We reported a mechanistic study on asymmetric O–H
insertion
reaction of α-diazoester with carboxylic acid using Rh2(OAc)4/chiral guanidine-amide as the cocatalyst by density
functional theory [B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/[6-31G**,
SDD] (SMD, Et2O)]. The catalytic reaction included two
stages: (i) formation of Rh–carbene species, subsequently by
the construction of C–O bond forming enol and (ii) chiral guanidinium
salt-assisted H-transfer to the enol. In cooperative catalysis, Rh2(OAc)4 helped to form an enol intermediate via
high-reactivity Rh–carbene species, while the in situ-formed
guanidium carboxylate acted as a chiral proton shuttle to construct
a hydrogen bonding net for the stereo-determinant protonation. The
repulsions between the phenyl group of the enol intermediate and the
cyclohexyl as well as the ortho-substituted isopropyl group of chiral
guanidine played important roles in controlling stereoselectivity.
A disadvantageous steric arrangement in si-face attack weakened the
stabilizing electrostatic and orbital interaction of reacting species
in the H-transfer step, enhancing the pathway to form a predominant
product with R-configuration in the two competing
pathways. A model was proposed to explain the asymmetric induction
of chiral guanidine-amide in protonation.
The mechanism and stereoselectivity of an asymmetric cyclopropanation reaction between 3-alkenyl-oxindole and sulfoxonium ylide catalyzed by a chiral N,N′dioxide−Mg(II) complex were explored using the B3LYP-D3(BJ) functional and the def2-TZVP basis set. The noncatalytic reaction occurred via a stepwise mechanism, with activation barriers of 21.6−23.5 kcal mol −1 . The C 2 −C α bond formed followed by the carbanion S N 2 substitution, constructing a three-membered ring in spiro-cyclopropyl oxindoles, accompanied by the release of dimethylsulfoxide. The electron-withdrawing Nprotecting t-butyloxy carbonyl (Boc) and acetyl (Ac) groups in isatin enhanced the local electrophilicity of the C2 atom and the repulsion between the two COPh groups in the reactants, contributing to high reactivity as well as good diastereoselectivity results. The N-Boc-3-phenacylideneoxindole coordinated to the chiral ligand (L-PiPr 2 ) in a bidentate fashion, forming a hexacoordinate-Mg(II) complex as the reactive species. The origin of enantioselectivity was from the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the si-face of oxindole. The repulsion between the SO(CH 3 ) 2 and COPh groups in 3-alkenyl-oxindole and the neighboring ortho-iPr group in the ligand directed the re-face of ylide to attack the re-face of oxindole preferably, contributing to the high diastereoselectivity of the product. A metal-ion−ligand matching relationship was important for a good asymmetric induction effect of the chiral N,N′-dioxide−metal catalyst. A large chiral cavity in the Zn(II) catalyst weakened the shielding effect of 2,6-diisopropylphenyl groups in the ligand toward the prochiral face of oxindole, leading to inferior enantioselectivity observed in the experiment.
The reaction mechanism and enantioselectivity
of the asymmetric
[2 + 2] cycloaddition between an alkynone (R1) and a cyclic enol silyl
ether (R2) were studied theoretically by the DFT method at the B3LYP-D3(BJ)/6-311G**(CH2Cl2,SMD)//B3LYP-D3(BJ)/def2-SVP(CH2Cl2,SMD) theoretical level. The noncatalytic reaction occurred
via a stepwise mechanism. The first C–C bond was constructed
by coupling two pseudo radical centers generated at the most nucleophilic
C2 atom in the cyclic enol silyl ether and the most electrophilic
terminal Cβ atom in the alkynone, which was responsible
for the regioselectivity of the reaction. The counterion NTf2
– could stabilize the Zn(II) complex by coordinating
to the center metal, forming a high-reactivity hexacoordinate Zn(II)-complex
intermediate. The bulky CF3 group in the NTf2
– ion adjusted the blocking effect of o-iPr in aniline of the ligand toward the reactive site (that is, the
Cβ atom in the alkynone) and induced the si face of the cyclic enol silyl ether to approach the alkynone
from its less hindered re face, achieving a high
enanotioselectivity of products. The Pauli repulsion between the Zn(II)-associated
moiety and cyclic enol silyl ether fragment was the main contributor
to the stereodifference of the two competing pathways in chiral N,N′-dioxide-Zn(II)-catalyzed [2
+ 2] cycloaddition. The unfavorable steric repulsion between the o-iPr group of aniline in the ligand and tert-butyldimethylsilyl (TBS) in the cyclic enol silyl ether
along the re face path translated into a more destabilizing
ΔE
Pauli value, leading to the predominant
cycloaddition product (P-RR) observed in experiments.
Variation of the linkage and chiral backbone could affect the repulsion
among the o-iPr in the ligand, the
counterion NTf2
–, and substrates, leading
to different stereochemical outcomes. These results are in good agreement
with experimental observations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.