New chiral phosphine-phosphite ligands in the enantioselective palladium-catalyzed allylic alkylation

A series of chiral phosphine-phosphite ligands 1-6 have been synthesized and used in the enantioselective palladium-catalyzed reaction of rac-1,3-diphenyl-2-propenyl acetate with dimethyl malonate as nucleophile. Ligands 1a, 2, 3, 5a, 6a, and 6b have been synthesized starting from racemic tert-butylphenylphosphinoborane. The use of dynamically resolved Li phosphide (-)-sparteine provided the optically pure ligands. Crystals of the allylpalladium (6a) complex were obtained, suitable for X-ray crystal structure determination. The X-ray crystal structure of the allylpalladium (6a) complex revealed a longer palladium-carbon bond distance trans to the phosphine moiety indicating that the attack of the nucleophile takes place at the carbon trans to the phosphine moiety. This was confirmed by the fact that the phosphine moiety did not affect the enantioselectivity directly. Under mild reaction conditions, enantioselectivities up to 83% were obtained (25 degrees C) with ligand 1e. Systematic variation of the ligand bridge and the phosphite moiety showed that the configuration of the product is controlled by the atropisomerism of the biphenyl substituent at the phosphite moiety. The conformation of the biphenyl group, in turn, is controlled by the substituent at the chiral carbon in the bridge. Ligands with large bite angles yielded higher enantioselectivities.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Unprecedented 1,14‐seco‐Crotofolanes from Croton insularis: Oxidative Cleavage of Crotofolin C by a Putative Homo‐Baeyer–Villiger Rearrangement

EBC‐162 isolated from Croton insularis, obtained from the northern rainforest of Australia, was structurally affirmed as crotofolin C ( 4 ). Novel oxidative degradation products, EBC‐233 and EBC‐300, which are the first crotofolane endoperoxides, were also isolated. Both endoperoxides were found to be stable intermediates, which are proposed to undergo an unprecedented homo‐Baeyer–Villiger biosynthetic rearrangement to give a new class of 1,14‐seco‐crotofolane diterpenes. Prolonged storage of all isolates assisted in authenticating their natural product status. Anticancer activities of reported compounds are presented.     

EBC-232 and 323: A Structural Conundrum Necessitating Unification of Five In Silico Prediction and Elucidation Methods

Structurally unique halimanes EBC-232 and EBC-323, isolated from the Australian rainforest plant Croton insularis, proved considerably difficult to elucidate. The two diastereomers, which consist an unusual oxo-6,7-spiro ring system fused to a dihydrofuran, were solved by unification and consultation of five in silico NMR elucidation and prediction methods [i.e., ACDLabs, olefin strain energy (OSE), DP4, DU8+ and TD DFT CD]. Structure elucidation challenges of this nature are prime test case examples for empowering future AI learning in structure elucidation.     

Anticancer Agents from the Australian Tropical Rainforest: Spiroacetals EBC‐23, 24, 25, 72, 73, 75 and 76

EBC‐23, 24, 25, 72, 73, 75 and 76 were isolated from the fruit of Cinnamomum laubatii (family Lauraceae) in the Australian tropical rainforests. EBC‐23 ( 1 ) was synthesized stereoselectively, in nine linear steps in 8 % overall yield, to confirm the reported relative stereochemistry and determine the absolute stereochemistry. Key to the total synthesis was a series of Tietze–Smith linchpin reactions. The novel spiroacetal structural motif, exemplified by EBC‐23 ( 1 ), was found to inhibit the growth of the androgen‐independent prostate tumor cell line DU145 in the mouse model, indicating potential for the treatment of refractory solid tumors in adults.     

A Robust, Environmentally Benign Catalyst for Highly Selective Hydroformylation

By a sol-gel process a rhodium complex containing a diphosphane with a large natural P-Rh-P bite angle is covalently anchored in a silica matrix (see picture). The immobilized catalyst is a very selective hydroformylation catalyst that is completely and conveniently separated from the product and can be reused in numerous cycles.     

New Casbanes and the First trans-Cyclopropane seco-Casbane from the Australian Rainforest Plant Croton insularis

Investigation of the Australian rainforest plant Croton insularis revealed seven new cis-, two new trans-cyclopropane casbanes, and the first trans-cyclopropane seco-casbane. The relative configuration of the cyclopropane moiety for all compounds (EBC-182, 217, 218, 220, 343, 357, 358, 361, 365, 373; EBC=EcoBiotics Compound) was assigned using ¹³C NMR data. Comparison of the experimental electronic circular dichroism (ECD) spectra with the theoretical curves, calculated by TD-DFT at the B3LYP/6-31+G**//B3LYP/6-31+G** level, in conjunction with NOE data afforded the absolute configuration. EBC-180, 181 and 220 displayed potent activity against cervical carcinoma (HeLa cells).