenyl groups may be added in up to >98% yield, >98:2 S<sub>N</sub>2′:S<sub>N</sub>2, and 99:1 enantiomeric ratio (er).
NHC–Cu-catalyzed
EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic
ester or aldehyde group proceed to provide the desired 1,4-diene products
in good yield and with high enantioselectivity despite the presence
of a sensitive stereogenic tertiary carbon center that could be considered
prone to epimerization. In most instances, the alternative approach
of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents
an incompatible option. The utility of the approach is illustrated
through applications to enantioselective synthesis of natural products
such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol
E.