In Situ
Methylene Capping: A General Strategy for
Efficient Stereoretentive Catalytic Olefin Metathesis. The Concept,
Methodological Implications, and Applications to Synthesis of Biologically Active Compounds
Posted on 2017-07-27 - 18:24
In
situ methylene capping is introduced as a practical and broadly
applicable strategy that can expand the scope of catalyst-controlled
stereoselective olefin metathesis considerably. By incorporation of
commercially available Z-butene together with robust
and readily accessible Ru-based dithiolate catalysts developed in
these laboratories, a large variety of transformations can be made
to proceed with terminal alkenes, without the need for a priori synthesis
of a stereochemically defined disubstituted olefin. Reactions thus
proceed with significantly higher efficiency and Z selectivity as compared to when other Ru-, Mo-, or W-based complexes
are utilized. Cross-metathesis with olefins that contain a carboxylic
acid, an aldehyde, an allylic alcohol, an aryl olefin, an α
substituent, or amino acid residues was carried out to generate the
desired products in 47–88% yield and 90:10 to >98:2 Z:E selectivity. Transformations were equally
efficient and stereoselective with a ∼70:30 Z-:E-butene mixture, which is a byproduct of crude
oil cracking. The in situ methylene capping strategy was used with
the same Ru catechothiolate complex (no catalyst modification necessary)
to perform ring-closing metathesis reactions, generating 14- to 21-membered
ring macrocyclic alkenes in 40–70% yield and 96:4–98:2 Z:E selectivity; here too, reactions were
more efficient and Z-selective than when the other
catalyst classes are employed. The utility of the approach is highlighted
by applications to efficient and stereoselective syntheses of several
biologically active molecules. This includes a platelet aggregate
inhibitor and two members of the prostaglandin family of compounds
by catalytic cross-metathesis reactions, and a strained 14-membered
ring stapled peptide by means of macrocyclic ring-closing metathesis.
The approach presented herein is likely to have a notable effect on
broadening the scope of olefin metathesis, as the stability of methylidene
complexes is a generally debilitating issue with all types of catalyst
systems. Illustrative examples of kinetically controlled E-selective cross-metathesis and macrocyclic ring-closing reactions,
where E-butene serves as the methylene capping agent,
are provided.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Xu, Chaofan; Shen, Xiao; Hoveyda, Amir H. (2017). In Situ
Methylene Capping: A General Strategy for
Efficient Stereoretentive Catalytic Olefin Metathesis. The Concept,
Methodological Implications, and Applications to Synthesis of Biologically Active Compounds. ACS Publications. Collection. https://doi.org/10.1021/jacs.7b06552
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
AUTHORS (3)
CX
Chaofan Xu
XS
Xiao Shen
AH
Amir H. Hoveyda
KEYWORDS
butenering-closing metathesis reactionsmacrocyclic ring-closing metathesiscross-metathesiacidE selectivitymethylenestrategyapproachscopemacrocyclic ring-closing reactions14- membered ring stapled peptideRu-based dithiolate catalystscatalyst-controlled stereoselective olefin metathesiscomplex21- membered ring macrocyclic alkenesEfficient Stereoretentive Catalytic Olefin Metathesis