Iodide-umpolung catalytic system for non-traditional amide coupling from nitroalkanes and amines.

An N-iodosuccinimide (NIS) catalyst was developed for use in the non-traditional synthesis of amide derivatives from nitroalkanes and amines. In contrast to traditional oxidative catalysis, this catalytic system involves reversing the polarities of two catalytic components (umpolung) by means of a hypervalent iodine reagent. A variety of functional groups were tolerated in the reaction, suggesting that they have the potential for use in other types of oxidative catalytic reactions.

Asymmetric 1,2-Carbamoyl Rearrangement of Lithiated Chiral Oxazolidine Carbamates and Diastereoselective Synthesis of α-Hydroxy Amides.

Asymmetric 1,2-carbamoyl rearrangement of lithiated 2-alkenyl carbamates has been investigated. Deprotonation of chiral 2-alkenyl oxazolidine carbamates with sec-butyllithium in ether at -78 °C followed by warming of the resulting 1-lithio-2-alkenyl derivatives to room temperature resulted in 1,2-carbamoyl rearrangement to provide α-hydroxy amides. The rearrangement proceeded with excellent diastereoselectivity and in good to excellent isolated yield of the α-hydroxy amide derivatives. The substrate scope of the reaction was investigated with a variety of 2-alkenyl and benzyl oxazolidine carbamates. A stereochemical model is provided to explain the stereochemical outcome associated with the rearrangement. Acid-catalyzed removal of the chiral oxazolidine afforded α-hydroxy acid in high optical purity.

Leveraging Electron-Deficient Iminium Intermediates in a General Synthesis of Valuable Amines.

The development of reactions converting alkenes and alkynes into valuable building blocks remains one of the main goals of synthetic chemistry. Herein, we present the leveraging of highly electron-deficient iminium ions, rare and fleeting intermediates, into a general amine synthesis. This enables the preparation of amines bearing e.g. valuable α-trifluoromethyl moieties under mild conditions. This broad concept is highlighted by the late-stage amination of quinine into a biologically interesting new analogue.

Enantioselective Total Synthesis of (+)-EBC-23, a Potent Anticancer Agent from the Australian Rainforest.

We describe here an enantioselective synthesis of (+)-EBC-23, a potent anticancer agent from the Australian rainforest. Our convergent synthesis features a [3+2] dipolar cycloaddition of an olefin-bearing 1,3-syn diol unit and an oxime segment containing 1,2-syn diol functionality as the key step. The segments were synthesized in a highly enantioselective manner using Noyori asymmetric hydrogenation of a ß-keto ester and Sharpless asymmetric dihydroxylation of an α,ß-unsaturated ester. Cycloaddition provided isoxazoline derivative which upon hydrogenolysis furnished the ß-hydroxy ketone expediently. A one-pot, acid-catalyzed reaction removed the isopropylidene group, promoted spirocyclization, constructed the complex spiroketal lactone core, and furnished EBC-23 and its C11 epimer. The C11 epimer was also converted to EBC-23 by chemoselective oxidation and reduction sequence. The present synthesis provides convenient access to this family of natural products in an efficient manner.

Multiple Inertial Measurement Unit Combination and Location for Center of Pressure Prediction in Gait.

Center of pressure (COP) during a gait cycle indicates crucial information with regard to fall risk such as balance capacity. The drawbacks of conventional research instruments include inconvenient use during activities of daily living and expensive costs. The present study illustrates the promising fall-relevant information predicted by acceleration and angular velocity data from different placement sensors with machine learning techniques. This approach is inspired by the emerging machine learning technique, specifically the long short-term memory (LSTM), which is often used in time series data and aims to decrease the burden of the user while using the novel wearable technology. The Jaccard similarity coefficient, which implies the consistency of profile alignment between prediction and real situation, achieved 94% accuracy in the walking direction. Furthermore, the number of sensors used and the placement influenced the feasibility of an application. The outcome revealed that the accuracy could exceed 90% with only one sensor placed on the foot in the walking direction, and the toe would be the best location for sensor placement. To examine the performance of machine learning, the current study employed two parameters from different perspectives. One is a commonly used parameter, which represented the error, and the other investigated the similarity between the prediction and ground truth. From a similarity perspective, the parameter can be used as a metric to assess the consistency of profile alignment.

A short synthesis of (±)-antroquinonol in an unusual scaffold of 4-hydroxy-2-cyclohexenone.

Antroquinonol, which was first isolated from a mushroom, Antrodia cinnamomea, found in Taiwan, is an anticancer compound with a unique core structure of 4-hydroxy-2,3-dimethoxycyclohex-2-enone carrying methyl, farnesyl and hydroxyl substituents in the 4,5-cis-5,6-trans configuration. A short synthesis of (±)-antroquinonol is accomplished in seven steps from 2,3,4-trimethoxyphenol, which is oxidized in methanol to a highly electron-rich substrate of 2,3,4,4-tetramethoxycyclohexadienone and then a Michael reaction with dimethylcuprate is performed as the key step, followed by alkylation, reduction and epimerization to incorporate the required substituents at three contiguous stereocenters.

Dynamics of structural relaxation of stilbene 3 in solution, cetyltrimethylammonium bromide micelle, and bis(2-ethylhexyl) sulfosuccinate reverse micelle.

The relaxation dynamics of the excited states of stilbene 3 in various solvents, confined environment cetyltrimethylammonium bromide (CTAB) micelle, and water/bis(2-ethylhexyl) sulfosuccinate (AOT)/hexane reverse micelle are investigated. In the time-resolved decay curves of fluorescence measured in solution at excitation wavelength 256 or 266 nm, stilbene 3 underwent initially an ultrafast internal conversion to the S2 state or was directly excited at the S2 then via a conformational relaxation with time constant 1.1-4.6 ps. This relaxation process displays a linear dependence on solvent viscosity. Slow relaxation in deuterated methanol and water is explained that the vibrational energy is efficiently coupled to the librational modes of solvent. The conformational relaxation rate decreases slightly in the CTAB micelle but is greatly hindered in the AOT reverse micelle with small cavities. According to the results of anisotropy measurements, in both CTAB and AOT reverse micelles with a cavity diameter as large as ∼7 nm, the dynamics of molecular rotation remain significantly hindered.

Enantioselective total synthesis of (+)-galbulin via organocatalytic domino Michael-Michael-aldol condensation.

A concise and practical enantioselective synthesis of (+)-galbulin has been achieved using organocatalytic domino Michael-Michael-aldol condensation and organocatalytic kinetic resolution as the key steps.

Dynamic kinetic asymmetric synthesis of five contiguous stereogenic centers by sequential organocatalytic stetter and Michael-aldol reaction: enantioselective synthesis of fully substituted cyclopentanols bearing a quaternary stereocenter.

A synthesis of fully substituted cyclopentanes bearing a quaternary carbon center and five contiguous stereogenic centers has been achieved by sequential organocatalyzed Stetter and Michael-Aldol reactions of heteroaromatic aldehydes, nitroalkenes, and α,ß-unsaturated aldehydes via the [1 + 2 + 2] annulation strategy with dynamic kinetic asymmetric transformation and excellent enantioselectivities (up to >99% ee).

Sequential organocatalytic Stetter and Michael-Aldol condensation reaction: asymmetric synthesis of fully substituted cyclopentenes via a [1 + 2 + 2] annulation strategy.

A stereoselective synthesis of fully substituted cyclopentenes has been achieved by a sequential organocatalyzed Stetter and Michael-aldol condensation of aromatic aldehydes, nitroalkenes, and α,ß-unsaturated aldehydes via the [1 + 2 + 2] annulation strategy with excellent diastereoselectivities and enantioselectivities (up to >99% ee).