In biology-oriented synthesis the underlying scaffold classes of natural products selected in evolution are used to define biologically relevant starting points in chemical structure space for the synthesis of compound collections with focused structural diversity. Here we describe a highly enantioselective synthesis of natural-product-inspired 3,3'-pyrrolidinyl spirooxindoles--which contain an all-carbon quaternary centre and three tertiary stereocentres. This synthesis takes place by means of an asymmetric Lewis acid-catalysed 1,3-dipolar cycloaddition of an azomethine ylide to a substituted 3-methylene-2-oxindole using 1-3 mol% of a chiral catalyst formed from a N,P-ferrocenyl ligand and CuPF(6)(CH(3)CN)(4). Cellular evaluation has identified a molecule that arrests mitosis, induces multiple microtubule organizing centres and multipolar spindles, causes chromosome congression defects during mitosis and inhibits tubulin regrowth in cells. Our findings support the concept that compound collections based on natural-product-inspired scaffolds constructed with complex stereochemistry will be a rich source of compounds with diverse bioactivity.

The synthesis of the o-phenylene-bridged ditin species o-C 6 H 4 (SnXMe 2 ) 2 (2, X ) Cl; 4, X ) F) and o-C 6 H 4 (SnCl 2 Me) 2 (3) is reported and the crystal structures of [o-C 6 H 4 (SnClMe 2 ) 2 ‚ Cl] -[(Ph 3 N) 2 P] + (5) and [o-C 6 H 4 (SnClMe 2 ) 2 ‚F] -[K‚C 20 H 24 O 6 ] + (7) are described. Variabletemperature 119 Sn and 19 F NMR studies indicate that 2 and 4 act as bidentate Lewis acids toward chloride and fluoride ions exclusively forming the stable anionic 1:1 complexes 5, 7, and [o-C 6 H 4 (SnFMe 2 ) 2 ‚F] -[Et 4 N] + ( 8). No formation of dianionic 1:2 adducts was observed even with excess of halide ions. The affinity of 2 toward fluoride is greater than toward chloride. Reaction of 2 with HMPA gives the neutral complex o-C 6 H 4 (SnClMe 2 ) 2 ‚(Me 2 N) 3 PO (10), the crystal structure of which is also described.

The synthesis of the aryldiphosphonic ester C 6 H 2 [P(O)(OEt) 2 ] 2 -1,3-t-Bu-5 (2) and of its organotin derivatives Cand C 6 H 3 [P(O)(OEt) 2 ] 2 -2,4-(Ph 2 RSn) 2 -1,5 (10, R ) Ph; 11, R ) Br). X-ray investigations reveal weak intramolecular Sn-O interactions for 6 (2.865(3)-3.063(4) Å), 9 (2.803(3) Å), and 10 (2.793(2) Å) but strong Sn-O coordinations for 7 (2.203(5)/2.278(6) Å) and 11 (2.379(3)/ 2.412(3) Å), indicating the high donor capacity of the new rigid O,C,O-and O,C-chelating ligands in these compounds. NMR studies confirm that the basic coordination geometry found in the solid state is maintained in solution.

Not only steric protection by bulky substituents but also intramolecular N→Sn coordination makes possible the isolation and characterization of dimeric organotin(I) compounds such as [{2,6‐(Me2NCH2)2C6H3}Sn]2 (see structure), which according to a crystallographic study exhibits a SnSn bond length of 2.9712(12) Å.

The triorgano bismuth compound [Bi(CH2C6H4Cl-2)3]2 (2) was characterized by an X-ray single-crystal structure analysis, which reveals the formation of a two-dimensional network as a result of bismuth−arene π-coordination and π−π-stacking interactions with distances of 3.659 Å (bismuth−arenecentroid) and 3.869 Å (arene centroids), respectively. In order to elucidate the nature of this bonding situation, a quantum mechanical study was carried out. Additionally, a detailed theoretical study on several model compounds of the type BiX3·C6H6 (X = H, Me, OH, OMe, F, Cl, Br) was carried out at the BSSE-corrected MP2/TZVP level of theory in order to develop a better understanding of the bismuth−arene coordination. The calculated bismuth−arene distances in the model compounds BiMe3·C6H6 (∼3.75 Å) and Bi(OMe)3·C6H6 (∼3.35 Å) compare well with experimental values for [Bi(CH2C6H4Cl-2)3]2 (2) and [Bi(OSiPh2 tBu)3]2 (1) of 3.659 and 3.340 Å, respectively. Interaction energies for the model compounds range from 7 kJ/mol for BiMe3·C6H6 to 41 kJ/mol for BiBr3·C6H6.