Synlett

Synlett 2022; 33: V-DOI: 10.1055/s-0041-1737399Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

This account highlights the role of restricted bond rotations in influencing the excited-state reactivity of organic molecules. It highlights the photochemical reactivity of various organic molecules and the design strategies that could be exploited by chemists to utilize restricted bond rotations to uncover new excited-state reactivity and to achieve selectivity.1 Introduction.2 NEER-Principle and Restricted Bond Rotations in the Excited State3 [2+2]-Photocycloaddition of Enamides4 [3+2]-Photocycloaddition vs. Paternò–Büchi Reaction of Enamides5 Divergent Photoreactivity of Enones Dictated by Restricted Bond Rotations: Norrish–Yang reactions vs. 6π-Photocyclization6 Divergent Photoreactivity of Imides with Alkenes: [2+2]-Photocycloaddition vs. Photoene Reaction7 Summary and Outlook

Three different heterocyclic systems (3-amidocoumarins, 3-amidoazacoumarins, and N-benzoylindol-2-carboxamides) were synthesized based on the strikingly different selectivity of copper-mediated C–O/C–N bond formation from azlactones under various heating conditions. The stereochemistry of the double bond dictated the nature of the products. Microwave irradiation played an important role in the isomerization of the trisubstituted olefin leading to the formation of 3-amidocoumarins and 3-amidoazacoumarins. Three products showed promising-to-good cytotoxic activities against a panel of cancer cell lines, including HepG2 (hepatoblastoma) and MOLT-3 (T-lymphoblast acute lymphoblastic leukemia).

A novel dimerization of 3-chlorooxindoles promoted by potassium ethylxanthate to access isoindigo derivatives is described. The reactions proceeded readily at room temperature in short reaction times. A mechanistic study revealed that the 3-chlorooxindole is initially converted into O-ethyl S-(2-oxo-2,3-dihydro-1H-indol-3-yl) dithiocarbonate, which subsequently undergoes dimerization with elimination of carbon disulfide. In almost all cases, analytically pure isoindigos were isolated in moderate to good yields without a requirement for chromatographic purification.

A facile and convenient reaction of o-alkynylisocyanobenzenes with various active-methylene compounds, including 1,3-diesters, 1,3-diketones, β-keto esters, and β-keto amides, under Brønsted basic conditions, has been developed. Diethyl malonate reacted smoothly with a collection of o-alkynylisocyanobenzenes to provide the corresponding 2-quinolin-2-yl malonates in excellent yields. Acetylacetone gave a mixture of quinolin-4-yl and quinolin-2-yl derivatives. Acetoacetate esters and acetoacetyl amide derivative initially gave 2-quinolin-2-yl adducts that underwent partial deacetylation under the reaction conditions.

By starting from two simple building blocks, benzannulated cyclooctenones were obtained in three steps. Subsequent Grignard/aryl lithium addition to the ketone yielded the corresponding tertiary alcohols that underwent stereoselective acid-catalyzed transannular cyclization to provide a cis-fused 5/5 bicyclic indanylindane framework exclusively. Subsequent stereoselective nucleophilic addition to the indanyl cation by hydride, water, or electron-rich aromatics furnished the 4b-aryltetrahydroindano[1,2-a]indenes in good to excellent yields (up to 92%) in the trans-C9–C9a form in up to a >99:1 diastereomeric ratio.

A visible-light-mediated C-3 formylation of indole catalyzed by eosin Y has been developed using tetramethylethylenediamine as a carbon source and air as an oxidant. This protocol shows high tolerance to a large quantity of functional groups under mild conditions and provides 3-formylated indoles with good yields. This method is a highly attractive alternative to the approach of traditional formylation.

A method for assembling chalcones, glycine ethyl ester hydrochloride, and elemental sulfur toward a synthesis of 4,5-disubstituted thiazoles is reported. The transformation presumably proceeds via a sequence of β-C–H amination, annulation, and dealkoxycarbonylation. This tactic represents a rare example of a method for obtaining such disubstituted thiazoles directly from chalcone C–H bonds.

The regioselectivity of the intramolecular cyclization of bifunctional α-phenyl alkenes can be controlled simply by the choice of the organic chromophore as the photocatalyst. The central photoredox catalytic reaction in both cases is a nucleophilic addition of the hydroxy function to the olefin function of the substrates. N,N-(4-Diisobutylaminophenyl)phenothiazine catalyzes exo-trig cyclizations, whereas 1,7-dicyanoperylene-3,4,9,10-tetracarboxylic acid bisimides catalyze endo-trig additions to products with anti-Markovnikov regioselectivity. We preliminarily report the photoredox catalytic conversions of 11 representative substrates into 20 oxaheterocycles in order to demonstrate the similarity, but also the complementarity, of these two variants in this photoredox catalytic toolbox.

Here we present our work on a Kiyooka aldol protocol for the stereoselective synthesis of tertiary alcohols. In the obtained products, three oxygenated carbon atoms that could further be differentiated flank the chiral tertiary alcohol. This methodology can be applied to simple aromatic or aliphatic aldehydes and more complex substrates bearing a chiral center in the α- and/or β-position. For complex substrates, an unexpected dependency between stereoselectivity and double-bond geometry of the ketene acetal was observed. Furthermore, applications in or towards the synthesis of natural products are presented.1 Introduction2 Scope of the Reaction3 Synthetic Applications4 Conclusion