We established a highly enantioselective Si-H insertion reaction to construct chiral centers at the carbon and silicon atoms, using a Ru(ii)-pheox catalyst. The catalytic asymmetric Si-H insertion reaction of α-methyl-α-diazoesters proceeded smoothly with excellent stereoinduction at both the neighboring carbon and silicon atoms (up to 99% yield and 99% ee).
The first highly enantioselective intramolecular cyclopropanation of electron-deficient olefins, in the presence of Ru(II)--Pheox catalyst, is reported. The corresponding cyclopropane-fused γ-lactones were obtained in high yields (up to 99%) with excellent enantioselectivities (ee up to 99%). Moreover, this method enables efficient access to enantioenriched dicarbonyl cyclopropane derivatives, which are important intermediates for the synthesis of various bioactive compounds.
We
have established a method for the highly regio- and enantioselective
functionalization of tert-butyl groups via intramolecular
amide carbene insertion into C–H bonds, yielding γ-lactams
with 91% ee in up to 99% yield. This reaction uses a ruthenium(II)
phenyl oxazoline (Ru(II)-Pheox) complex. The catalytic intramolecular
carbene transfer reaction to the primary C–H bond proceeds
rapidly and selectively compared to that with secondary C–H,
benzylic secondary C–H, tert-C–H, or
sp2C–H bonds in the presence of 1 mol % Ru(II)-Pheox
catalyst. This is the first example of a catalytic carbenoid insertion
into an unactivated tert-butyl group with enantiocontrol
at the carbenoid carbon.
Optically active spirocyclopropyloxindole derivatives were efficiently synthesized from diazooxindoles and olefins in the presence of a Ru(ii)-Pheox catalyst.
Computational chemical analysis of Ru(II)‐Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions was performed using density functional theory (DFT). In this study, cyclopropane ring–fused γ‐lactones, which are 5.8 kcal/mol more stable than the corresponding minor enantiomer, are obtained as the major product. The results of the calculations suggest that the enantioselectivity of the Ru(II)‐Pheox–catalyzed intramolecular cyclopropanation reaction is affected by the energy differences between the starting structures 5l and 5i. The reaction pathway was found to be a stepwise mechanism that proceeds through the formation of a metallacyclobutane intermediate. This is the first example of a computational chemical analysis of enantioselective control in an intramolecular carbene‐transfer reaction using C1‐symmetric catalysts.
A reusable and highly enantioselective catalyst for the intramolecular cyclopropanation of various diazo ester and Weinreb amide derivatives was developed. The reactions catalyzed by a water-soluble Ru(II)-Amm-Pheox catalyst proceeded smoothly at room temperature, affording the corresponding bicyclic cyclopropane ring-fused lactones and lactams in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). After screening of various catalysts, the Ru(II)-Amm-Pheox complex having an ammonium group proved to be crucial for the intramolecular cyclopropanation reaction in a water/ether biphasic medium. The water-soluble catalyst could be reused at least six times with little loss in yield and enantioselectivity.
A ligand exchange of one of the acetonitrile
ligands of the (acetonitrile)
4
Ru(II)–phenyloxazoline
complex (Ru(II)–Pheox)
by pyridine was demonstrated, and the location of the exchange reaction
was examined by density functional theory (DFT) calculations to study
the mechanism of its catalytic asymmetric reactions. The acetonitrile
was smoothly exchanged with a pyridine to afford the corresponding
(pyridine)(acetonitrile)
3
Ru(II)–Pheox complex with
a trans orientation (C–Ru–N(pyridine)) in a quantitative
yield, and the complex was analyzed by single-crystal X-ray analysis.
DFT calculations indicated that the most eliminable acetonitrile is
the trans group, which is consistent with the X-ray analysis. The
direction of the ligand exchange is thus determined on the basis of
the energy gap of the ligand elimination instead of the stability
of the metal complex. These results suggested that a reactant in a
Ru–Pheox-catalyzed reaction should approach trans to the C–Ru
bond to generate chirality on the Ru center.
This procedure opens up a route to the syntheses of pharmaceutical and natural products as DCG‐IV (VII), an anticonvulsant agent, and dysibetaine CPa (IX), a marine natural product of pharmacological interest.
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