Noncovalent Interactions of π Systems with Sulfur: The Atomic Chameleon of Molecular Recognition.

The relative strength of noncovalent interactions between a thioether sulfur atom and various π systems in designed top pan molecular balances was determined by NMR spectroscopy. Compared to its oxygen counterpart, the sulfur atom displays a remarkable ability to interact with almost equal facility over the entire range of π systems studied, with the simple alkene emerging as the most powerful partner. With the exception of the O⋅⋅⋅heteroarene interaction, all noncovalent interactions of sulfur with π systems are favoured over oxygen.

Noncovalent Lone Pair⋠⋠⋠(No-π!)-Heteroarene Interactions: The Janus-Faced Hydroxy Group.

A comparative study using NMR spectroscopy and designed top-pan molecular balances demonstrates that the noncovalent interaction of a hydroxy group with π-deficient pyrazine and quinoxaline units involves a lone pair-heteroarene interaction which is much stronger and solvent independent when measured relative to the classical π-facial hydrogen bond to a benzene ring. Alkyl fluorides also prefer the heteroarene rings over the benzene ring. The attractive interaction between a quinoxaline and a terminal alkyne is also stronger than the intramolecular hydrogen bond to an arene.

Surfing π†clouds for noncovalent interactions: arenes versus alkenes.

A comparative study of molecular balances by NMR spectroscopy indicates that noncovalent functional-group interactions with an arene dominate over those with an alkene, and that a π-facial intramolecular hydrogen bond from a hydroxy group to an arene is favored by approximately 1.2 kJ mol(-1). The strongest interaction observed in this study was with the cyano group. Analysis of the series of groups CH2CH3, CH=CH2, C≡CH, and C≡N shows a correlation between conformational free-energy differences and the calculated charge on the C(α) atom of these substituents, which is indicative of the electrostatic nature of their π interactions. Changes in the free-energy differences of conformers show a linear dependence on the solvent hydrogen bond acceptor parameter ß.

The cascade radical cyclisation approach to prenylated alkaloids: synthesis of stephacidin A and notoamide B.

A strategy for the synthesis of members of the prenylated indole alkaloid family is described, which involves a radical cascade process of an appropriately substituted diketopiperazine (DKP) core structure. Several approaches to the generation of the initial radical were explored, with the most successful involving treatment of a sulfenyl substituted DKP under classical reductive conditions by heating with Bu3SnH and a radical initiator. The required, fully substituted, radical precursor DKP structures were prepared using regio- and stereocontrolled enolate chemistry of simpler proline-tryptophan derived DKPs. The new approach allowed rapid access to a key polycyclic indoline structure, which was converted into either of the natural products stephacidin A or notoamide B.

Rapid access to polycyclic indolines related to the stephacidin alkaloids using a radical cascade.

A new and very rapid access to indoline intermediates useful for the synthesis of alkaloids related to the stephacidins has been established using a radical cascade process initiated from a sulphur-substituted diketopiperazine.