: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Visible-light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. Photocatalytic variants have been reported for many important transformations, such as cross-coupling reactions, α-amino functionalizations, cycloadditions, ATRA reactions, or fluorinations. To help chemists select photocatalytic methods for their synthesis, we compare in this Review classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed under milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, such as air, oxygen, or amines. Does visible-light photocatalysis make a difference in organic synthesis? The prospect of shuttling electrons back and forth to substrates and intermediates or to selectively transfer energy through a visible-light-absorbing photocatalyst holds the promise to improve current procedures in radical chemistry and to open up new avenues by accessing reactive species hitherto unknown, especially by merging photocatalysis with organo- or metal catalysis.

Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?

In this review, recent examples featuring C–H functionalization in the synthesis of complex natural products are discussed. A focus is given to the way in which C–H functionalization can influence the logical process of retrosynthesis, and the review is organized by the type and method of C–H functionalization.

Recent applications of C–H functionalization in complex natural product synthesis

Photokatalyse mit sichtbarem Licht: Welche Bedeutung hat sie für die organische Synthese?

Chemical synthesis generally requires labor-intensive, sometimes tedious trial-and-error optimization of reaction conditions. Here, we describe a plug-and-play, continuous-flow chemical synthesis system that mitigates this challenge with an integrated combination of hardware, software, and analytics. The system software controls the user-selected reagents and unit operations (reactors and separators), processes reaction analytics (high-performance liquid chromatography, mass spectrometry, vibrational spectroscopy), and conducts automated optimizations. The capabilities of this system are demonstrated in high-yielding implementations of C-C and C-N cross-coupling, olefination, reductive amination, nucleophilic aromatic substitution (SNAr), photoredox catalysis, and a multistep sequence. The graphical user interface enables users to initiate optimizations, monitor progress remotely, and analyze results. Subsequent users of an optimized procedure need only download an electronic file, comparable to a smartphone application, to implement the protocol on their own apparatus.

Reconfigurable system for automated optimization of diverse chemical reactions

Described are the first examples of ketene–alkene [2 + 2] cycloadditions promoted by Lewis acids. Notable features of this method include (1) substantial rate acceleration relative to traditional thermal reactions, (2) good diastereoselectivities and yields for the formation of the cyclobutanone products, and (3) inverse diastereoselectivity compared with related thermal cycloadditions for many examples. These studies not only provide access to synthetically versatile cyclobutanones that cannot be prepared by traditional thermal cycloadditions but also address important mechanistic questions regarding ketene–alkene [2 + 2] cycloaddition reactions.

Lewis Acid-Promoted Ketene–Alkene [2 + 2] Cycloadditions

The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene–alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp3)H oxidation. The synthesis requires only eight steps from norbornadiene.

Total Synthesis of Gracilioether F: Development and Application of Lewis Acid Promoted Ketene-Alkene [2+2] Cycloadditions and Late-Stage CH Oxidation

Described herein are synthetic efforts toward the synthesis of hippolachnin A. Two independently devised routes from the Brown and Wood groups allowed for the synthesis of hippolachnin A from the unusual starting material, quadricyclane, by harnessing the power of late-stage C–H oxidation. Collaborative union of the best features of the two routes allowed for preparation of the molecule with improved efficiency.

Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation

Origins of Diastereoselectivity in Lewis Acid Promoted Ketene–Alkene [2 + 2] Cycloadditions

Ketene–alkene [2+2] cycloadditions are an important class of reactions for chemical synthesis. These processes were exclusively carried out under thermal conditions, which ultimately lead to limitations regarding scope and stereoselectivity. Reviewed herein are recently developed Lewis acid promoted ketene–alkene [2+2] cycloadditions that address several of the problems known to plague these reactions.

Christopher M. Rasik

Papers

Lewis Acid-Promoted Ketene–Alkene [2 + 2] Cycloadditions

Total Synthesis of Gracilioether F: Development and Application of Lewis Acid Promoted Ketene-Alkene [2+2] Cycloadditions and Late-Stage CH Oxidation

Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation

Origins of Diastereoselectivity in Lewis Acid Promoted Ketene–Alkene [2 + 2] Cycloadditions

Intermolecular Ketene–Alkene [2+2] Cycloadditions: The Significance of Lewis Acid Promoted Variants

Christopher M. Rasik

Papers

Lewis Acid-Promoted Ketene–Alkene [2 + 2] Cycloadditions

Total Synthesis of Gracilioether F: Development and Application of Lewis Acid Promoted Ketene-Alkene [2+2] Cycloadditions and Late-Stage CH Oxidation

Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation

Origins of Diastereoselectivity in Lewis Acid Promoted Ketene–Alkene [2 + 2] Cycloadditions

Intermolecular Ketene–Alkene [2+2] Cycloadditions: The Significance of ­Lewis Acid Promoted Variants

Intermolecular Ketene–Alkene [2+2] Cycloadditions: The Significance of Lewis Acid Promoted Variants