The first asymmetric hydrogenation of β-cyanoacrylate esters has been developed to furnish chiral β-cyano esters with excellent yields and excellent enantioselectivities. Notably, the catalyst with a single H-bond donor in a precise position performed better than that with double H-bond donors.
Hydroformylation of 1,2-disubstituted alkenes usually occurs at the α position of the directing heteroatom such as oxygen atom and nitrogen atom. By contrast, to achieve hydroformylation on the β position of the heteroatom is a tough task. Herein, we report the asymmetric rhodium-catalyzed hydroformylation of 1,2-disubstituted alkenylsilanes with excellent regioselectivity at the β position (relative to the silicon heteroatom) and enantioselectivity. In a synthetic sense, we achieve the asymmetric hydroformylation on the β position of the oxygen atom indirectly by using the silicon group as a surrogate for the hydroxyl. Density functional theory (DFT) calculations are carried out to examine energetics of the whole reaction path for Rh/YanPhos-catalyzed asymmetric hydroformylation and understand its regioselectivity and enantioselectivity. Our computational study suggests that the silicon group can activate the substrate and is critical for the regioselectivity.
Excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (up to >99:1 d.r.) have been achieved in the desymmetrization of cyclopentenes by catalytic hydroformylation. This novel methodology provides an efficient and concise synthetic route to chiral cyclopentane carboxaldehydes. The key intermediate, (1S,3S)-(3-hydroxymethyl)cyclopentanol, for the synthesis of carbocyclic-ddA was obtained in three steps.
Transition metal-catalyzed [4 + 2 + 1] cycloaddition
of in situ generated ene/yne–ene–allenes
(from
ene/yne–ene propargyl esters) and carbon monoxide (CO) gives
the [4 + 2 + 1] cycloadducts rather than [2 + 2 + 1] cycloadducts.
Investigating the mechanism of this [4 + 2 + 1] reaction and understanding
why the [2 + 2 + 1] reaction does not compete and the role of the
allene moiety in the substrates are important. This is also helpful
to guide the future design of new [4 + 2 + 1] cycloadditions. Reported
here are the kinetic and computed studies of the [4 + 2 + 1] reactions
of ene–ene propargyl esters and CO. A quantum chemical study
(at the DLPNO-CCSD(T)//BMK level) revealed that the [4 + 2 + 1] reaction
includes four key steps, which are 1,3-acyloxy migration (rate-determining
step), oxidative cyclization, CO migratory insertion, and reductive
elimination. The allene moiety in the substrates is critical for providing
additional coordination to the rhodium center in the final step of
the catalytic cycle, which in turn favors the reductive elimination
transition state in the [4 + 2 + 1] rather than in the [2 + 2 + 1]
pathway. The CO insertion step in the [4 + 2 + 1] reaction, which
could occur through either the UP (favored here) or DOWN CO insertion
pathway, has also been deeply scrutinized, and some guidance from
this analysis has been provided to help the future design of new [4
+ 2 + 1] reactions. Quantum chemical calculations have also been applied
to explain why [4 + 2] and [4 + 1] cycloadditions do not happen and
how trienes as side products for some substrates are generated.
Lewis
base-catalyzed transformations of allenes have received much
attention over the last decades. However, this type of reaction has
so far been limited to activated allenes bearing an electron-withdrawing
group. On the other hand, cleavage of an amide C–N bond to
forge other chemical bonds has been widely reported but restricted
to low atom economy due to the waste of the amine moiety of amides.
We initiated a project of metal-catalyzed amino-acylation of allenes
via cleavage of amide C–N bonds. Surprisingly, an amino-acylation
of weakly activated aryl allenes was discovered via Lewis base catalysis,
providing 2-methyl-3-aroylindole products, “privileged structures”
in drug discovery. This is a unique example of Lewis base catalysis
of weakly activated allenes, which was not reported yet. Extensive
experimental and computational studies have been conducted to provide
insight into the reaction mechanism. The nucleophilic addition of
Lewis base catalyst to aryl allene is the rate-limiting step. A challenging
[1,3]-proton transfer is realized by nitrogen anion intermediate assisted
sequential [1,4]- and [1,6]-proton transfer in the reaction pathway.
Achieving transition-metal-catalyzed reactions of diene-ynes/diene-enes and carbon monoxide (CO) to deliver [4 + 2 + 1] cycloadducts, rather than the kinetically favored [2 + 2 + 1] products, is challenging. Here, we report that this can be solved by adding a cyclopropyl (CP) cap to the diene moiety of the original substrates. The resulting CP-capped diene-ynes/diene-enes can react with CO under Rh catalysis to give [4 + 2 + 1] cycloadducts exclusively without forming [2 + 2 + 1] products. This reaction has a broad scope and can be used to synthesize useful 5/7 bicycles with a CP moiety. Of the same importance, the CP moiety in the [4 + 2 + 1] cycloadducts can act as an intermediate group for further transformations so that other challenging bicyclic 5/7 and tricyclic 5/ 7/5, 5/7/6, and 5/7/7 skeletons, some of which are widely found in natural products, can be accessed. The mechanism of this [4 + 2 + 1] reaction has been investigated by quantum chemical calculations, and the role of the CP group in avoiding the possible side [2 + 2 + 1] reaction has been identified, showing that the [4 + 2 + 1] is controlled by releasing the ring strain in the methylenecyclopropyl (MCP) group (about 7 kcal/mol) in the CP-capped dienes.
Some new sydnonyl-substituted thiazolidine derivatives were synthesized in high yields by the modified Knoevenagel condensation of 3-aryl-4-formylsydnones with thiazolidine-2,4-dione and 2-thioxo-thiazolidine-4-one, respectively. All the synthesized thiazolidine derivatives were screened by paper-disc method to identify their antimicrobial activities against three bacteria viz. Staphylococcus aureus, Proteus vulgaris and Escherichia coli, and two fungal cultures viz. Aspergillus niger and Penicillium citrinum. The reference drugs were Norfloxacin and Griseofulvin, respectively. The screening data indicated that the tested sydnonyl-substituted thiazolidine derivatives exhibited no obvious antibacterial activity compared with the standard drug Norfloxacin. However, thiazolidine derivatives displayed significant antifungal activities against Penicillium citrinum and Aspergillus niger. Notably, all of the tested compounds showed growth inhibitory activity 1.5-4.4 times higher than that of the standard drug Griseofulvin against the two fungi.
An efficientr hodium-catalyzed asymmetric hydrogenation of challengingt etrasubstituted cyclic enamides has been developed, affording cyclic chiral amides with high yieldsa nd excellent enantioselectivities( up to 99% yield and > 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral cycloalkylamines with two contiguous stereogenic centers. Thep otential utility of this protocol in the synthesis of bioactive molecules is also disclosed.
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