Definition of Several Control Elements Relevant to the Stereodefined Serial Elaboration of Belted Poly(spirotetrahydrofurans) Fitted with a Cyclohexane Core

Abstract

The stereochemistry of the condensations of 2-cyclohexenones, alpha-arylidenecyclohexanones, and alpha-(tert-butyldimethylsiloxy)cyclohexanones carrying one or two (both syn and anti) spirotetrahydrofuran units adjacent to the carbonyl with allyl organometallics (especially indium) and with the Normant reagent (ClMgO(CH(2))(3)MgCl) is described. Good levels of anti stereoselection are observed in the alpha-arylidene series. Subsequent cyclization generates a second (or third) tetrahydrofuran ring possessing trans vicinal oxygens. Useful levels of matched and mismatched diastereoselection are also attainable by prior alpha-oxygenation. The intrinsic differences in diastereomer production between indium and magnesium organometallics are highlighted. A clear distinction regarding the anticipated direction of stereoselectivity is made on the grounds of chelation capabilities and the intra- or intermolecularity of carbon-carbon bond formation. Finally, the two protocols that are described in detail are shown to be iterative, a feature that augurs well for ultimately accessing the eight possible hexaspirocyclohexanes in an efficient and stereocontrolled manner.

Indium in Organic Synthesis

“…With α,β-unsaturated aldehydes and ketones a regioselective 1,2-attack was observed in indium-mediated allyl additions (Scheme 16). 69 Nevertheless, Lee et al found that with certain cyclic enones [2-cyclohexen-1-one, (R)-carvone, 2-cyclohepten-1-one, or chalcone] a 1,4-allyl addition became dominant when chlorotrimethylsilane (TMSCl) was added, although yields did not exceed 70%. With 2-cyclopenten-1-one, 2-methylcyclopenten-1-one, 4,4-dimethylcyclohexen-1-one and with acyclic α,β-unsaturated enones exclusively 1,2-addition was observed.…”

Synthesis and Conformational Properties of the Sterically CrowdedD3d-Symmetric all-trans Hexa(spirotetrahydrofuranyl)cyclohexane System

“…Equatorial attack on the all-equatorial oxygen conformation of 4 is therefore overwhelmingly favored kinetically [5] (Scheme 1). As a consequence, the oxygen atom at this center must be introduced last.…”

“…[3] As a component of the cell membrane, glycoconjugates fulfil important functions [2±4] during cell ± cell recognition, cell ± matrix interaction, and cell growth regulation, and thus also in the development of tumors. [5] Furthermore, they play a significant role in the interaction with biologically active factors such as enzymes, hormones, bacteriotoxins, and viruses. [1,4] The substructure of a carbohydrate, which undergoes permanent change [6] during the life cycle of a cell, influences the biological properties of peptides and proteins.…”

Synthese und konformative Eigenschaften des sterisch überladenen,D3d-symmetrischen all-trans-Hexa(spirotetrahydrofuranyl)cyclohexans

“…Der äquatoriale Angriff auf 4 in der Konformation, in der alle Sauerstoffatome äquatorial stehen, ist daher eindeutig kinetisch bevorzugt [5] …”