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Spiroketals and oxaspirolactones are widely found in biologically active natural products, serving as important structural motifs. In this study, we present a Cu(II)-catalyzed cascade cycloisomerization of 2-(5-hydroxyalkynyl)benzoates, enabling the regioselective synthesis of benzannulated [5,6]-oxaspirolactones containing an isochromen-1-one moiety. This strategy offers a rapid and efficient approach to access a diverse array of benzannulated [5,6]-oxaspirolactones. The methodology presented here showcases a broad substrate scope, delivering good yields and scalability up to gram scale. The structures of the oxaspirolactones were unequivocally confirmed through single-crystal X-ray analysis and by analogy using 1H and 13C{1H} NMR data.

A reliable method for enone transposition has been developed with the help of silyl group masking. Enantio-switching, substituent shuffling, and Z-selectivity are the highlights of the method. The developed method was applied for the first total synthesis of peribysin D along with its structural revision. Formal synthesis of E-guggulsterone and E-volkendousin was also claimed using a short sequence.

Using Artificial Neural Networks (ANNs), four distinct models have been developed for the prediction of solid-state properties of cocrystals: melting point, lattice energy, and crystal density. The models use three input parameters for the pure model compound (MC) and three for the pure coformer. In addition, as an input parameter the model uses the pKadifference between the MC and the coformer, and a 1:1 MC–conformer binding energy as calculated by a force field method. Notably, the models require no data for the actual cocrystals. In total, 61 CCs (two-component molecular cocrystals) were used to construct the models, and melting temperatures and crystal densities were extracted from the literature for four MCs: caffeine, theophylline, nicotinamide, and isonicotinamide. The data set includes 14 caffeine cocrystals, 9 theophylline cocrystals, 9 nicotinamide cocrystals, and 29 isonicotinamide cocrystals. Model-I is trained using known cocrystal melting temperatures, lattice energies, and crystal densities, to predict all three solid-state properties simultaneously. The average relative deviation for the training set is 2.49%, 6.21%, and 1.88% for the melting temperature, lattice energy, and crystal density, respectively, and correspondingly 6.26%, 4.58%, and 0.99% for the valdation set. Model-II, model-III, and model-IV were built using the same input neurons as in model-I, for separate prediction of each respective output solid–state property. For these models the average relative deviation for the training sets becomes 1.93% for the melting temperature model-II, 1.29% for the lattice energy model-III, and 1.03% for the crystal density model-IV, and correspondingly 2.23%, 2.40%, and 1.77% for the respective validation sets.

We present a streamlined, metal-free, one-pot domino approach to efficiently synthesize oxazolidinethione derivatives containing substituted quaternary amino acids. This method employs α-amino esters, aldehydes, and CS2under mild conditions, constructing three new bonds (C–N, C–C, and C–O) to produce oxazolidinethione compounds featuring a quaternary center and a beta-hydroxy derivative in high yields. This scalable protocol enables the creation of libraries of biologically significant, intricate amino acid derivatives using amino esters and aldehydes.

A method for the construction of heterocyclic scaffold 2,3-dihyro-1H-pyrrolo[1,2-a]indoles via arylsulfonyl radical-triggered cascade cyclization of unactivated alkene-tethered indoles in the absence of any external photocatalyst has been developed. This protocol features easily accessible starting materials such as sodium metabisulfite and aryldiazonium tetrafluoroborates at room temperature and offers good functional group compatibility, enabling the introduction of various functionalized sulfonyl and azo groups into pyrrolo[1,2-a]indoles.

This work showcases an unprecedented Au(III)-catalyzed cascade cyclization of 2-(4-hydroxyalkynyl)benzoates to access benzannulated [5,5]-oxaspirolactones related to biologically active natural products. This reaction proceeds through an initial 5-endo-dig mode of hydroalkoxylation of the alkynol segment to give the oxocarbenium species (via cyclic enol-ether) followed by the addition of carboxylate onto the oxocarbenium that delivers the oxaspirolactone scaffold. While testing this method’s scope, we found that the steric and electronic environment of the hydroxyl group could alter the reaction pathway that delivers isochromenone through a competitive 6-endo-dig mode of attack of the carboxylate onto the tethered alkyne.

A full account of our efforts toward the stereoselective total synthesis of sesquiterpenoid-derived natural products (±)-pleurospiroketals A and B is described. Commercially available 3-methyl-2-cyclohexenone and 2,2-dimethyloxirane were used as key building blocks, and the substrate-controlled stereoselection was exploited to access the entire stereochemistry of these natural products. Initially, a planned synthetic route involving a [6,5]-bicyclic lactone intermediate was found to be insurmountable, and the later strategy comprising OsO4-NMO-mediated dihydroxylation of 3-methyl-2-cyclohexenone, followed by Luche reduction, Eschenmoser methylenation, and Brønsted acid-induced spiroketalization steps, was ultimately identified as the reliable strategy.