Enantioselective synthesis of cyclic enol ethers and all-carbon quaternary stereogenic centers through catalytic asymmetric ring-closing metathesis.
The first examples of catalytic asymmetric ring-closing metathesis (ARCM) reactions of enol ethers are reported. To identify the most effective catalysts, various chiral Mo- and Ru-based catalysts were screened. Although chiral Ru catalysts (those that do not bear a phosphine ligand) promote ARCM in some cases, such transformations proceed in <10% ee. In contrast, Mo-based alkylidenes give rise to efficient ARCM and deliver the desired products in the optically enriched form. Thus, Mo-catalyzed enantioselective transformations allow access to various five- and six-membered cyclic enol ethers in up to 94% ee from readily available achiral starting materials. The first examples of catalytic ARCM that lead to the formation of all-carbon quaternary stereogenic centers are also disclosed. Mechanistic models that offer a plausible rationale for the identity of major enantiomers as well as the observed levels of enantioselectivity are provided. Representative examples demonstrate that the enol ether moiety and the unreacted alkene of the ARCM products can be discriminated with excellent site selectivity (>98%).
Lee
Ai-Lan
AL
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Malcolmson
Steven J
SJ
Puglisi
Alessandra
A
Schrock
Richard R
RR
Hoveyda
Amir H
AH
D000475:Alkenes / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D003516:Cycloparaffins / Q000138:chemical synthesis* / Q000737:chemistry; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D013237:Stereoisomerism
D000475:Alkenes; D003516:Cycloparaffins; D004988:Ethers, Cyclic