Polycyclic aromatic hydrocarbons are important structural motifs in organic chemistry, pharmaceutical chemistry, and materials science. The development of a new synthetic strategy toward these ...compounds is described based on the design principle of iron(III)-catalyzed carbonyl–olefin metathesis reactions. This approach is characterized by its operational simplicity, high functional group compatibility, and regioselectivity while relying on FeCl3 as an environmentally benign, earth-abundant metal catalyst. Experimental evidence for oxetanes as reactive intermediates in the catalytic carbonyl–olefin ring-closing metathesis has been obtained.
Transannular carbonyl-olefin metathesis reactions complement existing procedures for related ring-closing, ring-opening, and intermolecular carbonyl-olefin metathesis. We herein report the ...development and mechanistic investigation of FeCl
3
-catalyzed transannular carbonyl-olefin metathesis reactions that proceed
via
a distinct reaction path compared to previously reported ring-closing and ring-opening protocols. Specifically, carbonyl-ene and carbonyl-olefin metathesis reaction pathways are competing under FeCl
3
-catalysis to ultimately favor metathesis as the thermodynamic product. Importantly, we show that distinct Lewis acid catalysts are able to distinguish between these pathways to enable the selective formation of either transannular carbonyl-ene or carbonyl-olefin metathesis products. These insights are expected to enable further advances in catalyst design to efficiently differentiate between these two competing reaction paths of carbonyl and olefin functionalities to further expand the synthetic generality of carbonyl-olefin metathesis.
Transannular carbonyl-olefin metathesis reactions complement existing procedures for related ring-closing, ring-opening, and intermolecular carbonyl-olefin metathesis. This enables molecular editing of steroid-derived frameworks.
An eight-step enantioselective synthesis of lingzhiol is described herein. The sense of an asymmetric Michael reaction is reversed by the choice of metal source, enabling facile access to both ...enantiomers. A spontaneous semipinacol ring contraction enables mild construction of the lingzhiol core, and radical-mediated benzylic oxidation proceeds in the presence of an unprotected secondary alcohol. This represents the shortest enantioselective synthesis of lingzhiol to date and the only enantiodivergent approach to both enantiomers of this meroterpenoid natural product.
Catalytic carbonyl-olefin metathesis reactions have recently been developed as a powerful tool for carbon–carbon bond formation. However, currently available synthetic protocols rely exclusively on ...aryl ketone substrates while the corresponding aliphatic analogs remain elusive. We herein report the development of Lewis acid-catalyzed carbonyl-olefin ring-closing metathesis reactions for aliphatic ketones. Mechanistic investigations are consistent with a distinct mode of activation relying on the in situ formation of a homobimetallic singly bridged iron(III)-dimer as the postulated active catalytic species. These “superelectrophiles” function as more powerful Lewis acid catalysts that form upon association of individual iron(III)-monomers. While this mode of Lewis acid activation has previously been postulated to exist, it has not yet been applied in a catalytic setting. The insights presented are expected to enable further advancement in Lewis acid catalysis by building upon the activation principle of “superelectrophiles” and to broaden the current scope of catalytic carbonyl-olefin metathesis reactions.
Reagents and novel synthetic methodologies that were employed to bring about the synthesis of natural products are discussede, focusing on the strychnine structural elucidation in 1818. ...Stereochemical correlations observed in strychnine that were made in two different X-ray crystallographic reports published in 1951 are also addressed.
Allylations are practical transformations that forge C–C bonds while introducing an alkene for further chemical manipulations. Here, we report a photoenzymatic allylation of α-chloroamides with allyl ...silanes using flavin-dependent “ene”-reductases (EREDs). An engineered ERED can catalyze annulative allylic alkylation to prepare 5, 6, and 7-membered lactams with high levels of enantioselectivity. Ultrafast transient absorption spectroscopy indicates that radical termination occurs via β-scission of the silyl group to afford a silyl radical, a distinct mechanism by comparison to traditional radical allylations involving allyl silanes. Moreover, this represents an alternative strategy for radical termination using EREDs. This mechanism was applied to intermolecular couplings involving allyl sulfones and silyl enol ethers. Overall, this method highlights the opportunity for EREDs to catalyze radical termination strategies beyond hydrogen atom transfer.
Enantiodivergence is an important concept in asymmetric catalysis that enables access to both enantiomers of a product relying on the same chiral source as reagent. This strategy is particularly ...appealing as an alternate approach when only one enantiomer of the required chiral ligand is readily accessible but both enantiomers of the product are desired. Despite the potential significance, general catalytic methods to effectively reverse enantioselectivity by changing an achiral reaction parameter remain underdeveloped. Herein we report our studies focused on elucidating the origin of metal-controlled enantioselectivity reversal in Lewis acid-catalysed Michael additions. Rigorous experimental and computational investigations reveal that specific Lewis and Brønsted acid interactions between the substrate and ligand change depending on the ionic radius of the metal catalyst, and are key factors responsible for the observed enantiodivergence. This holds potential to further our understanding of and facilitate the design of future enantiodivergent transformations.
Enantiodivergence is an important concept in asymmetric catalysis that enables access to both enantiomers of a product relying on the same chiral source as reagent.
We recently defined a method for fabricating multilayer microdevices using poly(ethylene terephthalate) transparency film and printer toner, and showed these could be successfully applied to DNA ...extraction and amplification (Duarte et al., Anal. Chem. 2011, 83, 5182-5189). Here, we advance the functionality of these microdevices with flow control enabled by hydrophobic valves patterned using laser printer lithography. Laser printer patterning of toner within the microchannel induces a dramatic change in surface hydrophobicity (change in contact angle of DI water from 51° to 111°) with good reproducibility. Moreover, the hydrophobicity of the surface can be controlled by altering the density of the patterned toner via varying the gray-scale setting on the laser printer, which consequently tunes the valve's burst pressure. Toner density provided a larger burst pressure bandwidth (158 ± 18 Pa to 573 ± 16 Pa) than could be achieved by varying channel geometry (492 ± 18 Pa to 573 ± 16 Pa). Finally, we used a series of tuned toner valves (with varied gray-scale) for passive valve-based fluidic transfer in a predictable manner through the architecture of a rotating PeT microdevice. While an elementary demonstration, this presents the possibility for simplistic and cost-effective microdevices with valved fluid flow control to be fabricated using nothing more than a laser printer, a laser cutter and a laminator.
The ent-kaurenes represent a class of naturally occurring diterpenes of biological importance. Several members of the ent-kaurenes contain a common, tricyclic spirolactone core as a key structural ...motif. This study details a concise approach toward the development of a Mizoroki–Heck reaction to access this spirolactone core. The strategy described herein was enabled in microscale high-throughput experiments to allow for the rapid identification and optimization of superior reaction conditions.
This paper presents a simple and cost-effective polyester toner microchip fabricated with laser print and cut lithography (PCL) to use with a battery-powered centrifugal platform for fluid handling. ...The combination of the PCL microfluidic disc and centrifugal platform: (1) allows parallel aliquoting of two different reagents of four different volumes ranging from nL to μL with an accuracy comparable to a piston-driven air pipette; (2) incorporates a reciprocating mixing unit driven by a surface-tension pump for further dilution of reagents, and (3) is amenable to larger scale integration of assay multiplexing (including all valves and mixers) without substantially increasing fabrication cost and time. For a proof of principle, a 10 min colorimetric assay for the quantitation of the protein level in the human blood plasma samples is demonstrated on chip with a limit of detection of ∼5 mg mL
−1
and coefficient of variance of ∼7%.
A simple and cost-effective polyester toner microchip was fabricated to provide fluid handling on a centrifugal platform.
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